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Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients.Prospectively collected data from the AARC database were analyzed.Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores.Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT). Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant. The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p

We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I–II in 981 (74.6%) and grades III–IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p

Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-RThirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, RAPASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score 12 may be used as a futility criterion in APASL-ACLF patients.

We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF).We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision.Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p .001) and 12.8% and 10.6% higher than the day 7 MELD for 30-day predictions in validation set (p .001). The XGB model had the highest AUC for 7- and 90-day predictions as well (p .001). Day-7 creatinine, international normalized ratio (INR), circulatory failure, leucocyte count and day-4 sepsis were top features determining the 30-day outcomes. A simple decision tree incorporating creatinine, INR and circulatory failure was able to classify patients into high (~90%), intermediate (~60%) and low risk (~20%) of mortality. A web-based AARC-AI model was developed and validated twice with optimal performance for 30-day predictions.The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.

Background and aims The small bowel has, to date, remained a difficult area to access via endoscopy. The novel motorized power spiral enteroscopy, recently introduced, has more depth of insertion and is of shorter duration. Presented here is a case series of motorized spiral enteroscopies. Methods Motorized spiral enteroscopy is indicated for patients requiring deep enteroscopy (eg, for a diagnosis of obscure GI bleeding, suspected inflammatory bowel disorder) and for therapeutic interventions, such as polypectomy, hemostasis, or stricture dilatation. It is contraindicated in patients who are not eligible for general anesthesia, with perforation, or with coagulopathy and in the pediatric population. The contraindications for the anterograde route are gastroesophageal varices, foregut stenosis, eosinophilic esophagitis, and so on. The retrograde approach is contraindicated in active colitis, anal stenosis, or colonic stricture. Informed consent was sought from all the patients. Results The procedure was successful in 13 of 14 (92.8%) in that the target site was reached or panenteroscopy was confirmed. The diagnoses were stricture and ulcers of the jejunum or ileum. The procedures performed were argon plasma coagulation and stricture dilation. The average duration of anterograde enteroscopy was 61.1 minutes and retrograde enteroscopy was 90 minutes. The major adverse events were hypothermia (3 of 14) and pancreatitis (1 of 14), from which the patients recovered fully. Conclusions Novel motorized power spiral enteroscopy is a great tool in small-bowel diagnostics and therapeutics. Speed and ease add to the attractiveness of the procedure.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

OBJECTIVES Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

The Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology developed this evidence-based practice guideline for management of chronic constipation. A modified Delphi process was used to develop this consensus containing 29 statements, which were generated by electronic voting iteration as well as face to face meeting and review of the supporting literature primarily from India. These statements include 9 on epidemiology, clinical presentation, and diagnostic criteria; 8 on pathophysiology; and the remaining 12 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The members of the consensus team believe that this would be useful for teaching, clinical practice, and research on chronic constipation in India and in other countries with similar spectrum of the disorders.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

Functional gastrointestinal disorders (FGIDs) are disorders of gut-brain interaction. Nearly 40% of individuals globally suffer from FGIDs and have chronic fluctuating symptoms. Of all GI conditions, 30-45% are referable to intestinal motility disorders. Prokinetics act by different mechanisms and are effective in FGIDs with delayed gastric emptying or postprandial distress. When choosing a prokinetic, safety is the primary concern, particularly with regard to the central nervous system and cardiovascular risk. Here, we review the efficacy and safety of prokinetics in functional GI motility disorders and provide expert opinions for the use of prokinetics to manage upper GI motility disorders in the Indian context.

Aim: To study endoscopic collagen spray as a hemostatic agent in peptic ulcer bleeding not controlled by conventional therapy. Methods: In this prospective study, endoscopic collagen spray, VGM’s Haemoseal spray has been used in the treatment of peptic ulcer bleeding, as a single agent or in combination with other agents. Haemoseal Spray Kit consists of air pump, Haemoseal probe, a 7.5 Fr spray catheter, 230 cm in length and a pre-loaded collagen cartridge that contains 5 grams of powder. A maximum of 2 grams is applied depending on the area to be covered. Results: Eighteen consecutive patients, who presented with peptic ulcer bleeding were included. There were sixteen patients with duodenal ulcer and two patients with gastric ulcer. The hemorrhagic ulcers were Forrest classification category Ib in sixteen patients and Ia in two patients. After spraying collagen, the bleeding stopped within seconds in all the patients. Repeat endoscopy after 48 hours showed no rebleeding. One patient had an arterial spurt from duodenal ulcer. Collagen spray was used initially as there was poor visibility. After 24 hours, repeat endoscopy revealed visible vessel with no bleeding. Hemoclipping could be achieved. There were no side effects experienced by the patients. Conclusion: Collagen spray is a safe and effective endoscopic hemostatic agent in treatment of peptic ulcer bleeding not controlled by conventional therapy.

Although chronic hepatitis C virus (HCV) infection affects millions of people in India, few studies have assessed host, viral, and disease characteristics of chronically infected patients at national and regional levels. Such information is critical to support large scale screening and treatment initiatives for chronic HCV infection in India. Patients with known chronic HCV infection making routine or for-cause visits to the participating study centers were enrolled in this observational study. Patients attended a single outpatient visit during which demographics and medical history were collected, a physical examination was performed, and blood and urine samples were collected for laboratory assessments. Samples were analyzed to determine HCV genotypes and subtypes, and genotypes of interferon lambda 3 (IFNL3) single nucleotide polymorphism. No therapeutic interventions were administered. We enrolled 500 patients at 19 centers, categorized into four geographic regions (North, South, East, and West). All patients self-identified as Indian, and most (66 %) were male. Genotype 3 was the most common genotype overall (54 %); however, its prevalence varied greatly by region, ranging from 34 % in the South to 69 % in the East. Genotypes 1 (24 %) and 4 (6 %) were the next most common, and HCV genotype could not be determined for 16 % of patients. This prospective survey suggests that demographics, viral, and host factors in patients with chronic HCV infection are highly variable in India and pose significant challenges for the implementation of broad-scale screening and treatment initiatives.

Interferon treatment is the established option for the treatment of patients with chronic hepatitis B without decompensated liver disease. However, such treatment is expensive. We report here our data of a multi-center, open-label trial of the use of an indigenously produced interferon in the treatment of chronic HBeAg-positive chronic hepatitis B. Adult patients with chronic HBeAg-positive hepatitis B with elevated serum transaminase activity and positive serum HBV DNA test were treated with 5 MU/day of an indigenously produced interferon (Shanferon; Shantha Biotechnics, Hyderabad, India) for 4 months, and were then followed up for 6 months. Of the 39 patients enrolled, 36 completed the treatment and 33 completed the post-treatment follow-up. Of the 33 patients who completed the study, end-of-treatment biochemical and virological responses were observed in 10 (30%) and 5 (15%) respectively. Sustained biochemical and virological responses were observed in 15 (45%) and 7 (21%), patients respectively. Adverse effects led to the discontinuation of treatment in only one patient. Our data suggest that safety and efficacy of the indigenously produced interferon were similar to those previously reported results with interferon from other sources.

Phylogenetic analysis of the sequences of the 5′ noncoding regions (5′NCR) of 149 samples from hepatitis C virus (HCV) RNA-positive chronic carriers representing northern, southern, eastern, and western India showed that type 3 and type 1 are the predominant genotypes circulating in India, with an overall prevalence of 53.69 and 38.25%, respectively. Type 4 viruses (6.04%) were seen only in southern India. Sequence analysis of the core region of 51 of the above isolates enabled us to classify them further into subtypes as 1b (number of isolates [ n ] = 10), 1a ( n = 6), 3a ( n = 9), 3g ( n = 14), 3f ( n = 1), and 4d ( n = 3). Three new subtypes were identified for the first time and designated as 3i ( n = 5), 3j ( n = 2), and 6l ( n = 1). Sequencing the 5′NCR could differentiate HCV types, whereas classification at the level of subtype was possible with sequence analysis of the core region.