All Publications


  • High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California. Gastroenterology Cholankeril, G., Podboy, A., Aivaliotis, V. I., Tarlow, B., Pham, E. A., Spencer, S., Kim, D., Hsing, A., Ahmed, A. 2020

    View details for DOI 10.1053/j.gastro.2020.04.008

    View details for PubMedID 32283101

  • Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005-2014. Digestive diseases and sciences Kim, D., Yoo, E. R., Li, A. A., Tighe, S. P., Cholankeril, G., Ahmed, A. 2020

    Abstract

    BACKGROUND: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging.AIMS: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA.METHODS: We performed a retrospective analysis using the National Inpatient Sample, 2005-2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality.RESULTS: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44-1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of -3.1% (95% CI -5.7% to -0.3%).CONCLUSIONS: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade.

    View details for DOI 10.1007/s10620-020-06162-0

    View details for PubMedID 32124196

  • Treating Alcohol Use Disorder in Chronic Liver Disease. Clinical liver disease Yoo, E. R., Cholankeril, G., Ahmed, A. 2020; 15 (2): 77–80

    Abstract

    http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-yoo a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-yoo an interview with the author Answer questions and earn https://www.wileyhealthlearning.com/Activity/7036145/disclaimerspopup.aspx.

    View details for DOI 10.1002/cld.881

    View details for PubMedID 32226621

    View details for PubMedCentralID PMC7098671

  • Diet Quality and its Association with Nonalcoholic Fatty Liver Disease and All-cause and Cause-specific Mortality. Liver international : official journal of the International Association for the Study of the Liver Yoo, E. R., Kim, D., Vazquez-Montesino, L. M., Escober, J. A., Li, A. A., Tighe, S. P., Fernandes, C. T., Cholankeril, G., Ahmed, A. 2020

    Abstract

    Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD.We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis.Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose-dependent manner. During the median follow-up of 23 years, having a higher diet quality was associated with reduction in risk of all-cause mortality in the age, sex, Race/ethnicity-adjusted hazard ratio (HR) (Q4, HR:0.60 95% CI: 0.52-0.68) and the multivariate model (Q4, HR:0.81 95% CI: 0.71-0.92). Higher diet quality was associated with a lower risk for all-cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer-related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD.High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer-related and all-cause mortality in those without NAFLD.

    View details for DOI 10.1111/liv.14374

    View details for PubMedID 31910319

  • Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease. Hepatology (Baltimore, Md.) Kim, D., Vazquez-Montesino, L. M., Li, A. A., Cholankeril, G., Ahmed, A. 2020

    Abstract

    In general, physical activity (PA) and nonalcoholic fatty liver disease (NAFLD) have an inverse association. However, studies assessing the impact of the widely accepted Physical Activity Guidelines for Americans (PA Guidelines) on NAFLD are lacking. We performed a serial, cross-sectional analysis among adults by using the 2007-2016 United States National Health and Nutrition Examination Survey. NAFLD and advanced fibrosis were defined by using various noninvasive panels. A PA questionnaire assessed the leisure-time PA, occupation-related PA, transportation-related PA, and total sitting time as sedentary behavior. PA was categorized according to the PA Guidelines. Of the 24,588 individuals (mean age 47.4 years; 47.9% males), leisure-time PA (≥150 minutes/week) demonstrated 40% lower odds of NAFLD, whereas transportation-related PA was associated with 33% risk reduction in NAFLD. Analysis of total PA and sitting times simultaneously showed a dose-response association between sitting time and NAFLD (P for trend <0.001). Compliance with the PA Guidelines was lower in NAFLD versus non-NAFLD. The trends in compliance with the PA Guidelines for any type of PA remained stable in NAFLD except for a downtrend in transportation-related PA. In contrast, an improvement in compliance with the PA Guidelines for leisure-time was noted in the non-NAFLD cohort. Although PA demonstrated 10% stronger association with risk reduction of NAFLD in women, women showed a lower tendency of meeting the PA guidelines. Trends in total sitting time increased significantly regardless of NAFLD status. Conclusion: Sedentary behavior emerged as an independent predictor of NAFLD. Overall compliance with the PA Guidelines was lower in the NAFLD cohort with sex- and ethnicity-based differences. Implementation of these observations in clinical practice may improve our understanding as well as clinical outcomes.

    View details for DOI 10.1002/hep.31158

    View details for PubMedID 32012316

  • The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study. Drug and alcohol dependence Dennis, B. B., Akhtar, D., Cholankeril, G., Kim, D., Sanger, N., Hillmer, A., Chawar, C., D'Elia, A., Panesar, B., Worster, A., Marsh, D. C., Thabane, L., Samaan, Z., Ahmed, A. 2020; 209: 107917

    Abstract

    Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear.To determine whether CLD is associated with poor response to methadone treatment.Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model.CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001).CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients.

    View details for DOI 10.1016/j.drugalcdep.2020.107917

    View details for PubMedID 32088589

  • Regional Trends in Mortality from Alcohol-Induced Causes in the United States, 2000-2017. Journal of general internal medicine Cholankeril, G., Dennis, B. B., Kim, D., Ahmed, A. 2019

    View details for DOI 10.1007/s11606-019-05442-4

    View details for PubMedID 31792862

  • NATIONAL ESTIMATE OF THE FREQUENCY, TRENDS AND HEALTHCARE BURDEN OF CARE FRAGMENTATION IN READMISSIONS FOR END-STAGE LIVER DISEASE IN THE US Adejumo, A., Dennis, B., Cholankeril, G., Wong, R. J., Kim, D., Younossi, Z. M., Ahmed, A. WILEY. 2019: 449A
  • Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Yoo, E. R., Li, A. A., Fernandes, C. T., Tighe, S. P., Cholankeril, G., Hameed, B., Ahmed, A. 2019; 17 (11): 2379–81
  • Trends in hospitalizations for chronic liver disease-related liver failure in the United States, 2005-2014 LIVER INTERNATIONAL Kim, D., Cholankeril, G., Li, A. A., Kim, W., Tighe, S. P., Hameed, B., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 39 (9): 1661–71

    View details for DOI 10.1111/liv.14135

    View details for Web of Science ID 000485292200008

  • Suboptimal Use of Inpatient Palliative Care Consultation May Lead to Higher Readmissions and Costs in End-Stage Liver Disease. Journal of palliative medicine Adejumo, A. C., Kim, D., Iqbal, U., Yoo, E. R., Boursiquot, B. C., Cholankeril, G., Wong, R. J., Kwo, P. Y., Ahmed, A. 2019

    Abstract

    Background/Aims: Patients with end-stage liver disease (ESLD) have a high risk for readmission. We studied the role of palliative care consultation (PCC) in ESLD-related readmissions with a focus on health care resource utilization in the United States. Methods: We performed a retrospective longitudinal analysis on patients surviving hospitalizations with ESLD from January 2010 to September 2014 utilizing the Nationwide Readmissions Database with a 90-day follow-up after discharge. We analyzed annual trends in PCC among patients with ESLD. We matched PCC to no-PCC (1:1) using propensity scores to create a pseudorandomized clinical study. We estimated the impact of PCC on readmission rates (30- and 90-day), and length of stay (LOS) and cost during subsequent readmissions. Results: Of the 67,480 hospitalizations with ESLD, 3485 (5.3%) received PCC, with an annual increase from 3.6% to 6.7% (p for trend <0.01). The average 30- and 90-day annual readmission rates were 36.2% and 54.6%, respectively. PCC resulted in a lower risk for 30- and 90-day readmissions (hazard ratio: 0.42, 95% confidence interval [CI]: 0.38-0.47 and 0.38, 95% CI: 0.34-0.42, respectively). On subsequent 30- and 90-day readmissions, PCC was associated with decreased LOS (5.6- vs. 7.4 days and 5.7- vs. 6.9 days, p<0.01) and cost (US $48,752 vs. US $75,810 and US $48,582 vs. US $69,035, p<0.01). Conclusion: Inpatient utilization of PCC for ESLD is increasing annually, yet still remains low in the United States. More importantly, PCC was associated with a decline in readmission rates resulting in a lower burden on health care resource utilization and improvement in cost savings during subsequent readmissions.

    View details for DOI 10.1089/jpm.2019.0100

    View details for PubMedID 31397615

  • Depression is associated with non-alcoholic fatty liver disease among adults in the United States. Alimentary pharmacology & therapeutics Kim, D., Yoo, E. R., Li, A. A., Tighe, S. P., Cholankeril, G., Harrison, S. A., Ahmed, A. 2019

    Abstract

    BACKGROUND: Currently, the relationship between depression and non-alcoholic fatty liver disease (NAFLD) is not clearly defined.AIM: To determine whether depression is associated with NAFLD and NAFLD-related advanced fibrosis in a large population sample.METHODS: We performed a cross-sectional analysis using the 2007-2016 National Health and Nutrition Examination Survey database among adults (20years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ-9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis-4 score.RESULTS: Of the 10484 subjects (mean age 47.0years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6-2.2-fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17-1.87), HSI (OR 1.51 95% CI 1.04-2.19) and FLI (OR 2.01 95% CI 1.65-2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD-related advanced fibrosis.CONCLUSIONS: In a nationally representative sample of US adults, depression was independently associated with NAFLD.

    View details for DOI 10.1111/apt.15395

    View details for PubMedID 31328300

  • Trends in overall, cardiovascular and cancer-related mortality among individuals with diabetes reported on death certificates in the United States between 2007 and 2017 DIABETOLOGIA Kim, D., Li, A. A., Cholankeril, G., Kim, S. H., Ingelsson, E., Knowles, J. W., Harrington, R. A., Ahmed, A. 2019; 62 (7): 1185–94
  • Increasing Trends in Transplantation of HCV-Positive Livers Into Uninfected Recipients CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Li, A. A., Dennis, B. B., Toll, A. E., Kim, D., Bonham, C., Nair, S., Ahmed, A. 2019; 17 (8): 1634–36
  • Disparate Trends in Mortality of Etiology-Specific Chronic Liver Diseases Among Hispanic Subpopulations CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Li, A. A., Perumpail, R. B., Cholankeril, G., Gonzalez, S. A., Kim, W., Ahmed, A. 2019; 17 (8): 1607-+
  • Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States LIVER INTERNATIONAL Kim, D., Yoo, E. R., Li, A. A., Cholankeril, G., Tighe, S. P., Kim, W., Harrison, S. A., Ahmed, A. 2019; 39 (7): 1335–42

    View details for DOI 10.1111/liv.14110

    View details for Web of Science ID 000475387700019

  • Changing Trends in Etiology-Based and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States HEPATOLOGY Kim, D., Li, A. A., Perumpail, B. J., Gadiparthi, C., Kim, W., Cholankeril, G., Glenn, J. S., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 69 (3): 1064–74

    View details for DOI 10.1002/hep.30161

    View details for Web of Science ID 000459816500013

  • The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2019; 7 (1)

    Abstract

    Recent breakthrough in our understanding pertaining to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has pointed to dysregulation or derangement of the gut microbiome, also known as dysbiosis. This has led to growing interest in probiotic supplementation as a potential treatment method for NAFLD due to its ability to retard and/or reverse dysbiosis and restore normal gut flora. A thorough review of medical literature was completed from inception through July 10, 2018 on the PubMed database by searching for key terms such as NAFLD, probiotics, dysbiosis, synbiotics, and nonalcoholic steatohepatitis (NASH). All studies reviewed indicate that probiotics had a beneficial effect in patients with NAFLD and its subset NASH. Results varied between studies, but there was evidence demonstrating improvement in liver enzymes, hepatic inflammation, hepatic steatosis, and hepatic fibrosis. No major adverse effects were noted. Currently, there are no guidelines addressing the use of probiotics in the setting of NAFLD. In conclusion, probiotics appear to be a promising option in the treatment of NAFLD. Future research is necessary to assess the efficacy of probiotics in patients with NAFLD.

    View details for PubMedID 30823570

  • Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016. Hepatology international Kim, D., Kim, W., Adejumo, A. C., Cholankeril, G., Tighe, S. P., Wong, R. J., Gonzalez, S. A., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019

    Abstract

    BACKGROUND AND AIM: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample.METHODS: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index.RESULTS: The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p<0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks.CONCLUSIONS: Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study.

    View details for PubMedID 30694445

  • Trends in Mortality From Extrahepatic Complications in Patients With Chronic Liver Disease, From 2007 Through 2017. Gastroenterology Kim, D., Adejumo, A. C., Yoo, E. R., Iqbal, U., Li, A. A., Pham, E. A., Cholankeril, G., Glenn, J. S., Ahmed, A. 2019

    Abstract

    Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States (US).We performed a population-based study using US Census and the National Center for Health Statistics mortality records, from 2007 through 2017. We identified trends in age-standardized mortality using joinpoint trend analysis with estimates of annual percentage change.The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study age-standardized mortality from hepatitis B virus-related extrahepatic complications increased with an average annual percentage of 2.0%. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly.In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.

    View details for DOI 10.1053/j.gastro.2019.06.026

    View details for PubMedID 31251928

  • Temporal Trends Associated With the Rise in Alcoholic Liver Disease-related Liver Transplantation in the United States TRANSPLANTATION Cholankeril, G., Gadiparthi, C., Yoo, E. R., Dennis, B. B., Li, A. A., Hu, M., Wong, K., Kim, D., Ahmed, A. 2019; 103 (1): 131–39
  • Trends in Hospitalizations for Chronic Liver Disease-related Liver Failure in the United States, 2005-2014. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Cholankeril, G., Li, A. A., Kim, W., Tighe, S. P., Hameed, B., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019

    Abstract

    Current estimates of the population-based disease burden of liver failure or end-stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in-hospital mortality among patients with ESLD in the United States (US).A retrospective analysis was performed utilizing the National Inpatient Sample (NIS) from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in-hospital mortality were analyzed from 2005 to 2014.Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100,000 persons to 159.9/100,000 persons. In terms of HCC, hospitalization rates increased from 13.6/100,000 to 22.1/100,000. In patients with nonalcoholic fatty liver disease (NAFLD)-related decompensated cirrhosis, the hospitalization rate increased from 13.4/100,000 to 32.1/100,000 with an annual incremental increase of 10.6%, a magnitude two-fold higher than other etiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (29.3% to 27.6% for HCV; 39.0% to 37.4% for ALD). Although the overall in-hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD-related decompensated cirrhosis showed no significant change.Among etiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non-HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD-related hospitalizations and its impact on resource utilization. This article is protected by copyright. All rights reserved.

    View details for PubMedID 31081997

  • Hepatocellular carcinoma is leading in cancer-related disease burden among hospitalized baby boomers. Annals of hepatology Gadiparthi, C., Yoo, E. R., Are, V. S., Charilaou, P., Kim, D., Cholankeril, G., Pitchumoni, C., Ahmed, A. 2019

    Abstract

    Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC.It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied.Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P<0.001).HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend.

    View details for DOI 10.1016/j.aohep.2019.04.014

    View details for PubMedID 31164267

  • Increasing Mortality Among Patients With Diabetes and Chronic Liver Disease From 2007 Through 2017. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Cholankeril, G., Kim, S. H., Abbasi, F., Knowles, J. W., Ahmed, A. 2019

    View details for DOI 10.1016/j.cgh.2019.06.011

    View details for PubMedID 31220638

  • Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation. Scientific reports Cholankeril, G., Li, A. A., Dennis, B. B., Gadiparthi, C., Kim, D., Toll, A. E., Maliakkal, B. J., Satapathy, S. K., Nair, S., Ahmed, A. 2019; 9 (1): 8312

    Abstract

    Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.

    View details for DOI 10.1038/s41598-019-44814-y

    View details for PubMedID 31165776

  • Readmission Rates and Associated Outcomes for Alcoholic Hepatitis: A Nationwide Cohort Study. Digestive diseases and sciences Adejumo, A. C., Cholankeril, G., Iqbal, U., Yoo, E. R., Boursiquot, B. C., Concepcion, W. C., Kim, D., Ahmed, A. 2019

    Abstract

    Alcoholic hepatitis (AH) can lead to sudden and severe hepatic decompensation necessitating recurrent hospitalizations. We evaluated the trends, predictors, and healthcare cost burden of AH-related readmissions in the USA.Utilizing the National Readmissions Database 2010-2014, we performed a retrospective longitudinal analysis to identify the index readmission with AH for up to 90 days after discharge. Annual trends of 30- and 90-day AH-related readmissions were calculated. Predictors of 30- and 90-day readmission were determined by multivariate logistic regression. Annual healthcare cost burden associated with AH-linked readmissions was estimated.Of the 21,572 (unweighted: 50,769) AH-related hospitalizations, 4917 (22.8%) and 7890 (36.6%) were readmitted in 30 and 90 day, respectively, with rates that were statistically unchanged from 2010 to 2014. Predictors of 30-day readmissions included female gender, hepatitis C virus infection, cirrhosis, ascites, acute kidney injury, urinary tract infection, history of bariatric surgery, chronic pancreatitis, and high medical comorbidity index. Acute pancreatitis and palliative care consultation were associated with a lower risk of 30-day readmission. Predictors of 90-day readmission were similar to risk factors for 30-day readmission. From 2010 to 2014, the annual cost (and total hospitalization days) burden increased in 2014 to $164 million (22,244 days) and $321 million (42,772 days) for 30- and 90-day AH-related readmissions, respectively.Despite relatively stable trends in AH-related readmission, the total LOS and cost has been rising. A target-directed approach with a focus on high-risk subpopulations may help understand the unique challenges associated with the rising cost of AH-related readmissions.

    View details for DOI 10.1007/s10620-019-05759-4

    View details for PubMedID 31372912

  • Recent advances in liver transplantation with HCV seropositive donors. F1000Research Murag, S., Dennis, B. B., Kim, D., Ahmed, A., Cholankeril, G. 2019; 8

    Abstract

    The paradigm shift from interferon-based to direct-acting antiviral (DAA) therapy for the treatment of hepatitis C virus (HCV) infection has revolutionized the field of liver transplantation. These advances in effective HCV treatment, along with the persistent shortage in available liver grafts, have encouraged investigators to assess the need for adopting more inclusive donor policies. Owing to the poor outcomes following liver transplantation with recurrent HCV infection, liver transplantation using HCV seropositive donors (non-viremic and viremic) had been restricted. However, as a result of the growing supply of HCV seropositive donors from the recent opioid epidemic along with the advent of efficacious DAA therapy to treat HCV recurrence, there has been an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients. The review aims to discuss recent advances and associated outcomes related to the use of HCV seropositive grafts for liver transplantation.

    View details for DOI 10.12688/f1000research.20387.1

    View details for PubMedID 31942236

    View details for PubMedCentralID PMC6944251

  • An Unexpected Colonic Mass AMERICAN JOURNAL OF GASTROENTEROLOGY Li, A. A., Cholankeril, G., Berry, G. J., Fernandez-Becker, N. 2019; 114 (1): 180–81
  • Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary. Nutrition and metabolic insights Dibba, P., Li, A. A., Cholankeril, G., Ali Khan, M., Kim, D., Ahmed, A. 2019; 12: 1178638819847480

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) develops when the liver is unable to oxidize or export excess free fatty acids generated by adipose tissue lipolysis, de novo lipogenesis, or dietary intake. Although treatment has generally been centered on reversing metabolic risk factors that increase the likelihood of NAFLD by influencing lifestyle modifications, therapeutic modalities are being studied at the cellular and molecular level. The endocannabinoid system has been of recent focus. The agonism and antagonism of cannabinoid receptors play roles in biochemical mechanisms involved in the development or regression of NAFLD. Exocannabinoids and endocannabinoids, the ligands which bind cannabinoid receptors, have been studied in this regard. Exocannabinoids found in cannabis (marijuana) may have a therapeutic benefit. Our recent study demonstrated an inverse association between marijuana use and NAFLD among adults in the United States. This commentary combines knowledge on the role of the endocannabinoid system in the setting of NAFLD with the findings in our article to hypothesize different potential mechanisms that may influence the inverse relationship between cannabis and NAFLD.

    View details for DOI 10.1177/1178638819847480

    View details for PubMedID 31308686

    View details for PubMedCentralID PMC6612909

  • Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft. Journal of clinical and translational hepatology Liu, A., Galoosian, A., Kaswala, D., Li, A. A., Gadiparthi, C., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4): 420–24

    Abstract

    In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

    View details for PubMedID 30637220

  • Use of anti-platelet agents in the prevention of hepatic fibrosis in patients at risk for chronic liver disease: a systematic review and meta-analysis. Hepatology international Iqbal, U., Dennis, B. B., Li, A. A., Cholankeril, G., Kim, D., Khan, M. A., Ahmed, A. 2018

    Abstract

    BACKGROUND AND AIMS: While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.METHODS: We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.RESULTS: Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p≤0.0001). The statistical heterogeneity among the studies was insignificant.CONCLUSION: Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.

    View details for PubMedID 30539518

  • Disparities in mortality for chronic liver disease among Asian subpopulations in the United States from 2007 to 2016 JOURNAL OF VIRAL HEPATITIS Li, A. A., Kim, D., Kim, W., Dibba, P., Wong, K., Cholankeril, G., Jacobson, I. M., Younossi, Z. M., Ahmed, A. 2018; 25 (12): 1608–16

    View details for DOI 10.1111/jvh.12981

    View details for Web of Science ID 000451117100023

  • Low-Normal Thyroid Function is Associated with Advanced Fibrosis among Adults in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Yoo, E. R., Li, A. A., Fernandes, C. T., Tighe, S. P., Cholankeril, G., Hameed, B., Ahmed, A. 2018

    View details for PubMedID 30458247

  • Early Liver Transplantation is a Viable Treatment Option in Severe Acute Alcoholic Hepatitis ALCOHOL AND ALCOHOLISM Puri, P., Cholankeril, G., Myint, T. Y., Goel, A., Sarin, S., Harper, A. M., Ahmed, A. 2018; 53 (6): 716–18

    Abstract

    Liver transplantation is lifesaving for patients with severe acute alcoholic hepatitis (SAH) with preliminary data demonstrating favorable early post-transplant outcomes. Using the United Network for Organ Sharing database, we demonstrate that liver transplantation for SAH in the USA has steadily increased and is associated with similar 1- and 3-year post-transplant survival as well as comparable 30-day waitlist mortality to acute liver failure due to drug-induced liver injury.

    View details for PubMedID 30099535

    View details for PubMedCentralID PMC6203122

  • Disparate Trends in Mortality of Etiology-specific Chronic Liver Disease Among Hispanic Sub-Populations. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Li, A. A., Perumpail, R. B., Cholankeril, G., Gonzalez, S. A., Kim, W., Ahmed, A. 2018

    Abstract

    BACKGROUND & AIMS: Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to 2016.METHODS: We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change.RESULTS: Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans.CONCLUSIONS: We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups.

    View details for PubMedID 30391436

  • Association of Pre-Transplant Renal Function with Liver Graft and Patient Survival after Liver Transplantation in Patients with Nonalcoholic Steatohepatitis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Molnar, M. Z., Joglekar, K., Jiang, Y., Cholankeril, G., Abdul, M. K., Kedia, S., Gonzalez, H. C., Ahmed, A., Singal, A., Bhamidimarri, K. R., Aithal, G. P., Duseja, A., Wong, V. W., Gulnare, A., Puri, P., Nair, S., Eason, J. D., Satapathy, S. K., Global NAFLD Consortium 2018

    Abstract

    BACKGROUND: Nonalcoholic Steatohepatitis(NASH) is one of the top three indications for liver transplantation in western countries. It is unknown whether renal dysfunction at the time of liver transplantation has any effect on post-liver transplantation outcomes in recipients with NASH.METHODS: From the United Network for Organ Sharing-Standard Transplant Analysis and Research(UNOS-STAR) dataset, we identified 4,088 NASH recipients who received deceased donor liver transplant. We divided our recipients a priori into three categories: Group I with estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2 at the time of LT and/or received dialysis within 2 weeks preceding LT(n=937); Group II included recipients who had eGFR≥30 ml/min/1.73m2 and did not receive renal replacement therapy prior to LT(n=2,812); and Group III included recipients who underwent SLK transplantation(n=339). We examined the association of pre-transplant renal dysfunction with death with functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models.RESULTS: The mean±SD age of the cohort at baseline was 58±8 years, 55% were male, 80% were Caucasian, and average exception MELD score was 24±9. The median follow-up period was 5 years (median=1,816 days, interquartile range (IQR):1,090-2,723 days). Compared to Group I recipients, Group II recipients had 19% reduced trend for risk for death with functioning graft[Sub-Hazard Ratio(SHR)(95% CI):0.81(0.64-1.02)] and similar risk for graft loss [SHR(95% CI):1.25(0.59-2.62)] while Group III recipients had similar risk for death with functioning graft[SHR(95% CI):1.23(0.96-1.57)] and graft loss [SHR(95% CI):0.18(0.02-1.37)] using adjusted competing risk regression model.CONCLUSIONS: Recipients with preserved renal function before liver transplantation showed trend toward lower risk of death with functioning graft compared to SLK recipients and those with pre-transplant severe renal dysfunction in patients with NASH. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30369023

  • An Unexpected Colonic Mass. The American journal of gastroenterology Li, A. A., Cholankeril, G., Berry, G. J., Fernandez-Becker, N. 2018

    View details for PubMedID 30333533

  • Temporal Trends Associated with the Rise in Alcoholic Liver Disease Related Liver Transplantation in the United States. Transplantation Cholankeril, G., Gadiparthi, C., Yoo, E. R., Dennis, B. B., Li, A. A., Hu, M., Wong, K., Kim, D., Ahmed, A. 2018

    Abstract

    BACKGROUND: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation (LT).METHODS: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016.RESULTS: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD waitlist (WL) additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% CI: 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (> 60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low BMI (< 18.5) and diabetes mellitus were significant predictors for 1-year waitlist mortality.CONCLUSION: ALD-related WL registrations and LT have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.

    View details for PubMedID 30300285

  • Improved Short-Term Survival in HCV Seropositive Kidney Transplant Recipients during the Daa Era in the United States Wong, K., Cholankeril, G., Gadiparthi, C., Somasundar, P., Busque, S., Esquivel, C. O., Ahmed, A. WILEY. 2018: 140A
  • When to Initiate Weight Loss Medications in the NAFLD Population. Diseases (Basel, Switzerland) Yoo, E. R., Sallam, S., Perumpail, B. J., Iqbal, U., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression.

    View details for PubMedID 30274326

  • Increasing Trends in Transplantation of HCV-positive Livers into Uninfected Recipients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Li, A. A., Dennis, B. B., Toll, A. E., Kim, D., Bonham, C. A., Nair, S., Ahmed, A. 2018

    View details for PubMedID 30268562

  • Disparities in Mortality for Chronic Liver Disease among Asian Sub-Populations in the United States from 2007 to 2016. Journal of viral hepatitis Li, A. A., Kim, D., Kim, W., Dibba, P., Wong, K., Cholankeril, G., Jacobson, I. M., Younossi, Z. M., Ahmed, A. 2018

    Abstract

    The Asian-American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically-meaningful heterogeneity. We performed a population-based study using data from the United States (US) National Vital Statistics System. We determined the trends in age-standardized mortality rates for chronic liver disease stratified by etiology among the most populous US-based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis.Hepatitis C virus-related mortality rates were higher in non-Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age-standardized hepatitis B virus-related mortality rates were higher in all Asian subgroups as compared to non-Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age-standardized cirrhosis-related mortality rates were highest in non-Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma-related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non-Hispanic whites. In this population-based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of etiology-specific chronic liver disease among Asian subgroups in the US. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30112849

  • Changing Trends in Etiology- and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States. Hepatology (Baltimore, Md.) Kim, D., Li, A. A., Perumpail, B. J., Gadiparthi, C., Kim, W., Cholankeril, G., Glenn, J. S., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2018

    Abstract

    With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States (US). A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults aged ≥ 20 years from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% CI 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007-2014 to a 6.5% decline per year during 2014-2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and nonalcoholic fatty liver disease (NAFLD, APC 15.4%) increased over the same period, while mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality.CONCLUSION: Cirrhosis- and HCC-related mortality rates increased between 2007 and 2016 in the US. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014-2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, while HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30014489

  • Changing Trends in Etiology-based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016. Gastroenterology Kim, D., Li, A. A., Gadiparthi, C., Khan, M. A., Cholankeril, G., Glenn, J. S., Ahmed, A. 2018

    Abstract

    BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied the trends in age-standardized mortality of chronic liver diseases among adults 20 years or older in the United States (US), from 2007 through 2016.METHODS: We collected data from the US Census and National Center for Health Statistics mortality records, identifying individuals with HCV infection, ALD, nonalcoholic fatty liver disease (NAFLD), or hepatitis B virus (HBV) infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC).RESULTS: Age-standardized HCV-related mortality increased from 7.17/100,000 persons in 2007 to 8.14/100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09/100,000 persons in 2014 to 7.15/100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014, but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC of 2.3% from 2007 through 2013 and APC of 5.5% from 2013 through 2016) and NAFLD (APC of 6.1% from 2007 through 2013 and APC of 11.3% from 2013 through 2016). HBV-related mortality decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI, -3.0 to -1.2). Etiology-based mortality in minority populations were higher. HCV-related mortality (per 100,000 persons) was highest among non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest among non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for HBV infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks, and 0.47 for non-Hispanic whites).CONCLUSION: In our population-based analysis of chronic liver disease mortality in the US, the decline in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, while the mortality from ALD and NAFLD increased during the same period. Minorities in the US have disproportionately higher chronic liver disease-related mortality.

    View details for PubMedID 30009816

  • Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases (Basel, Switzerland) Li, A. A., Cholankeril, G., Cheng, X. S., Tan, J. C., Kim, D., Toll, A. E., Nair, S., Ahmed, A. 2018; 6 (3)

    Abstract

    In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.

    View details for PubMedID 29996536

  • Waitlist Outcomes in Liver Transplant Candidates with High MELD and Severe Hepatic Encephalopathy DIGESTIVE DISEASES AND SCIENCES Gadiparthi, C., Cholankeril, G., Yoo, E. R., Hu, M., Wong, R. J., Ahmed, A. 2018; 63 (6): 1647–53

    Abstract

    Organ Procurement and Transplantation Network and United Network for Organ Sharing (OPTN/UNOS) implemented the Share 35 policy in June 2013 to prioritize the sickest patients awaiting liver transplantation (LT). However, Model for End-Stage Liver Disease (MELD) score does not incorporate hepatic encephalopathy (HE), an independent predictor of waitlist mortality.To evaluate the impact of severe HE (grade 3-4) on waitlist outcomes in MELD ≥ 30 patients.Using the OPTN/UNOS database, we evaluated LT waitlist registrants from 2005-2014. Demographics, comorbidities, and waitlist survival were compared between four cohorts: MELD 30-34 with severe HE, MELD 30-34 without severe HE, MELD ≥ 35 with severe HE, and MELD ≥ 35 without severe HE.Among 10,003 waitlist registrants studied, 41.6% had MELD score 30-34 and 58.4% had MELD ≥ 35. Patients with severe HE had a higher 90-day waitlist mortality in both MELD 30-34 (severe HE 71.1% vs. no HE 56.6%; p < 0.001) and MELD ≥ 35 subgroups (severe HE 85% versus no HE 74.2%; p < 0.001). MELD 30-34 patients with severe HE had similar 90-day waitlist mortality as MELD ≥ 35 patients without severe HE (71.1 vs. 74.2%, respectively; p = 0.35). On multivariate Cox proportional hazards modeling, MELD ≥ 30 patients had 58% greater risk of 90-day waitlist mortality than those without severe HE (HR 1.58, 95% CI 1.53-1.62; p < 0.001).Patients awaiting LT with MELD score of 30-34 and severe HE should receive priority status for organ allocation with exception MELD ≥ 35.

    View details for PubMedID 29611079

  • Case Report of Isoniazid-Related Acute Liver Failure Requiring Liver Transplantation. Diseases (Basel, Switzerland) Li, A. A., Dibba, P., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (2)

    Abstract

    The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4⁻4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases. We report a case of a 67-year old male who developed subacute hepatic injury secondary to INH treatment for LTBI, and ultimately underwent liver transplantation due to the progression to hepatic decompensation, despite withdrawal of the medication. Because symptoms of INH hepatotoxicity are nonspecific and prognosis can be variable, clinicians must maintain a high index of suspicion for this adverse effect. As exemplified by this case, early recognition may be life-saving.

    View details for PubMedID 29783726

  • Impact of Drug Overdose Deaths on Solid Organ Transplantation in the United States. Journal of general internal medicine Cholankeril, G., Li, A. A., Cholankeril, R., Toll, A. E., Glenn, J. S., Ahmed, A. 2018

    View details for PubMedID 29766381

  • Expanding Donor Pool for Liver Transplantation by Utilizing Hepatitis C Virus-Infected Donors for Uninfected Recipients. Hepatology (Baltimore, Md.) Cholankeril, G., Gadiparthi, C., Kim, D., Ahmed, A. 2018

    View details for PubMedID 29672899

  • Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Snyder, H. S., Sakaan, S. A., March, K. L., Siddique, O., Cholankeril, R., Cummings, C. D., Gadiparthi, C., Satapathy, S. K., Ahmed, A., Cholankeril, G. 2018; 6 (2): 168–74

    Abstract

    Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

    View details for PubMedID 29951362

    View details for PubMedCentralID PMC6018310

  • Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients With Primary Biliary Cholangitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Gonzalez, H. C., Satapathy, S., Gonzalez, S. A., Hu, M., Khan, M. A., Yoo, E. R., Li, A. A., Kim, D., Nair, S., Wong, R. J., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Lindor, K. D., Ahmed, A. 2018

    Abstract

    BACKGROUND & AIMS: Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States.METHODS: Using the United Network for Organ Sharing (UNOS) registry, we collected data on patients with PBC on the liver transplant waitlist, and performed analysis with a focus on ethnicity and race-based variations clinical manifestations, waitlist mortality and LT rates from 2000 to 2014. Outcomes were adjusted for demographics, complications of portal hypertension, and Model for End-stage Liver Disease score at time of waitlist registration.RESULTS: Although the number of white PBC waitlist registrants and additions decreased from 2000 to 2014, there were no significant changes in the number of Hispanic PBC waitlist registrants and additions each year. The proportion of Hispanic patients with PBC on the liver transplant waitlist increased from 10.7% in 2000 to 19.3% in 2014. Hispanics had the highest percentage of waitlist deaths (20.8%) of any ethnicity or race evaluated. After adjusting for demographic and clinical characteristics, Hispanic patients with PBC had the lowest overall rate for undergoing LT (adjusted hazard ratio, 0.71; 95% CI, 0. 60-0.83; P < .001) and a significantly higher risk of death while on the waitlist, compared to whites (adjusted hazard ratio, 1.41; 95% CI, 1.15-1.74; P < .001). Furthermore, Hispanic patients with PBC had the highest proportion of waitlist removals due to clinical deterioration.CONCLUSIONS: In an analysis of data from UNOS registry focusing on outcomes, we observed differences in rates of LT and liver transplant waitlist mortality of Hispanic patients compared with white patients with PBC. Further studies are needed to improve our understanding of ethnicity and race-based differences in progression of PBC.

    View details for PubMedID 29427734

  • Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates WORLD JOURNAL OF GASTROENTEROLOGY Gadiparthi, C., Cholankeril, G., Perumpail, B. J., Yoo, E. R., Satapathy, S. K., Nair, S., Ahmed, A. 2018; 24 (3): 315–22

    Abstract

    Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

    View details for PubMedID 29391754

    View details for PubMedCentralID PMC5776393

  • Inpatient Outcomes for Gastrointestinal Bleeding Associated With Percutaneous Coronary Intervention. Journal of clinical gastroenterology Cholankeril, G., Hu, M., Cholankeril, R., Khan, M. A., Gadiparthi, C., Yoo, E. R., Perumpail, R. B., Nair, S., Howden, C. W. 2018

    Abstract

    GOALS: The goal of this study was to evaluate the impact of inpatient outcomes of gastrointestinal bleeding (GIB) related to percutaneous coronary intervention (PCI).BACKGROUND: With all-cause mortality increasing in patients undergoing PCIs, outcomes for GIB associated with PCI may be adversely impacted.STUDY: Using the National Inpatient Sample (2007 to 2012), we performed a nested case-control study assessing inpatient outcomes including incidence and mortality for PCI-related GIB hospitalizations. Multivariate logistic regression analyses were performed to determine significant predictors for GIB incidence and mortality.RESULTS: A total of 9332 (1.2%) of PCI hospitalizations were complicated by GIB with the age-adjusted incidence rate increasing 13% from 2007 (11.3 GIB per 1000 PCI) to 2012 (12.8). Patients ≥75 years of age experienced the steepest incline in GIB incidence, which increased 31% during the study period. Compared with non-GIB patients, mean length of stay (9.4d vs. 3.3d) and median cost of care ($29,236 vs. $17,913) was significantly higher. Significant demographic risk factors for GIB included older age and comorbid risk factors included gastritis or duodenitis, and Helicobacter pylori infection.In total, 1044 (11%) of GIB patients died during hospitalization with the GIB mortality rate increasing 30% from 2007 (95 deaths per 1000 GIB) to 2012 (123). Older age had the strongest association with inpatient mortality.CONCLUSIONS: Inpatient incidence and mortality for PCI-related GIB has been increasing particularly with a large increase in incidence among older patients. A multidisciplinary approach focused on risk-stratifying patients may improve preventable causes of GIB.

    View details for PubMedID 29351155

  • Judicious Use of Lipid Lowering Agents in the Management of NAFLD. Diseases (Basel, Switzerland) Iqbal, U., Perumpail, B. J., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, NAFLD is associated with an increased risk of hepatocellular carcinoma. Diabetes mellitus, hypertension, and dyslipidemia are components of metabolic syndrome and are commonly associated with NAFLD. Cardiovascular disease is the leading cause of mortality in patients with NAFLD. Therefore, it is important to pre-emptively identify and proactively treat conditions like hyperlipidemia in an effort to favorably modify the risk factors associated with cardiovascular events in patients with NAFLD. The management of hyperlipidemia has been shown to reduce cardiovascular mortality and improve histological damage/biochemical abnormalities associated with non-alcoholic steatohepatitis (NASH), a subset of NAFLD with advance liver damage. There are no formal guidelines available regarding the use of anti-hyperlipidemic drugs, as prospective data are lacking. The focus of this article is to discuss the utility of lipid-lowering drugs in patients with NAFLD.

    View details for PubMedID 30249980

  • Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease. Medicines (Basel, Switzerland) Dibba, P., Li, A., Cholankeril, G., Iqbal, U., Gadiparthi, C., Khan, M. A., Kim, D., Ahmed, A. 2018; 5 (2)

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden.

    View details for PubMedID 29843404

  • Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., Iqbal, U., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (3)

    Abstract

    Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with "AND (NAFLD or NASH)". Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb⁻drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread can be recommended.

    View details for PubMedID 30201879

  • Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis. European journal of gastroenterology & hepatology Farooqui, M. T., Khan, M. A., Cholankeril, G., Khan, Z., Mohammed Abdul, M. K., Li, A. A., Shah, N., Wu, L., Haq, K., Solanki, S., Kim, D., Ahmed, A. 2018

    Abstract

    An estimated 22 million adults use marijuana in the USA. The role of marijuana in the progression of hepatic fibrosis remains unclear.We carried out a systematic review and meta-analysis to evaluate the impact of marijuana on prevalence and progression of hepatic fibrosis in chronic liver disease.We searched several databases from inception through 10 November 2017 to identify studies evaluating the role of marijuana in chronic liver disease. Our main outcome of interest was prevalence/progression of hepatic fibrosis. Adjusted odds ratios (ORs) and hazards ratios (HRs) were pooled and analyzed using random-effects model.Nine studies with 5 976 026 patients were included in this meta-analysis. Prevalence of hepatic fibrosis was evaluated in nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis C and HIV coinfection by two, four, and one studies. Progression of hepatic fibrosis was evaluated by two studies. Pooled OR for prevalence of fibrosis was 0.91 (0.72-1.15), I=75%. On subgroup analysis, pooled OR among NAFLD patients was 0.80 (0.75-0.86), I=0% and pooled OR among HCV patients was 1.96 (0.78-4.92), I=77%. Among studies evaluating HR, pooled HR for progression of fibrosis in HCV-HIV co-infected patients was 1.03 (0.96-1.11), I=0%.Marijuana use did not increase the prevalence or progression of hepatic fibrosis in HCV and HCV-HIV-coinfected patients. On the contrary, we noted a reduction in the prevalence of NAFLD in marijuana users. Future studies are needed to further understand the therapeutic impact of cannabidiol-based formulations in the management of NAFLD.

    View details for PubMedID 30234644

  • Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD. Diseases (Basel, Switzerland) Dibba, P., Li, A. A., Perumpail, B. J., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (3)

    Abstract

    The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited.

    View details for PubMedID 30235807

  • Alcoholic Liver Disease Replaces Hepatitis C Virus Infection asthe Leading Indication for Liver Transplantation in the UnitedStates. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Ahmed, A. 2017

    View details for PubMedID 29199144

  • Direct-Acting Antiviral Therapy and Improvement in Graft Survival of Hepatitis C Liver Transplant Recipients TRANSPLANTATION Cholankeril, G., Li, A. A., Yoo, E. R., Ahmed, A. 2017; 101 (12): e349

    View details for PubMedID 28846556

  • Can Ribavirin be Avoided in the Management of Hepatitis C Genotype 3 Patients When Treated With Direct Acting Antivirals? A Systematic Review and Meta-Analysis Khan, M., Cholankeril, G., Gadiparthi, C., Siddiqui, M., Haq, K. F., Hahambis, T., Ahmed, A. NATURE PUBLISHING GROUP. 2017: S559–S560
  • Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends and Outcomes DIGESTIVE DISEASES AND SCIENCES Cholankeril, G., Wong, R. J., Hu, M., Perumpail, R. B., Yoo, E. R., Puri, P., Younossi, Z. M., Harrison, S. A., Ahmed, A. 2017; 62 (10): 2915–22

    Abstract

    Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in the US were studied.A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003-2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazards models.Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH -77.81%, 95% CI 76.37-79.25 vs. HCV -72.15%, 95% CI 71.37-72.93, P < .001). In the multivariate Cox proportional hazards model, NASH demonstrated significantly higher post-transplant survival compared to HCV (HR 0.75; 95% CI 0.71-0.79, P < .001).Currently, NASH is the most rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH remains the second leading indication for LT.

    View details for PubMedID 28744836

  • Declining Rate of Acute Graft Failure in Liver Transplant Recipients with Hepatitis C Cholankeril, G., Li, A. A., Yoo, E. R., Gonzalez, S. A., Nair, S., Ahmed, A. WILEY. 2017: 527A–528A
  • Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis NUTRIENTS Perumpail, B. J., Li, A. A., Cholankeril, G., Kumari, R., Ahmed, A. 2017; 9 (10)

    View details for DOI 10.3390/nu9101114

    View details for Web of Science ID 000414629900070

  • Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: a systematic review and meta-analysis EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Kamal, F., Khan, M., Khan, Z., Cholankeril, G., Hammad, T. A., Lee, W. M., Ahmed, A., Waters, B., Howden, C. W., Nair, S., Satapathy, S. K. 2017; 29 (10): 1109–17

    Abstract

    Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

    View details for PubMedID 28763340

  • Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease. Diseases (Basel, Switzerland) Cholankeril, G., Yoo, E. R., Perumpail, R. B., Liu, A., Sandhu, J. S., Nair, S., Hu, M., Ahmed, A. 2017; 5 (4)

    Abstract

    We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

    View details for PubMedID 28954412

  • Optimal Timing for Hepatitis C Antiviral Therapy in the Peri-Transplant Period? Hepatology (Baltimore, Md.) Cholankeril, G., Wong, R. J., Kim, D., Ahmed, A. 2017

    View details for DOI 10.1002/hep.29300

    View details for PubMedID 28586088

  • Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis. American journal of gastroenterology Kamal, S., Khan, M. A., Seth, A., Cholankeril, G., Gupta, D., Singh, U., Kamal, F., Howden, C. W., Stave, C., Nair, S., Satapathy, S. K., Ahmed, A. 2017

    Abstract

    Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD.We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies.We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding.Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.Am J Gastroenterol advance online publication, 6 June 2017; doi:10.1038/ajg.2017.170.

    View details for DOI 10.1038/ajg.2017.170

    View details for PubMedID 28585556

  • The Role of e-Health in Optimizing Task-Shifting in the Delivery of Antiviral Therapy for Chronic Hepatitis C. Telemedicine journal and e-health Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2017

    Abstract

    Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model.In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics.From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic.We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

    View details for DOI 10.1089/tmj.2016.0189

    View details for PubMedID 28375820

  • Sofosbuvir Use in the Setting of End-stage Renal Disease: A Single Center Experience. Journal of clinical and translational hepatology Aggarwal, A., Yoo, E. R., Perumpail, R. B., Cholankeril, G., Kumari, R., Daugherty, T. J., Lapasaran, A. S., Ahmed, A. 2017; 5 (1): 23-26

    Abstract

    Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15 treatment courses, patients completed the designated treatment duration. One patient was treated twice and developed SVR-12 with the retreatment. One patient was lost to follow-up and counted as a non-responder. Premature discontinuations were not due to DAA-related adverse effects. There were no reports of severe adverse effects or drug interactions. Conclusion: We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.

    View details for DOI 10.14218/JCTH.2016.00060

    View details for PubMedID 28507922

  • Treatment of Patients Waitlisted for Liver Transplant with an All-Oral DAAs is a Cost-Effective Treatment Strategy in the United States. Hepatology Ahmed, A., Gonzalez, S. A., Cholankeril, G., Perumpail, R. B., McGinnis, J., Saab, S., Beckerman, R., Younossi, Z. M. 2017

    Abstract

    All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with Hepatitis C (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre- vs. post-LT. The objective of this study was to analyze the cost-effectiveness of pre- vs. post-LT treatment with an all-oral DAA regimen among HCV patients with HCC (hepatocellular carcinoma) or DCC (decompensated cirrhosis).We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted (WL) for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age 50 over a 30 year time horizon from a third-party US payer perspective, and estimated their health and cost outcomes based on pre- vs. post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained viral response (SVR) rates were sourced from ASTRAL-4 and SOLAR-1, -2. Costs were sourced from RedBook, Medicare fee schedules, and published literature.In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years (QALYs) and $365,948 per patient lifetime costs vs. 10.39 and $283,696 in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy results in 9.27 per-patient QALYs and $304,800 per patient lifetime costs vs. 8.7 and $283,789 in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed results were most sensitive to the utility of patients post-LT, treatment SVR rates, LT costs, and baseline MELD score (DCC analysis only).The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research. Our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/hep.29137

    View details for PubMedID 28257591

  • Disparities in Liver Transplantation Resulting From Variations in Regional Donor Supply and Multiple Listing Practices CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Yoo, E. R., Perumpail, R. B., Younossi, Z. M., Ahmed, A. 2017; 15 (2): 313-315
  • The importance of a multidisciplinary approach to hepatocellular carcinoma. Journal of multidisciplinary healthcare Siddique, O., Yoo, E. R., Perumpail, R. B., Perumpail, B. J., Liu, A., Cholankeril, G., Ahmed, A. 2017; 10: 95-100

    Abstract

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative/hospice care in patients with metastatic HCC. In most tertiary care centers in the US, a multidisciplinary liver tumor board has become the standard of care and a key component of best practice protocol for patients with HCC.

    View details for DOI 10.2147/JMDH.S128629

    View details for PubMedID 28360525

  • Rising Rate of Liver Transplantation in the Baby Boomer Generation with Non-alcoholic Steatohepatitis in the United States. Journal of clinical and translational hepatology Siddique, O., Joseph-Talreja, M., Yoo, E. R., Perumpail, R. B., Cholankeril, G., Harrison, S. A., Younossi, Z. M., Wong, R. J., Ahmed, A. 2017; 5 (3): 193–96

    Abstract

    Background and Aims: Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade. We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965, the baby boomer (BB) generation. Methods: We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH. We stratified our study population into three birth cohorts: 1) birth before 1945, 2) birth between 1945 and 1965, and 3) birth after 1965. Results: The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group. From 2004 to 2015, the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth, 60.6% in 2004 versus 83.2% in 2015 (p < 0.01). Among the liver transplant recipients with NASH, the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p < 0.01). Conclusions: We report rising rates of waitlist registration and LT for the indication of NASH. More importantly, the BB sub-cohort was mainly responsible for these alarming trends.

    View details for PubMedID 28936399

  • Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents. Journal of clinical and translational hepatology Cholankeril, G., Joseph-Talreja, M., Perumpail, B. J., Liu, A., Yoo, E. R., Ahmed, A., Goel, A. 2017; 5 (4): 363–67

    Abstract

    Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin. As achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients, concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant period. On one hand, HCV treatment may improve hepatic function and negate the need for LT in some, which is crucial given the scarcity of donor organs and mortality on the waiting list in certain regions. On the other hand, HCV treatment may result in lowering the priority for LT without improving quality of life, thereby delaying potentially curative LT surgery. This review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.

    View details for PubMedID 29226102

  • Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis. Nutrients Perumpail, B. J., Li, A. A., Cholankeril, G., Kumari, R., Ahmed, A. 2017; 9 (10)

    Abstract

    The aim of this work is to develop a pragmatic approach in the assessment and management strategies of patients with cirrhosis in order to optimize the outcomes in this patient population.A systematic review of literature was conducted through 8 July 2017 on the PubMed Database looking for key terms, such as malnutrition, nutrition, assessment, treatment, and cirrhosis. Articles and studies looking at associations between nutrition and cirrhosis were reviewed.An assessment of malnutrition should be conducted in two stages: the first, to identify patients at risk for malnutrition based on the severity of liver disease, and the second, to perform a complete multidisciplinary nutritional evaluation of these patients. Optimal management of malnutrition should focus on meeting recommended daily goals for caloric intake and inclusion of various nutrients in the diet. The nutritional goals should be pursued by encouraging and increasing oral intake or using other measures, such as oral supplementation, enteral nutrition, or parenteral nutrition.Although these strategies to improve nutritional support have been well established, current literature on the topic is limited in scope. Further research should be implemented to test if this enhanced approach is effective.

    View details for PubMedID 29027963

  • Are proton pump inhibitors a threat for spontaneous bacterial peritonitis and hepatic encephalopathy in cirrhosis? Not so fast. Hepatology (Baltimore, Md.) Khan, M. A., Cholankeril, G., Howden, C. W. 2017; 65 (1): 393

    View details for PubMedID 27688049

  • Proton Pump Inhibitors and the Possible Development of Hepatic Encephalopathy in Cirrhotic Patients: True Association or Residual Confounding? Gastroenterology Khan, M. A., Cholankeril, G., Howden, C. W. 2017; 152 (8): 2076

    View details for PubMedID 28478154

  • Portomesenteric venous thrombosis complicated by a haemorrhagic shock: a rare complication of laparoscopic gastrectomy. BMJ case reports Copelin, E., Cholankeril, R., Somasundar, P., Cholankeril, G. 2017; 2017

    Abstract

    Portomesenteric venous thrombosis is a rare complication reported in only a few cases involving laparoscopic bariatric surgery. We report a case of a 44-year-old woman who presented 14 days after recent laparoscopic sleeve gastrectomy with the chief complaint of abdominal pain and associated nausea. Abdominal CT demonstrated thrombi in her superior mesenteric, portal and splenic veins. She was initiated on therapeutic heparin but developed haemorrhagic shock shortly afterwards. Subsequent CT angiogram failed to localise the source of her haemorrhage. Her haemodynamic instability improved following a 6-day intensive care unit stay requiring vasopressive agents and blood transfusions. Further hypercoagulable workup revealed that she was a heterozygous carrier of the prothrombin gene mutation, and thus started on lifelong oral anticoagulation.

    View details for PubMedID 28554887

  • Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World journal of gastroenterology Perumpail, B. J., Khan, M. A., Yoo, E. R., Cholankeril, G., Kim, D., Ahmed, A. 2017; 23 (47): 8263–76

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

    View details for PubMedID 29307986

    View details for PubMedCentralID PMC5743497

  • Improved Outcomes in HCV Patients Following Liver Transplantation During the Era of Direct Acting Antiviral Agents. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Li, A. A., March, K. L., Yoo, E. R., Kim, D., Snyder, H., Gonzalez, S. A., Younossi, Z. M., Ahmed, A. 2017

    View details for PubMedID 28838786

  • Hepatic encephalopathy: what the multidisciplinary team can do. Journal of multidisciplinary healthcare Liu, A., Yoo, E. R., Siddique, O., Perumpail, R. B., Cholankeril, G., Ahmed, A. 2017; 10: 113-119

    Abstract

    Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach.

    View details for DOI 10.2147/JMDH.S118963

    View details for PubMedID 28392702

  • Expanding Treatment Access for Chronic Hepatitis C with Task-shifting in the Era of Direct-acting Antivirals. Journal of clinical and translational hepatology Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2017; 5 (2): 130–33

    Abstract

    In the United States, the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years, but the results have been less than ideal. Historically, patients with chronic hepatitis C (CHC) were treated with interferon-based regimens, which were associated with frequent adverse effects, suboptimal response rates, and long durations of treatment - of up to 48 weeks. Expertise from specialist-physicians, such as hepatologists and gastroenterologists, was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse effects. However, the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety, tolerability, lack of adverse effects, efficacy, and truncated duration of therapy - 12 weeks or less - thereby making the need for close monitoring by specialist-physicians obsolete. With the recent approval of DAA agents by the Food and Drug Administration, the treatment model for CHC no longer relies on the limited number of specialist-physicians, which represented a major barrier to treatment access in the past, especially in underserved areas of the United States. We propose and share our experiences in adapting a task-shifting treatment model, one that utilizes a relatively larger pool of non-specialist healthcare providers, such as nursing staff (medical assistants, vocational licensed nurses, registered nurses, etc.) and advanced practice providers (nurse practitioners and physician assistants), to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV infection. Most recently, task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging results. Based on our experiences in implementing this model at our outreach clinics, the majority of HCV-infected patients treated with DAA agents can be easily monitored by non-specialist healthcare providers and physician extenders. Task-shifting can effectively address one of the major rate-limiting factors in expanding treatment access for HCV infection.

    View details for PubMedID 28660150

  • Task-shifting - A practical strategy to improve the global access to treatment for chronic hepatitis C INTERNATIONAL JOURNAL OF NURSING STUDIES Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2016; 62: 168-169
  • Underutilization of Living Donor Liver Transplantation in the United States: Bias against MELD 20 and Higher. Journal of clinical and translational hepatology Perumpail, R. B., Yoo, E. R., Cholankeril, G., Hogan, L., Deis, M., Concepcion, W. C., Bonham, C. A., Younossi, Z. M., Wong, R. J., Ahmed, A. 2016; 4 (3): 169-174

    Abstract

    Background and Aims: Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.). We evaluated the association between recipient MELD score at the time of surgery and survival following LDLT. Methods: All U.S. adult LDLT recipients with MELD < 25 were evaluated using the 1995-2012 United Network for Organ Sharing registry. Survival following LDLT was stratified into three MELD categories (MELD < 15 vs. MELD 15-19 vs. MELD 20-24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. Results: Overall, 2,258 patients underwent LDLT. Compared to patients with MELD < 15, overall 5-year survival following LDLT was similar among patients with MELD 15-19 (80.9% vs. 80.3%, p = 0.77) and MELD 20-24 (81.2% vs. 80.3%, p = 0.73). When compared to patients with MELD < 15, there was no significant difference in long-term post-LDLT survival among those with MELD 15-19 (HR: 1.11, 95% CI: 0.85-1.45, p = 0.45) and a non-significant trend towards lower survival in patients with MELD 20-24 (HR: 1.28, 95% CI: 0.91-1.81, p = 0.16). Only 14% of LDLTs were performed in patients with MELD 20-24 and the remaining 86% in patients with MELD < 20. Conclusion: LDLT is underutilized in patients with MELD 20 and higher.

    View details for PubMedID 27777886

  • Disparities in Liver Transplantation Resulting From Variations in Regional Donor Supply and Multiple Listing Practices. Clinical gastroenterology and hepatology Cholankeril, G., Yoo, E. R., Perumpail, R. B., Younossi, Z. M., Ahmed, A. 2016

    View details for DOI 10.1016/j.cgh.2016.08.036

    View details for PubMedID 27609705

  • Nonalcoholic Fatty Liver Disease: Epidemiology, Natural History, and Diagnostic Challenges. Hepatology Cholankeril, G., Perumpail, R. B., Pham, E. A., Ahmed, A., Harrison, S. A. 2016; 64 (3): 954-?

    View details for DOI 10.1002/hep.28719

    View details for PubMedID 27388553

  • Chronic Hepatitis B Is Associated with Higher Inpatient Resource Utilization and Mortality Versus Chronic Hepatitis C. Digestive diseases and sciences Cholankeril, G., Perumpail, R. B., Hu, M., Skowron, G., Younossi, Z. M., Ahmed, A. 2016; 61 (9): 2505-2515

    Abstract

    Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections remain one of the leading causes of chronic liver disease and hepatocellular carcinoma. Healthcare initiatives for chronic viral hepatitis to facilitate early diagnosis and linkage to care in an effort to reduce inpatient resource utilization associated with late diagnosis and end-stage liver disease have been partially successful.Our objective was to determine the impact of liver-related complications from chronic HBV and HCV infections on inpatient cost of care, length of stay, and mortality.Using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS), we studied the impact of chronic HBV and HCV infections on inpatient healthcare system following hospitalizations from 2003 to 2012.Of the 79,185,729 million hospitalizations among adult patients in the USA from 2003 to 2012, 143,896 (0.18 %) hospitalizations were HBV related and 1,073,269 (1.36 %) hospitalizations HCV related. HBV hospitalizations had a higher inpatient mortality (OR 1.34; 95 % CI 1.30, 1.38), median cost of care per hospitalization (+$2100.33; 95 % CI 1982.53, 2217.53), and increased length of hospitalization stay (+0.64 days; 95 % CI 0.60, 0.68; p < 0.01) compared to HCV.Despite higher per case resource utilization following hospitalization, HBV-infected patients demonstrate a lower inpatient survival in comparison with chronic HCV infection. These disparate observations underscore the need for early diagnosis of chronic HBV infection in at-risk population and prompt linkage to care.

    View details for DOI 10.1007/s10620-016-4160-z

    View details for PubMedID 27084385

  • Trends in Liver Transplantation Multiple Listing Practices Associated With Disparities in Donor Availability: An Endless Pursuit to Implement the Final Rule. Gastroenterology Cholankeril, G., Perumpail, R. B., Tulu, Z., Jayasekera, C. R., Harrison, S. A., Hu, M., Esquivel, C. O., Ahmed, A. 2016; 151 (3): 382–86.e2

    View details for PubMedID 27456386

  • Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome CASE REPORTS IN INFECTIOUS DISEASES Yoo, E. R., Perumpail, R. B., Cholankeril, G., Ahmed, A. 2016
  • Task-shifting - A practical strategy to improve the global access to treatment for chronic hepatitis C. International journal of nursing studies Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2016; 62: 168–69

    View details for PubMedID 27497192