Background and Aim MASLD affects 30–38% of Indian adults, yet the contribution of genetic risk variants to disease susceptibility and fibrosis progression remains poorly characterised. We investigated the association of 12 candidate SNPs with MASLD susceptibility and fibrosis severity in North Indian patients, benchmarking allele frequencies against IndiGenomes and global populations. Methods Sixty-nine MASLD patients (75.4% male; median BMI 29.8 kg/m2) from a tertiary care liver clinic in New Delhi were genotyped for 12 SNPs using Illumina custom BeadChip array and Sanger sequencing. Patients were stratified by liver stiffness measurement (LSM): significant fibrosis (≥8 kPa, n=38) versus no significant fibrosis (<8 kPa, n=31). Allele frequencies were compared with IndiGenomes (∼1,020 Indian individuals) and 1000 Genomes populations. Results PNPLA3 rs738409 G allele was the strongest within-cohort predictor of significant fibrosis (allelic OR 2.89, 95% CI 1.35–6.19, P=0.006; dominant model OR 3.94, P=0.008), with carriers demonstrating higher LSM (median 15.6 vs. 7.5 kPa, P=0.005). SAMM50 rs3761472 (OR 2.12, P=0.065) and FTO rs9939609 (OR 2.08, P=0.089) showed non-significant trends. In the population-level comparison, APOC3 rs2854116 T allele was the only variant significantly enriched after Bonferroni correction (64.0% vs. 47.9%; OR 1.93, 95% CI 1.35–2.77, P<0.001), followed by PNPLA3 (33.3% vs. 24.1%, OR 1.57, P=0.019) and SAMM50 (31.2% vs. 22.6%, OR 1.55, P=0.028). Notably, APOC3 showed no association with fibrosis (OR 0.96, P=1.000), suggesting a role in susceptibility rather than progression. All SNPs were in Hardy-Weinberg equilibrium. Conclusions In this exploratory cohort of North Indian MASLD patients, we observe a dissociation between genetic determinants of disease susceptibility and fibrosis progression. APOC3 rs2854116 is enriched relative to the Indian population reference, suggesting a potential susceptibility association, while PNPLA3 rs738409 is associated with fibrosis severity within established disease. These hypothesis-generating findings underscore the need for validation in larger, matched cohorts and support ancestry-specific approaches to genetic risk stratification in Indian MASLD.

Liver stiffness measurement (LSM) is a non-invasive surrogate for hepatic fibrosis that informs risk stratification and management. Vibration-controlled transient elastography (VCTE; FibroScan®) is well established. Endoscopic ultrasound–guided shear wave elastography (EUS-SWE) offers the potential to assess LSM during routine EUS; however, its diagnostic performance remains uncertain. In this prospective, single-center diagnostic accuracy study, consecutive adults without biliary obstruction who were undergoing EUS additionally underwent LSM measurement from the right hepatic lobe using EUS-SWE (Olympus ME3) and same-day VCTE. VCTE thresholds defined advanced chronic liver disease (ACLD; > 15 kPa), cirrhosis (> 12 kPa), and advanced fibrosis (> 8 kPa). EUS-SWE performance was evaluated using correlation, Bland–Altman agreement, and area under the receiver-operating characteristic curve (AUROC). Among 146 patients (median VCTE-LSM 6.05 kPa, range 3–53.3), 57, 41, and 31 had LSM ≥ 8, ≥ 12, and ≥ 15 kPa, respectively. EUS-SWE showed moderate correlation with VCTE (Spearman ρ = 0.65, p < 0.001) and reported higher values by 34.1

Epiphrenic diverticula (ED) are rare outpouchings of the lower esophagus, usually occurring due to abnormal esophageal muscle activity. Although high-resolution manometry (HRM) has significantly improved our understanding of the underlying motor abnormalities, a comprehensive overview of HRM findings in these patients is still lacking. We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, based on a pre-registered protocol (PROSPERO: CRD42021233228). PubMed, Web of Science, and Scopus were comprehensively searched from inception through May 31, 2025, for studies reporting HRM findings in adult patients with epiphrenic diverticula. Data were collected on patient demographics, diverticulum features, manometric metrics, and Chicago Classification diagnoses. Risk of bias was evaluated with the Joanna Briggs Institute appraisal tools. Due to significant heterogeneity in clinical and methodological aspects across studies, results were summarized narratively, rather than through meta-analysis. Twenty studies involving 226 patients with ED who underwent HRM during the evaluation of suspected esophageal motility disorders met the inclusion criteria. Abnormal HRM results were observed in 191 patients (84.5%). Achalasia was the most common diagnosis in 114 patients (50%), followed by hypercontractile esophagus in 20 patients (9%), esophagogastric junction outflow obstruction in 14 patients (6%), and distal esophageal spasm in 9 patients (4%), which together made up the main categories. About one in seven patients had normal motility. Some studies suggested a potential link between larger diverticula and higher lower esophageal sphincter pressures or spastic motility patterns; however, due to limited and varied data, consistent correlations could not be confirmed. This review demonstrates that abnormal high-resolution manometric findings are frequently reported among patients with ED undergoing evaluation for esophageal symptoms, with obstructive motility disorders, particularly achalasia being the predominant diagnoses. These findings support routine HRM as part of the pre-treatment evaluation of patients with ED.

As the global burden of cirrhosis shifts toward metabolic dysfunction-associated steatotic liver disease (MASLD), diabetes and metabolic syndrome act as key upstream drivers of liver injury. At the same time, diabetes is increasingly recognized even in cirrhosis of non-metabolic etiologies, including viral hepatitis, reflecting both shared risk factors and cirrhosis-related disturbances in glucose homeostasis. This coexistence amplifies morbidity, mortality, and therapeutic complexity, while conventional diabetes paradigms often prove inadequate in management of cirrhosis. This review synthesizes current evidence and proposes a pragmatic framework for managing diabetes across the full spectrum of cirrhosis. We examine the evolving concept of hepatogenous diabetes, limitations of HbA1c in advanced liver disease, and the complementary roles of oral glucose tolerance testing and continuous glucose monitoring in improving diagnostic accuracy. The pharmacologic landscape is critically evaluated, integrating contemporary diabetes guidelines with hepatic stage-specific considerations. Metformin remains the backbone of therapy in compensated cirrhosis. Among newer agents, GLP-1 receptor agonists and SGLT2 inhibitors show promise in compensated disease, particularly in patients with MASLD and cardio-renal comorbidities. In contrast, sulfonylureas, insulin secretagogues, and agents associated with fluid retention require caution or avoidance as hepatic reserve declines. Insulin therapy remains the cornerstone in decompensated cirrhosis and during hospitalization, where conservative dosing and dynamic titration are essential to minimize hypoglycemia. The review emphasizes nutritional optimization, frequent reassessment, and coordinated hepatology-endocrinology care. As diabetes in cirrhosis increasingly reflects the convergence of two metabolic disorders, management must prioritize hepatic safety, metabolic stability, and individualized outcomes over rigid glycemic targets.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory disorder. It is a highly heterogeneous entity, having a wide range of presentations from asymptomatic chronic hepatitis to cirrhosis and acute liver failure. In consonance with the variabilities in presentation, there are also variations in response to treatment, depending on disease phenotype, presentation, extent of fibrosis, and the presence of comorbidities. In addition, pediatric AIH and AIH postliver transplant have their individual nuances. Addressing such areas to identify strategies for best practices is an unmet goal in this population of "difficult to treat" AIH. While established guidelines exist for AIH overall, specific guidance documents for phenotypes of difficult-to-treat AIH are lacking. The current document provides consensus-based guidance statements on definitions and criteria for determining difficult-to-treat AIH, encompassing the spectrum from acute AIH to AIH with compensated and decompensated cirrhosis, drug-induced autoimmune-like hepatitis, overlap syndromes, AIH in the presence of pregnancy, unique populations of pediatrics and postliver transplant AIH, and the impact of concomitant comorbidities.

Mucinous cystic neoplasms of the liver (MCN-L) are rare cystic tumors defined by the presence of ovarian-type subepithelial stroma beneath mucin-secreting epithelium and carry a risk of malignant transformation, necessitating complete surgical excision. Giant MCN-L lesions are exceptionally uncommon, and data regarding minimally invasive management of such large tumors remain limited. A 44-year-old woman (American Society of Anesthesiologists I) presented with a six-month history of progressive right-sided abdominal fullness. Contrast-enhanced computed tomography revealed a large 27 × 18 × 19 cm thin-walled, unilocular cystic lesion arising from the posterior segments of the right hepatic lobe, extending into the pelvis. Laboratory investigations demonstrated microcytic hypochromic anemia (hemoglobin 9.6 g/dL), with preserved liver and renal function. Serum tumor markers showed carcinoembryonic antigen of 0.70 ng/mL, carbohydrate antigen 19-9 of 11.33 U/mL, cancer antigen-125 of 13.3 U/mL, and alpha-fetoprotein of 9.27 ng/mL. Hydatid serology was negative. The patient underwent laparoscopic right posterior sectionectomy (segments VI and VII) with cholecystectomy. Approximately 4.5 L of clear fluid was aspirated in a controlled manner to decompress the cyst and improve operative exposure. Complete excision of the cyst-replaced posterior sector was achieved. The operative time was approximately 210 minutes with an estimated blood loss of 150 mL. Histopathological examination confirmed mucinous cystic neoplasm with mucin-secreting epithelium (cytokeratin 7 positive, cytokeratin 20 negative) and characteristic ovarian-type stroma expressing estrogen and progesterone receptors, without dysplasia or malignancy. The postoperative course was uneventful, and the patient was discharged in stable condition. At one-year follow-up, there was no evidence of recurrence. This case highlights that laparoscopic right posterior sectionectomy is feasible for giant MCN-L, even when the lesion exceeds 25 cm, provided careful decompression and appropriate surgical expertise are available. At 27 cm, this represents one of the largest MCN-L successfully managed using a purely laparoscopic approach. Complete excision remains essential due to the malignant potential of these lesions.

INTRODUCTION:With the rising burden of obesity in India, accurate assessment of body and visceral fat has become essential for risk stratification and monitoring treatment response, both in clinics and at home. Bioelectrical impedance analysis (BIA) offers a practical alternative to advanced imaging-based methods such as dual-energy X-ray absorptiometry (DEXA) or magnetic resonance imaging (MRI), which, while precise, are expensive and not widely accessible. Among BIA devices, the InBody 770 is regarded as a clinical reference standard, but its high cost and large size restrict routine use. Portable and affordable BIA devices provide a potential solution, but their accuracy requires validation against established methods. PATIENTS AND METHODS:This cross-sectional study was conducted at the Fatty Liver and Obesity Clinic, Sir Ganga Ram Hospital, New Delhi, which manages patients with obesity, diabetes, and related metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). A total of 343 consecutive adults underwent body and visceral fat measurement using both the portable Omron HBF-702T and the InBody 770 devices. Agreement between the two devices was assessed using Pearson correlation coefficients and Bland-Altman plots, with subgroup analyses by gender and body mass index (BMI). RESULTS:The mean age of participants was 45 years, and 76.7% were male. Omron demonstrated excellent correlation with InBody 770 for total body fat percentage (r = 0.91). Subgroup analysis showed consistently high correlations in males (r = 0.87) and in patients with BMI ≥30 (r = 0.90). For visceral fat, Omron showed a good overall correlation (r = 0.73) but weaker performance in females (r = 0.68) and patients with BMI <30 (r = 0.40). CONCLUSION:The portable BIA device Omron HBF-702T provides reliable estimates of total body fat, comparable to the InBody 770, in individuals with obesity and diabetes. Visceral fat estimation shows variability in certain subgroups, particularly females and those with lower BMI. Despite these limitations, the Omron remains a practical and affordable tool for routine monitoring in both clinics and homes, especially relevant in the era of lifestyle interventions and glucagon-like peptide-1 (GLP-1)-based therapies.

BackgroundNonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), represent an increasing clinical and public health burden in India. Despite their high prevalence, there are limited data on their diagnostic and management approaches among Indian health care providers. Real-world evidence on how Indian gastroenterologists and hepatologists diagnose and manage these conditions remains limited. ObjectiveThis study aimed to understand the current disease perspectives, diagnostic modalities, and management practices for NAFLD and NASH among Indian hepatologists and gastroenterologists. MethodsA nationwide, web-based cross-sectional survey was conducted online between May 2023 and July 2023 among practicing gastroenterologists and hepatologists from health care setups, clinics, and hospitals located across India. The structured, self-administered questionnaire included 34 items covering 3 domains: disease perspectives (n=16), diagnostic modalities (n=4), and management strategies (n=14). Descriptive statistics were used to summarize responses as counts and percentages. ResultsA total of 609 physicians completed the online survey (gastroenterologists: n=556, 91.3%; hepatologists: n=53, 8.7%). For 336 (55.2%) physicians, NAFLD accounted for 25% to 50% of the patients consulted per month, and 220 (36.1%) physicians reported that 10% to 20% of patients with NAFLD had NASH. Obesity (n=583, 95.7%) and diabetes (n=579, 95.1%) were cited as leading risk factors for NAFLD. Transient elastography was the diagnostic tool preferred by 558 (91.6%) physicians, followed by NAFLD fibrosis score (n=378, 62.1%) and Fibrosis-4 score (n=356, 58.5%); only 154 (25.3%) physicians used liver biopsy. For treatment, 414 (68%) physicians managed patients using pharmacotherapy and dietary and lifestyle modifications, while 195 (32%) relied on lifestyle modification alone. Antioxidant vitamins (n=543, 89.2%) and saroglitazar (n=522, 85.7%) were the most frequently prescribed therapies. The main barriers to optimal NASH management reported were lack of patient awareness (n=466, 76.5%) and limited availability of effective pharmacological options (n=303, 49.8%). ConclusionsThis large, nationwide survey highlights that NAFLD and NASH constitute a major part of gastroenterology and hepatology practice in India. Although transient elastography and pharmacological agents such as saroglitazar and vitamin E are widely used, considerable heterogeneity exists in diagnostic and management approaches. The lack of patient awareness and effective treatment options remain the major hurdles in managing NAFLD and NASH. These findings underscore the need for the wider implementation of existing India-specific consensus recommendations, continued physician education, and future research focusing on tailored interventions in the management of NAFLD and NASH for the Indian population.

Aims and Background: Endoscopic submucosal dissection (ESD) is an effective alternative to surgery for early gastrointestinal (GI) cancers. Curative and non-curative ESD criteria are primarily derived from high-volume centres within structured screening programs, where pathological assessment guides post-resection management. However, real-world validation of these criteria in routine clinical practice, particularly in centres with evolving ESD expertise, remains limited. We evaluated outcomes of ESD-treated early GI cancers using standard guideline-defined curative criteria in a tertiary-care centre in India. Methods: This retrospective descriptive study included patients with early epithelial GI cancers (pTis–pT1) treated by ESD a tertiary care centre. Resected specimens were processed using International Collaboration on Cancer Reporting datasets and classified as curative or non-curative according to European Society of Gastrointestinal Endoscopy and Japan Gastroenterological Endoscopy Society criteria. Clinical outcomes, additional therapy, follow-up status analysed. Results: Seventeen early GI cancers underwent ESD, with en-bloc resection achieved in 88%. After excluding two indeterminate resections, curative ESD was achieved in 60% (9/15). Median follow-up was 18 months (range 6–36 months). All patients with curative ESD remained disease-free without additional therapy. Non-curative ESD occurred in 40% (6/15), leading to additional surgery or locoregional therapy in 29% (5/17). Residual tumour was identified in three patients, and lymph node metastasis was detected in one patient despite absence of residual primary tumour. Conclusions: Application of standard guideline-based curative criteria in routine Indian clinical practice reliably predicted outcomes and guided post-resection management, supporting the generalizability of established ESD decision frameworks beyond expert screening-based settings.

Background:Type 2 diabetes (T2D) is closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the burden of clinically significant and advanced liver fibrosis, including cirrhosis, from community-based Indian populations remains poorly defined, with most prior studies limited by small size, referral bias, or single-centre design. Methods:The DiaFib-Liver Study was a cross-sectional investigation conducted between January and July 2024 across multiple centres in India. Consecutive adults with T2D, asymptomatic for liver disease, who had undergone vibration-controlled transient elastography (VCTE) within the preceding six months were enrolled by diabetologists and endocrinologists across India. Patients with competing liver diseases or hepatology referrals were excluded. Liver stiffness measurement (LSM) thresholds defined clinically significant fibrosis (≥8.0 kPa), advanced fibrosis (≥10.0 kPa), and probable cirrhosis (≥15.0 kPa). Hepatic steatosis was assessed using the controlled attenuation parameter (CAP), with CAP ≥248 dB/m used to define steatosis. Predictors of clinically significant fibrosis were assessed with multivariable logistic regression. Findings:A total of 9202 adults with T2D were included (mean age 53.3 years [SD 11.8]; 61% [5617/9202] male). Overall, 26% (2433/9202) had clinically significant fibrosis, 14% (1289/9202) advanced fibrosis, and 5% (491/9202) had LSM values consistent with probable cirrhosis (≥15.0 kPa). Among participants with CAP data, 65% (5289/8136) had CAP-defined hepatic steatosis (CAP ≥248 dB/m). Importantly, 13% (370/2847) of patients without steatosis (CAP <248 dB/m) already had clinically significant fibrosis, including 4% (107/2847) with probable cirrhosis (LSM ≥15.0 kPa). Independent predictors of clinically significant fibrosis included obesity (OR 1.98, 95% CI 1.80-2.19), dyslipidaemia (OR 1.21, 95% CI 1.10-1.34), reduced eGFR (OR 1.23, 95% CI 1.02-1.49), and diabetes duration ≥10 years (OR 1.12, 95% CI 1.00-1.24). Regional variation was evident, with prevalence ranging from 21% (256/1241) in central to 30% (643/2126) in southern India. Among non-obese patients (BMI <25), 19% (752/3996) had clinically significant fibrosis, with age as the only independent predictor. Interpretation:One in four adults with T2D in India has clinically significant liver fibrosis and one in twenty already has probable cirrhosis based on elastography thresholds, establishing advanced liver disease as a "fourth major complication" of diabetes. Fibrosis-not steatosis-should be the focus of systematic assessment in diabetes care. These findings highlight the urgent need to integrate fibrosis screening into national diabetes programs. Prospective outcome studies and cost-effectiveness analyses are warranted to inform strategies for MASLD in T2D. Funding:This study did not receive any funding.

Background: Portal hypertension is a major consequence of liver cirrhosis and leads to the development of esophageal varices, whichare associated with significant morbidity and mortality. Upper gastrointestinal endoscopy (UGIE) remains the gold standard for diagnosis;however, it is invasive, costly, and not universally accessible. Non-invasive predictors such as the liver stiffness–platelet count–spleensize score (LSPS) have emerged as promising alternatives for predicting esophageal varices. Objectives: To evaluate the correlation between LSPS and the grading of esophageal varices in patients with liver cirrhosis and to assessthe utility of LSPS as a non-invasive tool for risk stratification. Methods: This cross-sectional observational study was conducted in the Department of Medicine, Government Medical College and Rajindra Hospital, Patiala. One hundred adult patients with liver cirrhosis confirmed clinically, biochemically, radiologically, and bytransient elastography (FibroScan® liver stiffness measurement ≥12.5 kPa) were included. Liver stiffness measurement, spleen bipolardiameter, platelet count, and upper gastrointestinal endoscopy findings were recorded. LSPS was calculated using the formula: liverstiffness (kPa) × spleen diameter (cm) / platelet count (×10⁹/L). Statistical analysis included chi-square test, t-test, and ANOVA. Results: The mean age of participants was 49.4 ± 13.4 years, with male predominance (68%). Alcohol-related cirrhosis was the mostcommon etiology (32%), followed by hepatitis C infection and metabolic associated steatohepatitis (20% each). Esophageal variceswere present in 52% of patients, including Grade 1 varices in 32%, Grade 2 in 12%, and Grade 3 in 8%. High-risk varices were identified in20% of patients. Mean LSPS among study participants was 1.72 ± 1.43. Patients with higher grades of esophageal varices demonstratedsignificantly elevated LSPS values. LSPS showed a positive correlation with variceal grade and effectively identified patients with highriskvarices. Conclusion: LSPS is a simple, reliable, and non-invasive predictor of esophageal varices and correlates positively with variceal severityin cirrhotic patients. It may serve as a useful screening and risk stratification tool, especially in resource-limited settings, potentiallyreducing unnecessary endoscopic procedures.

Acute-on-chronic liver failure (ACLF) is a severe syndrome in patients with chronic liver disease, marked by rapid multi-organ failure and high short-term mortality. Managing ACLF requires intensive care, but standardized global guidelines were previously lacking. The APASL ACLF Research Consortium (AARC) developed this position paper to establish a unified, evidence-based consensus for its critical care management. A global collaboration of 109 experts employed a systematic methodology to address key aspects of ACLF care. Sections were drafted by specialist teams, with recommendations developed using the GRADE system. Draft statements underwent iterative review and refinement, followed by an expert panel consensus process consisting of open show-of-hands voting during the APASL Annual Conference in March 2025 in Beijing and a subsequent anonymous online voting round. The consensus delivers 104 position statements. Key recommendations include using prognostic scores (AARC, CLIF-C ACLF, GIC) for ICU transfer and treatment decisions, and aggressively managing precipitating factors or complications like infections. It details organ-specific support for liver, kidney, and brain failure, advocating for early, targeted antibiotics and careful fluid management. The role of bridging therapies (plasma exchange, artificial liver systems) and nutritional support is emphasized. For transplantation, the guidelines provide criteria for patient selection and timing, particularly for alcohol-related ACLF. The APASL ACLF Beijing Position Paper provides a comprehensive, standardized framework for managing critically sick ACLF patients. Integrating multidisciplinary expertise and current evidence, these guidelines aim to optimize care, inform clinical decisions, and improve survival for this high-risk population. As a few recommendations are supported predominantly by data from different continents, they should therefore be interpreted in local contexts.