Andrew A. Li, MD

All Publications

• Novel Modified Endoscopic Suction Overtube for Clearance of Gastric Blood Clots During Urgent Upper Endoscopy Joseph, A., Li, A., Friedland, S. LIPPINCOTT WILLIAMS & WILKINS. 2024: S2153

  View details for DOI 10.14309/01.ajg.0001042120.39605.12

  View details for Web of Science ID 001359318700041

• Efficacy and safety of covered self-expandable metal stent for malignant hilar biliary obstruction: A systematic review and meta-analysis. Gastrointestinal endoscopy Chung, K. H., Lee, K. J., Joseph, A. A., Huang, R. J., Li, A., Hwang, J. H., Yoon, S. B. 2024

  Abstract

  Covered self-expanding metal stents (C-SEMS) are used for malignant hilar biliary obstruction (MHBO) management. Despite increasing evidence, comprehensive evaluation of the efficacy and safety of C-SEMS in MHBO management is lacking.PubMed, EMBASE, and the Cochrane Library were screened up to March 31, 2024 for studies including MHBO treated by a C-SEMS. Studies meeting predefined inclusion criteria, including adult MHBO patients treated with C-SEMS placement, reporting technical success, clinical success, and adverse event rates, were selected. Data synthesis and statistical analysis were performed using the random effects model, with heterogeneity and publication bias assessment.From 401 articles, seven studies were included. Pooled technical and clinical success rate of C-SEMS was 96.7% (95% CI 92.6-98.6%, I2=0%) and 91.6% (95% CI 86.1-95.0%, I2=0%). Overall adverse events were reported in 16.6% (95% CI 11.2-23.9%, I2=24%) of cases which included cholangitis (7.4%), pancreatitis (5.9%), liver abscess (5.9%), and cholecystitis (2.8%). Stent migration and recurrent biliary obstruction were observed in 8.9% and 49.6% of cases, respectively, with a median time to recurrent biliary obstruction of 142 days. Reintervention was successful in 92.5% of cases (95% CI 83.1-96.9%, I2=0%) CONCLUSION: Our meta-analysis revealed high technical and clinical success rates of C-SEMS in MHBO. Adverse events, notably cholangitis, cholecystitis, and pancreatitis were <10%. RBO and stent migration was mitigated by C-SEMS removal and successful reintervention. Our findings highlight the efficacy and safety of C-SEMS in managing MHBO, warranting further research to optimize treatment strategies.

  View details for DOI 10.1016/j.gie.2024.09.037

  View details for PubMedID 39357660

• GASTRIC PER-ORAL ENDOSCOPIC MYOTOMY OUTCOMES STRATIFIED BY GASTROPARESIS ETIOLOGY AND RESPONSE TO PRIOR INTRAPYLORIC BOTULINUM TOXIN INJECTION - A RETROSPECTIVE ANALYSIS IDENTIFYING POSSIBLE PATIENT SELECTION CRITERIA Li, A., Callahan, M., Podboy, A., Hwang, J. MOSBY-ELSEVIER. 2024: AB1144

  View details for Web of Science ID 001278323004297

• LONG TERM OUTCOMES OF NON-CURATIVE ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL LESIONS Almario, J., Hiroyuki, A., Kumar, A., Schlachterman, A., Maluf-Filho, F., Othman, M., Jawaid, S., Teshima, C., Mosko, J., Draganov, P., Bechara, R., Schiavone, G., Le, J., Madaka, P., Kawaguti, F., Moura, R., Khalaf, M., King, W., Northern, N., Al-Shamali, H., Dang, F., Samarasena, J., Joseph, A., Friedland, S., Hwang, J., Li, A., Tomizawa, Y., Lucaciu, L., Subramanian, R., Despott, E., Ngamruengphong, S. MOSBY-ELSEVIER. 2024: AB469-AB470

  View details for Web of Science ID 001278323001422

• OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS NEOPLASMS: A MULTICENTER NORTH AMERICAN EXPERIENCE Subrahmanyan, R., Almario, J., Aihara, H., Kumar, A., Schlachterman, A., Friedland, S., Hwang, J., Othman, M., Jawaid, S., Ferri, L., Teshima, C., Mosko, J., Bechara, R., Samarasena, J., Yang, D., Ujiki, M., Tomizawa, Y., Schiavone, G., Madaka, P., Joseph, A., Li, A., Khalaf, M., Qatomah, A., Al-Shamali, H., Dang, F., Tavangar, A., Rwigema, J., King, W., Northern, N., Draganov, P., Ngamruengphong, S. MOSBY-ELSEVIER. 2024: AB992-AB993

  View details for Web of Science ID 001278323004037

• NORTH AMERICAN EXPERIENCE OF ENDOSCOPIC SUBMUCOSAL DISSECTION OF DISTAL RECTAL LESIONS EXTENDING TO THE DENTATE LINE - A LARGE SCALE MULTICENTER STUDY Malik, T., Khan, A., Gopakumar, H., Dahiya, D., Vohra, I., Zelt, C., Flanagan, M., Ladd, A., Aadam, A., Kang, A., Saeed, A., Khalaf, M., Othman, M., Ngamruengphong, S., Arayakarnkul, S., Yang, D., Bilal, M., DeLeon, M., Schlachterman, A., Madaka, P., Kamal, F., Kumar, A., Thompson, B., Kedia, P., Diehl, D., Shah, S., Sedarat, A., Wang, A., Dhaliwal, A., Mizrahi, M., Kahaleh, M., Andrawes, S., Dewitt, J., Obaitan, I., Ali, A., Hwang, J., Li, A., Friedland, S., Draganov, P., Sharma, N. MOSBY-ELSEVIER. 2024: AB470-AB471

  View details for Web of Science ID 001278323001423

• SAFETY AND EFFICACY OF PERORAL ENDOSCOPIC MYOTOMY (POEM) AS AN EMERGENCY TREATMENT IN HOSPITALIZED SEVERELY SYMPTOMATIC PATIENTS WITH ACHALSIA Fayyaz, F., Jagannath, P., Almardini, M., Bejjani, M., Mondragon, O., Robles, M., Schlachterman, A., Le, J., Chang, K., Dang, F., Hwang, J., Li, A., Sadeghi, E., Eleftheriadis, N., Bechara, R., Parvizian, M., Yoo, I., Pioche, M., Moll, F., Kim, R., Canakis, A., Othman, M., Khalaf, M., Estremera-Arevalo, F., Albeniz, E., Inoue, H., Shiwaku, H., Chung, C., Seewald, S., Pawa, R., Pawa, S., Khashab, M. MOSBY-ELSEVIER. 2024: AB959-AB960

  View details for Web of Science ID 001278323003393

• OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS NEOPLASMS: A MULTICENTER NORTH AMERICAN EXPERIENCE Subrahmanyan, R., Almario, J., Aihara, H., Kumar, A., Schlachterman, A., Friedland, S., Hwang, J., Othman, M., Jawaid, S., Ferri, L., Teshima, C., Mosko, J., Bechara, R., Samarasena, J., Yang, D., Ujiki, M., Tomizawa, Y., Schiavone, G., Madaka, P., Joseph, A., Li, A., Khalaf, M., Qatomah, A., Al-Shamali, H., Dang, F., Tavangar, A., Rwigema, J., King, W., Northern, N., Draganov, P., Ngamruengphong, S. MOSBY-ELSEVIER. 2024: AB1068-AB1069

  View details for Web of Science ID 001278323004174

• SAFETY AND EFFICACY OF PERORAL ENDOSCOPIC MYOTOMY (POEM) AS AN EMERGENCY TREATMENT IN HOSPITALIZED SEVERELY SYMPTOMATIC PATIENTS WITH ACHALSIA Fayyaz, F., Jagannath, P., Almardini, M., Bejjani, M., Mondragon, O., Robles, M., Schlachterman, A., Le, J., Chang, K., Dang, F., Hwang, J., Li, A., Sadeghi, E., Eleftheriadis, N., Bechara, R., Parvizian, M., Yoo, I., Pioche, M., Moll, F., Kim, R., Canakis, A., Othman, M., Khalaf, M., Estremera-Arevalo, F., Albeniz, E., Inoue, H., Shiwaku, H., Chung, C., Seewald, S., Pawa, R., Pawa, S., Khashab, M. MOSBY-ELSEVIER. 2024: AB1031-AB1032

  View details for Web of Science ID 001278323004112

• A VALIDATED NOVEL PREDICTIVE TOOL FOR CLINICAL RESPONSE POST GASTRIC PER-ORAL ENDOSCOPIC MYOTOMY (G-POEM) AT 6-12 MONTHS: A LARGE INTERNATIONAL MULTI-CENTER COHORT STUDY Ichkhanian, Y., Salame, M., Hwang, J., Li, A., Yang, J., Broucek, J., Esfandyari, T., Joseph, S., Ujiki, M., Williams, A., Moremen, J., Gouda, Z., Schlachterman, A., Hugova, K., Martinek, J., Geng, C., Podboy, A., Wang, A., Lajin, M., Gregor, L., Albunni, H., Wo, J., Stainko, S., Saito, A., Siwiec, R., Nowak, T., Dewitt, J., Al-Haddad, M. MOSBY-ELSEVIER. 2024: AB1132-AB1133

  View details for Web of Science ID 001278323004281

• A COMPREHENSIVE ANALYSIS ON THE DIAGNOSIS AND THE MANAGEMENT OF CLINICAL FAILURE POST GASTRIC PERORAL ENDOSCOPIC MYOTOMY: AN INTERNATIONAL COHORT STUDY Ichkhanian, Y., Salame, M., Wo, J., Nowak, T., Stainko, S., Saito, A., Siwiec, R., Hwang, J., Li, A., Yang, J., Broucek, J., Esfandyari, T., Joseph, S., Ujiki, M., Williams, A., Moremen, J., Gouda, Z., Schlachterman, A., Hugova, K., Martinek, J., Geng, C., Podboy, A., Wang, A., Lajin, M., Gregor, L., Albunni, H., Dewitt, J., Al-Haddad, M. MOSBY-ELSEVIER. 2024: AB1130-AB1131

  View details for Web of Science ID 001278323004279

• Peroral Endoscopic Myotomy For Spastic Esophageal Dysmotility Among Opioid Users: Multicenter Propensity Score Match Study. Gastrointestinal endoscopy Bani Fawwaz, B., Zhang, Y., Farooq, A., Gorrepati, V. S., Forde, J. F., Canakis, A., Kim, R., Ma, M., Benias, P., Che, S., Ujiki, M. B., Li, A. A., Hwang, J. H., Eke, C., Kedia, P., Yu, A., Inayat, I., Khalaf, M., Othman, M., Jawaid, S., Hasan, M. K., Sharma, N., Pomenti, S., Sethi, A., Draganov, P. V., Yang, D. 2024

  Abstract

  Opioid induced esophageal disorder (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). We aimed to evaluate and compare clinical outcomes of POEM for SEDs and EGJOO among opioid users and non-users.Propensity-score (PS) match study of consecutive opioid users and non-users who underwent POEM for SEDs and EGJOO between January 2018 to September 2022. The following covariates were used for PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as post-POEM Eckardt score ≤3.A total of 277 consecutive patients underwent POEM during the study period. PS match resulted in the selection of 64 pairs of strictly 1:1 matched patients (n=128) with no statistically significant differences in demographics, baseline and procedural characteristics or in the parameters considered for the PS between the two groups. Clinical response to POEM was significantly lower among opioid users (51/64; 79.7%) vs non-users (60/64; 93.8%) (p=0.03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood for failure to respond to POEM (Odds Ratio: 4.59; 95% CI: 1.31-3.98; p=0.02).Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users vs. non-users. There was dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.

  View details for DOI 10.1016/j.gie.2023.12.034

  View details for PubMedID 38184116

• Multicenter evaluation of recurrence in endoscopic submucosal dissection and endoscopic mucosal resection in the colon: A Western perspective. World journal of gastrointestinal endoscopy Wei, M. T., Zhou, M. J., Li, A. A., Ofosu, A., Hwang, J. H., Friedland, S. 2023; 15 (6): 458-468

  Abstract

  BACKGROUND: While colon endoscopic mucosal resection (EMR) is an effective technique, removal of larger polyps often requires piecemeal resection, which can increase recurrence rates. Endoscopic submucosal dissection (ESD) in the colon offers the ability for en bloc resection and is well-described in Asia, but there are limited studies comparing ESD vs EMR in the West.AIM: To evaluate different techniques in endoscopic resection of large polyps in the colon and to identify factors for recurrence.METHODS: The study is a retrospective comparison of ESD, EMR and knife-assisted endoscopic resection performed at Stanford University Medical Center and Veterans Affairs Palo Alto Health Care System between 2016 and 2020. Knife-assisted endoscopic resection was defined as use of electrosurgical knife to facilitate snare resection, such as for circumferential incision. Patients ≥ 18 years of age undergoing colonoscopy with removal of polyp(s) ≥ 20 mm were included. The primary outcome was recurrence on follow-up.RESULTS: A total of 376 patients and 428 polyps were included. Mean polyp size was greatest in the ESD group (35.8 mm), followed by knife-assisted endoscopic resection (33.3 mm) and EMR (30.5 mm) (P < 0.001). ESD achieved highest en bloc resection (90.4%) followed by knife-assisted endoscopic resection (31.1%) and EMR (20.2%) (P < 0.001). A total of 287 polyps had follow-up (67.1%). On follow-up analysis, recurrence rate was lowest in knife-assisted endoscopic resection (0.0%) and ESD (1.3%) and highest in EMR (12.9%) (P = 0.0017). En bloc polyp resection had significantly lower rate of recurrence (1.9%) compared to non-en bloc (12.0%, P = 0.003). On multivariate analysis, ESD (in comparison to EMR) adjusted for polyp size was found to significantly reduce risk of recurrence [adjusted hazard ratio 0.06 (95%CI: 0.01-0.57, P = 0.014)].CONCLUSION: In our study, EMR had significantly higher recurrence compared to ESD and knife-assisted endoscopic resection. We found factors including resection by ESD, en bloc removal, and use of circumferential incision were associated with significantly decreased recurrence. While further studies are needed, we have demonstrated the efficacy of ESD in a Western population.

  View details for DOI 10.4253/wjge.v15.i6.458

  View details for PubMedID 37397977

• CLINICAL OUTCOMES OF PERORAL ENDOSCOPIC MYOTOMY (POEM) IN PATIENTS WITH SPASTIC ESOPHAGEAL MOTILITY DISORDERS ON CHRONIC OPIOID USE: A MULTICENTER STUDY Fawwaz, B., Gorrepati, V., Forde, J., Canakis, A., Gerges, P., Farooq, A., Kim, R., Ma, M., Benias, P., Che, S., Ujiki, M., Li, A., Hwang, J., Eke, C., Kedia, P., Hayat, M., Inayat, I., Khalaf, M., Othman, M., Jawaid, S., Hasan, M., Draganov, P., Yang, D. MOSBY-ELSEVIER. 2023: AB1083-AB1084

  View details for Web of Science ID 001038022802429

• Initial Multicenter Experience of Traction Wire Endoscopic Submucosal Dissection TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY Joseph, A., Kahaleh, M., Li, A. A., Haber, G. B., Kedia, P., Makiguchi, M., Sharma, N. R., Ha Hwang, J., Chak, A., Al-Taee, A. M., Braun, D., Mok, S., Mehta, N. A., Gorgun, E., Vargo, J., Abe, S., Saito, Y., Stevens, T., Bhatt, A. 2023; 25 (1): 21-29

  View details for DOI 10.1016/j.tige.2022.10.002

  View details for Web of Science ID 001035713900001

• Understanding the Principles of Electrosurgery for Endoscopic Surgery and Third Space Endoscopy. Gastrointestinal endoscopy clinics of North America Li, A. A., Zhou, M. J., Hwang, J. H. 2023; 33 (1): 29-40

  Abstract

  Electrosurgery is the application of high-frequency electrical alternating current to biologic tissue to cut, coagulate, desiccate, and/or fulgurate. Electrosurgery is commonly used in gastrointestinal endoscopy, with applications including biliary sphincterotomy, polypectomy, hemostasis, the ablation of lesions, and endoscopic surgery. Understanding electrosurgical principles is important in endoscopic surgery to achieve the desired therapeutic effect, optimize procedural outcomes, and minimize risks or adverse events. This article describes fundamental principles that apply to electrosurgical units, operator technique, and practical considerations for achieving desired tissue effects in endoscopic surgery; and provides practical guidance and safety considerations when using electrosurgical units in endoscopic surgery.

  View details for DOI 10.1016/j.giec.2022.07.001

  View details for PubMedID 36375884

• Multimodal Image-Text Matching Improves Retrieval-based Chest X-Ray Report Generation Jeong, J., Tian, K., Li, A., Hartung, S., Behzadi, F., Calle, J., Osayande, D., Pohlen, M., Adithan, S., Rajpurkar, P., Noble, J., Li, Oguz, Styner, M., Baumgartner, C., Rusu, M., Heinmann, T., Kontos, D., Landman, B., Dawant, B. JMLR-JOURNAL MACHINE LEARNING RESEARCH. 2023: 978-990

  View details for Web of Science ID 001221108600058

• Role of gastric per-oral endoscopic myotomy (G-POEM) in post-lung transplant patients: a multicenter experience. Endoscopy international open Ichkhanian, Y., Hwang, J. H., Ofosu, A., Li, A. A., Szvarca, D., Draganov, P. V., Yang, D., Alsheik, E., Zuchelli, T., Piraka, C., Mony, S., Khashab, M. A. 2022; 10 (6): E832-E839

  Abstract

  Background and study aims Gastroparesis post-lung transplant (LTx) can lead to increased risk of gastroesophageal reflux (GER) and accelerated graft dysfunction. We aimed to evaluate the efficacy and safety of gastric per-oral endoscopic myotomy (G-POEM), a promising tool in patients with refractory gastroparesis, for managing refractory gastroparesis and GER in post-LTx patients. Patents and methods This was a multicenter retrospective study on post-LTx patients who underwent G-POEM for management of gastroparesis and GER that were refractory to standard medical therapy. The primary outcome was clinical success post-G-POEM. Secondary outcomes included the rate of post-G-POEM objective esophageal pH exam normalization, rate of gastric emptying scintigraphy (GES) normalization, technical success, and adverse events. Results A total of 20 patients (mean age 54.7 ± 14.1 years, Female 50 %) underwent G-POEM at a median time of 13 months (interquartile range 6.5-13.5) post-LTx. All G-POEM procedures were technically successful. Clinical success was achieved in 17 (85 %) patients during a median follow-up time of 8.9 (IQR: 3-17) months post-G-POEM. Overall GCSI and two of its subscales (bloating and postprandial fullness/early satiety) improved significantly following G-POEM. Two patients (10 %) developed post-procedural AEs (delayed bleeding 1, pyloric stenosis 1, both moderate in severity). Post-G-POEM GES improvement was achieved in 12 of 16 patients (75 %). All 20 patients were on proton pump inhibitors pre-G-POEM, as opposed to five post-G-POEM. Post-G-POEM PH study normalization was noted in nine of 10 patients (90 %) who underwent both pre- and post-G-poem pH testing. Conclusions G-POEM is a promising noninvasive therapeutic tool for management of refractory gastroparesis and GER post-LTx.

  View details for DOI 10.1055/a-1797-9587

  View details for PubMedID 35692909

• Gastric Peroral Endoscopic Myotomy (GPOEM) Improves Symptoms and Need for Hospital Admission for Gastroparesis and Lung Transplant Patients Li, A., Ofosu, A., Kim, W., Podboy, A., Esquivel, M., Hwang, J. LIPPINCOTT WILLIAMS & WILKINS. 2021: S466-S467

  View details for Web of Science ID 000717526101452

• Endoscopic Strictureplasty and Stent Placement for a Recalcitrant Esophageal Peptic Stricture Li, A., Hwang, J. LIPPINCOTT WILLIAMS & WILKINS. 2021: S875

  View details for Web of Science ID 000717526103420

• Peroral Endoscopic Myotomy for Achalasia Subtypes and Esophagogastric Outflow Obstruction: Clinical Success and GERD Li, A., Podboy, A., Kim, W., Esquivel, M., Hwang, J. LIPPINCOTT WILLIAMS & WILKINS. 2021: S467

  View details for Web of Science ID 000717526101453

• EUS-guided cholecystoduodenostomy and ERCP in a patient with surgically altered anatomy with a double-balloon endoluminal interventional platform. VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy Li, A. A., Ofosu, A., Hwang, J. H. 2021; 6 (8): 368-371

  Abstract

  Video 1EUS-guided cholecystoduodenostomy and ERCP in a patient with surgically altered anatomy with a double-balloon endoluminal interventional platform.

  View details for DOI 10.1016/j.vgie.2021.04.010

  View details for PubMedID 34401634

• Sticky Situation: Bleeding Duodenal Lymphangiectasias Treated with Lymphatic Glue Embolization. Digestive diseases and sciences Li, A. A., Raghu, P., Chen, A., Triadafilopoulos, G., Park, W. 2021

  View details for DOI 10.1007/s10620-021-06898-3

  View details for PubMedID 33638090

• Author Spotlight: Andrew A. Li. Digestive diseases and sciences Li, A. A. 2021

  View details for DOI 10.1007/s10620-021-06897-4

  View details for PubMedID 33611691

• Association of Sarcopenia and NAFLD: An Overview. Clinical liver disease Li, A. A., Kim, D., Ahmed, A. 2020; 16 (2): 73–76

  View details for DOI 10.1002/cld.900

  View details for PubMedID 32922754

• 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

• 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. n., Vazquez-Montesino, L. M., Escober, J. A., Li, A. A., Tighe, S. P., Fernandes, C. T., Cholankeril, G. n., Ahmed, A. n. 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

• The Role of Gastroenterologists in the Management of Obesity Yamada’s Textbook of Gastroenterology Cholankeril, G., Li, A. A., Streett, S. 2020
• Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease. Hepatology (Baltimore, Md.) Kim, D. n., Vazquez-Montesino, L. M., Li, A. A., Cholankeril, G. n., Ahmed, A. n. 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

• 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

  View details for DOI 10.1016/j.cgh.2018.11.024

  View details for Web of Science ID 000486629300005

• DIET QUALITY AND ITS ASSOCIATION WITH NONALCOHOLIC FATTY LIVER DISEASE AND MORTALITY - A POPULATION-BASED STUDY Yoo, E., Li, A., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2019: 726A

  View details for Web of Science ID 000488653502351

• 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

• 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

  View details for DOI 10.1007/s00125-019-4870-9

  View details for Web of Science ID 000471176200009

• 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

• 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

  View details for DOI 10.1016/j.cgh.2018.09.036

  View details for Web of Science ID 000471783300035

• 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-+

  View details for DOI 10.1016/j.cgh.2018.10.045

  View details for Web of Science ID 000471783300032

• Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association HEPATOBILIARY SURGERY AND NUTRITION Li, A. A., Ahmed, A., Kim, D. 2019; 8 (3): 260–61

  View details for DOI 10.21037/hbsn.2018.12.10

  View details for Web of Science ID 000470015000008

• Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association. Hepatobiliary surgery and nutrition Li, A. A., Ahmed, A., Kim, D. 2019; 8 (3): 260-261

  View details for DOI 10.21037/hbsn.2018.12.10

  View details for PubMedID 31245407

  View details for PubMedCentralID PMC6561878

• 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., Khan, M., Kim, D., Ahmed, A. 2019; 12

  View details for DOI 10.1177/1178638819847480

  View details for Web of Science ID 000471073200001

• 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

• 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

  Abstract

  AIMS/HYPOTHESIS: The determination of diabetes as underlying cause of death by using the death certificate may result in inaccurate estimation of national mortality attributed to diabetes, because individuals who die with diabetes generally have other conditions that may contribute to their death. We investigated the trends in age-standardised mortality due to diabetes as underlying or contributing cause of death and cause-specific mortality from cardiovascular disease (CVD), complications of diabetes and cancer among individuals with diabetes listed on death certificates in the USA from 2007 to 2017.METHODS: Using the US Census and national mortality database, we calculated age-standardised mortality due to diabetes as underlying or contributing cause of death and cause-specific mortality rates among adults over 20years with diabetes listed on death certificates. A total of 2,686,590 deaths where diabetes was underlying or contributing cause of death were analysed. We determined temporal mortality rate patterns by joinpoint regression analysis with estimates of annual percentage change (APC).RESULTS: Age-standardised diabetes mortality rates compared among underlying cause of death, contributing cause of death and all-cause mortality were 32.2 vs 75.7 vs 105.1 per 100,000 individuals during the study period. The age-standardised mortality rates due to diabetes as underlying or contributing cause of death declined from 112.2 per 100,000 individuals in 2007 to 104.3 per 100,000 individuals in 2017 with the most pronounced decline noted from 2007 to 2014 (APC -1.4%; 95% CI -1.9%, -1.0%) and stabilisation in decline from 2014 to 2017 (APC 1.1%; 95% CI -0.6%, 2.8%). In terms of cause-specific mortality among individuals with diabetes listed on death certificates, the age-standardised mortality rates for CVD declined at an annual rate of 1.2% with a marked decline of 2.3% between 2007 and 2014. Age-standardised diabetes-specific mortality rates as underlying cause of death decreased from 2007 to 2009 (APC -4.5%) and remained stable from 2009 to 2017. Age-standardised mortality rates for cancer steadily decreased with an average APC of -1.4% (95% CI -1.8%, -1.0%) during the 11-year period. Mortality in the subcategory of CVD demonstrated significant differences.CONCLUSIONS/INTERPRETATION: Current national estimates capture about 30% of all-cause mortality among individuals with diabetes listed as underlying or contributing cause of death on death certificates. The age-standardised mortality due to diabetes as underlying or contributing cause of death and cause-specific mortality from CVD in individuals with diabetes listed as underlying or contributing cause of death plateaued from 2014 onwards except for hypertensive heart disease and heart failure.

  View details for PubMedID 31011776

• Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States Kim, D., Yoo, E., Li, A., Cholankeril, G., Tighe, S., Kim, W., Harrison, S., Ahmed, A. ELSEVIER SCIENCE BV. 2019: E300

  View details for Web of Science ID 000463481701163

• Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Yoo, E. R., Li, A. A., Cholankeril, G., Tighe, S. P., Kim, W., Harrison, S. A., Ahmed, A. 2019

  Abstract

  BACKGROUND AND AIMS: The relationship between bisphenol A (BPA) and non-alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD.METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data.RESULTS: Of the first 7605 participants (mean age 47years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P<0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39-2.04) and 1.44 (95% CI 1.19-1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05-1.98, P for trend=0.012).CONCLUSIONS: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation.

  View details for PubMedID 30924602

• 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 Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2019; 7 (1)

  View details for DOI 10.3390/diseases7010027

  View details for Web of Science ID 000684004800027

• 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

• 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., Abdul, M., Li, A. A., Shah, N., Wu, L., Haq, K., Solanki, S., Kim, D., Ahmed, A. 2019; 31 (2): 149–56

  View details for DOI 10.1097/MEG.0000000000001263

  View details for Web of Science ID 000458405800001

• An Unexpected Colonic Mass AMERICAN JOURNAL OF GASTROENTEROLOGY Li, A. A., Cholankeril, G., Berry, G. J., Fernandez-Becker, N. 2019; 114 (1): 180–81

  View details for DOI 10.1038/s41395-018-0363-6

  View details for Web of Science ID 000463156500034

• 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., Ahmed, A. 2019; 13 (1): 84–90

  View details for DOI 10.1007/s12072-018-9918-2

  View details for Web of Science ID 000457481500010

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

• Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gut and liver Li, A. A., Ahmed, A. n., Kim, D. n. 2019

  Abstract

  Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage.

  View details for DOI 10.5009/gnl19069

  View details for PubMedID 31195434

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

• 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

  View details for DOI 10.1097/TP.0000000000002471

  View details for Web of Science ID 000455044100030

• 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. n., Cholankeril, G. n., Li, A. A., Kim, W. n., Tighe, S. P., Hameed, B. n., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. n. 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

• 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

• 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

• 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

• Pre-Operative Magnitude in the Rise of Meld Score Is a Predictor of Survival Following Liver Transplantation Cholankeril, G., Yoo, E. R., Li, A. A., Kim, D., Ahmed, A. WILEY. 2018: 690A–691A

  View details for Web of Science ID 000446020501418

• Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis LIVER INTERNATIONAL Kim, D., Li, A. A., Ahmed, A. 2018; 38 (10): 1839–48

  View details for DOI 10.1111/liv.13886

  View details for Web of Science ID 000445622400017

• 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

  View details for DOI 10.14218/JCTH.2018.00010

  View details for Web of Science ID 000457289300011

• 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., Cholankeril, G., Glenn, J. S., Ahmed, A. 2018; 155 (4): 1154-+

  View details for DOI 10.1053/j.gastro.2018.07.008

  View details for Web of Science ID 000446327500041

• Use of Antiplatelet Agents for the Prevention of Hepatic Fibrosis: A Systematic Review and Meta-Analysis Iqbal, U., Li, A. A., Dibba, P., Yoo, E. R., Cholankeril, G., Khan, M., Kim, D., Ahmed, A. WILEY. 2018: 1141A

  View details for Web of Science ID 000446020503231

• Trends in Causes of Mortality in Liver Transplantation Recipients: Comparison Among Nash, ALD, and HCV Cohorts Yoo, E. R., Cholankeril, G., Li, A. A., Dibba, P., Iqbal, U., Khan, M., Gadiparthi, C., Kim, D., Ahmed, A. WILEY. 2018: 966A–967A

  View details for Web of Science ID 000446020502493

• 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

• The Role of Vitamin E in the Treatment of 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. 2018; 6 (4)

  Abstract

  There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

  View details for PubMedID 30249972

• 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; 33 (9): 1423–25

  View details for DOI 10.1007/s11606-018-4477-8

  View details for Web of Science ID 000442642300005

• 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

• Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients With Primary Biliary Cholangitis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Gonzalez, H. C., Satapathy, S. K., Gonzalez, S. A., Hu, M., Khan, M., 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; 16 (6): 965-+

  View details for DOI 10.1016/j.cgh.2017.12.017

  View details for Web of Science ID 000432676600031

• Leukocyte Telomere Shortening Is Associated With Nonalcoholic Fatty Liver Disease-Related Advanced Fibrosis. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Li, A. A., Ahmed, A. 2018

  Abstract

  BACKGROUND AND AIM: Telomere length and telomerase has been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis is in a large national population sample is not well understood.METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected NAFLD was diagnosed if serum alanine aminotransferase was > 30 IU/L for men and > 19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index, and FIB-4 score.RESULTS: Of the 6,738 participants (mean age 46.3 years, 48.4% male), suspected NAFLD prevalence was inversely associated with leukocyte telomere length in young adults aged 20-39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leukocyte telomere length (longest to shortest). The shortest quartile of leukocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol, and high-density lipoprotein cholesterol (P for trend < 0.05, respectively).CONCLUSIONS: In this large nationally-representative sample of American adults, leukocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected NAFLD independent of other known risk factors. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29797393

• 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

• Hepatitis C in Pregnancy. Diseases (Basel, Switzerland) Dibba, P., Cholankeril, R., Li, A. A., Patel, M., Fayek, M., Dibble, C., Okpara, N., Hines, A., Ahmed, A. 2018; 6 (2)

  Abstract

  The prevalence of hepatitis C in pregnancy is as high as 3.6% in large cohorts. The prevalence of hepatitis C acquired by vertical transmission is 0.2% to 0.4% in the United States and Europe. Although screening is not recommended in the absence of certain risk factors, the importance of understanding hepatitis C in pregnancy lies in its association with adverse maternal and neonatal outcomes. There is potential for those infants infected by vertical transmission to develop chronic hepatitis C, cirrhosis or hepatocellular carcinoma. The risk of vertical transmission is increased when mothers are co-infected with Human Immunodeficiency Virus (HIV) or possess a high viral load. There is no clear data supporting that mode of delivery increases or reduces risk. Breastfeeding is not associated with increased risk of transmission. Premature rupture of membranes, invasive procedures (such as amniocentesis), intrapartum events, or fetal scalp monitoring may increase risk of transmission. In pregnant patients, hepatitis C is diagnosed with a positive ELISA-3 and detectable Hepatitis C Virus (HCV) RNA viral load. Infants born to HCV-infected mothers should be tested for either HCV RNA on at least two separate occasions. Although prevention is not possible, there may be a role for newer direct acting anti-viral medications in the future.

  View details for PubMedID 29702563

• 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

• The Role of Cannabinoids in the Setting of Cirrhosis. Medicines (Basel, Switzerland) Dibba, P. n., Li, A. A., Cholankeril, G. n., Iqbal, U. n., Gadiparthi, C. n., Khan, M. A., Kim, D. n., Ahmed, A. n. 2018; 5 (2)

  Abstract

  Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.

  View details for PubMedID 29890719

• Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., Iqbal, U. n., Sallam, S. n., Shah, N. D., Kwong, W. n., Cholankeril, G. n., Kim, D. n., Ahmed, A. n. 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. n., Khan, Z. n., Mohammed Abdul, M. K., Li, A. A., Shah, N. n., Wu, L. n., Haq, K. n., Solanki, S. n., Kim, D. n., Ahmed, A. n. 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. n., Li, A. A., Perumpail, B. J., John, N. n., Sallam, S. n., Shah, N. D., Kwong, W. n., Cholankeril, G. n., Kim, D. n., Ahmed, A. n. 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

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

• 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

• 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 DOI 10.3390/nu9101114

  View details for PubMedID 29027963

  View details for PubMedCentralID PMC5691730

• Demographics and Clinical Characteristics of Hepatitis C Virus-Positive Donors and Recipients Li, A. A., Yoo, E. R., Sandhu, K., Perumpail, R. B., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2017: 894A–895A

  View details for Web of Science ID 000412089802034

• 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

  View details for Web of Science ID 000412089801128

• Hispanics with Primary Biliary Cholangitis present for Liver Transplant Listing at a Younger Age and with more Severe Hepatic Decompensation Yoo, E. R., Li, A. A., Imam, M., Hu, M., Cholankeril, G., Lindor, K. D., Ahmed, A. WILEY. 2017: 174A–175A

  View details for Web of Science ID 000412089800309

• Increasing Acceptance of Severe Acute Alcoholic Hepatitis as an Indication for Liver Transplantation with Outcomes comparable to Fulminant Hepatic Failure Cholankeril, G., Liu, A., Sandhu, J., Yoo, E. R., Li, A. A., Goel, A., Puri, P., Sarin, S. K., Ahmed, A. WILEY. 2017: 18A

  View details for Web of Science ID 000412089800033

• Trends in Liver Transplantation among Patients with Primary Biliary Cholangitis Cholankeril, R., Rahim, U., Yoo, E. R., Li, A. A., Sandhu, K., Perumpail, R. B., Hu, M., Cholankeril, G., Ahmed, A. WILEY. 2017: 198A–199A

  View details for Web of Science ID 000412089800354

• National Drug Overdose Epidemic is a Significant Contributor to Deceased Donor Liver Organ Pool Cholankeril, G., Li, A. A., Cholankeril, R., Sandhu, J., Kim, D., Ahmed, A. WILEY. 2017: 397A

  View details for Web of Science ID 000412089800738

• Need to Improve Organs Transplanted Per Donor Despite the Rising Utilization of Hepatitis C Virus-Positive Donors in the United States Li, A. A., Rahim, U., Yoo, E. R., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2017: 887A

  View details for Web of Science ID 000412089802020

• 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

• Nonalcoholic Steatohepatitis Remains the Fastest Growing Indication for Liver Transplantation in Patients with Hepatocellular Carcinoma in the United States Li, A. A., Yoo, E. R., Cholankeril, G., Kim, D., Puri, P., Harrison, S. A., Younossi, Z. M., Ahmed, A. WILEY. 2017: 749A

  View details for Web of Science ID 000412089801539

• Implementation of Share 35 Policy has Improved Survival following Liver Transplantation Cholankeril, G., Li, A. A., Nair, S., Ahmed, A., Stanford Univ WILEY. 2017: 883A

  View details for Web of Science ID 000412089802012

• Improved Short-Term Survival in HCV Patients following Liver Transplantation in the Era of Direct Acting Antiviral Agents Cholankeril, G., Li, A. A., Yoo, E. R., Gonzalez, S. A., Younossi, Z. M., Ahmed, A. WILEY. 2017: 2A–3A

  View details for Web of Science ID 000412089800005

• Alcohol Liver Disease is now the most rapidly rising Indication for Liver Transplant Waitlist Registration in the United States Rahim, U., Cholankeril, G., Yoo, E. R., Liu, A., Li, A. A., Kim, D., Kwo, P. Y., Ahmed, A., Goel, A. WILEY. 2017: 708A

  View details for Web of Science ID 000412089801457

• The Declining Burden of HCV on the Liver Transplant Waitlist associated with the DAA era Cholankeril, G., March, K. L., Yoo, E. R., Li, A. A., Cholankeril, R., Perumpail, R. B., Satapathy, S. K., Ahmed, A. WILEY. 2017: 72A

  View details for Web of Science ID 000412089800124

• 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. n., Li, A. A., March, K. L., Yoo, E. R., Kim, D. n., Snyder, H. n., Gonzalez, S. A., Younossi, Z. M., Ahmed, A. n. 2017

  View details for PubMedID 28838786

• EMRE is an essential component of the mitochondrial calcium uniporter complex. Science (New York, N.Y.) Sancak, Y., Markhard, A. L., Kitami, T., Kovács-Bogdán, E., Kamer, K. J., Udeshi, N. D., Carr, S. A., Chaudhuri, D., Clapham, D. E., Li, A. A., Calvo, S. E., Goldberger, O., Mootha, V. K. 2013; 342 (6164): 1379-82

  Abstract

  The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include the EF-hand-containing calcium-binding proteins mitochondrial calcium uptake 1 (MICU1) and MICU2 and the pore-forming subunit mitochondrial calcium uniporter (MCU). We sought to achieve a full molecular characterization of the uniporter holocomplex (uniplex). Quantitative mass spectrometry of affinity-purified uniplex recovered MICU1 and MICU2, MCU and its paralog MCUb, and essential MCU regulator (EMRE), a previously uncharacterized protein. EMRE is a 10-kilodalton, metazoan-specific protein with a single transmembrane domain. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU.

  View details for DOI 10.1126/science.1242993

  View details for PubMedID 24231807

  View details for PubMedCentralID PMC4091629

• MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PloS one Plovanich, M., Bogorad, R. L., Sancak, Y., Kamer, K. J., Strittmatter, L., Li, A. A., Girgis, H. S., Kuchimanchi, S., De Groot, J., Speciner, L., Taneja, N., Oshea, J., Koteliansky, V., Mootha, V. K. 2013; 8 (2): e55785

  Abstract

  Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.

  View details for DOI 10.1371/journal.pone.0055785

  View details for PubMedID 23409044

  View details for PubMedCentralID PMC3567112

• Alternate protein kinase A activity identifies a unique population of stromal cells in adult bone. Proceedings of the National Academy of Sciences of the United States of America Tsang, K. M., Starost, M. F., Nesterova, M., Boikos, S. A., Watkins, T., Almeida, M. Q., Harran, M., Li, A., Collins, M. T., Cheadle, C., Mertz, E. L., Leikin, S., Kirschner, L. S., Robey, P., Stratakis, C. A. 2010; 107 (19): 8683-8

  Abstract

  A population of stromal cells that retains osteogenic capacity in adult bone (adult bone stromal cells or aBSCs) exists and is under intense investigation. Mice heterozygous for a null allele of prkar1a (Prkar1a(+/-)), the primary receptor for cyclic adenosine monophosphate (cAMP) and regulator of protein kinase A (PKA) activity, developed bone lesions that were derived from cAMP-responsive osteogenic cells and resembled fibrous dysplasia (FD). Prkar1a(+/-) mice were crossed with mice that were heterozygous for catalytic subunit Calpha (Prkaca(+/-)), the main PKA activity-mediating molecule, to generate a mouse model with double heterozygosity for prkar1a and prkaca (Prkar1a(+/-)Prkaca(+/-)). Unexpectedly, Prkar1a(+/-)Prkaca(+/-) mice developed a greater number of osseous lesions starting at 3 months of age that varied from the rare chondromas in the long bones and the ubiquitous osteochondrodysplasia of vertebral bodies to the occasional sarcoma in older animals. Cells from these lesions originated from an area proximal to the growth plate, expressed osteogenic cell markers, and showed higher PKA activity that was mostly type II (PKA-II) mediated by an alternate pattern of catalytic subunit expression. Gene expression profiling confirmed a preosteoblastic nature for these cells but also showed a signature that was indicative of mesenchymal-to-epithelial transition and increased Wnt signaling. These studies show that a specific subpopulation of aBSCs can be stimulated in adult bone by alternate PKA and catalytic subunit activity; abnormal proliferation of these cells leads to skeletal lesions that have similarities to human FD and bone tumors.

  View details for DOI 10.1073/pnas.1003680107

  View details for PubMedID 20421483

  View details for PubMedCentralID PMC2889322