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Background & Aims: Despite a high prevalence of risk factors associated with hepatitis delta virus (HDV) infection among safety-net populations, data evaluating HDV testing and prevalence are limited. We aim to evaluate HDV testing practices and HDV prevalence among an ethnically diverse, multi-center cohort of safety-net patients with chronic hepatitis B (CHB)., Methods: We retrospectively evaluated 13,218 patients with CHB (54.2% male, 57.9% non-White minorities, 12.5% human immunodeficiency virus, and 23.0% hepatitis C virus) across 3 United States safety-net health systems from 2010 to 2022 to evaluate proportion tested for HDV and proportion positive among those tested. Adjusted multivariate logistic regression models evaluated for predictors of HDV testing and predictors of anti-HDV positive., Results: Anti-HDV testing was performed in 6.1% overall and in 4.9% that met American Association for the Study of Liver Diseases criteria for HDV testing. Greater odds of testing were observed in men vs women (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.27-1.75), Asian individuals vs White individuals (OR, 2.18; 95% CI, 1.74-2.72), Black/African American individuals vs White individuals (OR, 1.29; 95% CI, 1.07-1.56), and patients with Medicare or Medicaid. Among patients with CHB tested for HDV, 15.7% were positive (22.9% among those meeting American Association for the Study of Liver Diseases HDV testing criteria). Only 2 patients (1.6%) had follow-up HDV RNA testing. Greater proportion of anti-HDV positive was observed in patients with baseline cirrhosis (47.4% vs 13.3%; P < .001), and patients with Medicare or Medicaid vs those with commercial insurance., Conclusions: Among an ethnically diverse, multi-center safety-net cohort of patients with CHB, low rates of HDV testing were observed, even among those with high-risk HDV risk factors. Among those tested, 15.7% were positive, only 2 had follow up RNA testing. This highlights the need for greater awareness, education, and advocacy to improve HDV testing rates., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Timely treatment of chronic hepatitis B (CHB) reduces risks of cirrhosis and hepatocellular carcinoma. Gaps in timely treatment persist, especially among underserved safety-net populations. We aim to evaluate gaps and disparities in CHB treatment in the United States., Methods: Adults with treatment-naive CHB without human immunodeficiency virus were identified from 2010 to 2018 across 3 safety-net health systems. CHB treatment eligibility was assessed using American Association for the Study of Liver Diseases (AASLD) criteria and alternative criteria, including the Simplified Approach for Hepatitis B Algorithm. Differences in CHB treatment between groups were evaluated using χ 2 methods, adjusted Kaplan-Meier methods, and adjusted Cox proportional hazards models., Results: Among 3749 patients with treatment-naive CHB (51.5% women, 38.7% White, 33.7% African American, 19.6% Asian, 24.6% cirrhosis), 30.0% were AASLD treatment eligible, among whom 31.0% were treated. Men were more likely than women to be treated (33.5% vs 26.6%, P < .01). On multivariable regression, there remained a trend toward greater treatment in men versus women (adjusted hazard ratio [aHR], 1.21 [95% confidence interval {CI}, .96-1.54]). Disparities by race/ethnicity and insurance status were observed. When exploring outcomes using SABA criteria, similar trends were observed. Among treatment-eligible patients, greater likelihood of treatment was observed in men versus women (aHR, 1.40 [95% CI, 1.14-1.70]) and in Asians versus Whites (aHR, 1.50 [95% CI, 1.16-1.94])., Conclusions: Among an ethnically diverse multicenter safety-net cohort of CHB patients, less than one-third of treatment-eligible patients received antiviral treatment. Significant disparities in CHB treatment were observed by sociodemographic characteristics., Competing Interests: Potential conflicts of interest. R. J. W. has received research grants (to his institution) from Gilead Sciences, Exact Sciences, Theratechnologies, and Durect Corporation, and has served in consulting roles without compensation for Gilead Sciences. M. K. J. has received investigator-initiated grant funding from Gilead Sciences paid to her institution. G. T. has received funding from Gilead Sciences (to his institution) not related to this study. M. T. has received investigator-initiated grant funding from Gilead Sciences paid to her institution. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, impacts 30% of the global population. This educational pilot focused on the role primary care providers may play in the delivery of guidelines-based metabolic dysfunction-associated steatohepatitis (MASH) care., Objective: Accelerate the application of guidelines-based MASH care pathways to clinical workflows., Methods: A panel of six hepatologists was convened in 2021 to develop the care pathway and the subsequent pilot occurred between 2022 - 2023. The pilot was conducted across three U.S. health systems: Boston Medical Center (Boston), Methodist Health System (Dallas), and Weill Cornell Medicine (New York). Clinicians were educated on the care pathway and completed baseline/follow-up assessments. 19 primary care clinicians participated in the educational pilot baseline assessment, nine primary care clinicians completed the two-month assessment, and 15 primary care clinicians completed the four-month assessment. The primary endpoint was to assess clinician-reported adherence to and satisfaction with the care pathway. The pilot was deemed exempt by the Western Consensus Group Institutional Review Board., Results: At baseline, 38.10% (n = 8) of respondents felt they had received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and 42.86% (n = 9) had not referred any patients suspected of metabolic dysfunction-associated liver disease to hepatology within a month. At four months post-intervention, 79% (n = 15) of respondents agreed or strongly agreed they received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and there was a 25.7% increase in self-reported adherence to the institution's referral guidelines. Barriers to care pathway adherence included burden of manually calculating fibrosis-4 scores and difficulty ordering non-invasive diagnostics., Conclusions: With therapeutics anticipated to enter the market this year, health systems leadership must consider opportunities to streamline the identification, referral, and management of patients with metabolic dysfunction-associated steatohepatitis. Electronic integration of metabolic dysfunction-associated steatohepatitis care pathways may address implementation challenges., (© 2024. The Author(s).)

Introduction: Early (i.e., without mandated period of abstinence) liver transplant (LT) for alcohol-associated hepatitis is the fastest-growing indication for LT in the United States and Europe. Harmful alcohol use after LT is associated with poor outcomes, but the distinction of establishing abstinence after return to drinking (i.e., reabstinence) is understudied. This study aims to characterize the survival outcomes of achieving reabstinence after post-LT harmful alcohol use., Methods: We analyzed early LT recipients from 12 US LT centers between 2006 and 2021. Post-LT alcohol use was characterized as harmful using criteria of "binge" (≥5 [men] or ≥4 [women] drinks in < 24 hours) or "frequent" (≥4 days in one week) by interview or phosphatidylethanol >20 ng/mL. Reabstinence was defined as ≥12 consecutive months without harmful alcohol use after harmful alcohol use., Results: Among 347 LT recipients (64% male, median age 43, median Model for End-Stage Liver Disease-Sodium score 38) with median post-LT follow-up of 2.2 years (interquartile interval 1.1-3.6), 276 (80%) recipients had no evidence of harmful alcohol use, 35 (10%) recipients had reabstinence, and 36 (10%) recipients had continued harmful alcohol use without reabstinence. Five-year predicted survival, adjusted for age, sex, and Model for End-Stage Liver Disease-Sodium score, was lowest among LT recipients with continued harmful alcohol use (77%), but similar among those with no harmful use (93%) and reabstinence (94%)., Discussion: Achieving reabstinence after post-LT harmful alcohol use is associated with similar 5-year post-LT survival compared with those without evidence of post-LT harmful alcohol use. Our findings highlight the importance of early detection and treatment of post-LT alcohol use., (Copyright © 2024 by The American College of Gastroenterology.)

Importance: Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes., Objective: To evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis., Design, Setting, and Participants: This survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19-related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023., Main Outcome and Measures: HCC surveillance knowledge was assessed with 6 questions querying the respondent's ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic-related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians., Results: Overall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P < .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P < .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P < .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays., Conclusions and Relevance: In this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system-level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.

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., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Timely initiation of antiviral therapy in chronic hepatitis B virus (CHB) reduces risk of disease progression. We evaluate overall treatment rates and predictors of treatment among treatment-eligible safety-net CHB patients., Methods: We retrospectively evaluated adults with CHB from 2010 to 2018 across 4 large safety-net health systems in the United States. CHB was identified with ICD-9/10 diagnosis coding and confirmed with laboratory data. Treatment eligibility was determined using American Association for the Study of Liver Diseases (AASLD) guidelines. Comparison of CHB treatment rates among treatment-eligible patients were performed using χ2 testing, Kaplan Meier methods and log-rank testing. Adjusted multivariate Cox proportional hazards models evaluated independent predictors of receiving treatment among eligible patients., Results: Among 5157 CHB patients (54.7% male, 34.6% African American, 22.3% Asian), 46.8% were treatment-eligible during the study period. CHB treatment rates were 48.4% overall and 37.3% among CHB patients without human immunodeficiency virus. Significantly lower odds of treatment were observed in females versus males (odds ratio: 0.40, 95% confidence interval: 0.33-0.49, P<0.001) and patients age 65 years or above versus age below 45 years (odds ratio: 0.68, 95% confidence interval: 0.51-0.92, P=0.012). Conversely, significantly greater odds of treatment were observed in African American and Asians versus non-Hispanic whites, CHB patients with indigent care versus commercially insured patients, and non-English speaking versus English speaking patients., Conclusion: Among a large multicentered, safety-net cohort of CHB patients, 46.8% of treatment-eligible CHB patients overall and 37.3% of treatment-eligible CHB patients without human immunodeficiency virus received antiviral therapy. Improving CHB treatment rates among treatment-eligible patients represents "low hanging fruit," given the clear benefits of antiviral therapy in mitigating disease progression., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Hepatorenal index (HRI) has been shown to be an effective, noninvasive ultrasound tool to screen patients for those with or without >5% hepatic steatosis., Objective: The aim of this study was to further refine this HRI tool in order to stratify patients according to their degree of liver steatosis and give direction as to which patients should undergo random liver biopsy., Methods: We conducted a retrospective review of 267 consecutive patients from 2015 to 2017 who had abdominal ultrasounds and a subsequent random liver biopsy within one month. The HRI was calculated and compared with the percent steatosis as assessed by histology., Results: An HRI of ≤1.17 corresponds with >95% positive predictive value of ≤5% steatosis. Between HRI values 1.18 and 1.39, performance of steatosis prediction is mixed. However, for values <1.37 there is an increased likelihood of steatosis ≤5% and likewise the opposite for values >1.37. An HRI of ≥1.4 corresponds with >95% positive predictive value of ≥10% steatosis., Conclusion: HRI is an accurate noninvasive tool to quantify degree of steatosis and guide who should undergo random liver biopsy, potentially significantly reducing the total number of necessary liver biopsies.

Introduction: To evaluate the impact of chronic hepatitis B virus infection (CHB) treatment on risk of cirrhosis, liver-related outcomes, and death among a diverse CHB cohort with a large proportion of African Americans., Methods: Adults with noncirrhotic CHB without human immunodeficiency virus from 2010 to 2018 were retrospectively evaluated across 4 US safety-net health systems. CHB was identified with International Classification of Diseases, Ninth Revision/Tenth Revision diagnosis coding and confirmatory laboratory data. Propensity-score matching, Kaplan-Meier methods, and adjusted Cox proportional hazards models were used to evaluate impact of CHB treatment on risk of cirrhosis, hepatocellular carcinoma (HCC), death, and composite of cirrhosis, HCC, or death., Results: Among 4,064 CHB patients (51.9% female, 42.0% age <45 years, 31.6% African American, 26.6% Asian, 26.7% Hispanic), 23.2% received CHB antiviral therapy and 76.8% did not. Among the propensity score-matched cohort (428 treated and 428 untreated), CHB treatment was associated with lower risk of cirrhosis (hazards ratio 0.65, 95% confidence interval 0.46-0.92, P = 0.015) and composite of cirrhosis, HCC, or death (hazards ratio 0.67, 95% confidence interval 0.49-0.94, P = 0.023). Females vs males and African Americans vs non-Hispanic whites had significantly lower risk of cirrhosis. When treatment effects were stratified by age, sex, and ethnicity, the benefits of antiviral therapies in reducing risk of cirrhosis were seen primarily in CHB patients who were females, age <45 years, and of Asian ethnicity., Discussion: Our propensity score-matched cohort of noncirrhotic CHB patients demonstrated significant reductions in risk of cirrhosis due to CHB treatment., (Copyright © 2021 by The American College of Gastroenterology.)

Liver transplantation (LT) using allografts from hepatitis C virus (HCV)-viremic/nucleic acid testing-positive donors' (DNAT+) organs into HCV-aviremic recipients (rHCV-) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post-LT with direct-acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV- as a routine standard of care. Following verification of DAA access, absence of critical drug-drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV- received an LT. Forty-seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post-LT. Of these 292 patients, 61 rHCV- received DNAT+ livers (study group), and 231 rHCV- received DNAT- (aviremic donors [nuclear acid test-negative donors]) livers (control group). Recipient and donor characteristics as well as 1-year post-LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post-LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9 days (interquartile range [IQR], 36-68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR-12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV- and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT- allografts., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Background Gastrointestinal (GI) symptoms impact quality of life and increase health care utilization after liver transplantation (LTx). Esophagogastroduodenoscopy (EGD) is commonly used to investigate these symptoms. Aims The aim of this study was to investigate the diagnostic yield and utilization of EGD after LTx for common GI symptoms. Methods This single-center retrospective cohort study was conducted at a large liver transplant center and included all adults who underwent EGD within the first year after receiving LTx between January 1, 2015, and December 31, 2016. Biliary procedures were excluded. Results Of 437 patients who underwent LTx during the study period, 64 (15%) underwent EGD for the evaluation of GI symptoms within the first year of transplantation. After applying exclusion criteria, 57 (13%) cases were analyzed. GI hemorrhage (hematemesis/melena) was the most common reason (4%; n=18) for evaluation with EGD followed by nausea/anorexia (3%; n=12). Symptoms were investigated with EGD, including epigastric/abdominal pain (2%; n=9), dysphagia/odynophagia (2%; n=8), anemia (1%; n=5), diarrhea (1%; n=4), and heartburn (0.2%; n=1). The diagnostic yield of EGD was highest with GI hemorrhage (83%) followed by dysphagia/odynophagia (75%). EGD diagnostic yield was lower for the other symptoms, ranging from 0% to 25%. Conclusions EGD was commonly utilized within the first year of LTx, with the highest diagnostic yields for GI hemorrhage and dysphagia/odynophagia. Because of the low diagnostic yield of EGD for other symptoms, we recommend a careful selection of patients for EGD following LTx., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Daglilar et al.)

Background & Aims: Non-alcoholic steatohepatitis (NASH) is characterized by hepatocyte steatosis, ballooning, and lobular inflammation which may lead to fibrosis. Lipotoxicity activates caspases, which cause apoptosis and inflammatory cytokine (IL-1β and IL-18) production. Emricasan is a pan-caspase inhibitor that decreases serum aminotransferases and caspase activation in patients with NASH. This study postulated that 72 weeks of emricasan treatment would improve liver fibrosis without worsening of NASH., Methods: In this double-blind, placebo-controlled study 318 patients were randomized 1:1:1 to twice-daily treatment with emricasan (5 mg or 50 mg) or matching placebo for 72 weeks. Patients had definite NASH and NASH CRN fibrosis stage F1-F3, as determined by a central reader, on a liver biopsy obtained within 6 months of randomization., Results: Emricasan treatment did not achieve the primary objective of fibrosis improvement without worsening of NASH (emricasan 5 mg: 11.2%; emricasan 50 mg: 12.3%; placebo: 19.0%; odds ratios vs. placebo 0.530 and 0.588, with p = 0.972 and 0.972, respectively) or the secondary objective of NASH resolution without worsening of fibrosis (emricasan 5 mg: 3.7%; emricasan 50 mg: 6.6%; placebo: 10.5%; odds ratios vs. placebo 0.334 and 0.613, with p = 0.070 and 0.335, respectively). In the small subset of patients with consistent normalization of serum alanine aminotransferase over 72 weeks, emricasan may have improved histologic outcomes., Conclusions: Emricasan treatment did not improve liver histology in patients with NASH fibrosis despite target engagement and may have worsened fibrosis and ballooning. Caspase inhibition lowered serum alanine aminotransferase in the short-term but may have directed cells to alternative mechanisms of cell death, resulting in more liver fibrosis and hepatocyte ballooning., Clinical Trial Number: Clinical Trials.gov #NCT02686762., Lay Summary: Non-alcoholic steatohepatitis (NASH) is characterized by fat accumulation in liver cells, which leads to inflammation and fibrosis. Emricasan was previously shown to inhibit some of the liver enzymes which lead to liver inflammation and fibrosis. In this study, emricasan did not improve liver inflammation or fibrosis in patients with NASH and pre-existing liver fibrosis., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The occurrence of acute kidney injury (AKI) in patients with end-stage liver disease constitutes one of the most challenging clinical scenarios in in-hospital and critical care medicine. Hepatorenal syndrome type 1 (HRS-1), which is a specific type of AKI that occurs in the context of advanced cirrhosis and portal hypertension, is associated with particularly high mortality. The pathogenesis of HRS-1 is largely viewed as a functional derangement that ultimately affects renal vasculature tone. However, new insights suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms, including those traditionally associated with HRS-1 and non-traditional factors, might contribute to the development of AKI in patients with cirrhosis. Moreover, histological evidence of morphological abnormalities in the kidneys of patients with cirrhosis and renal dysfunction has prompted the functional nature of HRS-1 to be re-examined. From a clinical perspective, a diagnosis of HRS-1 guides utilization of vasoconstrictive therapy and decisions regarding renal replacement therapy. Patients with cirrhosis are at risk of AKI owing to a wide range of factors. However, the tools currently available to ascertain the diagnosis of HRS-1 and guide therapy are suboptimal. Short of liver transplantation, goal-directed haemodynamically targeted pharmacotherapy remains the cornerstone of treatment for this condition; improved understanding of the underlying pathogenic mechanisms might lead to better clinical outcomes. Here, we examine our current understanding of the pathophysiology of HRS-1 and existing challenges in its diagnosis and treatment.

Background & Aims: Although serological markers of disease severity improve after hepatitis C virus (HCV) treatment, it is unclear if all patients experience sustained improvement. We aim to evaluate longitudinal changes in aspartate (AST), alanine (ALT) aminotransferase, platelet count (PLT), and fibrosis-4 (FIB-4) after HCV treatment., Methods: All adult chronic HCV patients who received antiviral therapy from January 2011 to February 2017 at four large urban hospital systems were evaluated to assess changes in AST, ALT, PLT, and FIB-4 from pre-treatment to post-treatment annually up to 4 years after HCV therapy. Comparisons used Student's t -test and analysis of variance, and were stratified by sex, race, ethnicity, age, body mass index (BMI), and diabetes mellitus., Results: Among 2691 patients (62.2% men, 76.9% aged 45-65 years, 56.5% white), all markers of disease severity demonstrated sustained improvements from pre-treatment to 4 years post-treatment (AST 53 U/L to 27.5 U/L, ALT 53 U/L to 29 U/L, PLT 168 × 10 3 to 176 × 10 3 , FIB-4 2.51 to 1.68). However, Hispanics and patients with BMI >30 kg/m 2 experienced rebound increases in AST, ALT, and FIB-4 at 4 years post-treatment after experiencing initial improvements in these serological markers in the first-year post-treatment. Sustained improvements in PLT were observed in all groups, including Hispanics and patients with BMI >30 kg/m 2 ., Conclusion: HCV treatment in a large community-based cohort demonstrated sustained improvements in AST, ALT, PLT, and FIB-4. Rebound increases in AST, ALT, and FIB-4 observed in Hispanics and those with BMI >30 kg/m 2 may reflect persisting nonalcoholic fatty liver disease., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Early 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., Methods: We 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., Results: Patients 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 (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores., Conclusions: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months 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 increase in 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 the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Early liver transplant (LT) for alcohol-associated disease (i.e., without a specific sobriety period) is controversial but increasingly used. Using the multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) cohort, we aimed to develop a predictive tool to identify patients pretransplant with low risk for sustained alcohol use posttransplant to inform selection of candidates for early LT. We included consecutive ACCELERATE-AH LT recipients between 2012 and 2017. All had clinically diagnosed severe alcoholic hepatitis (AH), no prior diagnosis of liver disease or AH, and underwent LT without a specific sobriety period. Logistic and Cox regression, classification and regression trees (CARTs), and least absolute shrinkage and selection operator (LASSO) regression were used to identify variables associated with sustained alcohol use post-LT. Among 134 LT recipients for AH with median period of alcohol abstinence pre-LT of 54 days, 74% were abstinent, 16% had slips only, and 10% had sustained alcohol use after a median 1.6 (interquartile range [IQR]: 0.7-2.8) years follow-up post-LT. Four variables were associated with sustained use of alcohol post-LT, forming the Sustained Alcohol Use Post-LT (SALT) score (range: 0-11): >10 drinks per day at initial hospitalization (+4 points), multiple prior rehabilitation attempts (+4 points), prior alcohol-related legal issues (+2 points), and prior illicit substance abuse (+1 point). The C statistic was 0.76 (95% confidence interval [CI]: 0.68-0.83). A SALT score ≥5 had a 25% positive predictive value (95% CI: 10%-47%) and a SALT score of <5 had a 95% negative predictive value (95% CI: 89%-98%) for sustained alcohol use post-LT. In internal cross-validation, the average C statistic was 0.74. Conclusion: A prognostic score, the SALT score, using four objective pretransplant variables identifies candidates with AH for early LT who are at low risk for sustained alcohol use posttransplant. This tool may assist in the selection of patients with AH for early LT or in guiding risk-based interventions post-LT., (© 2018 by the American Association for the Study of Liver Diseases.)

Direct-acting antivirals (DAA) for hepatitis C virus (HCV) became available in 2014, but the role of mental health or substance use disorders (MH/SUD) on access to treatment is unknown. The objective of this study was to examine the extent and predictors of HCV treatment in the pre-DAA and post-DAA periods in four large, diverse health care settings in the United States. We conducted a retrospective analysis of 29,544 adults with chronic HCV who did or did not receive treatment from January 1, 2011, to February 28, 2017. Kaplan-Meier curve was used to examine cumulative risk for receiving HCV treatment stratified by MH/SUD. Predictors of HCV treatment in the pre-DAA (January 1, 2011, to December 31, 2013) and post-DAA (January 1, 2014, to February 28, 2017) cohorts were analyzed using multivariate generalized estimating equations and a modified Poisson model. Overall, 21.7% (2,879/13,240) of those with chronic HCV post-DAA were treated compared with 3.5% (574/16,304) in the pre-DAA period. Compared with non-Hispanic whites, Hispanic whites (adjusted odds ratio [AOR] 0.36; 95% confidence interval [CI], 0.25, 0.52) were less likely to be treated in the post-DAA period. Those with concurrent nonalcoholic fatty liver disease (AOR 1.39; 95% CI, 1.05, 1.83), cirrhosis (AOR 2.00; 95% CI, 1.74, 2.31), and liver transplant (AOR 2.72; 95% CI, 1.87, 3.94) were more likely to be treated post-DAA. Those with MH/SUD were less likely to be treated both before (AOR 0.46; 95% CI, 0.36, 0.60) and after (AOR 0.63; 95% CI, 0.55, 0.71) DAA therapy was available. Overall, the cumulative risk for receiving HCV treatment from 2011 to 2017 among those with versus without MH/SUD was 13.6% versus 21.6%, respectively (P < 0.001). Conclusion: The volume of patients treated for HCV has increased in the post-DAA period, especially among those with liver-related comorbidities, but disparities in access to treatment continue among those with MH/SUD., (© 2018 by the American Association for the Study of Liver Diseases.)

Objective: Despite availability of highly effective direct acting antivirals (DAA), barriers in access to these therapies limit our ability to achieve HCV eradication. We aim to evaluate overall rates and predictors of HCV treatment across four community-based health-care systems focusing on race/ethnicity and insurance-specific disparities., Methods: We retrospectively evaluated all adults with chronic HCV at four health care systems from 1 January 2011 to 28 February 2017, which included a large proportion of ethnic minorities, two safety-net systems, and a broad payer mix across four states. Overall and stratified HCV treatment rates were calculated using Kaplan-Meier methods. Multivariate logistic regression models evaluated for predictors of receiving treatment., Results: Among 29,544 chronic HCV patients (60.5% male, 38.4% black, 8.8% Hispanic, 18.7% Medicaid, 25.9% Medicare, 22.5% private/commercial), overall annual treatment rates were stable from 2011 (0.5%) to 2013 (2.0%), but increased from 2014 (4.8%) to 2017 (16.9%) after availability of DAAs. While similar treatment rates were observed by sex, significantly lower odds of treatment were observed in Hispanics (OR 0.48, 95% CI 0.39-0.60, p < 0.001) compared to non-Hispanic whites and among those with Medicaid (OR 0.21, 95% CI 0.20-0.24, p < 0.001) compared to commercially insured patients., Conclusions: Among our cohort of 29,544 chronic HCV patients, we observed significant improvements in HCV treatment rates after the availability of DAAs in 2014, but overall treatment rates remained <20% in 2017. The lowest rates of treatment were seen among Hispanics and those with Medicaid or indigent care insurance, which is concerning given these are particularly vulnerable populations.

Background & Aims: The 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., Methods: We 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., Results: Among 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)., Conclusions: In 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 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants 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., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1- and 3-year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re-transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic-type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The objective of this study was to prospectively evaluate the use of point shear wave elastography for the assessment of liver fibrosis and to determine the usefulness and optimal location for obtaining elastography measurements in native and transplanted livers. Point shear wave elastography measurements were obtained from 100 consecutive patients presenting for percutaneous liver biopsy. Measurements were acquired within both the superior right hepatic lobe (segments VII/VIII) via an intercostal approach and the inferior right hepatic lobe (segments V/VI) via a subcostal approach. Analysis of variance was used to assess statistical differences between the degree of fibrosis on percutaneous liver biopsy and elastography measurements. No statistical difference was present when comparing elastography measurements in patients with hepatic steatosis compared with patients without steatosis (P = 0.2759). There was no difference in the accuracy of elastography measurements in native livers versus transplanted livers (P = 0.221). Point shear wave elastography can accurately differentiate between patients with no-to-mild hepatic fibrosis (F0-F1) and moderate-to-severe hepatic fibrosis (≥F2) with sensitivity of 72% and specificity of 69%. Point shear wave elastography can be used as a noninvasive method to assess fibrosis in patients with native or transplanted livers. In addition, measurements can be combined or taken separately from either the superior or inferior right hepatic lobe. The presence of hepatic steatosis does not affect the accuracy of point shear wave elastography. However, shear wave elastography values in patients with body mass index greater than 40 should be interpreted with caution.

Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease (NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease (NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.

Background: Long-term survival after paediatric liver transplantation is now the rule rather than the exception. Improving long-term outcomes after transplantation must consider not only the quantity but also the quality of life years restored., Objectives: To characterize health-related quality of life (HRQOL) of LT recipients ≥15 years after paediatric LT., Methods: Recipients of a paediatric LT performed before December 1996 in a single institution with continuous follow-up at either the paediatric or adult partner centre were identified. Patients with severe developmental or neurological impairment were excluded. HRQOL was assessed using the Pediatric Quality of Life Inventory 4.0, the Medical Outcomes Study Short Form-36 version 2 and the Pediatric Liver Transplant Quality of Life Tool., Results: A total of 27 (67% male) subjects (mean age 24.3±6.7 years [median 23.2 years; range 16.6 to 40.3 years]) participated. The median age at transplant was 1.7 years (range 0.5 to 17.0 years). Seven (26%) participants underwent retransplantation. Seventeen (63%) participants were engaged in full-time work/study. Mean Short Form-36 version 2 scores included physical (49.6±11.1) and mental (45.3±12.5) subscale scores. The mean score for the disease-specific quality of life tool for paediatric liver transplant recipients (the Pediatric Liver Transplant Quality of Life Tool) was 64.70±15.2. The physical health of the young adults strongly correlated with level of involvement in work/study (r=0.803; P<0.05)., Conclusions: The self-reported HRQOL of participants <18 years of age was comparable with a standardized healthy population. In contrast, participants between 18 and 25 years of age had HRQOL scores that were more similar to a group with chronic illness. Participants engaged in full-time work/study experienced enhanced physical health.

Background: Poor diet and a sedentary lifestyle can contribute to nonalcoholic fatty liver disease (NAFLD)., Objective: Our aim was to compare diet and physical activity of patients with NAFLD and healthy controls with current recommendations., Design: This was a cross-sectional study., Participants/settings: Seventy-four patients with biopsy-proven NAFLD (33 simple steatosis and 41 steatohepatitis [NASH]) and 27 healthy controls participated between 2003 and 2011., Main Outcome Measures: Food records and activity logs were completed for 7 days. Results were compared with Dietary Reference Intakes and Canadian Physical Activity Guidelines. Plasma vitamin C was measured to assess food record accuracy., Statistical Analyses Performed: Intake/activity for each participant was compared with the recommendations and proportion of subjects not meeting the requirements was calculated. Groups were compared by Kruskal-Wallis and Mann-Whitney U test or z-test with Bonferroni adjustment., Results: More patients with NASH (58.5%) were obese compared with patients with simple steatosis (24.2%) and healthy controls (7.4%; P<0.01). Patients with NAFLD showed more insulin resistance than healthy controls. The reported energy intake was below estimated requirements in all groups (P≤0.001). The proportion of subjects from each group exceeding acceptable energy intake from fat was as follows: simple steatosis: 27.3%; NASH: 46.3%; healthy controls: 63.0% (simple steatosis vs health controls; P<0.05) and from saturated fat: simple steatosis: 42.4%; NASH: 70.7%; healthy controls: 63.0% (simple steatosis vs. NASH; P<0.05). In each group, >80% of subjects did not consume enough linoleic or linolenic acid, vitamin D, and vitamin E, and >60% exceeded the upper intake level for sodium. Only 53.1% of patients with simple steatosis and 53.8% of patients with NASH, but 84.6% of healthy controls, met recommendations for physical activity (P=0.020). Plasma vitamin C was normal, similar among groups, and correlated with vitamin C intakes., Conclusions: All participants followed a similar Western diet with high fat and sodium intakes and suboptimal micronutrient intakes. However, physical activity was lower in NAFLD compared with healthy controls and was associated with higher body mass index and insulin resistance., (Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Dense tissue infiltrates of IgG4(+) plasma cells >50/high-powered field (HPF) are purportedly highly specific for IgG4-related disease. However, the frequency and significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing cholangitis (PSC) applying these cut-offs has not been determined. We sought to determine the incidence of intrahepatic IgG4-positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be mild (10-29 IgG4(+) cells/HPF) in 23.0%, moderate (30-50/HPF) in 9.0% and marked (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4(+) staining (P < 0.001). No patient had marked peripheral IgG4(+) staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post-transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4(+) staining, whereas mild staining was seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4(+) lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4(+) , this does not seemingly associate with clinical disease course., (© 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.)

Background: Hepatitis B immunoglobulin (HBIG) given in combination with a nucleos(t)ide analogue has reduced the rate of recurrent hepatitis B virus (HBV) infection following liver transplantation (LT); however, the most effective protocol remains unclear., Objective: To evaluate the use of tenofovir disoproxil fumarate (TDF) in combination with one year of low-dose HBIG., Methods: Twenty-four adults who underwent LT for HBV-related liver disease at the University Health Network (Toronto, Ontario) and received TDF (± lamivudine) and one year of HBIG to prevent recurrent HBV infection from June 2005 to June 2011 were evaluated., Results: The median length of follow-up post-LT was 29.1 months. Three patients died during the follow-up period. Patient survival was 100% and 84.1% at one and five years, respectively. None of the patients developed recurrent HBV infection. No significant adverse event was observed due to TDF administration; renal function pre- and post-LT were also acceptably preserved., Conclusion: The present study demonstrated that a short, finite course of low-dose HBIG combined with maintenance of long-term TDF staring before LT is cost-effective and safe. However, further prospective study involving a larger patient cohort with a longer follow-up period is required to confirm the results.

Background: In 2005, the results published by the Scientific Registry of Transplant Recipients showed that Ochsner Clinic Foundation's patient and graft survival rates were statistically lower than expected, and the United Network for Organ Sharing Membership and Professional Standards Committee placed our center under peer review., Methods: In response, patient outcomes prior to August 2005 were carefully reviewed in a transparent fashion and protocols were written to standardize treatments. We renewed the focus on patient-related outcomes and regulatory adherence and empowered frontline staff to express their views, allowing for real teamwork to develop. Multiple changes were implemented in the everyday running of the program. A quality assurance and performance improvement plan (QAPI) was initiated to improve outcomes., Results: In 2012, the Ochsner liver transplant program became the largest liver transplant program in the United States by volume and in 2013 was awarded the prestigious CareChex award, acknowledging it as the number one program in terms of quality of care and outcomes for liver transplantation., Conclusion: The methodical application of this QAPI program achieved a remarkable transformation of the Ochsner liver transplant program and exemplifies what is possible with strong teamwork from dedicated and talented staff.

Unlabelled: Survival outcomes for liver retransplantation (LRTx) after graft loss in HCV patients (HCV-LRTx) are generally considered inferior to those after non-HCV-LRTx. Between January 1, 2005 and June 30, 2011, our center performed 663 LTx, including 116 (17.5%) LRTx, 41 (35.3%) of which were more than 90 d after the LTx. Twenty-nine (70.7%) LRTx were performed in HCV antibody-positive individuals. We compared patient demographics, baseline characteristics and outcomes of our HCV-LRTx group with the HCV-LRTx patients from the most recent OPTN database covering the same time period. Our Kaplan-Meier HCV-LRTx one-, three-, and five-yr HCV-LRTx patient survival rates were 86.2%, 79.0%, and 72.4%, respectively compared with the OPTN one-, three-, and five-yr HCV-LRTx survival rates of 73.3%, 59.0%, and 51.3% respectively. Likewise, our graft survival rates were higher than OPTN rates at all time points studied. We performed a higher percentage of HCV-LRTx as simultaneous liver/kidney transplants (SLK) (37.9% vs. 21.8%) and recorded shorter warm (30 ± 4 vs. 45 ± 23 min) and cold ischemic times (5:44 ± 1:53 vs. 7:36 ± 3:12 h:min)., Conclusion: In our experience, HCV-LRTx patient and graft survival rates are comparable to LTx survival rates and are higher than the rates described by OPTN., (© 2013 John Wiley & Sons A/S.)

Background: Obesity is thought to be associated with higher rates of morbidity and mortality after liver transplantation (LT); however, its actual impact is difficult to evaluate, in part because of the confounding effects of fluid accumulation on body mass index (BMI)., Objective: We sought to define the effects of conventional BMI (cBMI) and modified BMI (mBMI; calculated by multiplying the BMI by serum albumin level to compensate for fluid accumulation), on the outcome of LT recipients overall., Methods: A cohort of 507 patients who underwent LT from April 2000 to August 2006 were analyzed., Results: Pre-LT diabetes mellitus was seen somewhat more frequently in the higher mBMI group (P = .054), whereas there was no difference across cBMI categories. The recipients at extremes of cBMI (>40 kg/m(2) and <18.5 kg/m(2)) had significantly lower patient and graft survival than other groups (P = .038 and P = .010, respectively); however, no statistically significant differences were found in overall patient and graft survival across mBMI categories. There were no differences in duration of intensive care unit stay, duration of overall hospital stay, and vascular complications after LT among mBMI categories., Conclusions: Pre-LT obesity alone, when estimated by mBMI rather than by cBMI, should not be a contraindication for LT., (Copyright © 2013. Published by Elsevier Inc.)

The use of livers from hepatitis B surface antigen-negative (HBsAg- )/hepatitis B core antibody-positive (HBcAb+ ) donors in liver transplantation (LT) for HBsAg(-) /HBcAb- recipients is still controversial because of a lack of standard antiviral prophylaxis and long-term follow-up. We present our 13-year experience with the use of HBcAb+ donor livers in HBcAb- recipients. Patients received prophylaxis with hepatitis B immunoglobulin at the time of LT and then lamivudine daily. De novo hepatitis B virus (HBV) was defined as positive HBV DNA detection. Between January 1999 and December 2010, 1013 adult LT procedures were performed at our center. Sixty-four HBsAg- /HBcAb- patients (6.3%) received an HBsAg- /HBcAb+ liver. All donor sera were negative for HBcAb immunoglobulin M and HBV DNA. The mean follow-up was 48.8 ± 40.1 months (range = 1.2-148.8). Both the patient survival rates and the graft survival rates were 92.2% and 69.2% at 1 and 5 years, respectively. No graft losses or deaths were related to de novo HBV. Nine of the 64 patients (14.1%) developed de novo HBV. The mean time from LT to de novo HBV was 21.4 ± 26.1 months (range = 10.8-92.8 months). De novo HBV was successfully treated with adefovir or tenofovir. In conclusion, HBcAb+ allografts can be safely used in HBcAb- recipients without increased mortality or graft loss. Lifelong prophylaxis, continuous surveillance, and compliance are imperative for success. Should a de novo infection occur, our experience suggests that a variety of treatments can be employed to salvage the graft and obtain serum HBV DNA clearance., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Nonalcoholic fatty liver disease (NAFLD) is associated with altered hepatic lipid composition. Animal studies suggest that the hepatic ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) contributes to steatogenesis and inflammation. This ratio may be influenced by dysregulation of the PE N-methyltransferase (PEMT) pathway or by a low-choline diet. Alterations in the liver may also influence lipid composition in circulation such as in erythrocytes, which therefore may have utility as a biomarker of hepatic disease. Currently, no study has assessed both liver and erythrocyte PC/PE ratios in NAFLD. The aim of this study was to compare the PC/PE ratio in the liver and erythrocytes of patients with simple steatosis (SS) or nonalcoholic steatohepatitis (NASH) with that of healthy controls. PC and PE were measured by mass spectrometry in 28 patients with biopsy-proven NAFLD (14 SS, 14 NASH) and 9 healthy living liver donors as controls. The hepatic PC/PE ratio was lower in SS patients (median [range]) (1.23 [0.27-3.40]) and NASH patients (1.29 [0.77-3.22]) compared with controls (3.14 [2.20-3.73]); both p < 0.001) but it was not different between SS and NASH. PC was lower and PE higher in the liver of SS patients compared with controls, whereas in NASH patients only PE was higher. The PC/PE ratio in erythrocytes was also lower in SS and NASH patients compared with controls because of lower PC in both patient groups. PE in erythrocytes was not different among the groups. In conclusion, NAFLD patients have a lower PC/PE ratio in the liver and erythrocytes than do healthy controls, which may play a role in the pathogenesis. The underlying mechanisms require further investigation.

Background: Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy., Objective: To determine the optimal timing of protocol liver biopsies in this setting., Methods: A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained., Results: The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05)., Conclusion: The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.

Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as a major cause of mortality after liver transplantation (LT) for HCV-related end-stage liver disease. We conducted this large, single-center, retrospective study to ascertain the long-term impact of virological response to treatment of recurrent hepatitis C on survival of LT recipients. From August 1987 to October 2011, 285 patients have received interferon-based antiviral therapy for recurrent hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred and twenty-six patients (51.4%) achieved sustained virological response (SVR). Relapsers (undetectable HCV-RNA at end of treatment, becoming positive afterward) comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV-RNA) 39.6% (97/245). The median follow-up after completion of antiviral treatment was 2081 days. Using Kaplan-Meier method, patients who achieved SVR were shown to have significantly better 5-year patient survival (95.2%) than the NR group (49.9%) (P < 0.001), and a trend toward better 5-year survival than relapsers (87.5%) (P = 0.14); relapsers had a significantly longer survival than NR group (P = 0.005). When compared with NR, SVR and relapse appeared to be significant predictors of better survival, independent of underlying characteristics. In conclusion, virological response, especially SVR, translates into markedly improved long-term patient outcomes in patients transplanted for hepatitis C., (© 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.)

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long-term nucleos(t)ide analog in combination with one yr of low-dose HBIG. One hundred and fifty-two adults with HBV-related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long-term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow-up post-transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long-term follow-up, demonstrates that short course of low-dose HBIG (without anti-HBs monitoring) combined with the use of long-term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use., (© 2012 John Wiley & Sons A/S.)

Background: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized., Objective: To measure utility scores and HRQoL across disease states associated with CHB infection., Methods: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities., Results: A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores., Conclusions: HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.

Background: Biliary atresia is a progressive biliary injury which occurs only in infants., Aims: To review the experience of patients surviving into adulthood without the need for liver transplantation in childhood., Methods: A multicentre review of patients with biliary atresia treated surgically who survived into adulthood without the need for transplantation., Results: Twenty-two patients were identified across four centres. Median age at the last follow-up was 25 years (range: 18-46), and 21 patients had clinical features of portal hypertension. At last follow-up values of liver enzymes varied from normal to 15 × the upper limit of normal (ULN) for ALT (median 2.11 × ULN) and 9 × the ULN for ALP (median 2.02 × ULN). Six patients had a serum bilirubin > 50 μmol/l. Pruritus and jaundice were noted in 8 of 20 patients (40%) and 11 of 22 patients (50%) respectively. Thirteen patients (59.1%) were shown to have imaging features of sclerosing cholangitis, with strictures of intrahepatic bile duct(s) (IHBD), dilatation of IHBD (n = 8), or stone(s) within the IHBD (n = 5). A history of presumed bacterial cholangitis was present in 11 patients (50%). Successful pregnancies were recorded in three of fourteen female patients. Four patients underwent transplant between the ages of 20-27 years. Twenty-one patients (95.5%) were alive, including 18 (81.8%) with their native liver at the time of last follow-up., Conclusions: Some patients treated for biliary atresia will survive into adulthood with their native liver, but commonly with secondary biliary disease including cholangitis and portal hypertension., (© 2011 John Wiley & Sons A/S.)

Liver transplantation has become the best and most durable treatment for both acute and chronic liver disease. Over 1400 liver transplants have been performed at the Ochsner Clinic since the first successful transplant in 1987. Since its inception, the program has gone through several changes and advancements and has become one of the largest liver transplant programs in the United States. We have helped evolve steroid sparing immunosuppression and the use of extended criteria, donor organs. Establishment of criteria for the selection of recipients for re-transplantation has resulted in better than expected short and long-term results. Our center has faced the challenge of Hurricane Katrina and overcome it. We have improved steadily in both outcomes and transplants performed. The Ochnser Clinic Liver Transplant program will continue to improve access and outcomes for all patients with liver disease.

Background: Hepatitis C virus (HCV) is the most common indication for liver transplantation, but HCV recurrence is frequent after 1 year and is associated with increased morbidity and mortality. Oxidative stress (OxS) is involved in the pathogenesis of HCV, but little is known about its presence prior to disease recurrence., Aim: To determine if at 6 months HCV-positive liver recipients (HCV-OLT) without recurrence were oxidatively stressed., Methods: 33 HCV-OLTs, 12 controls, and 39 HCV-positive nontransplant patients (HCV-NTs). OxS was assessed by using commercial kits to measure liver lipid peroxidation (LPO) and antioxidant potential (AOP). Plasma vitamin E, retinol (HPLC), and vitamin C (spectrophotometry) were assessed. We collected Anthropometry and 3-day food records. We performed analysis by the Kruskal-Wallis test expressing data as mean values +/- standard errors of the mean., Result: Waist-hip ratio was higher in both HCV-OLTs and HCV-NTs compared to the controls. HCV-OLTs showed higher hepatic LPO (mumol malondialdehyde/g tissue) versus controls (1.4 +/- 0.20 vs 0.54 +/- 0.10; P = .010) and compared to HCV-NTs (0.98 +/- 0.17; P = .030). No significant differences were found among the groups regarding hepatic AOP. However, lower plasma AOP (micromols UEA) were observed in HCV-OLTs (0.07 +/- 0.008) versus controls (0.17 +/- .040; P = .021) or HCV-NTs (0.08 +/- 0.009; P = .015) versus controls. Plasma gamma-tocopherol was higher in HCV-OLTs and HCV-NTs compared to controls (P = .001). We observed lower vitamin A intake in HCV-OLTs compared with the other two groups (P = .001)., Conclusions: HCV-OLTs without disease recurrence are oxidatively stressed compared with control and HCV-NTs. Future research is needed to determine the impact of this increased oxidative stress on HCV disease recurrence.

Background: Little is known about donors' perception and psychologic impact of the physical changes that occur after (open) living donor hepatectomy. The aim of this study was to examine the body image and scar satisfaction after donor hepatectomy and to measure the relationship to postdonation quality of life., Methods: Questionnaires measuring body image, cosmesis, and health-related quality of life were administered to 142 adults who underwent right lobe living donor hepatectomy between 2000 and 2007., Results: Liver donors reported a significantly lower body image and lower cosmetic satisfaction with their scar when compared with published data on donors who underwent open nephrectomy. Donors' predonation health concerns and the perception that the recipient was engaging in risky behavior posttransplant were associated with lower postdonation body image scores. In addition, younger age and non-white ethnicity were associated with lower cosmetic scores after donation. Donors with a lower perception of body image and cosmesis reported lower physical and mental health, based on scores on the 36-item Short-Form Health Survey health-related quality of life index, and significantly greater interference in both spousal relationships and their sex life. Younger donors and donors with perioperative complications were also more likely to report decreased confidence after donation., Conclusion: There are unique risk factors that predict a decreased perception of body image and cosmesis postdonation that may be useful in the donor evaluation process. Donors identified to be at risk for the development of a low perception of body image and cosmesis may require close follow-up and additional psychiatric services during the donation process.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.

Many centers require a minimal graft to body weight ratio (GBWR) >or= 0.8 as an arbitrary threshold to proceed with right-lobe living donor liver transplantation (RL-LDLT), and there is often hesitancy about transplanting lower volume living donor (LD) liver grafts into sicker patients. The data supporting this dogma, based on the early experience with RL-LDLT at Asian centers, are weak. To determine the effect of LD liver volume in the modern era, we investigated the impact of GBWR on the outcome of RL-LDLT with a GBWR as low as 0.6 at the University of Toronto. Between April 2000 and September 2008, 271 adult-to-adult RL-LDLT procedures and 614 deceased donor liver transplants were performed. Twenty-two living donor liver transplantation (LDLT) cases with a GBWR of 0.59 to 0.79 (group A) were compared with 249 LDLT cases with a GBWR >or= 0.8 (group B) and with 66 full-graft deceased donor liver transplants (group C), who were matched 3:1 according to donor and recipient age, Model for End-Stage Liver Disease score, and presence of hepatitis C and hepatocellular carcinoma with the low-GBWR group. Portal vein shunts were not used. Markers of reperfusion injury [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], graft function (international normalized ratio and bilirubin), complications graded by the Clavien score, and graft and patient survival were compared. As expected, LD recipients had a significantly shorter cold ischemia time (94 +/- 43 minutes for A, 96 +/- 57 minutes for B, and 453 +/- 152 minutes for C, P = 0.0001). However, the peak AST, peak ALT, absolute decrease in the international normalized ratio, day 7 bilirubin level, postoperative creatinine clearance, complication rate graded by the Clavien score, and median hospital stay were similar in all groups. The rate of biliary complications was higher with LD grafts than deceased donor grafts (19% for A versus 10% for B and 0% for C, P = 0.2). Patient survival was similar in all groups at 1, 3, and 5 years (91% for A versus 89% for B and 93% for C at 1 year, 87% for A versus 81% for B and 89% for C at 3 years, and 83% for A versus 81% for B and 87% for C at 5 years, P = 0.63). A Cox proportional regression analysis revealed only hepatitis C virus as a risk factor for poorer graft survival and not GBWR as a continuous or categorical variable. In conclusion, we found no evidence of inferior outcomes with smaller size grafts versus larger size LD grafts or full-size deceased donor grafts. Further studies are warranted to examine the factors affecting the function of smaller grafts for living liver donation and thereby define the safe lower limits for transplantation.

Background: Efficacy and long-term outcome of antiviral therapy for recurrent hepatitis C after liver transplantation is poorly defined., Aim: This study aimed at assessing the efficacy of antiviral therapy regarding sustained hepatitis C virus (HCV) clearance, liver histology, and patient survival., Methods: We retrospectively reviewed all 446 patients who received a liver allograft at our institution for HCV-related cirrhosis between January 1992 and December 2006. Two hundred thirty-two patients (52%) were eligible for antiviral therapy based on predefined criteria (Metavir stage > or =1 and/or grade > or =2; protocol biopsies). One hundred seventy-two patients (39%) had no contraindication for treatment, received more than or equal to 1 dose of interferon-alpha-based combination therapy, and form the basis of this analysis. Therapy was aimed for 48 weeks; median posttreatment follow-up was 68 months., Results: The overall sustained virological response (SVR) rate was 50% (genotype 1/4: 40%; genotype 2/3: 76%). SVR was higher on cyclosporine A (CsA) (56%) than on tacrolimus (44%, P=0.05), largely because of a lower relapse rate (6% vs. 19%, P=0.01). In multivariate analysis, genotype 2/3, CsA use, donor age, and pretreatment necroinflammatory activity were independently associated with SVR. SVR significantly improved histology and long-term survival (actuarial 5-year survival 96% vs. 69% in nonresponders, P<0.0001)., Conclusion: Antiviral therapy of recurrent hepatitis C after liver transplantation is able to clear HCV in half the patients, more likely on CsA than on tacrolimus, and markedly improves outcome.

The ability to inform prospective donors of the psychosocial risks of living liver donation is currently limited by the scant empirical literature. The present study was designed to examine donor perceptions of the impact of donation on financial, vocational, and interpersonal life domains and identify demographic and clinical factors related to longer recovery times and greater life interference. A total of 143 donors completed a retrospective questionnaire that included a standardized measure of life interference [Illness Intrusiveness Rating Scale (IIRS)] and additional questions regarding the perceived impact of donation. Donor IIRS scores suggested that donors experience a relatively low level of life interference due to donation [1.60 +/- 0.72, with a possible range of 1 ("not very much" interference) to 7 ("very much" interference)]. However, approximately 1 in 5 donors reported that donating was a significant financial burden. Logistic regression analysis revealed that donors with a psychiatric diagnosis at or prior to donation took longer to return to their self-reported predonation level of functioning (odds ratio = 3.78, P = 0.016). Medical complications were unrelated to self-reported recovery time. Multiple regression analysis revealed 4 independent predictors of greater life interference: less time since donation (b = 0.11, P < 0.001), income lower than CAD$100,000 (b = 0.28, P = 0.038), predonation concerns about the donation process (b = 0.24, P = 0.008), and the perception that the recipient is not caring for the new liver (b = 0.12, P = 0.031). In conclusion, life interference due to living liver donation appears to be relatively low. Donors should be made aware of risk factors for greater life disruptions post-surgery and of the potential financial burden of donation.

Background: Hepatitis C virus (HCV) reinfection after liver transplantation is universal and progresses to cirrhosis in 10% to 30% of patients. Several risk factors are associated with progression. Oxidative stress may be involved because it has a role in the pathogenesis of HCV., Objective: To determine whether HCV liver recipients with disease recurrence are more oxidatively stressed than those with no recurrence., Methods: Measurements were performed at 12 months posttransplantation, and in a subgroup of patients at 6 months. Liver lipid peroxidation (LPO), antioxidant potential, plasma vitamin E, retinol, and vitamin C were measured. Demographic data, pretransplantation viral load, anthropometry, and 3-day food records were also obtained. Data were log-transformed; analysis was performed using the independent t test, Pearson correlation, and multivariate regression analysis., Results: Recipients of HCV livers with recurrence (n = 21) had higher liver LPO (mean [SEM] micromoles of malondialdehyde per gram of liver tissue, 1.66 [0.28]) vs those with no recurrence (n = 16; 0.88 [0.13]) (P = .02). A significant relationship was found between liver LPO and HCV recurrence, and this significance continued when accounting for pretransplantation viral load and donor age. Six patients with recurrence and 11 with no recurrence also had measurements obtained at 6 months posttransplantation. Those with recurrence at 12 months had significantly higher hepatic LPO at 6 months (1.86 [0.62]) compared with those with no recurrence (0.75 [0.14]) (P = .04)., Conclusions: Recipients of HCV livers with recurrence are more oxidatively stressed at 6 and 12 months compared with those with no recurrence. Accounting for viral load and donor age, oxidative stress was independently associated with recurrence. More research is needed to confirm this association.

We studied the role of donor and recipient age in transplantation/ischemia-reperfusion injury (TIRI) and short- and long-term graft and patient survival. Eight hundred twenty-two patients underwent deceased donor liver transplantation, with 197 donors being > or = 60 years old. We evaluated markers of reperfusion injury, graft function, and clinical outcomes as well as short- and long-term graft and patient survival. Increased donor age was associated with more severe TIRI and decreased 3- and 5-year graft survival (73% versus 85% and 72% versus 81%, P < 0.001) and patient survival (77% versus 88% and 77% versus 82%, P < 0.003). Hepatitis C virus (HCV) infection and recipient age were the only independent risk factors for graft and patient survival in patients receiving an older graft. In the HCV(+) cohort (297 patients), patients > or = 50 years old who were transplanted with an older graft versus a younger graft had significantly decreased 3- and 5-year graft survival (68% versus 83% and 64% versus 83%, P < 0.009). In contrast, HCV(+) patients < 50 years old had similar 3- and 5-year graft survival if transplanted with either a young graft or an old graft (81% versus 82% and 81% versus 82%, P = 0.9). In conclusion, recipient age and HCV status affect the graft and patient survival of older livers. Combining older grafts with older recipients should be avoided, particularly in HCV(+) patients, whereas the effects of donor age can be minimized in younger recipients., (Copyright 2009 AASLD)