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Background: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol‐associated acute‐on‐chronic liver failure (ACLF). Methodology: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. Results: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P =.007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P =.014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06‐2.24, P =.023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30‐day mortality (aHR 1.91, 95% CI 1.41‐2.59, P <.001), independent of age, CTP, MELD and AARC scores. Conclusion: Overweight/obesity and dyslipidaemia increase the severity of alcohol‐associated ACLF, and the former also increases the short‐term mortality in these patients. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. NCT04238416 (clinicaltrials.gov). • Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with high morbidity and mortality. • Oral branched-chain amino acids (BCAA) are helpful in HE in cirrhosis but role of intravenous BCAA in ACLF is unknown. • We describe the use of intravenous BCAA for HE in ACLF. • IV BCAA given in a short 3-day course helps in early resolution of HE which translated to shorter ICU stay. • The improvement in HE by IV BCAA was not sustained at day 3 or day 7 and there was no 28-day survival benefit. [ABSTRACT FROM AUTHOR]

Summary: Background: Point‐of‐care echocardiography (POC‐Echo) is an essential intensive care hemodynamic monitoring tool. Aims: To assess POC‐Echo parameters [i.e., cardiac index (CI), systemic vascular resistance index (SVRI) and cirrhotic cardiomyopathy (CCM) markers] and serum biomarkers in predicting circulatory failure (need for vasopressors) and mortality in patients with acute‐on‐chronic liver failure (ACLF) having sepsis‐induced hypotension. Methods: We performed serial POC‐Echo within 6 hours (h) of presentation and subsequently at 24, 48 and 72 h in patients with ACLF and sepsis‐induced hypotension admitted to our liver intensive care unit. Clinical data, POC‐Echo data and serum biomarkers were collected prospectively. Results: We enrolled 120 patients [59% men, aged 49 ± 12 years, 56% alcohol‐related disease and median MELDNa of 30 (27–32)], of whom 68 (56.6%) had circulatory failure, with overall mortality of 60%. CCM was present in 52.5%. The predictors of circulatory failure were CI (aHR −1.5; p = 0.021), N‐terminal brain natriuretic peptide (aHR −1.1; p = 0.007) and CCM markers; e′ septal mitral velocity (aHR −0.5; p = 0.039) and E/e′ ratio (aHR −1.2; p = 0.045). Reduction in CI by 20% and SVRI by 15% at 72 h predicted mortality with a sensitivity of 84% and 72%, and specificity 76% and 65%, respectively (p < 0.001). The MELD‐CCM model and CLIF‐CCM model were computed as MELDNa + 1.815 × E/e′ (septal) + 0.402 × e′ (septal) and CLIF‐C ACLF + 1.815 × E/e′ (septal) + 0.402 × e′ (septal), respectively, based on multivariable logistic regression. Both scores outperformed MELDNa (z‐score = −2.073, p = 0.038) and CLIF‐C ACLF score (z score = −2.683, p‐value = 0.007), respectively, in predicting 90‐day mortality. Conclusion: POC‐Echo measurements such as CCM markers (E/e' and e' velocity) and change in CI reliably predict circulatory failure and mortality in ACLF with severe sepsis. CCM markers significantly enhanced the CLIF‐C ACLF and MELDNa predictive performance. [ABSTRACT FROM AUTHOR]

Background: We evaluated the prevalence, risk factors, and impact of bacterial/fungal infections in acute liver failure (ALF) patients. Methods: We analyzed clinical, biochemical, and microbiological data of ALF patients with and without bacterial/fungal infections admitted at an institute over the last 5 years. Results: We enrolled 143 patients, 50% males, median age 25 years, with acute viral hepatitis (32.2%), drug-induced injury (18.2%), and tropical illness (14%) as aetiologies of ALF. 110 patients (76.9%) developed bacterial/fungal infections [Bacterial infection: MDR: 70%, PDR: 7%, ESBL: 40%, CRE: 30%, CRAB: 26.6%, MDR-EF: 13.3% and fungal infection: 19 (17.3%)]. On univariable analysis, SIRS (33.6% vs.3%), ICU admission (78.2% vs. 45.5%), mechanical ventilation (88.2% vs. 51.5%), inotropes (39.1% vs. 6.1%), invasive catheters (91.8% vs. 39.4%), and prolonged catheterization (6 days vs. 0 days) were significant risk factors for infections (p < 0.05, each). In contrast, SIRS and catheterization independently predicted infection on multivariable regression. Organ failures [3 (2–4) vs. 1 (0–2)], grade-III–IV HE (67.3% vs. 33.3%), circulatory failure (39.1% vs. 6.1%), coagulopathy (INR > 2.5: 58.2% vs. 33.3%), renal injury (28.2% vs. 6.1%) (p < 0.05), MELD (32.9 ± 8.2 vs. 26.7 ± 8.3) and CPIS [3(2–4) vs. 2(0–2)] were higher in infected vs. non-infected patients (p < 0.001). 30-day survival was significantly lower in infected vs. non-infected patients (17.3% vs. 75.8%, p < 0.001), while no patient survived with fungal infections. Refractory septic shock was the commonest cause of mortality in patients. Conclusions: Infections due to MDR organisms are high, fungal infections are fatal, and refractory septic shock is the dominant reason for mortality, implying bacterial and fungal infections as the major killer in ALF patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Telemedicine is an evolving tool to provide health‐care services. We evaluated the suitability of telemedicine to deliver effective consultation for hepatobiliary disorders. Methods: In this prospective study spanning over a year, we interviewed hepatologists delivering the teleconsultations through a pre‐validated questionnaire. A consult was deemed suitable based on the physician's judgment in the absence of unplanned hospitalization. We evaluated factors determining the suitability through inferential statistics and machine learning models, namely, extreme gradient boosting (XGB) and decision tree (DT). Results: Of 1118 consultations, 917 (82.0%) were deemed suitable. On univariable analysis, patients with skilled occupation, higher education, out‐of‐pocket expenses, and diseases such as chronic hepatitis B, C, and non‐alcoholic fatty liver disease (NAFLD) without cirrhosis were associated with suitability (P < 0.05). Patients with cirrhosis (compensated or decompensated), acute‐on‐chronic liver failure (ACLF), and biliary obstruction were likely unsuitable (P < 0.05). XGB and DT models predicted suitability with an area under the receiver operating curve of 0.808 and 0.780, respectively. DT demonstrated that compensated cirrhosis with higher education or skilled occupation with age < 55 years had 78% chance of suitability whereas hepatocellular carcinoma, decompensated cirrhosis, and ACLF patients were unsuitable with a 60–95% probability. In non‐cirrhotic liver diseases, hepatitis B, C, and NAFLD were suitable, with a probability of 89.7%. Biliary obstruction and previous failure of teleconsultation were unsuitable, with a probability of 70%. Non‐cirrhotic portal fibrosis, dyspepsia, and dysphagia not requiring intervention were suitable (probability: 88%). Conclusion: A simple decision tree can guide the referral of unsuitable and the management of suitable patients with hepatobiliary diseases through telemedicine. [ABSTRACT FROM AUTHOR]

The article aims to generate a unique MELDNa-Actvity-Chairstands-Quality of Life Hepatic Encephalopathy Score (MASQ-HE) score as a bedside tool for the prediction of the first episode of overt hepatic encephalopathy (OHE).

Gastrointestinal candidiasis is often neglected and potentially serious infection in cirrhosis patients. Therefore, we evaluated the prevalence, risk factors, and outcomes of esophageal candidiasis (EC) in cirrhotics and did a systematic review to summarize EC's available evidence in cirrhosis. Consecutive patients with cirrhosis posted for esophagogastroduodenoscopy (EGD) at a tertiary care institute were screened for EC (cases) between January 2019 and March 2020. EC was diagnosed on EGD findings and / or brush cytology. Controls (without EC) were recruited randomly, and EC's risk factors and outcomes were compared between cases and controls. Four electronic databases were searched for studies describing EC in cirrhosis. Prevalence estimates of EC were pooled on random-effects meta-analysis, and heterogeneity was assessed by I2. A checklist for prevalence studies was used to evaluate the risk of bias in studies. EC was diagnosed in 100 of 2762 patients with cirrhosis (3.6%). Patients with EC had a higher model for end-stage liver disease (MELD) (12.4 vs. 11.2; P = 0.007), acute-on-chronic liver failure (ACLF) (26% vs. 10%; P = 0.003) and concomitant bacterial infections (24% vs. 7%; P = 0.001), as compared with controls. A multivariable model, including recent alcohol binge, hepatocellular carcinoma (HCC), upper gastrointestinal (UGI) bleed, ACLF, diabetes, and MELD, predicted EC's development in cirrhosis with excellent discrimination (C-index: 0.918). Six percent of cases developed the invasive disease and worsened with multiorgan failures, and four patients with EC died on follow-up. Of 236 articles identified, EC's pooled prevalence from 8 studies (all with low-risk of bias) was 2.1% (95% CI: 0.8–5.8). Risk factors and outcomes of EC in cirrhosis were not reported in the literature. EC is not a rare infection in cirrhosis patients, and it may predispose to invasive candidiasis and untimely deaths. Alcohol binge, HCC, UGI bleed, ACLF, diabetes, and higher MELD are the independent predictors of EC in cirrhosis. At-risk patients with cirrhosis or those with deglutition symptoms should be rapidly screened and treated for EC. [ABSTRACT FROM AUTHOR]