Cirrhosis Liver

Introduction: Decompensated cirrhosis has traditionally been considered an irreversible stage of liver disease, associated with poor survival and frequent complications such as ascites, variceal bleeding, and hepatic encephalopathy. However, emerging evidence challenges this paradigm, suggesting that effective etiological treatment can lead to “recompensation,” defined as resolution of decompensating events with sustained improvement in liver function. This evolving concept represents a fundamental shift in cirrhosis management, moving from palliation toward potential disease modification. Summary: This systematic review and meta-analysis involving over 9000 patients demonstrates that recompensation occurs in approximately one-third of patients with decompensated cirrhosis, particularly in viral etiologies such as hepatitis B. Importantly, recompensation is associated with significantly lower risks of hepatocellular carcinoma and mortality, highlighting its prognostic and clinical relevance. Despite these promising findings, heterogeneity across studies and limited high-quality evidence indicate that predictors, durability, and mechanisms of recompensation remain incompletely understood. Clinical Implication: Recompensation should be recognised as an achievable and meaningful therapeutic endpoint, emphasising early etiological treatment, aggressive disease modification, and a dynamic approach to cirrhosis care rather than a static irreversible model.

Introduction Management of alcohol use disorder in patients with cirrhosis remains a clinical challenge, where drug safety is as critical as efficacy. Acamprosate is generally preferred due to renal clearance, while baclofen has been considered safe even in advanced liver disease. However, comparative real-world safety data between these two commonly used agents in compensated alcohol-associated cirrhosis have been limited. Problem Statement Despite guideline endorsement of both baclofen and acamprosate, uncertainty persists regarding their relative hepatic safety. Clinicians often face a dilemma in choosing therapy, particularly in patients at risk of decompensation, where even small differences in adverse outcomes can significantly impact prognosis. Summary This large, multicenter, real-world cohort study using a target trial emulation framework compared baclofen and acamprosate in compensated alcohol-associated cirrhosis. After robust propensity matching, baclofen was associated with a higher incidence of major adverse liver outcomes at one year compared to acamprosate (34.3% vs 27.4%). Notably, the increased risk was primarily driven by a higher incidence of hepatic encephalopathy, while other decompensation events and mortality did not differ significantly. The risk appeared more pronounced in older patients. These findings suggest that while baclofen remains an option, acamprosate may be the safer first-line agent in compensated cirrhosis, particularly in patients at risk for encephalopathy. This study provides important real-world evidence to guide individualised therapeutic decision-making in this vulnerable population.

Introduction Endoscopic band ligation (EBL) remains the standard of care for managing esophageal varices, both in acute variceal bleeding and for prophylaxis. However, post-banding ulcer bleeding (PBUB) is an important and often under-recognized complication, associated with significant morbidity and mortality. Identifying patients at higher risk for PBUB is clinically relevant, particularly in acute settings where outcomes are already compromised. Problem Statement Despite increasing recognition of PBUB, risk stratification remains inconsistent in clinical practice. Recent data have suggested that urgent EBL and renal dysfunction may increase PBUB risk, but real-world validation across larger cohorts is limited, and standardized definitions are lacking. Summary In this large real-world analysis of 920 EBL procedures, PBUB occurred in 3.4% overall, with a significantly higher incidence following urgent EBL compared to elective procedures (7.5% vs 1.4%). Urgent EBL emerged as a strong independent predictor of PBUB, reinforcing the vulnerability of patients undergoing intervention during acute bleeding episodes. Additionally, renal dysfunction was identified as a key risk factor, with patients having serum creatinine ≥1.5 mg/dL demonstrating markedly higher bleeding rates and independent risk. These findings are consistent with prior literature and highlight a simple, clinically applicable framework combining urgency of EBL and renal function to identify high-risk patients. This approach may help guide closer monitoring and preventive strategies in routine practice.

Introduction Ammonia has long been recognised as a central neurotoxin in the pathogenesis of hepatic encephalopathy, but its clinical use in cirrhosis has remained inconsistent because of major variability in sampling, processing, reporting, and interpretation. This international ISHEN Delphi consensus is important because it is the first structured, evidence-based effort to define when ammonia should be measured, how it should be measured, and how clinicians should interpret it in both outpatient and inpatient cirrhosis care. The document moves the field beyond the old debate of whether ammonia is useful at all and instead places ammonia within a practical clinical framework. Summary The consensus makes a strong methodological point that ammonia is only clinically useful when measured properly. It recommends a minimum 4-hour fasting period, venous sampling for routine practice, transport on ice, centrifugation within 15 minutes, and measurement within 2 hours. It also advises that ammonia should be reported both as an absolute value and as a multiple of the upper limit of normal to improve comparability across laboratories. In the outpatient setting, ammonia is positioned as a useful biomarker for risk stratification, especially for predicting overt hepatic encephalopathy, liver-related decompensation, and death, with a level greater than 1.4 times the upper limit of normal emerging as an important prognostic threshold. In patients undergoing elective TIPS, pre-procedure ammonia may help predict post-TIPS encephalopathy. In the inpatient setting, ammonia is not considered a standalone diagnostic test for overt hepatic encephalopathy, but a normal value should prompt clinicians to question the diagnosis and search for alternative causes of altered mental status. The consensus also emphasises that serial ammonia measurement has value during treatment, because falling ammonia levels are associated with better neurological recovery and improved survival, whereas persistent or rising ammonia suggests poor response and worse prognosis. Conclusion The major clinical message of this ISHEN consensus is that ammonia should no longer be dismissed as an unreliable biomarker, but neither should it be used in isolation. When measured under standardised conditions and interpreted within the full clinical context, ammonia provides meaningful diagnostic, prognostic, and therapeutic information in cirrhosis. This document is likely to influence day-to-day hepatology practice, future trial design, and global harmonisation of care in hepatic encephalopathy.

Introduction Harmful alcohol use remains a major cause of chronic liver disease, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality worldwide. Despite advances in hepatology care, effective pharmacologic strategies that simultaneously address alcohol use behaviour and liver disease progression are limited. Recent anecdotal observations have suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—commonly used for diabetes and obesity—may reduce alcohol craving and consumption. However, their potential impact on liver-related outcomes and mortality in individuals with harmful alcohol use has not been well studied. Summary In this target trial emulation study using US Veterans' electronic health records, investigators evaluated the association between GLP-1 RA use and liver outcomes in patients with harmful alcohol use. A total of 8,040 GLP-1 RA initiators with positive AUDIT-C scores were propensity-score matched with 8,040 nonusers and followed longitudinally. GLP-1 RA therapy was associated with a 30% lower risk of composite liver-related outcomes (hepatic decompensation, hepatocellular carcinoma, liver-related death, or all-cause mortality) (adjusted HR 0.70). Importantly, all-cause mortality was reduced by 57% (adjusted HR 0.43). Among semaglutide users, higher weekly doses were linked with even greater reductions in liver outcomes and mortality. Additionally, GLP-1 RA users showed lower odds of continued harmful alcohol use during follow-up (adjusted OR 0.75). Conclusion GLP-1 receptor agonists may offer dual benefits in patients with harmful alcohol use—reducing alcohol consumption and improving liver-related outcomes and survival. These findings suggest a potential novel therapeutic role for GLP-1 RAs in alcohol-associated liver disease, although randomized clinical trials are needed for confirmation.