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Background and Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality in those with hepatic encephalopathy (HE). Polyethylene glycol (PEG) 3350 electrolyte solution can ensure rapid gut catharsis, which may resolve HE more effectively than lactulose. In this open-label-randomized trial, we compared PEG+lactulose versus lactulose alone in ACLF with HE grade ≥ 2 for efficacy and outcome.Patients and Methods: Patients were randomized to receive PEG (2 L q12 h) followed by lactulose (30 mL q8 h) or standard medical treatment [SMT, lactulose (titrated 30 mL q8 h)]. Endpoints were HE grade improvement at 24 hours, 48 hours, and 7 days using hepatic encephalopathy scoring algorithm (HESA), ammonia reduction, HE resolution, and survival benefit.Results: Of 60 patients, 29 were randomized to PEG+lactulose arm and 31 to SMT. In the PEG arm, early reduction in HESA score was noted in more persons [18 (62.1%) vs. 10 (32.2%); P = 0.021] with a shorter median time to HE resolution [4.5 (3 to 9) d vs. 9 (8 to 11) d; P = 0.023]. On multivariate analysis, age [hazard ratio (HR),1.06 (1.00 to 1.13); P = 0.03], HESA score [HR, 6.01 (1.27 to 28.5); P = 0.024], and model for end-stage liver disease [HR, 1.26 (1.01 to 1.53); P = 0.022] were predictors of mortality at 28 days. Ammonia level or reduction did not correlate with HE grades. Adverse events included excessive diarrhea (20.6% vs. 9.6%) in the PEG and SMT arms, albeit without dyselectrolytemia or worsened renal function. In the PEG versus SMT arm, survival at 28 days were 93.1% versus 67.7% (P = 0.010) and at 90 days was 68.9% versus 48.3% (P = 0.940), respectively, with fewer persons relapsing with HE in the PEG arm.Conclusions: PEG resulted in early and sustained HE resolution with improved short-term survival making, it a suitable and safe drug in patients with acute HE in ACLF.

Immune‐mediated liver injury (ILI) following coronavirus disease 2019 (COVID‐19) vaccination is not well‐characterized. Therefore, we systematically reviewed the literature on ILI after COVID‐19 vaccination. We searched PubMed, Cochrane, Ovid, Embase, and gray literature to include articles describing ILI following COVID‐19 vaccination. Reports without confirmatory evidence from liver biopsy were excluded. Descriptive analysis, and study quality were reported as appropriate. Of the 1,048 articles found, 13 (good/fair quality; 23 patients) were included. Studies were primarily from Europe ( n = 8), America ( n = 2), Asia ( n = 2), or Australia ( n = 1). Patients were predominantly females (62.5%) of age 55.3 years (49.1–61.4), with an antecedent exposure to Moderna messenger RNA (mRNA)–1273 (47.8%), Pfizer‐BioNTech BNT162b2 mRNA (39.2%), or ChAdOx1 nCoV‐19 vaccine (13%). Pre‐existing comorbidities (69.6%) were common, including liver disease in 26.1% and thyroid disorders in 13% of patients. About two‐thirds of the patients were on concurrent medications (paracetamol, levothyroxine, statins, and non‐steroidal anti‐inflammatory drugs). Jaundice was the most common symptom (78.3%). Peak bilirubin, alanine aminotransferase, and alkaline phosphatase levels were 10.8 (6.8–14.8) mg/dl, 1,106.5 (757.0–1,702.5) U/L, and 229 (174.6–259.6) U/L, respectively. Histological findings were intense portal lymphoplasmacytic infiltrate with interface hepatitis. Steroids were used in 86.9% of patients, and complete response, recovering course, and death were reported in 56.5%, 39.1%, and 4.3% of patients, respectively. ILI following COVID‐19 vaccination is rare. The diagnosis is established on temporal correlation, biochemical findings, and histopathology. Prognosis is excellent with corticosteroids. Causality establishment remains a challenge.

Nonalcoholic steatohepatitis (NASH) is the fastest growing indication for liver transplant (LT)worldwide and is deemed to be the foremost indication in the near future. Recurrence of NASH can occur post LT and has been observed to be a common phenomenon. Baseline metabolic co-morbidities and worsening of metabolic profile post LT are the principal drivers of NASH recurrence. Liver biopsy remains the gold standard for establishing the diagnosis. However, noninvasive methods including transient elastography (TE) and magnetic resonance imaging (MRI) seem to be promising. The implications of recurrent NASH on post LT outcomes, graft steatosis, progression to fibrosis, overall survival, and cardiovascular associations warrant careful evaluation. Control of metabolic parameters and weight gain along with tailored immunosuppression remain the cornerstone of management. Extrapolation of the everincreasing armamentarium of NASH pharmacotherapy specifically in this population of recurrent NAFLD remains a challenge for the future.