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Early liver transplantation (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT, but prediction of harmful alcohol use post-LT remains limited. Among 10 ACCELERATE-AH centers, we examined psychosocial evaluations from consecutive LT recipients for AH from 2006 to 2017. A multidisciplinary panel used content analysis to develop a maximal list of psychosocial variables. We developed an artificial intelligence model to predict post-LT harmful alcohol use. The cohort included training (N = 91 among 8 centers) and external validation (N = 25 among 2 centers) sets, with median follow-up of 4.4 (IQR 3.0-6.0) years post-LT. In the training set, AUC was 0.930 (95%CI 0.862-0.998) with positive predictive value of 0.891 (95%CI 0.620-1.000), internally validated through fivefold cross-validation. In the external validation set, AUC was 0.692 (95%CI 0.666-0.718) with positive predictive value of 0.82 (95%CI 0.625-1.000). The model identified specific variables related to social support and substance use as highly important to predict post-LT harmful alcohol use. We retrospectively developed and validated a model that identified psychosocial profiles at LT predicting harmful alcohol use post-LT for AH. This preliminary model may inform selection and post-LT management for AH and warrants prospective evaluation in larger studies among all alcohol-associated liver disease being considered for early LT. more...

Experts have forewarned about the coronavirus disease 2019 (COVID-19) pandemic environment fomenting the rising incidence of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). We performed a cross-sectional study of ALD at our liver transplantation (LT) center, located in the initial U.S. epicenter, New York City. Centered around the "stay at home" order date in New York state, March 22, 2020, we defined three time periods: "pre-COVID" (January 1, 2020-March 21, 2020), "COVID-quarantine" (March 22, 2020-April 22, 2020), and "declining-COVID" (April 23, 2020-August 25, 2020). We found a 62% increase in interhospital patient transfers for ALD from pre-COVID (20 of 93, 21%) to the declining-COVID period (43 of 127, 34%). Our inpatient liver census with ALD also increased: 38% pre-COVID, 45% COVID-quarantine, and 49% declining-COVID. Among 30 patients with severe alcoholic hepatitis (AH) not responding to medical therapy since March 22, 2020, 9 underwent early LT for AH (16% of the total number of early LT during our 8-year program). Three of 9 early-LT recipients reported specific COVID-related stressors. All 25 previous LT recipients with established abstinence pre-COVID maintained abstinence at follow-up visits during the declining-COVID period. Of the 6 recipients with sustained alcohol use within 6 months before March 22, 2020, half regained abstinence during the declining-COVID period. Our findings help confirm the predictions of rising AUD and ALD as an immediate consequence of the COVID-19 pandemic. This aftershock particularly affected ethnically diverse patients with ALD with high inpatient mortality, reflecting the disproportionate impact of COVID-19 on underserved and minority populations. Alcohol relapse did not occur in long-term early LT for AH recipients during the time of COVID-19. This lends further support to AH being a viable indication for LT, with recipients able to demonstrate ongoing resilience in the face of this unprecedented universal stressor. more...

The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous global impact since it began in November of 2019. However, there are concerns that the COVID-19 pandemic will not affect all equally and that some populations will be particularly vulnerable. Relevant to liver disease, patients with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) may be among the populations that are the most severely impacted. The reasons for this include being at a higher risk of severe COVID-19 infection due to a depressed immune system and high-risk underlying comorbidities, the injurious effect of COVID-19 on the liver, the inability to attend regular visits with providers, diversion of hospital resources, and social isolation leading to psychological decompensation and increased drinking or relapse. As a result, we fear that there will be a dramatic rising tide of alcohol relapse, admissions for decompensated ALD, and an increase in newly diagnosed patients with AUD/ALD post-COVID-19 pandemic. Providers and their institutions should implement preemptive strategies such as telehealth and aggressive patient outreach programs now to curb this anticipated problem. Liver transplantation (LT) centers should adapt to the pandemic by considering leniency to some LT candidates with ALD who cannot access appropriate alcohol treatment due to the current situation. In conclusion, the COVID-19 pandemic will likely be especially detrimental to patients with AUD/ALD, and actions need to be taken now to limit the scope of this anticipated problem. more...

In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown.Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use.A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94).Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT. more...

In summary, early LT for AH has evolved from the early era of LT to become an emerging and effective rescue therapy for patients with severe AH who are not responding to medical therapy, in highly selected cases with favorable psychosocial profiles. more...

Early liver transplantation (LT) for severe alcoholic hepatitis (AH) is a rescue therapy for highly selected patients with favorable psychosocial profiles not responding to medical therapy. Given the expected increase of AH candidate referrals requiring complex care and comprehensive evaluations, increased workload and cost might be expected from implementing an early LT program for AH but have not been determined. Some centers may also view AH as a strategy to expeditiously increase LT volume and economic viability. The aim of this study was to determine the health care use and costs of an early LT program for AH. Analyses of prospective databases of AH, interhospital transfers, and the hospital accounting system at a single center were performed from July 2011 to July 2016. For 5 years, 193 patients with severe AH were evaluated at our center: 143 newly referred transfers and 50 direct admissions. Annual increases of 13% led to 2 to 3 AH transfers/month and AH becoming the top reason for transfer. There were 169 (88%) nonresponders who underwent psychosocial evaluations; 15 (9%) underwent early LT. The median cost of early LT was $297,422, which was highly correlated with length of stay (r = 0.83; P more...

Background & Aims Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. Methods Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006–2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. Results Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n = 103; 71%), pattern 2 [late/non-heavy](n = 9; 6.2%), pattern 3 [early/non-heavy](n = 22; 15%), pattern 4 [early/heavy](n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. Conclusions A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care. more...

Alcohol-associated liver disease (ALD) can be coded in United Network for Organ Sharing (UNOS) as either alcoholic cirrhosis or alcoholic hepatitis (AH), without having specific criteria to assign either diagnosis. In this multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) study, we sought to assess the concordance of the clinician diagnosis of AH at liver transplantation (LT) listing versus UNOS data entry of AH as listing diagnosis. In a prior study, consecutive early LT recipients transplanted for AH between 2012 and 2017 were identified by chart review at 10 ACCELERATE-AH sites. In this current study, these same LT recipients were identified in the UNOS database. The primary UNOS diagnostic code was evaluated for concordance with the chart-review assignment of AH. In cases where the primary listing diagnosis in UNOS was not AH, we determined the reason for alternate classification. Among 124 ACCELERATE-AH LT recipients with a chart-review diagnosis of AH, only 43/124 (35%) had AH as listing diagnosis in UNOS; 80 (64%) were listed as alcoholic cirrhosis, and 1 (1%) as fulminant hepatic necrosis. Of the 81 patients missing AH as a UNOS listing diagnosis code, the reasons for alternate classification were 44 (54%) due to a lack of awareness of a separate diagnosis code for AH; 13 (16%) due to concomitant clinical diagnosis of AH and alcoholic cirrhosis in the chart; 12 (15%) due to clinical uncertainty regarding the diagnosis of AH versus acute decompensated alcoholic cirrhosis; and 12 (15%) due to a data entry error. In conclusion, in a large cohort of LT recipients with AH, only 35% were documented as such in UNOS. Increased education and awareness for those performing UNOS data entry, the establishment of specific criteria to define AH in the UNOS database, and the ability to document dates of alcohol use would allow future research on ALD to be more informative. more...

COVID-19 is a global pandemic that started in Wuhan, China. COVID-19 related liver enzyme elevations have been described however the clinical presentation, enzyme kinetics, and associated laboratory abnormalities of these patients have not been well described. Five cases of COVID-19 associated liver enzyme elevations are reported here. We found that COVID-19 related liver enzyme elevations occurred in a hepatocellular pattern and persisted throughout the initial hospitalization in all patients. Abnormalities in lactate dehydrogenase and ferritin levels were seen in all five cases. In conclusion, abnormalities in aminotransferase, lactate dehydrogenase, and ferritin levels are commonly seen in COVID-19 related liver injury. Elevated aminotransferase levels often persist throughout the entire hospitalization. However, the clinical course of COVID-19 related liver injury appears benign. more...

While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder. more...

Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is mostly supportive. The short-term prognosis of acute alcoholic hepatitis depends on liver recovery, and ranges widely from rapid improvement to grim multiorgan failure despite treatment. Refinement of scoring systems have enhanced prognostication to guide clinical decision making in alcoholic hepatitis. Recent advances in the treatment of alcoholic hepatitis have solidified corticosteroids as the cornerstone of treatment to enhance short-term survival, but not intermediate or long-term survival. more...

This review provides a brief overview of key concepts in addiction medicine and provides tips and tricks as it pertains to treating patients with alcohol addiction in the setting of advanced alcohol-related liver disease (ALD). Understanding the brain disease model of addiction by both providers and patients is a vital springboard for establishing a therapeutic relationship. Despite a paucity of high-quality evidence, psychosocial treatments have withstood the test of time and still form the foundation of alcohol use disorder (AUD) treatment in advanced ALD. Despite the inescapable link between AUD) and advanced ALD, there are no FDA-approved medications for use in this special population. In this urgent subgroup, only baclofen, used off-label, has been shown to be effective for AUD in randomized controlled trials. An integrated, multidisciplinary and longitudinal approach remains the best option for the management of AUD in advanced ALD. more...

Background & Aims While abstinence-promoting behavioral and pharmacotherapies 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 United States (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. more...

AIM To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response - the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response (SVR) 12] - were calculated on an intention-to-treat basis. Costs were calculated from the payer’s perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression. RESULTS SVR12 rates were as follows: 86% (95%CI: 80%-91%) among 178 patients on SMV/SOF ± RBV; 62% (95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78% (95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR12 were $174442 (standard deviation: ± $18588) for SMV/SOF ± RBV; $223003 (± $77946) for SOF/RBV; and $126496 (± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio (OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin (OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR12 (OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs. more...

Although liver transplantation (LT) for alcohol-associated liver disease (ALD) is a well-accepted practice, LT for severe alcoholic hepatitis (AH) remains controversial due to concerns about the limited organ supply and the risk of return to harmful drinking. Recognizing an increasing body of favorable evidence, a convergence of practice guideline recommendations from leading hepatology and gastroenterology societies have suggested that the length of abstinence should not be a sole criterion for LT selection and, thus, that LT may be considered in carefully selected severe AH patients with favorable psychosocial profiles not responding to medical therapy. We sought to examine this new consensus in greater detail, debating whether candidate selection criteria for LT in AH should be tightened or loosened. more...

Background & aimsEarly liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.MethodsWe developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.ResultsPatients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.ConclusionsIn a modeling study of assumed carefullyselected patients with AH, early vs delayed liver transplantation (6months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increasein life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate thebenefits of early transplantation. Strategies are needed toprevent and treat posttransplantation use of alcohol. more...

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 as25% 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. more...

Background Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver. Methods A cohort of 233 patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3 T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model. Findings Obesity was common amongst patients with AH, seen in 19% of individuals. Obesity (HR 2.22, 95%CI 1.1–4.3, p = .022) and underweight (HR 2.38, 1.00–5.6, p = .049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models showed that alcohol induced CXCL11 expression in AT, but not in liver. Interpretation Obesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH. Fund This work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. more...

Background: Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver. Methods: A cohort of patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model. Findings: Obesity was common amongst patients with AH, seen in 19% of individuals. cBMI correlated with volume AT (r2= 0.623, p more...

Background & aimsThe American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients.MethodsWe performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained.ResultsAmong 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P= .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P= .01).ConclusionsIn a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1year (94%) and 3 years (84%), similar to patients receiving livertransplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes. more...

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 more...

We would like to respond to Scott et al. and the accompanying editorial.1,2 Concentrated factor products like recombinant activated factor VII (NovoSeven®, Novo Nordisk Pharmaceuticals Inc.) and prothrombin complex concentrate (Kcentra®, CSL Behring GmbH) are agents that can rapidly reverse coagulopathy for invasive procedures. This article is protected by copyright. All rights reserved. more...

Patients with liver disease and portal hypertension are at increased risk of complications from surgery. Recent advances have allowed better optimization of patients with cirrhosis before surgery and a reduction in postoperative complications. Despite this progress, the estimation of surgical risk in a patient with cirrhosis is challenging. The MELD score has shown promise in predicting postoperative mortality compared with the Child-Turcotte-Pugh score. This article addresses current concepts in the perioperative evaluation of patients with liver disease and portal tension, including a preoperative liver assessment (POLA) checklist that may be useful towards mitigating perioperative complications. more...

The patient is a 50-year-old Caucasian woman with a history of a pancreas and two kidney transplants complicated by chronic rejection of her latest kidney allograft and currently undergoing hemodialysis, who was referred for fever of unknown origin and elevated liver tests. She suffered a self-limited acute diarrheal illness with fever 3 months prior to referral and then experienced a persistent, undulating fever pattern. An exhaustive evaluation involving many consultants was undertaken, but failed to determine the etiology of her symptoms. Given her history, persistently elevated liver tests, and abnormal but nonspecific liver biopsy findings, infection with hepatitis E virus (HEV) was entertained. Several serum and stool samples were sent to the Centers for Disease Control for detection of HEV that were positive and ultimately consistent with autochthonous chronic HEV infection. The patient was treated with ribavirin and achieved normalization of her transaminase activities and resolution of her fever after 1 month, and undetectable HEV polymerase chain reaction at treatment month 6 and 10, at which time treatment was stopped. There has been renewed interest in HEV in light of recent studies demonstrating the existence of a chronic form of HEV infection occurring in immunosuppressed patients, such as solid-organ-transplant recipients. This report highlights a case of chronic HEV infection in a pancreas-kidney-transplant recipient with an unusual clinical presentation and highlights the need for increased awareness of chronic HEV infection in the hepatology and transplant community. more...

Background & Aims Several risk factors have been identified for the development of recurrent Clostridium difficile infection (CDI) that alter host immunity and disrupt colonic flora. Although the function of the appendix has been debated, its active, gut-associated lymphoid tissue and biofilm production indicate potential roles in recovery from initial CDI and protection against recurrent CDI. We investigated whether the presence or absence of an appendix is associated with CDI recurrence. Methods We reviewed the medical records of adult inpatients with CDI who were admitted to a tertiary-care teaching hospital from 2005 to 2007 to identify those with and without an appendix. The primary dependent variable for statistical analysis was CDI recurrence. Results In a multivariate analysis of 11 clinical variables, the presence of an appendix was associated inversely with CDI recurrence (P Conclusions The presence of an appendix has a significant and independent, inverse association with CDI recurrence, but this finding requires validation in a prospective study. Assessing the presence or absence of an appendix might be useful in predicting CDI recurrence. more...

A 51-year-old man from Puerto Rico with Child-Turcotte-Pugh Class C decompensated cirrhosis due to genotype 1a chronic hepatitis C was referred for worsening jaundice and diuretic-resistant ascites. He began experiencing symptoms of hepatic decompensation 5 months prior to referral with new-onset ascites and spontaneous bacterial peritonitis, evolving into diuretic-resistant ascites, increasing jaundice, and a MELD increase from 12 to 29. During his hospitalization, his MELD score increased to >40 from a rapidly increasing international normalized ratio (INR) and evolving type 1 hepatorenal syndrome. Clinically, the patient appeared quite well despite such a high MELD score. After an extensive pretransplant evaluation and exclusion of infection, he underwent successful orthotopic liver transplantation. After histologic examination of the explanted liver, he subsequently admitted to 5 months of daily use of a detoxifying supplement known as MaxOne (®), containing D-ribose- L-cysteine, consistent with a drug-induced acute-on-chronic liver failure. The use of complementary and alternative medicines and its potential for causing drug-induced liver injury and acute-on chronic liver failure requires a high index of suspicion and increased awareness among health care providers. more...

Patients with liver disease and portal hypertension are at increased risk of complications from surgery. Recent advances have allowed better optimization of patients with cirrhosis before surgery and a reduction in postoperative complications. Despite this progress, the estimation of surgical risk in a patient with cirrhosis is challenging. The MELD score has shown promise in predicting postoperative mortality compared with the Child-Turcotte-Pugh score. This article addresses current concepts in the perioperative evaluation of patients with liver disease and portal tension, including a preoperative liver assessment (POLA) checklist that may be useful towards mitigating perioperative complications. more...

Alcoholic liver cirrhosis is the second most common indication for liver transplantation in the United States. Studies have shown that these patients do as well as those transplanted for nonalcoholic liver disease. Recently, transplantation of patients with alcoholic liver disease has come under closer scrutiny following an article in the New England Journal of Medicine demonstrating comparable outcomes and survival in patients transplanted for acute alcoholic hepatitis. This article reviews the literature and data on the evaluation and selection of patients with alcoholic cirrhosis for liver transplant, and discusses the most recent indication (once a contraindication), acute alcoholic hepatitis. more...

Background EUS-guided liver biopsy by Trucut yields variable specimen adequacy at high cost, limiting its utility. A modified EUS-guided technique with reliable adequacy could be a viable alternative to standard techniques in cost-effective clinical settings. Objective To describe our experience with EUS-guided liver biopsy by 19-gauge FNA, non-Trucut, needle in a cost-effective setting: patients with abnormal liver test results of unclear etiology referred for EUS to exclude biliary obstruction in whom an unrevealing EUS would have prompted a next-step liver biopsy by the referring physician. Design Prospective case series. Setting Tertiary-care teaching hospital. Patients Consecutive patients with abnormal liver tests referred for EUS. Interventions EUS-guided liver biopsy by 19-gauge FNA needle (non-Trucut). Main Outcome Measurements Diagnostic yield, specimen adequacy, and complications. An adequate specimen was defined as a length of 15 mm or longer and 6 or more complete portal tracts (CPTs). Results Between July 2008 and July 2011, 22 of 31 consecutive patients meeting inclusion criteria underwent unrevealing EUS with same-session EUS-guided liver biopsy by 19-gauge FNA needle. A median of 2 FNA passes (range 1-3) yielded a median specimen length of 36.9 mm (range 2-184.6 mm) with a median of 9 CPTs (range 1-73 CPTs). EUS-guided liver biopsies yielded a histologic diagnosis and adequate specimens in 20 of 22 patients (91%). Expanded experience led to improved specimen adequacy. There were no complications. Limitation Small study size. Conclusions EUS-guided liver biopsy by using a 19-gauge FNA needle appears to be feasible and safe and provides excellent diagnostic yield and specimen adequacy. more...