Aparna Goel

All Publications

• Treatment of Autoimmune Hepatitis. Clinics in liver disease Goel, A., Kwo, P. 2024; 28 (1): 51-61

  Abstract

  The goal of autoimmune hepatitis treatment is to achieve clinical and biochemical remission, which is associated with significantly improved outcomes. Induction treatment with corticosteroids and the subsequent addition of steroid-sparing therapy with gradual tapering of corticosteroids remains the standard of care. Several alternatives to azathioprine and second-line agents, such as mycophenolate mofetil, tacrolimus, cyclosporine, sirolimus, or rituximab, have been evaluated in those with intolerance or inadequate response to standard-of-care therapy. Treatment withdrawal is achievable in less than 20% of patients after 2 years of sustained remission. Liver transplantation should be considered in those with progressive liver disease or those with complications such as hepatocellular carcinoma.

  View details for DOI 10.1016/j.cld.2023.07.001

  View details for PubMedID 37945162

• Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models. Transplantation Sedki, M., Kwong, A., Bhargava, M., Ahmed, A., Daugherty, T., Kwo, P., Dronamraju, D., Kumari, R., Kim, W. R., Esquivel, C., Melcher, M., Bonham, C. A., Gallo, A., Nelson, A., Norwood, A., Hussain, F., Goel, A. 2023

  Abstract

  The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse.A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared.Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%).AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.

  View details for DOI 10.1097/TP.0000000000004800

  View details for PubMedID 37899485

• Targeted Electronic Patient Portal Messaging Increases Hepatitis C Virus Screening in Primary Care: a Randomized Study. Journal of general internal medicine Halket, D., Dang, J., Phadke, A., Jayasekera, C., Kim, W. R., Kwo, P., Downing, L., Goel, A. 2022

  Abstract

  IMPORTANCE: Electronic health record (EHR) tools such as direct-to-patient messaging and automated lab orders are effective at improving uptake of preventive health measures. It is unknown if patient engagement in primary care impacts efficacy of such messaging.OBJECTIVE: To determine whether more engaged patients, defined as those who have an upcoming visit scheduled, are more likely to respond to a direct-to-patient message with an automated lab order for hepatitis C virus (HCV) screening.DESIGN: Randomized trial PARTICIPANTS: One thousand six hundred randomly selected Stanford Primary Care patients, 800 with an upcoming visit within 6 months and 800 without, born between 1945 and 1965 who were due for HCV screening. Each group was randomly divided into cohorts of 400 subjects each. Subjects were followed for 1 year.INTERVENTION: One 400 subject cohort in each group received a direct-to-patient message through the EHR portal with HCV antibody lab order.MAIN OUTCOME AND MEASURE: The EHR was queried on a monthly basis for 6 months after the intervention to monitor which subjects completed HCV screening. For any subjects screened positive for HCV, follow-up through the cascade of HCV care was monitored, and if needed, scheduled by the study team.KEY RESULTS: Of 1600 subjects, 538 (34%) completed HCV screening. In the stratum without an upcoming appointment, 18% in the control group completed screening compared to 26% in intervention group (p<0.01). Similarly, in the stratum with an upcoming appointment, 34% in the control group completed screening compared to 58% in the intervention group (p<0.01).CONCLUSION: Direct-to-patient messaging coupled with automated lab orders improved HCV screening rates compared to standard of care, particularly in more engaged patients. Including this intervention in primary care can maximize screening with each visit, which is particularly valuable in times when physical throughput in the healthcare system may be low.

  View details for DOI 10.1007/s11606-022-07460-1

  View details for PubMedID 35230622

• Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Kwong, A. J., Devuni, D., Wang, C., Boike, J., Jo, J., VanWagner, L., Serper, M., Jones, L., Sharma, R., Verna, E. C., Shor, J., German, M. N., Hristov, A., Lee, A., Spengler, E., Koteish, A. A., Sehmbey, G., Seetharam, A., John, N., Patel, Y., Kappus, M. R., Couri, T., Paul, S., Salgia, R. J., Nhu, Q., Frenette, C. T., Lai, J. C., Goel, A., Re-Evaluating Age Limits in Transplantation (REALT) Consortium 2020

  Abstract

  The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P<0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1year and 82.4% at 3years compared with 88.9% at 1year and 80.4% at 3years for non-NASH patients (log-rank P=0.58 and P=0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

  View details for DOI 10.1002/lt.25863

  View details for PubMedID 33047893

• Natural History of Primary Biliary Cholangitis in the Ursodeoxycholic Acid Era: Role of Scoring Systems. Clinics in liver disease Goel, A., Kim, W. R. 2018; 22 (3): 563-578

  Abstract

  Primary biliary cholangitis (PBC) is a chronic disease that progresses to end-stage liver disease. Ursodeoxycholic acid (UDCA), the standard treatment for PBC for several decades, is associated with improved survival without liver transplantation. Approximately 40% of patients do not respond to UDCA. Because of disease variability, several prognostic models exist that incorporate various factors including biochemical response to UDCA. Useful for patient care and counseling as well as risk stratification for research and clinical trials, the role of these models in the pre-UDCA and UDCA eras is discussed.

  View details for DOI 10.1016/j.cld.2018.03.007

  View details for PubMedID 30259853

• Liver Simulated Allocation Modeling: Were the Predictions Accurate for Share 35? Transplantation Goel, A. n., Kim, W. R., Pyke, J. n., Schladt, D. P., Kasiske, B. L., Snyder, J. J., Lake, J. R., Israni, A. K. 2018

  Abstract

  The liver simulated allocation model (LSAM) can be used to study likely effects of liver transplant allocation policy changes on organ offers, acceptance, waitlist survival, and posttransplant survival. Implementation of Share 35 in June 2013 allowed for testing how well LSAM predicted actual changes.LSAM projections for 1 year of liver transplants before and after the Share 35 policy change were compared with observed data during the same period. Numbers of organs recovered, organ sharing, transplant rates, and waitlist mortality rates (per 100 waitlist years) were evaluated by LSAM and compared with observed data.Candidate, recipient, and donor characteristics in the LSAM cohorts were similar to those in the observed population before and after Share 35. LSAM correctly predicted more accepted organs and fewer discarded organs with Share 35. LSAM also predicted increased regional and national sharing, consistent with observed data, although the magnitude was overestimated. Transplant rates were correctly projected to increase and waitlist death rates to decrease.Although the absolute number of transplants was underestimated and waitlist deaths overestimated, the direction of change was consistent with observed data. LSAM correctly predicted change in discarded organs, regional and national sharing, waitlist mortality, and transplants after Share 35 implementation.

  View details for PubMedID 29309379

• Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis. Alimentary pharmacology & therapeutics Goel, A. n., Rahim, U. n., Nguyen, L. H., Stave, C. n., Nguyen, M. H. 2017

  Abstract

  The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad-spectrum antibiotics.To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP.A literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta-analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random-effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).Five studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16-1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19-0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11-0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis.Rifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo.

  View details for PubMedID 28994123

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

  Abstract

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

  View details for PubMedID 29226102

• A systematic model improves hepatitis C virus birth cohort screening in hospital-based primary care. Journal of viral hepatitis Goel, A., Sanchez, J., Paulino, L., Feuille, C., Arend, J., Shah, B., Dieterich, D., Perumalswami, P. V. 2016

  Abstract

  Despite national and local governing board recommendations in the United States of America to perform an HCV screening test in baby boomers, screening rates remain low. Our goal was to study the impact of an HCV screening and link to care program with patient navigation in two New York City primary care practices. This was a two-year prospective study of patients born between 1945-1965 ("baby boomers") with encounters at two primary care practices at the Mount Sinai Hospital between November 1, 2013 and November 30, 2015. Baseline HCV screening rates were collected for four months. A multifaceted intervention was sequentially implemented involving electronic alerts, housestaff education, data feedback and patient navigation. HCV screening rates and link to care, defined as attending an appointment with a viral hepatitis specialist, were compared before and after these interventions. There were 14,642 primary care baby boomer patients of which 4,419 (30.2%) were newly screened during the study. There was a significant increase in HCV screening rates from 55% to 75% (p<0.01) and the HCV seropositive rate was 3.3%. Factors associated with being HCV seropositive included older age (p<0.01), male sex (p<0.01), African American race (p<0.01) and receiving care in the housestaff practice (p<0.01). With patient navigation, 78 of 84 (93%) newly diagnosed HCV infected persons were referred to a specialist and 60 (77%) attended their first appointment. A structured, multifaceted HCV screening program using well-studied principles identifies a large number of undiagnosed baby boomers within hospital-based primary care and improves access to specialty providers in a timely manner. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/jvh.12669

  View details for PubMedID 28039935

• A Real-World Evaluation of Repeat Paracentesis-guided Management of Spontaneous Bacterial Peritonitis. Journal of clinical gastroenterology Goel, A., Biewald, M., Huprikar, S., Schiano, T., Im, G. Y. 2016

  Abstract

  Spontaneous bacterial peritonitis (SBP) is a common infection in cirrhosis associated with high mortality. More than 20% of patients with SBP do not respond to initial antibiotics. Guidelines differ in recommendations to repeat paracentesis (retap) to confirm antibiotic efficacy. We aim to evaluate the effect of retap-guided management of SBP on antibiotic escalation and 30-day transplant-free survival.Retrospective cohort study of cirrhotic patients with SBP admitted to a single transplant center from 2010 to 2014. Patients were divided into 2 groups: retap-guided management versus no retap. Prevalence of initial antibiotic treatment failure, defined as <25% decrease in ascitic polymorphonuclear cells, and factors associated with treatment failure, antibiotic escalation and 30-day transplant-free survival were evaluated.Out of 210 patients, 146 (age 58, 74% male, mean model for end-stage liver disease score, 25) had retap and treatment failure was noted in 28 (22%). Gram-positive bacteria accounted for 44% of all positive cultures and third-generation cepahalosporin resistance was noted in 23%. Thirty-day transplant-free survival was 72% and 62% in retap and control groups, respectively (P=0.07). Treatment failure independently doubled the 30-day mortality rate (hazard ratio: 2.15, 1.03 to 4.50, P=0.04). After adjusting for age, model for end-stage liver disease and nosocomial infection, retap-guided management was not associated with improved survival (P=0.34).The prevalence of initial treatment failure is high (22%) in patients with SBP and doubles the 30-day mortality risk, supporting recommendations to retap all patients with SBP.

  View details for DOI 10.1097/MCG.0000000000000704

  View details for PubMedID 27661968

• Hepatic Artery and Biliary Complications in Liver Transplant Recipients Undergoing Pretransplant Transarterial Chemoembolization LIVER TRANSPLANTATION Goel, A., Mehta, N., Guy, J., Fidelman, N., Yao, F., Roberts, J., Terrault, N. 2014; 20 (10): 1221-1228

  Abstract

  Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional therapies for HCC are often used to reduce tumor burden, bridge patients to LT, and down-stage HCC so that patients are eligible for LT. We hypothesized that prior endovascular antitumor therapy may increase the risk of hepatic artery (HA) and biliary complications after LT. The aim of this study was to compare HA and biliary complications in LT recipients with HCC who received transarterial chemoembolization (TACE) before LT with complications in LT recipients with HCC who did not receive TACE before LT. This was a retrospective cohort study of HCC patients at two transplant centers. The prevalence of HA complications (HA thrombosis, stenosis, or pseudoaneurysm) and biliary complications (nonanastomotic stricture, bile leak, and diffuse injury) were compared between patients treated with or without TACE. There were 456 HCC patients with a median age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%) received TACE before LT. The overall prevalence of HA complications was 4.7% in the no-TACE group and 7.9% in the TACE group (P = 0.22). All HA stenosis complications (n = 14) occurred in the TACE group (P = 0.018 versus the no-TACE group). An older donor age and a lower albumin level significantly increased the odds of HA complications. There was a nonstatistically significant increased odds of HA complications in the TACE group versus the no-TACE group according to an adjusted analysis (odds ratio = 2.02, 95% confidence interval = 0.79-5.16, P = 0.14). The overall prevalence of biliary complications was 16.4% in the no-TACE group and 19.8% in the TACE group (P = 0.40). In conclusion, a lower pre-LT albumin level and an older donor age were significantly associated with higher odds of HA complications after LT. TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. Further studies are warranted to confirm the HA stenosis findings and elucidate the pathogenesis.

  View details for DOI 10.1002/lt.23945

  View details for Web of Science ID 000343012000010

  View details for PubMedID 25045002

• Transplant selection simulation: Liver transplantation for alcohol-associated hepatitis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Im, G. Y., Goel, A., Asrani, S., Singal, A. K., Wall, A., Sherman, C. B. 2023

  Abstract

  Liver transplantation (LT) for alcohol-associated hepatitis (AH) remains controversial due to concerns about candidate selection subjectivity, post-LT alcohol relapse and the potential exacerbation of LT disparities. Our aim was to design, perform and examine the results of a simulated selection of candidates for LT for AH. Medical histories, psychosocial profiles and scores, and outcomes of four simulation candidates were presented and discussed at two multidisciplinary societal conferences with real-time polling of participant responses. Candidate psychosocial profiles represented a wide spectrum of alcohol relapse risk. The predictive accuracy of four psychosocial scores, Dallas consensus criteria, SALT, SIPAT and QuickTrans, were assessed. Overall, 68 providers, mostly academic transplant hepatologists, participated in the simulation. Using a democratic process of selection, a significant majority from both simulations voted to accept the lowest psychosocial risk candidate for LT (72% and 85%) and decline the highest risk candidate (78% and 90%). For the two borderline risk candidates, a narrower majority voted to decline (56% and 65%; 64% and 82%). Two out of four patients had post-LT relapse. Predictive accuracies of Dallas, SIPAT and Quicktrans scores were 50%, while SALT was 25%. Majority voting outcomes were concordant with post-LT relapse in three out of four patients. When defining "success" in LT for AH, providers prioritized allograft health and quality of life rather than strict abstinence. In this simulation of LT for AH using a democratic process of selection, we demonstrate its potential as a learning model to evaluate the accuracy of psychosocial scores in predicting post-LT relapse and the concordance of majority voting with post-LT outcomes. Provider definitions of "success" in LT for AH have shifted towards patient-centered outcomes.

  View details for DOI 10.1097/LVT.0000000000000305

  View details for PubMedID 38009866

• Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Alimentary pharmacology & therapeutics Mayo, M. J., Vierling, J. M., Bowlus, C. L., Levy, C., Hirschfield, G. M., Neff, G. W., Galambos, M. R., Gordon, S. C., Borg, B. B., Harrison, S. A., Thuluvath, P. J., Goel, A., Shiffman, M. L., Swain, M. G., Jones, D. E., Trivedi, P., Kremer, A. E., Aspinall, R. J., Sheridan, D. A., Dörffel, Y., Yang, K., Choi, Y. J., McWherter, C. A. 2023

  Abstract

  Seladelpar is a potent and selective peroxisome proliferator-activated receptor-δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti-cholestatic, anti-inflammatory and anti-pruritic effects.To evaluate the long-term safety and efficacy of seladelpar in patients with PBC.In an open-label, international, long-term extension study, patients with PBC completing seladelpar lead-in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non-alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years.There were no serious treatment-related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2.Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year.gov: NCT03301506; Clinicaltrialsregister.eu: 2017-003910-16.

  View details for DOI 10.1111/apt.17755

  View details for PubMedID 37904314

• Hepatitis C Screening in Post-Baby Boomer Generation Americans: One Size Does Not Fit All. Mayo Clinic proceedings Sripongpun, P., Udompap, P., Mannalithara, A., Downing, N. L., Vidovszky, A. A., Kwong, A. J., Goel, A., Kwo, P. Y., Kim, W. R. 2023; 98 (9): 1335-1344

  Abstract

  To analyze the impact of access to routine health care, as estimated by health insurance coverage, on hepatitis C virus (HCV) infection prevalence in US adults born after 1965 (post-baby boomer birth cohort [post-BBBC]) and to use the data to formulate strategies to optimize population screening for HCV.Adult examinees in the National Health and Nutrition Examination Survey with available anti-HCV data were divided into era 1 (1999-2008) and era 2 (2009-2016). The prevalence of HCV infection, as defined by detectable serum HCV RNA, was determined in post-BBBC adults. In low prevalence groups, prescreening modalities were considered to increase the pretest probability.Of 16,966 eligible post-BBBC examinees, 0.5% had HCV infection. In both eras, more than 50% had no insurance. In era 2, HCV prevalence was 0.26% and 0.83% in those with and without insurance, respectively (P<.01). As a prescreening test, low alanine aminotransferase level (<23 U/L in women and 32 U/L in men) would identify 54% of post-BBBC adults with an extremely low (0.02%) HCV prevalence. Based on these data, a tiered approach that tests all uninsured directly for HCV and prescreens the insured with alanine aminotransferase would reduce the number to test by 56.5 million while missing less than 1% infections.For HCV elimination, passive "universal" screening in routine health care settings is insufficient, although the efficiency of screening may be improved with alanine aminotransferase prescreening. Importantly, for individuals with limited access to health care, proactive outreach programs for HCV screening are still needed.

  View details for DOI 10.1016/j.mayocp.2023.02.009

  View details for PubMedID 37661141

• Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology (Baltimore, Md.) Hirschfield, G. M., Shiffman, M. L., Gulamhusein, A., Kowdley, K. V., Vierling, J. M., Levy, C., Kremer, A. E., Zigmond, E., Andreone, P., Gordon, S. C., Bowlus, C. L., Lawitz, E. J., Aspinall, R. J., Pratt, D. S., Raikhelson, K., Gonzalez-Huezo, M. S., Heneghan, M. A., Jeong, S. H., Ladrón de Guevara, A. L., Mayo, M. J., Dalekos, G. N., Drenth, J. P., Janczewska, E., Leggett, B. A., Nevens, F., Vargas, V., Zuckerman, E., Corpechot, C., Fassio, E., Hinrichsen, H., Invernizzi, P., Trivedi, P. J., Forman, L., Jones, D. E., Ryder, S. D., Swain, M. G., Steinberg, A., Boudes, P. F., Choi, Y. J., McWherter, C. A. 2023; 78 (2): 397-415

  Abstract

  ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

  View details for DOI 10.1097/HEP.0000000000000395

  View details for PubMedID 37386786

  View details for PubMedCentralID PMC10344437

• Change in Platelet Count After Transjugular Intrahepatic Portosystemic Shunt Creation: An Advancing Liver Therapeutic Approaches (ALTA) Group Study. Journal of vascular and interventional radiology : JVIR Wong, R. J., Ge, J., Boike, J., German, M., Morelli, G., Spengler, E., Said, A., Desai, A., Couri, T., Paul, S., Frenette, C., Verna, E. C., Goel, A., Fallon, M., Thornburg, B., VanWagner, L., Lai, J. C., Kolli, K. P. 2023

  Abstract

  To evaluate platelet recovery after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery following TIPS creation.Adults with cirrhosis who underwent TIPS creation at 9 US hospitals from 2010-15 were included in this retrospective analysis. Change in platelets from pre- to 4 months post-TIPS was characterized. Logistic regression was used to assess factors associated with top quartile % platelet increase post-TIPS. Subgroup analyses were performed among patients with pre-TIPS platelets ≤50x109/L.601 patients were included. Median absolute change in platelets was 1x109/L (-26x109/L - 25x109/L). Patients with top quartile % platelet increase had ≥32% platelet increase. In multivariable analysis, pre-TIPS platelets (OR, 0.97 per 109/L; 95% CI, 0.97-0.98), age (OR, 1.24 per 5y; 95% CI, 1.10-1.39), and pre-TIPS MELD (OR, 1.06 per point; 95% CI, 1.02-1.09) were associated with top quartile (≥32%) platelet increase. 94 patients (16%) had platelets ≤50x109/L pre-TIPS. Median absolute platelet change was 14x109/L (2x109/L-34x109/L). 54% of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5y; 95% CI, 1.11-2.02) was the only factor associated with top quartile platelet increase in this subgroup.TIPS creation did not result in significant platelet increase, except among patients with platelet ≤50x109/L pre-TIPS. Lower pre-TIPS platelets, older age, and higher pre-TIPS MELD were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with pre-TIPS platelets ≤50x109/L.

  View details for DOI 10.1016/j.jvir.2023.04.015

  View details for PubMedID 37100199

• Letter to the Editor: Insurance should cover vancomycin for primary sclerosing cholangitis. Hepatology (Baltimore, Md.) Ali, A. H., Buness, C. W., Fischer, R., Holtmann, G. J., Shah, A., Lewindon, P., Shah, S., Ragnekar, A. S., Taylor, A. E., Goel, A., Cox, K. L., Alrabadi, L., Wadsworth, S., Kulkarni, S. S., Lindor, K. D. 2023

  View details for DOI 10.1097/HEP.0000000000000304

  View details for PubMedID 36705026

• The impact of right atrial pressure on outcomes in patients undergoing TIPS, An ALTA group study. Hepatology (Baltimore, Md.) Bommena, S., Mahmud, N., Boike, J. R., Thornburg, B. G., Kolli, K. P., Lai, J. C., German, M., Morelli, G., Spengler, E., Said, A., Desai, A. P., Junna, S., Paul, S., Frenette, C., Verna, E. C., Goel, A., Gregory, D., Padilla, C., VanWagner, L. B., Fallon, M. B. 2023

  Abstract

  Single-center studies in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database.883 patients in ALTA multicenter TIPS database from 2010-2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure (HF). Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model non-linear relationship. Logistic regression was used to assess RAP association with secondary outcomes.Pre-TIPS RAP was independently associated with overall mortality (sHR 1.04 per mmHg, 95% CI 1.01, 1.08, P=0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction and HF. Pre-TIPS RAP was positively associated with MELD, BMI, Native American and Black race, and lower platelets.Pre-TIPS RAP is an independent risk factor for overall mortality following TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact.

  View details for DOI 10.1097/HEP.0000000000000283

  View details for PubMedID 36651170

• Clinical characteristics and outcomes in those with primary extrahepatic malignancy and malignant ascites. BMC gastroenterology Alshuwaykh, O., Cheung, A., Goel, A., Kwong, A., Dhanasekaran, R., Ghaziani, T. T., Ahmed, A., Daugherty, T., Dronamraju, D., Kumari, R., Nguyen, M., Kim, W. R., Kwo, P. Y. 2022; 22 (1): 410

  Abstract

  BACKGROUND: Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites.METHODS: 241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis.RESULTS: Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC.CONCLUSIONS: Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.

  View details for DOI 10.1186/s12876-022-02487-4

  View details for PubMedID 36064324

• Incidence of hepatocellular carcinoma in chronic hepatitis B virus infection in those not meeting criteria for antiviral therapy. Hepatology communications Alshuwaykh, O., Daugherty, T., Cheung, A., Goel, A., Dhanasekaran, R., Ghaziani, T. T., Ahmed, A., Dronamraju, D., Kumari, R., Kwong, A., Nguyen, M., Kim, W. R., Kwo, P. Y. 2022

  Abstract

  Chronic hepatitis B virus (HBV) infection is the leading risk factor for hepatocellular carcinoma (HCC). The aim of this study was to explore the incidence of HCC in a cohort of subjects with HBV and correlate with HBV treatment current guidance. We identified 2846 subjects with HBV over the study period. HCC was diagnosed in 386 of 2846 (14%) subjects; 209 of 386 (54%) were on nucleos(t)ide analogue (NA) therapy at time of HCC diagnosis, and 177 of 386 (46%) were not on NA therapy. Of the 177 subjects not on NAs who developed HCC during follow-up, 153 of 177 (86%) had cirrhosis. Within the 177 subjects not on NAs, 158 of 177 (89%) had undetectable HBV DNA, 10 of 177 (6%) had detectable HBV DNA < 2000 IU/L, and 9 of 177 (5%) had HBV DNA > 2000 IU/L. Of those with cirrhosis and undetectable HBV DNA, 115 of 141 had compensated cirrhosis, and 26 of 141 had decompensated cirrhosis. Significant predictors of HCC on time to event analysis included cirrhosis (hazard ratio [HR] 10, 95% confidence interval [CI] 5.8-17.5; p < 0.001), alanine aminotransferase level (HR 1.004, 95% CI 1.002-1.006; p < 0.001), age (HR 1.04, 95% CI 1.03-1.06; p < 0.001), (HR 1.9, 95% CI 1.2-3.1; p 0.007), and nonalcoholic fatty liver disease (HR 1.7, 95% CI 1.1-2.8; p 0.02). Kaplan-Meier analysis demonstrated the cumulative incidence of HCC in subjects with compensated cirrhosis receiving NA therapy was significantly lower compared to subjects with compensated cirrhosis outside current HBV treatment practice guidance (undetectable HBV DNA) (32% vs. 51%; p < 0.001). Conclusion: Those with untreated compensated cirrhosis with undetectable HBV DNA who do not meet current guidance for treatment had higher rates of HCC than those with compensated cirrhosis and suppressed HBV DNA by NA therapy. This study highlights the need for earlier diagnosis and treatment of HBV.

  View details for DOI 10.1002/hep4.2064

  View details for PubMedID 36004713

• Ethical and allocation issues in liver transplant candidates with alcohol related liver disease. Translational gastroenterology and hepatology Sedki, M., Ahmed, A., Goel, A. 2022; 7: 26

  Abstract

  In the past decade, alcohol-related liver disease (ALD) has become the leading indication for liver transplantation (LT) in the United States. Despite this major development, there still remains some controversy in a distinct subset of this patient population, those presenting with alcoholic hepatitis (AH). There is significant debate within the transplant community regarding acceptance criteria for patients with AH requiring LT, especially those with less than 6 months of sobriety. With that being said, LT in the setting of ALD and AH has shown an improvement in survival rates; additionally, many studies have reported that careful selection of patients with ALD has produced excellent post-transplant outcomes even if transplant occurred with less than 6 months of sobriety. In this review, we aim to discuss the ethical and allocation-associated issues that arise when considering ALD and/or AH for LT; furthermore, we delve into the history, controversies, current guidelines, and future directions of LT in this subgroup.

  View details for DOI 10.21037/tgh-2020-13

  View details for PubMedID 35892052

  View details for PubMedCentralID PMC9257533

• CAQ Corner: Disease Recurrence After Liver Transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Goel, A., Kwong, A. 2022

  View details for DOI 10.1002/lt.26492

  View details for PubMedID 35466545

• A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. Journal of hepatology Bowlus, C. L., Galambos, M. R., Aspinall, R. J., Hirschfield, G. M., Jones, D. E., Dorffel, Y., Gordon, S. C., Harrison, S. A., Kremer, A. E., Mayo, M. J., Thuluvath, P. J., Levy, C., Swain, M. G., Neff, G. W., Sheridan, D. A., Stanca, C. M., Berg, C. P., Goel, A., Shiffman, M. L., Vierling, J. M., Boudes, P., Steinberg, A., Choi, Y., McWherter, C. A. 2022

  Abstract

  BACKGROUND & AIMS: We examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with primary biliary cholangitis (PBC) at risk for disease progression (alkaline phosphatase [ALP] ≥1.67*upper limit of normal [ULN]) receiving or intolerant to ursodeoxycholic acid.METHODS: In this 52-week, phase 2, dose-ranging, open-label study, patients were randomized (1:1) to seladelpar 5 (N=53) or 10 mg/day (N=55) or assigned to 2 mg/day (N=11; United Kingdom sites after interim analysis) for 12 weeks. Doses could then be uptitrated to 10 mg/day. Primary efficacy endpoint was ALP change from baseline to Week 8.RESULTS: Mean baseline ALP was 300, 345, and 295 U/L in the 2-mg, 5-mg, and 10-mg cohorts, respectively. Twenty-one percent of patients had cirrhosis, 71% had pruritus. At Week 8, mean±standard error ALP reductions from baseline were 26±2.8%, 33±2.6%, and 41±1.8% in the 2-mg (N=11), 5-mg (N=49), and 10-mg (N=52) cohorts (all p<0.005), respectively. Responses were maintained or improved at Week 52, after dose escalation in 91% and 80% of the 2-mg and 5-mg cohorts, respectively. At Week 52, composite response (ALP <1.67*ULN, ≥15% ALP decrease, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2-mg, 5-mg, and 10-mg cohorts, respectively. Pruritus visual analog scale score was decreased in the 5-mg and 10-mg cohorts. There were no treatment-related serious adverse events (AEs), and 4 patients discontinued due to AEs.CONCLUSIONS: Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in PBC patients at risk for disease progression. Seladelpar appeared safe and well tolerated with no increase in pruritus.LAY SUMMARY: Current treatment options for patients living with primary biliary cholangitis (PBC) are not optimal due to inadequate effectiveness or undesirable side effects. Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses (2, 5, or 10 mg/day) for 1 year had clinically significant, dose-dependent improvements in key liver tests. Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores.CLINICALTRIALS: GOV NUMBER: NCT02955602 CLINICALTRIALSREGISTER.EU NUMBER: 2016-002996-91.

  View details for DOI 10.1016/j.jhep.2022.02.033

  View details for PubMedID 35367282

• Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation. Journal of hepatology Montano-Loza, A. J., Ronca, V., Ebadi, M., Hansen, B. E., Hirschfield, G., Elwir, S., Alsaed, M., Milkiewicz, P., Janik, M. K., Marschall, H. U., Burza, M. A., Efe, C., Calışkan, A. R., Harputluoglu, M., Kabaçam, G., Terrabuio, D., de Quadros Onofrio, F., Selzner, N., Bonder, A., Parés, A., Llovet, L., Akyıldız, M., Arikan, C., Manns, M. P., Taubert, R., Weber, A. L., Schiano, T. D., Haydel, B., Czubkowski, P., Socha, P., Ołdak, N., Akamatsu, N., Tanaka, A., Levy, C., Martin, E. F., Goel, A., Sedki, M., Jankowska, I., Ikegami, T., Rodriguez, M., Sterneck, M., Weiler-Normann, C., Schramm, C., Donato, M. F., Lohse, A., Andrade, R. J., Patwardhan, V. R., van Hoek, B., Biewenga, M., Kremer, A. E., Ueda, Y., Deneau, M., Pedersen, M., Mayo, M. J., Floreani, A., Burra, P., Secchi, M. F., Beretta-Piccoli, B. T., Sciveres, M., Maggiore, G., Jafri, S. M., Debray, D., Girard, M., Lacaille, F., Lytvyak, E., Mason, A. L., Heneghan, M., Oo, Y. H. 2022

  Abstract

  The impact of recurrent autoimmune hepatitis (AIH) post-liver transplant on patient and graft survival is not well characterised. We evaluated a large, international multi-center cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.We included 736 patients (77% female, mean age, 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients with higher risk of recurrence of AIH based on histological diagnosis.AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (HR, 3.15; 95% CI, 1.22-8.16; p=0.02), use of mycophenolate mofetil post-LT (HR, 3.06; 95% CI, 1.39-6.73; p=0.005), donor and recipient sex mismatch (HR, 2.57; 95% CI, 1.39-4.76; p=0.003) and high IgG pre-LT (HR, 1.04; 95% CI, 1.01-1.06; p=0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression with time-dependent covariate, recurrent AIH significantly associated with graft loss (HR, 10.79, 95% CI 5.37-21.66, p<0.001) and death (HR, 2.53, 95% CI 1.48-4.33, p=0.001).Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting ongoing efforts to better characterize, prevent and treat recurrent AIH.Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of antirejection medications. Recurrent autoimmune hepatitis negatively affects the outcome after liver transplant.

  View details for DOI 10.1016/j.jhep.2022.01.022

  View details for PubMedID 35143897

• Selection Criteria for Liver Transplantation for Acute Alcohol-Associated Hepatitis. Clinics in liver disease Goel, A., Daugherty, T. 2021; 25 (3): 635-644

  Abstract

  Severe acute alcohol-associated hepatitis that is nonresponsive to medical therapy has an extremely high mortality. Liver transplantation is a feasible treatment option and available at certain transplant centers globally. Selection criteria for liver transplantation are not, uniform but there are important key criteria shared across protocols. Of equal importance to the management of liver disease is the treatment of alcohol use disorder. A thorough assessment of candidates involves input from an addiction specialist and psychiatrist. With careful selection practices, graft and patient survival among transplant recipients with severe alcohol-associated hepatitis is similar to other etiologies of chronic liver disease.

  View details for DOI 10.1016/j.cld.2021.03.007

  View details for PubMedID 34229845

• Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study. The American journal of gastroenterology Boike, J. R., Mazumder, N. R., Kolli, K. P., Ge, J., German, M., Jest, N., Morelli, G., Spengler, E., Said, A., Lai, J. C., Desai, A. P., Couri, T., Paul, S., Frenette, C., Verna, E. C., Rahim, U., Goel, A., Gregory, D., Thornburg, B., VanWagner, L. B., Advancing Liver Therapeutic Approaches (ALTA) Study Group 2021

  Abstract

  INTRODUCTION: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications.METHODS: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT).RESULTS: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13).DISCUSSION: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.

  View details for DOI 10.14309/ajg.0000000000001357

  View details for PubMedID 34158464

• Predictors of Outcomes of Patients Referred to a Transplant Center for Urgent Liver Transplantation Evaluation. Hepatology communications Alshuwaykh, O., Kwong, A., Goel, A., Cheung, A., Dhanasekaran, R., Ahmed, A., Daugherty, T., Dronamraju, D., Kumari, R., Kim, W. R., Nguyen, M. H., Esquivel, C. O., Concepcion, W., Melcher, M., Bonham, A., Pham, T., Gallo, A., Kwo, P. Y. 2021; 5 (3): 516-525

  Abstract

  Liver transplantation (LT) is definitive treatment for end-stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty-two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol-associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait-listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non-Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End-Stage Liver Disease (MELD)-Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF-C) score >51.5 (OR, 1.26; P = 0.03), acute-on-chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3-month mortality included CLIF-C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P < 0.001). Conclusion: MELD-Na, albumin, hyponatremia, ACLF grade 3, HRS, respiratory failure, public insurance, Hispanic race, Asian race, and non-Hispanic ethnicity predicted liver transplant outcome. Lack of psychosocial support was a major reason for being declined for LT. The CLIF-C score predicted being declined for LT and mortality.

  View details for DOI 10.1002/hep4.1644

  View details for PubMedID 33681683

  View details for PubMedCentralID PMC7917272

• Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis. Inflammatory bowel diseases Kulkarni, C., Murag, S., Cholankeril, G., Fardeen, T., Mannalithara, A., Lerrigo, R., Kamal, A., Ahmed, A., Goel, A., Sinha, S. R. 2020

  Abstract

  BACKGROUND: Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing acute cholangitis. The majority of patients with PSC have comorbid inflammatory bowel disease, and many take immunosuppressive medications. The epidemiological risks for the development of acute cholangitis in patients with PSC, including the impact of immunosuppressive therapy, are unknown.METHODS: We conducted a 2-center, retrospective cohort study using data from 228 patients at Stanford University Medical Center and Santa Clara Valley Medical Center (CA), a county health care system. Patient demographics, medications, PSC disease severity, and inflammatory bowel disease status were extracted. Using stepwise variable selection, we included demographic and covariate predictors in the multiple logistic regression model assessing risk factors for cholangitis. Time-to-event analysis was performed to evaluate specific immunosuppressive medications and development of cholangitis.RESULTS: Thirty-one percent of patients had at least 1 episode of acute cholangitis (n = 72). Anti-tumor necrosis factor (TNF) therapy was associated with increased odds of acute cholangitis (odds ratio, 7.29; 95% confidence interval, 2.63-12.43), but immunomodulator use was protective against acute cholangitis (odds ratio, 0.23; 95% confidence interval, 0.05-0.76). Anti-TNF therapy was associated with decreased time-to-cholangitis, with a median time of 28.4 months; in contrast, only 11.1% of patients who were prescribed immunomodulators developed cholangitis over the same time period (P < 0.001).CONCLUSIONS: Our observations suggest that classes of immunosuppressive medications differentially modify the odds of acute cholangitis. Biologic therapy, ie, anti-TNF therapy, was shown to have significantly higher odds for patients developing acute cholangitis whereas immunomodulator therapy was shown to have a potential protective effect. These findings may help guide physicians in decision-making for determining appropriate immunosuppressive therapy.

  View details for DOI 10.1093/ibd/izaa317

  View details for PubMedID 33300561

• Provider Attitudes and Practices for Alcohol Screening, Treatment and Education in Patients with Liver Disease: a Survey from the AASLD ALD SIG. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Im, G. Y., Mellinger, J. L., Winters, A., Aby, E. S., Lominadze, Z., Rice, J., Lucey, M. R., Arab, J. P., Goel, A., Jophlin, L. L., Sherman, C. B., Parker, R., Chen, P., Devuni, D., Sidhu, S., Dunn, W., Szabo, G., Singal, A. K., Shah, V. H. 2020

  Abstract

  BACKGROUND & AIMS: While abstinence-promoting behavioral and pharmaco-therapies are part of the therapeutic foundation for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), these therapies, along with alcohol screening and education, are often underutilized. Our aim was to examine provider attitudes and practices for alcohol screening, treatment and education in patients with liver disease.METHODS: We conducted a survey of primarily (89%) hepatology and gastroenterology providers within (80%) and outside the US (20%). Surveys were sent to 921 providers with 408 complete responses (44%), of whom 343 (80%) work in a tertiary liver transplant center.RESULTS: While alcohol screening rates in liver disease patients was nearly universal, less than half of providers reported practicing with integrated addiction providers, using alcohol biomarkers and screening tools. Safe alcohol use by liver disease patients was felt to exist by 40% of providers. While 60% of providers reported referring AUD patients for behavioral therapy, 71% never prescribed AUD pharmacotherapy due to low comfort (84%). Most providers (77%) reported low addiction education and 90% desired more during GI/hepatology fellowship training. Amongst prescribers, baclofen was preferred, but with gaps in pharmacotherapy knowledge. Overall, there was low adherence to the 2019 AASLD practice guidance for ALD, although higher in hepatologists and experienced providers.CONCLUSIONS: While our survey of hepatology and gastroenterology providers demonstrated higher rates of alcohol screening and referrals for behavioral therapy, we found low rates of prescribing AUD pharmacotherapy due to knowledge gaps from insufficient education. Further studies are needed to assess interventions to improve provider alignment with best practices for treating patients with AUD and ALD.

  View details for DOI 10.1016/j.cgh.2020.10.026

  View details for PubMedID 33069880

• Tenofovir Alafenamide Attenuates Effects of Diabetes and Body Mass on Serum Alanine Aminotransferase Activities in Patients with Chronic Hepatitis B. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Sripongpun, P. n., Kim, W. R., Mannalithara, A. n., Kwong, A. n., Daugherty, T. n., Goel, A. n., Kwo, P. Y. 2020

  View details for DOI 10.1016/j.cgh.2020.11.047

  View details for PubMedID 33285291

• Dead Meat: Glecaprevir/Pibrentasvir-Induced Statin Myonecrosis. Digestive diseases and sciences Wong, K., Podboy, A., Lavezo, J., Goel, A. 2020

  View details for DOI 10.1007/s10620-019-05993-w

  View details for PubMedID 31894484

• NAFLD and Diabetes are Associated with Post-TIPS Renal Dysfunction: An ALTA Group Study. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Ge, J. n., Lai, J. C., Boike, J. R., German, M. n., Jest, N. n., Morelli, G. n., Spengler, E. n., Said, A. n., Lee, A. n., Hristov, A. n., Desai, A. P., Junna, S. n., Pokhrel, B. n., Couri, T. n., Paul, S. n., Frenette, C. n., Christian-Miller, N. n., Laurito, M. n., Verna, E. C., Rahim, U. n., Goel, A. n., Das, A. n., Pine, S. n., Gregory, D. n., VanWagner, L. B., Kolli, K. P. 2020

  Abstract

  Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well-characterized. Here, we describe renal function and characteristics associated with renal dysfunction at 30-days post-TIPS.Adults with cirrhosis who underwent TIPS at nine hospitals in the US 2010-2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤ -15ml/min/1.73m2 and eGFR ≤ 60ml/min/1.73m2 , or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions.Of 673 patients: median age 57 years, 38% female, 26% had diabetes, median MELDNa 17. Thirty days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared to those with stable renal function, were more likely to have NAFLD (33% versus 17%, p = 0.01) and comorbid diabetes (42% versus 24%, p < 0.01). Multivariate logistic regressions showed NAFLD (OR 2.04, 95%CI 1.00 to 4.17, p = 0.05), serum sodium (OR 1.06 per mEq/L, 95%CI 1.01 to 1.12, p = 0.03), and diabetes (OR 2.04, 95%CI 1.16 to 3.61, p = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed those with post-TIPS renal dysfunction were at higher sub-hazard of death (sHR 1.74, 95%CI 1.18 to 2.56, p = 0.01).In this large multi-center cohort, we found NAFLD, diabetes, and baseline serum sodium associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities prior to proceeding with the procedure.

  View details for DOI 10.1002/lt.25949

  View details for PubMedID 33217178

• Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel. BMJ open gastroenterology Pate, J., Gutierrez, J. A., Frenette, C. T., Goel, A., Kumar, S., Manch, R. A., Mena, E. A., Pockros, P. J., Satapathy, S. K., Yimam, K. K., Gish, R. G. 2019; 6 (1): e000256

  Abstract

  Background and aims: This article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.Methods: In May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.Results: These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.Conclusions: Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

  View details for PubMedID 30815273

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

  Abstract

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

  View details for PubMedID 30099535

  View details for PubMedCentralID PMC6203122

• Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C Adolescent Health, Medicine and Therapeutics Yang, C. H., Goel, A., Ahmed, A. 2018; 9: 103—110

  Abstract

  Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%-2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

  View details for DOI 10.2147/AHMT.S147896

  View details for PubMedCentralID PMC6071628

• Improved Post-Transplant Mortality After Share 35 for Liver Transplantation. Hepatology (Baltimore, Md.) Kwong, A. J., Goel, A., Mannalithara, A., Kim, W. R. 2017

  Abstract

  The Share 35 policy was implemented in June 2013 to improve equity in access to liver transplantation (LT) between patients with fulminant liver failure and those with cirrhosis and severe hepatic decompensation. The aim of this study was to assess post-LT outcomes after Share 35.Relevant donor, procurement, and recipient data were extracted from the OPTN/UNOS database. All adult deceased donor LT from January 1, 2010 to March 31, 2016 were included in the analysis. One-year patient survival before and after Share 35 was assessed by multivariable Cox proportional hazards analysis, with adjustment for variables known to affect graft survival.Of 34,975 adult LT recipients, 16,472 (47.1%) were transplanted after the implementation of Share 35, of whom 4,599 (27.9%) had a Model for End-Stage Liver Disease (MELD) ≥35. One-year patient survival improved from 83.9% to 88.4% after Share 35 (p<0.01) for patients with MELD ≥35. There was no significant impact on survival of patients with MELD <35 (p=0.69). Quality of donor organs, as measured by Donor Risk Index without the regional share component, improved for patients with MELD ≥35 (p<0.01) and worsened for patients with lower MELD (p<0.01). In multivariable Cox regression analysis, Share 35 was associated with improved one-year patient survival (hazard ratio 0.69, 95% confidence interval 0.60-0.80) in recipients with MELD ≥35.Share 35 has had a positive impact on survival after transplantation in patients with MELD ≥35, without a reciprocal detriment in patients with lower acuity. This was in part a result of a more favorable donor-recipient matching. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/hep.29301

  View details for PubMedID 28586179

• An Atypical Cause of a Typical Symptom. Gastroenterology Menezes, A., Goel, A., Sam, G. 2016

  View details for DOI 10.1053/j.gastro.2016.06.019

  View details for PubMedID 27591422

• The features of mucosa-associated microbiota in primary sclerosing cholangitis ALIMENTARY PHARMACOLOGY & THERAPEUTICS Torres, J., Bao, X., Goel, A., Colombel, J., Pekow, J., Jabri, B., Williams, K. M., Castillo, A., Odin, J. A., Meckel, K., Fasihuddin, F., Peter, I., Itzkowitz, S., Hu, J. 2016; 43 (7): 790-801

  Abstract

  Little is known about the role of the microbiome in primary sclerosing cholangitis.To explore the mucosa-associated microbiota in primary sclerosing cholangitis (PSC) patients across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)-only patients and healthy controls.Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies.Forty-four patients were recruited: 20 with PSC (19 with PSC-IBD and one with PSC-only), 15 with IBD-only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order.The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated-microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order.

  View details for DOI 10.1111/apt.13552

  View details for Web of Science ID 000371742300004

  View details for PubMedID 26857969

• Early Liver Transplantation for Severe Alcoholic Hepatitis in the United StatesA Single-Center Experience AMERICAN JOURNAL OF TRANSPLANTATION Im, G. Y., Kim-Schluger, L., Shenoy, A., Schubert, E., Goel, A., Friedman, S. L., Florman, S., Schiano, T. D. 2016; 16 (3): 841-849

  Abstract

  Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States.

  View details for DOI 10.1111/ajt.13586

  View details for Web of Science ID 000371240500016

  View details for PubMedID 26710309

• Reply: To PMID 25045002. Liver transplantation Goel, A., Terrault, N. 2015; 21 (3): 416-?

  View details for DOI 10.1002/lt.24066

  View details for PubMedID 25530165

• Identification of Liver Transplant Candidates With Hepatocellular Carcinoma and a Very Low Dropout Risk: Implications for the Current Organ Allocation Policy LIVER TRANSPLANTATION Mehta, N., Dodge, J. L., Goel, A., Roberts, J. P., Hirose, R., Yao, F. Y. 2013; 19 (12): 1343-1353

  Abstract

  It has been shown that patients with hepatocellular carcinoma (HCC) meeting the United Network for Organ Sharing T2 (Milan) criteria have an advantage in comparison with patients without HCC under the current organ allocation system for liver transplantation (LT). We hypothesized that within the T2 HCC group, there is a subgroup with a low risk of wait-list dropout that should not receive the same listing priority. This study evaluated 398 consecutive patients with T2 HCC listed for LT with a Model for End-Stage Liver Disease exception from March 2005 to January 2011 at our center. Competing risk (CR) regression was used to determine predictors of dropout. The probabilities of dropout due to tumor progression or death without LT according to the CR analysis were 9.4% at 6 months and 19.6% at 12 months. The median time from listing to LT was 8.8 months, and the median time from listing to dropout or death without LT was 7.2 months. Significant predictors of dropout or death without LT according to a multivariate CR regression included 1 tumor of 3.1 to 5 cm (versus 1 tumor of 3 cm or less), 2 or 3 tumors, a lack of a complete response to the first locoregional therapy (LRT), and a high alpha-fetoprotein (AFP) level after the first LRT. A subgroup (19.9%) that met certain criteria (1 tumor of 2 to 3 cm, a complete response after the first LRT, and an AFP level ≤ 20 ng/mL after the first LRT) had 1- and 2-year probabilities of dropout of 1.3% and 1.6%, respectively, whereas the probabilities were 21.6% and 26.5% for all other patients (P = 0.004). In conclusion, a combination of tumor characteristics and a complete response to the first LRT define a subgroup of patients with a very low risk of wait-list dropout who do not require the same listing priority. Our results may have important implications for the organ allocation policy for HCC.

  View details for DOI 10.1002/lt.23753

  View details for Web of Science ID 000327431600009

  View details for PubMedID 24285611

• The Housestaff Incentive Program improving the timeliness and quality of discharge summaries by engaging residents in quality improvement BMJ QUALITY & SAFETY Bischoff, K., Goel, A., Hollander, H., Ranji, S. R., Mourad, M. 2013; 22 (9): 768-774

  Abstract

  Quality improvement has become increasingly important in the practice of medicine; however, engaging residents in meaningful projects within the demanding training environment remains challenging.We conducted a year-long quality improvement project involving internal medicine residents at an academic medical centre. Resident champions designed and implemented a discharge summary improvement bundle, which employed an educational curriculum, an electronic discharge summary template, regular data feedback and a financial incentive. The timeliness and quality of discharge summaries were measured before and after the intervention. Residents and faculty were surveyed about their perceptions of the project; primary care providers were surveyed about their satisfaction with hospital provider communication.With implementation of the bundle, the average time from patient discharge to completion of the discharge summary fell from 3.5 to 0.61 days (p<0.001). The percentage of summaries completed on the day of discharge rose from 38% to 83% (p<0.001) and this improvement was sustained for 6 months following the end of the project. The percentage of summaries that included all recommended elements increased from 5% to 88% (p<0.001). Primary care providers reported a lower likelihood of discharge summaries being unavailable at the time of outpatient follow-up (38% to 4%, p<0.001). Residents reported that the systems changes, more than the financial incentive, accounted for their behaviour change.Our discharge summary improvement project provides an instructive example of how residents can lead clinically meaningful quality improvement projects.

  View details for DOI 10.1136/bmjqs-2012-001671

  View details for Web of Science ID 000329777400009

  View details for PubMedID 23704085