Artificial intelligence to identify harmful alcohol use after early liver transplant for alcohol-associated hepatitis.

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.

Patterns of Alcohol Use After Early Liver Transplantation for Alcoholic Hepatitis.

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.

Low Rates of Hepatitis B Virus Treatment Among Treatment-Eligible Patients in Safety-Net Health Systems.

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.

Antiviral Therapy Reduces Risk of Cirrhosis in Noncirrhotic HBV Patients Among 4 Urban Safety-Net Health Systems.

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.

Liver Transplantation Using Hepatitis C Virus-Viremic Donors Into Hepatitis C Virus-Aviremic Recipients as Standard of Care.

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.

A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis.

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-1ß 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.

Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis.

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.

Has Access to Hepatitis C Virus Therapy Changed for Patients With Mental Health or Substance Use Disorders in the Direct-Acting-Antiviral Period?

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.

Predicting Low Risk for Sustained Alcohol Use After Early Liver Transplant for Acute Alcoholic Hepatitis: The Sustained Alcohol Use Post-Liver Transplant Score.

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.

Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis.

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.

Underestimation of Liver Transplantation for Alcoholic Hepatitis in the National Transplant Database.

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.

Race/ethnicity and insurance status disparities in access to direct acting antivirals for hepatitis C virus treatment.

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.

Health-related quality of life in long-term survivors of paediatric liver transplantation.

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.

HISTORIQUE: La survie à long terme après une transplantation du foie (TF) en pédiatrie est maintenant la règle plutôt que l'exception. Il faut tenir compte à la fois de la quantité et de la qualité des années de vie récupérées dans l'amélioration des résultats après la TF. OBJECTIFS: Caractériser la qualité de vie liée à la santé (QdVLS) des greffés du foie de 15 ans et plus après une TF en pédiatrie. MÉTHODOLOGIE: Les chercheurs ont dépisté des greffés du foie opérés avant décembre 1996 dans un seul établissement et recevant un suivi continu au centre pédiatrique ou au centre partenaire pour adultes. Les patients ayant une grave atteinte développementale et neurologique étaient exclus. La QdVLS était évaluée au moyen de l'inventaire de la qualité de vie en pédiatrie 4.0, de la version 2 du formulaire court sur les résultats médicaux en 36 questions et de l'outil sur la qualité de vie des greffés du foie en pédiatrie. RÉSULTATS: Au total, 27 sujets (67 % d'hommes, âge moyen de 24,3±6,7 ans [médiane de 23,2 ans; plage de 16,6 à 40,3 ans]) ont participé. Ils avaient un âge médian de 1,7 an au moment de la transplantation (plage de 0,5 à 17,0 ans). Sept participants (26 %) ont dû subir une autre transplantation. Dix-sept participants (63 %) travaillaient ou étudiaient à temps plein. La version 2 du formulaire court en 36 questions incluait des scores de sous-échelle physique (49,6±11,1) et mentale (45,3±12,5). Le score moyen pour l'outil de qualité de vie propre à la maladie (outil de qualité de vie des greffés du foie en pédiatrie) était de 64,70±15,2. La santé physique des jeunes adultes était fortement corrélée avec le taux d'investissement dans le travail ou l'étude (r=0,803, P<0,05). CONCLUSIONS: La QdVLS autodéclarée des participants de moins de 18 ans était comparable à celle d'une population en santé standardisée. En revanche, les participants de 18 à 25 ans avaient un score de QdVLS qui ressemblait davantage à celui d'un groupe ayant une maladie chronique. Les participants qui s'investissaient dans un emploi ou des études à temps plein présentaient une meilleure santé physique.

Frequency and significance of IgG4 immunohistochemical staining in liver explants from patients with primary sclerosing cholangitis.

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.

Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance.

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.

Liver transplantation in hepatitis B core-negative recipients using livers from hepatitis B core-positive donors: a 13-year experience.

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.

Virological response for recurrent hepatitis C improves long-term survival in liver transplant recipients.

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.

Biliary atresia and survival into adulthood without transplantation: a collaborative multicentre clinic review.

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.

The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver 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.

Health state utilities and quality of life in patients with hepatitis B.

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.