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Background: Concerns about HBV reactivation (HBVr) have been raised with the introduction of DAA for HCV treatment. The aim of the study was to assess the risk of HBVr in chronic HCV patients during or after DAA., Methods: A cohort of 166 chronic HCV patients who were treated with SOF-based DAA regimens and initially positive for HBcAb total were evaluated; 10 HBsAg-positive, 156 had past HBV exposure (HBsAg-negative/HBcAb-positive). Laboratory investigations, including liver functions tests, HBV-DNA, LSM by Transient elastography, and ARFI together with serum markers of fibrosis; APRI and FIB-4 were done at baseline and after 12 weeks of DAAs therapy. HBV-DNA levels and liver functions were monitored for assessment of HBVr., Results: Virological HBVr was diagnosed by ≥ 1 log10 IU/ml HBV-DNA levels in 2/166 patients (1.2%) among the whole HCV cohort, who were initially positive for HBsAg; 20%. Clinical HBVr (>3 folds liver enzyme elevation) was detected in one patient with virological HBVr. Conversely, none of past HBV-infected patients experienced HBVr. All patients achieved SVR12 and had a significant decline in serum transaminases, bilirubin, APRI, and LSM measurements after HCV eradication., Conclusion: HBVr might be considered after successful eradication of HCV following DAAs therapy, especially among patients who are positive for HBsAg, while past HBV infection does not seem to be a predisposing condition to HBVr., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases with simple steatosis on one end and hepatocellular carcinoma on the other. Although obesity is a known risk factor for NAFLD, individuals with normal body mass index (BMI) also have hepatic fatty infiltration, now termed "lean-NAFLD". It represents a distinct entity with a strong underlying genetic component. The present study aimed to sequence the complete exonic regions of individuals with lean-NAFLD to identify germline causative variants associated with disrupted hepatic fatty acid metabolism, thereby conferring susceptibility to NAFLD., Methods: Whole blood was collected from patients with lean-NAFLD (n = 6; BMI < 23.0 kg/m 2 ) and matched lean controls (n = 2; discovery set). Liver fat was assessed using acoustic radiation force impulse (ARFI) imaging. Patients with ultrasound-detected NAFLD (n = 191) and controls (n = 105) were part of validation set. DNA was isolated, and whole-exome sequencing (WES) was performed in the discovery cohort (Ion Proton™; Ion AmpliSeq™ Exome RDY Kit). Data were analyzed (Ion Reporter software; Life Technologies), and variants identified. Validation of variants was carried out (Taqman probes; Real time-PCR). Student's t test and Fisher's exact test were used to analyze the statistical significance., Results: Although WES identified ∼74,000 variants in individual samples, using various pipelines. variants in genes namely phosphatidylethanolamine N-methyltransferase (PEMT) and oxysterol-binding protein-related protein10 (OSBPL10) that have roles in dietary choline intake and regulation of cholesterol homeostasis, respectively, were identified (discovery set). Furthermore, significant differences were noted in BMI (p = 0.006), waist/hip circumference (p > 0.001), waist/hip ratio (p > 0.001), aspartate aminotransferase (p > 0.001), alanine aminotransferase (p > 0.001), and triglycerides (p = 0.002) between patients and controls. Validation of variants (rs7946-PEMT and rs2290532-OSBPL10) revealed that variant in PEMT but not OSBPL10 gene was associated (p = 0.04) with threefold increased risk of NAFLD in lean individuals., Conclusion: Our results demonstrate the association of rs7946 with lean-NAFLD. WES may be an effective strategy to identify causative variants underlying lean-NAFLD., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Liver diseases occurring during pregnancy can be serious and can progress rapidly, affecting outcomes for both the mother and fetus. They are a common cause of concern to an obstetrician and an important reason for referral to a hepatologist, gastroenterologist, or physician. Liver diseases during pregnancy can be divided into disorders unique to pregnancy, those coincidental with pregnancy, and preexisting liver diseases exacerbated by pregnancy. A rapid differential diagnosis between liver diseases related or unrelated to pregnancy is required so that specialist and urgent management of these conditions can be carried out. Specific Indian guidelines for the management of these patients are lacking. The Indian National Association for the Study of the Liver (INASL) in association with the Federation of Obstetric and Gynaecological Societies of India (FOGSI) had set up a taskforce for development of consensus guidelines for management of patients with liver diseases during pregnancy, relevant to India. For development of these guidelines, a two-day roundtable meeting was held on 26-27 May 2018 in New Delhi, to discuss, debate, and finalize the consensus statements. Only those statements that were unanimously approved by most members of the taskforce were accepted. The primary objective of this review is to present the consensus statements approved jointly by the INASL and FOGSI for diagnosing and managing pregnant women with liver diseases. This article provides an overview of liver diseases occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and the recommended treatment options.

Liver injury due to herbal and dietary supplements are well described in literature and its incidence has been on the rise in the past decade. Labelling an herbal product as non-medicinal and as a supplement precludes protocols needed for testing, trials and marketing criteria. This has led to rampant use of clinically unproven multi-herb-based drugs use for a myriad of lifestyle diseases. In this report, we discuss a new dietary weight loss supplement, Safe Lean™ that was found to be the cause of liver injury in a young obese woman, that resolved after discontinuation, and discuss current literature on component, toxicology and chemical analysis of the offending drug.

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

Hepatitis B virus (HBV) is one of the most common causes of liver cirrhosis and hepatocellular carcinoma. Despite recent strides in pharmacotherapy, complete cure of HBV infection still remains an enigma. The biggest obstacle in HBV therapy is clearance of covalently closed circular deoxyribonucleic acid (cccDNA). We discuss about the role of cccDNA in HBV life cycle, efficacy and shortcomings of currently available antivirals as well as promising novel targets to achieve ideal HBV cure.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

As the liver transplant journey in India reaches substantial numbers and suggests quality technical expertise, it is time to dispassionately look at the big picture, identify problems, and consider corrective measures for the future. Several features characterize the current scenario. Although the proportion of deceased donor liver transplants is increasing, besides major regional imbalances, the activity is heavily loaded in favor of the private sector and live donor transplants. The high costs of the procedure, the poor participation of public hospitals, the lack of a national registry, and outcomes reporting are issues of concern. Organ sharing protocols currently based on chronology or institutional rotation need to move to a more justiciable severity-based system. Several measures can expand the deceased donor pool. The safety of the living donor continues to need close scrutiny and focus. Multiple medical challenges unique to the Indian situation are also being thrown up. Although many of the deficits demand state intervention and policy changes the transplant community needs to take notice and highlight them. The future of liver transplantation in India should move toward a more accountable, equitable, and accessible form. We owe this to our citizens who have shown tremendous faith in us by volunteering to be living donors as well as consenting for deceased donation.

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and childhood. These are autosomal recessive in inheritance. The estimated incidence is about 1 per 50,000 to 1 per 100,000 births, although exact prevalence is not known. These diseases affect both the genders equally and have been reported from all geographical areas. Based on clinical presentation, laboratory findings, liver histology and genetic defect, these are broadly divided into three types-PFIC type 1, PFIC type 2 and PFIC type 3. The defect is in ATP8B1 gene encoding the FIC1 protein, ABCB 11 gene encoding BSEP protein and ABCB4 gene encoding MDR3 protein in PFIC1, 2 and 3 respectively. The basic defect is impaired bile salt secretion in PFIC1/2 whereas in PFIC3, it is reduced biliary phospholipid secretion. The main clinical presentation is in the form of cholestatic jaundice and pruritus. Serum gamma glutamyl transpeptidase (GGT) is normal in patients with PFIC1/2 while it is raised in patients with PFIC3. Treatment includes nutritional support (adequate calories, supplementation of fat soluble vitamins and medium chain triglycerides) and use of medications to relieve pruritus as initial therapy followed by biliary diversion procedures in selected patients. Ultimately liver transplantation is needed in most patients as they develop progressive liver fibrosis, cirrhosis and end stage liver disease. Due to the high risk of developing liver tumors in PFIC2 patients, monitoring is recommended from infancy. Mutation targeted pharmacotherapy, gene therapy and hepatocyte transplantation are being explored as future therapeutic options.

Hepatitis B is one of the major causes of end-stage liver disease and liver cancer worldwide. A number of host and viral factors influence the disease course and outcomes. One such viral factor is hepatitis B virus (HBV) genotypes. There are eight major HBV genotypes described from various geographic regions of the world. Although direct sequencing appears to be the gold standard for HBV genotyping, it is expensive and laborintensive and therefore cannot be applied for routine clinical use. The newer molecular methods including serotyping have made genotyping easier and simple to apply to large number of samples rapidly. The data collected mainly over the last decade have suggested that HBV genotypes may have a bearing over the natural course of the disease and its response to therapy. This review summarizes the available literature and highlights how genotyping could be incorporated into routine clinical practice in order to improve delivery of care to HBV-infected individuals.

Crigler-Najjar syndrome (CN) is a congenital defect in bilirubin conjugation due to complete or partial deficiency of uridine 5'-diphosphate-glucuronosyltransferase (UGT). It is of two types: CN type I and CN type II. Patients with CN type II present with indirect hyperbilirubinemia in adulthood. We report a CN type II with homozygous mutation in UGT1A1 gene. This is the first case report of mutation analysis in CN type II from India.