Health-related quality of life is dynamic in alcoholic hepatitis and responds to improvement in liver disease and reduced alcohol consumption.

BACKGROUND: The impact of alcoholic hepatitis (AH) on health-related quality of life (HRQOL) remains inadequately described. We aimed to characterize HRQOL in AH and heavy drinkers (HD), and its associations with clinical variables and outcomes. METHODS: This is a post hoc analysis of participants in the Translational Research and Evolving Alcoholic Hepatitis Treatment 001 study (NCT02172898). HRQOL was measured using Short Form Health Survey (SF-36). Mean SF-36 scores were compared in AH and HD with two-sample t-tests. Associations among clinical characteristics, 30-day mortality, and SF-36 mental and physical component scores (MC, PC) were investigated with generalized linear and logistic multivariate regression models. Trends of MC and PC scores were analyzed using one-way ANOVA. RESULTS: Participants with AH (n = 258) and HD (n = 181) were similar demographically. AH cases had a mean Model for End-stage Liver Disease (MELD) score of 23 (7). AH cases had lower PC scores [37 (10) vs. 48 (11), p < 0.001] but higher MC scores [37 (13) vs. 32 (13), p < 0.001]. MC scores were independently associated with age, male gender, and daily alcohol consumption; PC scores were independently associated with age, BMI, alanine aminotransferase concentration, alkaline phosphatase concentration, white blood cell counts, and the presence of ascites. With each 5-point decrease in the baseline PC score, the adjusted odds of dying within 30 days increased by 26.7% (95% CI 1% to 46%). Over time, HRQOL in AH improved (day 0 to day 180 delta PC score: 4.5 ± 1.7, p = 0.008; delta MC score: 9.8 ± 2.0, p < 0.001). Participants with a MELD score <15 by day 180 had greater increases in PC scores than those with MELD score ≥15 (delta PC score 7.1 ± 1.8 vs. -0.7 ± 2.3, p = 0.009), while those abstinent by day 180 had greater increases in MC scores than those who were not abstinent (delta MC score 9.1 ± 1.8 vs. 2.8 ± 2.4, p = 0.044). CONCLUSIONS: HRQOL is poor in AH and HD in a domain-specific pattern. Independent of MELD score, lower baseline HRQOL is associated with higher 30-day mortality. Over time, HRQOL improves with greater gains seen in individuals with improved MELD scores and those who were abstinent.

Posttraumatic Stress Disorder in Patients with Heavy Alcohol Consumption and Alcoholic Hepatitis.

BACKGROUND: Lifetime prevalence of posttraumatic stress disorder (PTSD) in the general population is reported to be 6.8%. Individuals with alcohol dependence and substance abuse have high prevalence of PTSD. However, the prevalence of PTSD in heavy drinkers with alcoholic hepatitis (AH) is not known.The study's aim was to determine the prevalence of PTSD in heavy drinkers with and without AH. METHODS: We screened for PTSD using the Primary Care-PTSD questionnaire among heavy drinkers with (n = 115) and without (n = 64) AH participating in a multicenter observational study in which participants were followed up to 12 months following their enrollment. RESULTS: The prevalence of PTSD in heavy drinkers with AH was 34% and was not different from heavy drinking controls without liver disease (34%). In the entire group screened for PTSD, the presence of PTSD was associated with higher alcohol consumption as reported by average drinks per last 30 days and average grams of alcohol consumed per day (p = 0.047 for both tests), but not associated with relapse of heavy drinking or mortality. Similarly, patients with AH and PTSD did not have higher relapse rate or higher mortality compared to patients with AH but no PTSD. CONCLUSIONS: Compared to previously reported prevalence in general population, heavy drinking individuals with or without AH have significantly higher prevalence of PTSD. However, PTSD was not associated with higher relapse rate or higher mortality in this population.

Challenges in Patient Enrollment and Retention in Clinical Studies for Alcoholic Hepatitis: Experience of the TREAT Consortium.

The TREAT Consortium has carried out clinical studies on alcoholic hepatitis (AH) for over 4 years. We encountered problems with participant recruitment, retention, and eligibility for specific protocols. To improve our ability to carry out such trials, we reviewed recruitment screening logs, end of study logs, and surveyed study coordinators to learn the reasons for missing patients, why patients declined enrollment, and the number of patients eligible for treatment trials. Associations of the recruited subjects' demographics with their adherence to follow-up appointments were examined. Three hundred eight-seven patients (AH and heavy drinking controls) were enrolled in the observational study, and 55 AH patients were recruited into treatment trials. About half of patients identified with AH could not be recruited; no specific reason could be determined for about two-thirds of these. Among the patients who gave a reason for not participating, the most common reasons were feeling too sick to participate, desire to concentrate on abstinence, and lack of interest in research. Approximately a quarter of the AH patients met eligibility criteria for treatment trials for moderate or severe AH and we were able to recruit half to two-thirds of those eligible. Approximately 35% of participants in the observational study returned for both 6- and 12-month follow-up visits. We did not identify biopsychosocial or demographic correlates of retention in the study. This analysis revealed that attempts at recruitment into trials for AH miss some subjects because of structural issues surrounding their hospital admission, and encounter a high rate of patient refusal to participate. Nonetheless, more than half of the patients who met the eligibility criteria for moderate or severe AH were entered into clinical trials. Retention rates for the observational study are relatively low. These findings need to be accounted for in clinical trial design and power analysis.

[Effect of silymarin on liver health and quality of life. Results of a non-interventional study]. / Einfluss von Silymarin auf Lebergesundheit und Lebensqualität.

BACKGROUND: Many drugs are known to have hepatotoxic side effects. The effect of silymarin on liver function and liver-injury-impaired quality of life under daily practice conditions in patients with elevated values of liver enzymes was evaluated in the present non-interventional study. METHOD: Patients with drug-induced elevated aminotransferase levels and indication for silymarin (Legalon forte) treatment for 2 to 3 months were documented prospectively over 4 months. At baseline, after 2 and 4 months, respectively, the following parameters were documented: alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase, total bilirubin, presence of liver-related skin symptoms and discoloured urine, severity of liver-related symptoms and quality of life. RESULTS: In total, 190 patients (53.2% male, median age 60.0 years [range 19-81]) from 48 centres participated in the non-interventional study. Among potentially hepatotoxic drugs, analgesics/anti-inflammatory drugs were used most frequently (45.8%). These drugs have been administered for a median period of 2.8 years (range 0.0-26.1). At baseline, all patients had elevated levels of ALT, AST or GGT. Fatigue, flatulence, upper abdominal discomfort, lethargy, and joint complaints were the most severe liver-related symptoms and prevalent in over 62% of patients. Quality of life was affected in 88.7% of patients. Significant reductions were achieved in all documented laboratory parameters (p < 0.001), leading to marked improvement in liver-related symptoms and increased quality of life already after 2 months. The percentage of patients with liver enzymes in the normal range increased considerably within 4 months. No adverse drug reactions were observed. CONCLUSIONS: Silymarin is a safe and efficacious treatment option for patients with elevated liver enzymes. A benefit in terms of liver-related symptoms as well as quality of life and performance was demonstrated already after 2 months of treatment.

The place of liver transplantation in the treatment of severe alcoholic hepatitis.

Although most patients with alcoholic liver disease experience positive outcomes following liver transplantation, data on the outcome after liver transplantation in patients with severe alcoholic hepatitis are limited. Furthermore, predicting which patients with severe alcoholic hepatitis will maintain sobriety after transplantation is especially difficult. We review the arguments in favour and against extending liver transplantation to selected patients with severe alcoholic hepatitis. In conclusion, we propose that liver transplantation should be a rescue option for occasional patients with severe alcoholic hepatitis who meet the following criteria: those with severe alcoholic hepatitis that has failed medical management, who fulfil all other standard criteria for transplantation, including a thorough psychosocial assessment, yet who are unlikely to survive a mandatory 6-month abstinence period.

Treatment retention in a specialized alcohol programme after an episode of alcoholic hepatitis: Impact on alcohol relapse.

AIMS: Alcoholic hepatitis (AH) is a life-threatening complication of alcohol use disorder (AUD). Alcohol abstinence is the main predictor of the long-term prognosis of AH. It is unknown whether AUD treatment retention (TR) after an AH episode impacts alcohol relapse and mortality or what baseline factors influence TR. METHODS: Design: case-control study; Study population: hospitalized patients (1999-2012) with an episode of biopsy-proven AH were included (n = 120); Assessment: demographic and clinical data, the High-Risk Alcoholism Relapse (HRAR) scale, mortality and alcohol relapse were assessed through clinical records and telephone or personal interviews; Follow-up period: short-term and long-term TRs were assessed at 12 and 24 months, respectively. RESULTS: The overall short-term and long-term TRs were 37% and 27.8%, respectively. The severity of liver disease at baseline predicted both short-term and long-term TR (OR 3.7 and 3.3, respectively), whereas HRAR >3 and a history of psychiatric disorders predicted long-term TR (OR 2.9 and 2.6, respectively). Moreover, HRAR >3 (OR 3.0) and previous treatment for AUD (OR 2.9) increased the risk of relapse in the short term. Importantly, receiving alcohol therapy in a centre different from the hospital where the patient was admitted was associated with increased risk of alcohol relapse over the long term (OR 5.4). CONCLUSION: Experiencing an alcohol-related life-threatening complication is insufficient motivation to seek treatment for AUD. AUD treatment after an episode of AH is suboptimal, with a low TR rate, high risk of alcohol relapse and poor impact of treatment on alcohol relapse.

Liver Transplantation for Severe Alcoholic Hepatitis, Updated Lessons from the World's Largest Series.

BACKGROUND: Six-month sobriety before transplantation for alcoholic liver disease is typically required but poorly supported by data. We initiated a pilot program after a report of liver transplantation for severe alcoholic hepatitis (SAH) in which the 6-month rule was waived. We previously reported early outcomes; we now provide longer follow-up in the largest cohort of early liver transplantation for SAH in the literature to date. STUDY DESIGN: Forty-six carefully selected patients with SAH underwent liver transplantation from October 2012 through July 2017; none had been abstinent for 6 months. We also examined 34 patients with alcoholic cirrhosis who received liver transplants under standard protocols with at least 6 months sobriety. We identified patient characteristics and primary outcomes of patient and graft survival, as well as alcohol recidivism. Secondary outcomes included post-transplantation infection, malignancy, and rejection. RESULTS: Compared with patients with alcoholic cirrhosis, SAH patients were younger and with shorter drinking history and higher Model for End-Stage Liver Disease scores at listing and at transplantation. Of these patients, 46% received preoperative steroids; all were nonresponders by Lille score. At a median follow-up time of 532 days (interquartile range 281 to 998 days), there were no significant differences between groups by log-rank testing of Kaplan-Meier estimates for patient and graft survival or alcohol recidivism. CONCLUSIONS: In the largest cohort of patients reported, outcomes after liver transplantation for SAH had excellent 1-year outcomes, similar to those seen in patients who received transplants with 6 months of sobriety. Recidivism was similar in the 2 groups. Early liver transplantation for SAH represents life-saving therapy for patients with otherwise high mortality, calling into question the utility of the 6-month rule in predicting outcomes in patients receiving transplants for alcoholic liver disease.

Koro syndrome associated with alcohol-induced systemic disease in a Zulu.

A case report is presented of the genital retraction syndrome, koro, associated with alcoholic hepatitis, avitaminosis and urinary tract infection, occurring in a Zulu male. Treatment of the physical conditions resulted in resolution of the koro symptomatology. The nosological status of koro is discussed and it is proposed that the condition be regarded as a symptom-complex reaction to a variety of psychological or physical stressors rather than as a purely culture-bound syndrome.

Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis.

BACKGROUND/AIMS: In alcoholic hepatitis (AH), soluble TNF alpha receptor-1 (sTNF-R1) is increased. Elevated TNF alpha predicts mortality, but infection influences TNF alpha values. In patients with AH, we determined the prognostic value of TNF alpha, sTNF-R1, and lipopolysaccharide binding protein (LBP) and CD14, both involved in endotoxemia-associated inflammation. METHODS: One hundred and eight cirrhotic patients (Pugh score 10 [6-13]) and biopsy-proven AH (Maddrey's DF <32: n=46; > or =32: n=62) without associated infection were included within 8 days of admission and followed-up for 3 months. Cytokines were measured using specific immunoassays. Patients with severe AH received steroids. RESULTS: Twenty four patients died at a median time of 35 days (range: 3-89). The overall survival was 78%. Multivariate Cox regression analysis showed that sTNF-R1 was an independent predictor of mortality, (OR 4.33: 95% CI [1.12-16.75]). Pugh's score (P=0.618), Maddrey's DF (P=0.182), creatinine (P=0.197), TNF alpha (P=0.319), LBP (P=0.362), and CD14 (P=0.347) were not related to survival. CONCLUSIONS: In patients with AH, sTNF-R1 measured at admission is an independent predictor of survival at 3 months. Provided that TNF-R1 mediates the cytotoxic actions of TNFalpha, these results support the concept of dysregulated TNF alpha metabolism in AH.