Alcohol Rehabilitation Within 3 Months after Alcohol Hepatitis and Survival - A National Analysis.

BACKGROUND AND AIMS: There is limited understanding of the benefits of alcohol rehabilitation after alcohol hepatitis (AH). METHODS: We conducted a 2012-2021 national longitudinal study involving adult inpatients diagnosed with AH in France. We assessed the primary outcome of liver transplantation or death within one year after AH, including in its complicated form (CAH) defined as ≥ 2 hepatic or extrahepatic complications within 4 weeks after AH. The primary exposure was in-hospital alcohol rehabilitation within 3 months following AH. Patients who died (6.5%, n=5,282) or were censored (12.5%, n=10,180) ≤ 4 weeks after AH were excluded. We measured adjusted hazard ratios (aHR) and odds ratios (aOR) within the full cohort and propensity-matched samples. RESULTS: Among 65,737 patients (median age 52; IQR 44-60; 76% male), 12% died or underwent liver transplantation. In-hospital alcohol rehabilitation was noted for 25% of patients (15.2% among CAH patients) and was the primary discharge diagnosis for 13.3%. The one-year transplant-free survival rates were 94% (95% CI: 94% to 95%) for rehabilitated patients, compared to 85% (85% to 86%) for those without [aHR 0.62 (0.57 to 0.69) p < 0.001]. Among CAH patients, transplant-free survival was 78% (76% to 81%) with rehabilitation versus 70% (69% to 71%) without [aHR 0.82 (0.68 to 0.98) p = 0.025]. In propensity-matched samples, rehabilitation was linked to an aOR of 0.54 (0.49 to 0.55, p < 0.001) overall, and 0.73 (0.60 to 0.89, p = 0.002) among matched CAH patients. CONCLUSIONS: In-hospital alcohol rehabilitation within 3-months after AH and CAH improve transplant-free survival rate but remain underutilized. FUNDING: No external funding.

Serum bile acids profiles are altered without change of the gut microbiota composition following a seven-day prednisolone therapy in severe alcoholic hepatitis.

Severe Alcoholic Hepatitis (sAH) is an acute form of liver injury caused by chronic and heavy alcohol drinking. A one-month corticosteroids course is the only sAH reference treatment, and its interactions with the Gut Microbiota (GM), which is a key contributor to liver injury, remain unknown. To evaluate the evolution of the GM in sAH patients, we retrospectively investigated the composition of the GM of 27 sAH patients at the Amiens University Hospital before (D0) and after (D7) a 7-day corticotherapy course using fecal metagenomics sequencing. We also quantified fecal Short-Chain Fatty Acids (SCFA) and fecal and serum Bile Acids (BA), as well as serum Lipopolysaccharide-Binding Protein (LBP). Overall, the community and taxonomical analyses did not reveal any GM evolution between D0 and D7, nor did the SCFA profiles analysis. However, in serum but not fecal samples, the ratio of glyco-conjugated to tauro-conjugated BA was significantly reduced at D7, independently of the response to treatment, while two BA were enriched in non-responder patients. LBP concentration significantly diminished between D0 and D7, which may indicate an improvement of the gut barrier. The stability of the GM of sAH is interesting in the perspective of new treatments based on GM modulation.

There is a gap in the understanding of the effects of corticosteroids on the gut microbiota of severe alcoholic hepatitis patients.In this study, the composition of the Gut Microbiota of sAH patients treated with prednisolone remains unchanged after 7 days of prednisolone treatment.Short-Chain Fatty Acid profiles are not impacted by the treatment, while Bile Acids profiles change in serum but not in stool samples.Responders and non-responders show different lipopolysaccharide-binding protein serum concentration evolution across time, as well as distinct Bile Acid profiles.

Mechanisms of chronic alcohol exposure-induced aggressiveness in cellular model of HCC and recovery after alcohol withdrawal.

Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments. Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to chronic alcohol exposure (CAE), at different doses for 6 months followed by 1-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270 mM dose, CAE decreased cell viability by about 50% and 80%, respectively, in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of cancer stem cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3ß signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly, we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies. Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients.