Plasma exchange (PLEX) improves survival in acute liver failure (ALF); however, there is no study specifically analyzing its utility in hepatitis A virus-related ALF (HAV-ALF). A few reports suggest that ALF patients who are not on inotropes tolerate PLEX better. We aimed at comparing the efficacy of PLEX and of standard medical treatment (SMT) to treat HAV-ALF. We retrospectively compared consecutive HAV-ALF patients treated with PLEX (2018–2024) vs. SMT (2011–2024) at 13 centers across India. We compared in-hospital native liver survival in both groups. In the subset of patients not on inotropes, we compared survival and assessed predictors of poor outcome in PLEX and SMT groups. Eighty-four HAV-ALF patients in PLEX group (61 males; age = 23.5 [21–33] years, median [IQR]; King’s College Criteria [KCC] fulfilled = 22 patients, 26.2

BACKGROUND:Patients with liver cirrhosis undergo repeated contrast-enhanced imaging procedures. We investigated the risk factors for contrast-induced acute kidney injury (CI-AKI) in cirrhotic patients with normal renal function. METHODS:A prospective observational cohort study included 110 consecutive patients with cirrhosis who underwent iodinated contrast (IC)-based imaging procedures. Baseline demographic, clinical, and laboratory data and Renal Resistive Index (RRI) were recorded prior to imaging. All patients were assessed for the development of CI-AKI 48-72 hours after contrast administration. RESULTS:A total of 34 (30.9%) patients developed CI-AKI after contrast administration. Prior history of acute kidney injury (AKI) was seen in 18 (52.9%) patients who developed CI-AKI and 4 (5.3%) patients who did not develop CI-AKI (p < 0.001). Alcohol-related liver disease was the major etiological factor of cirrhosis in 18 (52.9%) patients with CI-AKI as opposed to 23 (30.3%) patients without CI-AKI (p = 0.047). Baseline estimated glomerular filtration rate (eGFR) and serum creatinine levels were not associated with an increased risk of CI-AKI. Higher values of baseline RRI were seen in patients who developed CI-AKI. On univariate analysis, gender, prior history of AKI, grade III ascites, hepatic encephalopathy, Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease-Sodium (MELD-Na), and Renal Resistive Index (RRI) were found to be significant risk factors for predicting CI-AKI. On multivariate analysis, Renal Resistive Index (RRI), CTP score, and MELD-Na score were associated with an increased risk of CI-AKI. Preprocedural RRI >0.62, CTP score >10, and MELD-Na >24 had significant predictive value for the occurrence of CI-AKI. CONCLUSION:Advanced liver cirrhosis was associated with an increased risk of CI-AKI. RRI is an easily available and simple radiologic technique to predict the occurrence of CI-AKI among patients with liver cirrhosis with normal renal function tests.

Background/Aims:Despite their high sensitivity, common non-invasive tests (NITs) have relatively lower specificity and are more suited for ruling out advanced fibrosis (F ≥ 3) and cirrhosis (F4). AGILE 3+ and AGILE 4 scores are novel NITs designed to have high specificity for ruling-in advanced fibrosis and cirrhosis, respectively, and reduce the associated grey zone. We validated AGILE 3+ and AGILE 4 in Indian patients with non-alcoholic fatty liver disease (NAFLD) and compared the discriminatory ability, diagnostic performance, and grey zone of AGILE scores with other common NITs. Methods:Data of all NAFLD patients with liver biopsy (n = 381, males: 63.7%, age: 42 [33-50] years) recruited across 35 centres over 4 years (n = 8043) were analysed. Results:AGILE 3+ had sensitivity and specificity of 70% and 89.4%, respectively, with an area under the curve (AUC) of 0.78 (0.74-0.83) for F ≥ 3 which was significantly better than AST-platelet ratio index (APRI), NAFLD Fibrosis Score (NFS), and Fibrosis-4 (FIB-4) but not liver stiffness measurement (LSM). The AUC of AGILE 4 (0.82 (0.77-0.85]) for F4 was significantly better than APRI and NFS but not FIB-4 or LSM, with a sensitivity and specificity of 69.2% and 94.7%, respectively. The proportion of patients falling in the grey zone with AGILE 3+ (12.07%) and AGILE 4 (14.2%) were significantly less than that with APRI, FIB-4, NFS, and LSM. Combined sequential approach using LSM followed by AGILE 3+ had a sensitivity and specificity of 80% and 89.4%, respectively, for F ≥ 3, with a grey zone of 9.1%. Combined sequential approach using LSM followed by AGILE 4 had a sensitivity and specificity of 81.8% and 95%, respectively, for F4, with a grey zone of 12.6%. Conclusion:The AGILE scores have comparable AUC as LSM for detecting advanced fibrosis or cirrhosis with a significantly smaller grey zone. Combined sequential use of LSM followed by the AGILE scores improves sensitivity without compromising specificity or the grey zone.

Background:The association between diabetes mellitus and liver fibrosis is well studied in patients with nonalcoholic fatty liver disease (NAFLD). With the recent change in nomenclature and definition, similar data are not available in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The present study aims to analyse the association of advanced fibrosis (stage 3 or 4 on liver biopsy) and type 2 diabetes mellitus (T2DM) in patients with MASLD. Methods:In an ongoing multicentre study of the Indian Consortium on MASLD(ICOM-D) including 30 centres, data for the last 4 years were analysed for the factors responsible for the histological severity of liver disease in patients with MASLD. Results:The study included 400 biopsy-proven patients with MASLD [mean age 42 ± 11 years, mean BMI 27 ± 9 kg/m2, 258(64.5%) males]. Metabolic syndrome was present in 159(39.7%) of patients, T2DM was present in 93(23.3%) patients. The fibrosis stages were stage 0 in 114(28.5%), 1 in 130(32.5%), 2 in 73(18.3%), 3 in 35(8.8%) and 4 in 48(12%). Patients with advanced fibrosis (versus F0-F2) had higher age (46.6 ± 11.8 years versus 41.4 ± 11.4 years, P = 0.000), higher prevalence of T2DM [32/83, (38.6%) versus 61/317 (19.2%), P = 0.000)], female gender [40/83 (48.2%) versus 102/317 (32.2%), P = 0.010), triglycerides >150 mg/dl [20/83 (24.1%) versus 158/317 (49.8%), P = 0.000)] and lower HDL [64/83 (77.1%) versus 207/317 (65.3%), P = 0.048)]. The multivariate analysis model including age, gender and DM showed that age [OR 1.025 (95% CI 1.001-1.049, P = 0.042] and T2DM [OR 1.943 (95% CI 1.099-3.433, P = 0.022] were significant predictors of advanced fibrosis. A total of 32/93(34.4%) patients with T2DM had advanced fibrosis as compared to 51/307(16.6%) in the non-DM group (P = 0.000). Conclusion:In comparison to those without T2DM, the risk of advanced fibrosis is almost twice in patients with MASLD and type 2 DM. Both higher age and T2DM were associated with advanced fibrosis in patients with MASLD.

Background:A resurgence of hepatitis A virus (HAV) outbreak unfolded in the state of Kerala despite high sanitation and socioeconomic standards. Clinicians observed a possible new emerging phenotype marked by atypical features like persistent fever after the appearance of clinical jaundice, early renal and pulmonary involvement, and hemophagocytic lymphohistiocytosis (HLH). Methods:We conducted a multicenter, hospital-based study across six tertiary care centers, prospectively enrolling patients with serologically confirmed HAV (anti-HAV IgM positive) presenting with acute liver injury. Patients with ≥2 atypical manifestations (persistent fever, acute kidney injury [AKI], HLH, or pulmonary involvement) comprised the a-HAV arm, while outpatients with usual symptoms (u-HAV) served as the comparator. Results:A total of 324 patients (a-HAV: 179, u-HAV: 145) were included (mean age: 32 ± 12.8, 68.2% males). The a-HAV arm had a significantly higher incidence of hepatomegaly (64% vs 44%), splenomegaly (30% vs 17%), ascites (30% vs 9%), encephalopathy (21%), prolonged cholestasis (19%), higher mean levels of total leukocyte count (TLC), bilirubin, aspartate aminotransferase, international normalized ratio (INR), triglycerides, ferritin, and lactate dehydrogenase. Atypical features included continuing fever (93%), pulmonary complications (16.8%), AKI (13.4%), and HLH (12.8%). a-HAV required aggressive therapeutic interventions with higher steroid use (30% vs 4.1%), plasma exchange (21%; mean: 2.68 ± 1.26 cycles, 2240 ± 634.45 mL exchanged), continuous renal replacement therapy (7.8%), and mechanical ventilation (10%). Also, progression to acute-on-chronic liver failure (7.3%), autoantibodies (18%), metabolic acidosis (6.7%), readmissions (9%), and mortality (11.7%) were higher in the a-HAV arm. On multivariable analysis, the model incorporating baseline ammonia (odds ratio [OR]: 1.11), TLC (OR: 2.21), and INR (OR: 7.20) demonstrated the highest discriminative performance for 90-day mortality (area under the receiver operating characteristic curve: 0.994). Genotyping revealed the strain to be of genotype IIIA. Conclusion:The study provides a strong indication regarding the changing clinical presentation and virulence of HAV. Unlike previous outbreaks, a significant number of patients had severe presentations marked by immune dysregulation and multiorgan involvement. Early recognition and tailored management are the keys to improving patient outcomes.

Upper gastrointestinal bleeding is an important gastrointestinal emergency medical condition; however, there is a lack of multi-centre national data on this condition for India. Hence, the Indian Society of Gastroenterology (ISG) constituted a task force on upper gastrointestinal bleeding (UGIB) to collect and create a database representative of every part of India. The aim of this pan-India multi-centre study was to determine the etiology and clinical characteristics of UGIB in India and to identify the risk factors that determine the overall outcome in these patients. In consultation with the members of the task force, a protocol and case record form were developed and members of the ISG were invited to participate in data collection. Overall, 93 centres from different parts of India joined this study. A prospective longitudinal cohort study was designed and data was acquired between October 2014 and September 2018. All 93 participating centres were instructed to recruit patients with UGIB as per the approved protocol. All patients were followed up for 30 days either telephonically or during a hospital visit for re-bleeding rate up to 30 days from the first presentation, requirement for surgery and 30-day mortality. Statistical Package for the Social Sciences (SPSS) software (version 17.0, SPSS, Chicago, IL., USA) was used for all statistical analyses. Of 12,500 patients, 10,564 patients with UGIB were included in this study, 6450 (61.1

BACKGROUND AND AIM:Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of liver-related morbidity and mortality in people living with HIV/AIDS infection (PLHIV), with the advent of newer antiretroviral drugs. However, the metabolic alterations, biochemical analysis, and associated significant fibrosis, when compared to primary MASLD, remain poorly understood. We conducted a study comparing PLHIV with MASLD and primary MASLD subjects. METHODS:We enrolled 120 consecutive PLHIV with MASLD and 120 age- and sex-matched primary MASLD patients based on the MASLD diagnostic criteria. All patients underwent evaluation of metabolic parameters, anthropometric assessment, ultrasonography, and transient elastography. Significant and advanced fibrosis was defined as transient elastography (TE)≥ 8.2 kPa and ≥ 9.7 kPa, respectively. RESULTS:The metabolic risk factors (diabetes mellitus, systemic hypertension, dyslipidemia, and metabolic syndrome) were comparable between the two groups. "Lean" MASLD was more prevalent in the PLHIV group (p<0.001). Hand-grip strength was comparable among groups (p=0.728). Visceral fat (p<0.001), BMI (p<0.001), waist circumference (p<0.001), hip circumference (p<0.001), and waist-hip ratio (p=0.004) were significantly higher in the primary MASLD group. Significant and advanced fibrosis was higher in the PLHIV with MASLD compared to the primary MASLD group (p=0.026). CONCLUSION:Despite having a comparable metabolic profile and lower body fat, PLHIV tends to have conspicuously higher "lean" MASLD and more significant or advanced liver fibrosis compared to primary MASLD. There is an unmet need for active screening and aggressive treatment of PLHIV with MASLD, mainly because they tend to have a higher number of "lean" MASLD.

Background and aim: Acute-on-chronic liver failure (ACLF) is associated with rapid deterioration and very high short-term mortality. In addition to the traditional prognostic indices used in cirrhosis, various agencies have proposed scores to predict the survival of these conditions. This study aimed to compare the accuracy of the five most important prognostic scores in ACLF. Patients and methods: In this prospective observational study, 103 patients diagnosed with ACLF were included based on APASL criteria. Baseline characteristics, CTP, MELD, AARC, CLIF-C OF, and CLIF-C ACLF scores were estimated within 24 hours of admission to the hospital. Mortality after 28 days of admission was assessed on follow-up. The discriminative ability of the scores was primarily assessed using Harrell's concordance index (C-Index) from Cox proportional hazards models. Receiver operating characteristics (ROC) curve analysis was performed as an ancillary evaluation. Results: All patients completed the 28-day follow-up, with an overall mortality of 44.7%. Mortality rates were 9.1% in grade I, 31.4% in grade II, and 100% in grade III ACLF. Among patients who met the EASL-CLIF definition of ACLF (51.4%), the 28-day mortality was 76.1%. Harrell's C index values were: AARC - 0.831 (95% CI: 0.779-0.882), CLIF-C ACLF - 0.796, CLIF-C OF - 0.794, MELD - 0.769, and CTP - 0.673. On ROC analysis, AUROCs for AARC, CLIF-C ACLF, CLIF-C OF, MELD, and CTP scores were 0.876, 0.850, 0.840, 0.821, and 0.696. Differences among AUROCs of AARC, CLIF-C ACLF, CLIF-C OF, and MELD were not statistically significant. AARC score has the highest AUROCs among patients with ACLF defined by the EASL-CLIF definition (0.84) as well as in ACLF caused by alcoholic hepatitis (0.94). Conclusion: Patients with ACLF, defined by APASL criteria, have high short-term mortality. Acute-on-chronic liver failure-specific scores and the MELD score demonstrated useful discriminative ability, with the AARC score showing relatively higher predictive accuracy for short-term survival.

The transition from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a paradigm shift in hepatology, emphasising metabolic dysfunction as the central driver in patients with MASLD. This inclusive terminology, endorsed by over 70 international organisations including the Indian National Association for Study of the Liver (INASL), reduces stigma of ‘fatty and alcohol’ and allows the co-existence of other liver disease etiologies along with MASLD. In the present commentary, we discuss the implications of the adoption of new nomenclature of MASLD on the INASL guidance paper on NAFLD, which was published in 2023, before the Delphi consensus on MASLD.