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Background and Aim: Hepatitis C virus (HCV) treatment fails to achieve sustained virological response at 12 weeks (SVR12) in 5-10 % and requires retreatment with second-line drugs. We report our experience of sofosbuvir/velpatasvir/voxilaprevir use for HCV retreatment in a small cohort of difficult-to-treat Indian patients., Methods: We reviewed our HCV databases to identify the patients who had failed to achieve SVR12 after treatment with sofosbuvir in combination with either daclatasvir, ledipasvir, or velpatasvir with/without ribavirin on one or more occasions. Participants were excluded if they had (i) decompensated cirrhosis, (ii) HIV coinfection or (iii) chronic kidney disease, or (iv) prior organ transplantation. All the participants were treated with sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for 12 weeks. Treatment outcome was categorized as successful or failure if HCV RNA was undetectable or detectable at SVR12, respectively., Results: Fifteen patients (male 67 %; genotype-3 80 %) were included in the analysis. Ten (67 %) had cirrhosis. Five, eight, and two participants had previously failed one, two, and three courses of pegylated-interferon free, sofosbuvir containing direct acting antiviral (DAA) regimens respectively. Fourteen participants had failed to at least one course of the sofosbuvir/velpatasvir combination. Fourteen patients achieved SVR12, and one patient was lost to follow-up. Treatment was successful in 100 % and 93.3 % of per-protocol (PP) and intention to treat (ITT) analyses, respectively., Conclusion: Sofosbuvir/velpatasvir/voxilaprevir combination is an effective second-line therapy in India for difficult-to-treat HCV patients., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: 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., Patients and Methods: 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)., Results: 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)., Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF., Trial Registration No: NCT04238416 (clinicaltrials.gov)., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India., Methods: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC., Results: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P  = 0.034), high albumin (OR 1.91 [1.05-3.48], P  = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P  = 0.020) predicted complete response., Conclusion: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background/aim: Hormonal changes and hepatic osteodystrophy are less often studied complications of cirrhosis. This study describes the variance in hormones and osteodystrophy between Frail and Not frail patients with cirrhosis., Methods: 116 outpatients with cirrhosis were prospectively enrolled in this study. Frailty assessment was done using Liver Frailty Index (LFI). Sociodemographic assessment, anthropometry, nutritional assessment, hormone profile, and dual-energy X-ray absorptiometry scan were done in all patients., Results: 116 patients, predominantly males (100 (86.2%) with mean age of 50.16 years (95% CI, 48.43-51.89) were included. Malnutrition was more common in Frail group as compared to Not frail group. Subjective global assessment (SGA) class-B patients were significantly more in Frail group (37 (74%) vs 3 (4.5%), P  = 0.001). The prevalence of lower parathyroid hormone (PTH) (14 (28%) vs 2 (3%)), testosterone (33 (66%) vs 15 (22.7%)), vitamin D3 (44 (88%) vs 39 (59.1%)), and cortisol (37 (74%) vs 37 (56.1) levels was higher in Frail group ( P < 0.05). The number of patients diagnosed with osteodystrophy (34 (68%) vs 21 (31.8%), P  = 0.001) was significantly higher in Frail group. The marker of osteoclastic activity, β-cross laps, was significantly elevated in the Frail group both in males (736 (655-818) vs 380 (329-432), P  = 0.001) and (females 619 (479-758) vs 313 (83-543), P  = 0.02). Bone mineral density (BMD) at lumbar spine (LS) and neck of femur (NF) had significant correlation with LFI (ρ = 0.60, P  = 0.001 for LS and ρ = 0.59, P  = 0.001 for NF), serum testosterone (ρ = 0.58, P  = 0.001 for LS and ρ = 0.53, P  = 0.001 for NF), β-cross laps (ρ = 0.38, P  = 0.001for LS and ρ = 0.35, P  = 0.000 for NF), vitamin D3 (ρ = 0.23, P  = 0.04 for LS and ρ = 0.25, P  = 0.01 for NF), PTH (ρ = 0.52, P  = 0.001 for LS and ρ = 0.48. P  = 0.001 for NF), and cortisol (ρ = 0.50, P  = 0.001 for LS and ρ = 0.45, P  = 0.001 for NF) levels., Conclusion: This is the first study that highlights the high prevalence of hormonal changes and hepatic osteodystrophy in frail patients with cirrhosis and opens a new dimension for research and target of therapy in this field., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: There is no "gold standard" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis., Methods: 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period., Results: 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4-51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) ( P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4-54.2)], alcohol-related cirrhosis [OR 4.2 (1.1-16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4-2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1-0.4)] scores., Conclusions: LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Spontaneous bacterial peritonitis (SBP) heralds increased mortality in cirrhosis, mandating strategies for prophylaxis. Norfloxacin has been the recommended choice for SBP prevention. However, its use has raised concerns about antibiotic resistance. Rifaximin has been suggested as an alternative. We investigated the efficacy of rifaximin against norfloxacin in primary and secondary prophylaxis of SBP., Methods: In this open-labeled randomized trial, patients with either advanced cirrhosis having ascitic fluid protein levels (<1.5 g/l), Child-Pugh score ≥9 points, serum bilirubin ≥3 mg/dl or impaired renal function (primary prophylaxis group), or those with prior SBP (secondary prophylaxis group) received either norfloxacin (400 mg once daily) or rifaximin (550 mg twice daily). All patients were followed for six months, with the primary endpoint being the development of incident SBP., Results: 142 patients were assessed for eligibility, of which 132 met the enrolment criteria; 12 were lost to follow-up, while 4 discontinued treatment. In patients on primary prophylaxis, occurrence of SBP was similar (14.3% vs. 24.3%, P  = 0.5), whereas in secondary prophylaxis SBP recurrence was lower with rifaximin (7% vs. 39% P  = 0.004). Rifaximin significantly reduced the odds for SBP development in secondary prophylaxis [OR (95% CI0.14 (0.02-0.73; P  = 0.02)]. Patients receiving rifaximin as secondary prophylaxis also had fewer episodes of hepatic encephalopathy (23.1% vs. 51.5%, P  = 0.02). 180-day survival between the arms in either group was similar ( P  = 0.5, P  = 0.2)., Conclusion: In comparison to norfloxacin, rifaximin significantly reduces incident events of SBP, as well as HE when used as a secondary prophylaxis, whereas for primary prophylaxis both have similar effects (NCT03695705)., Clinical Trial Registration: ClinicalTrials.gov number: NCT03695705., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Competing Interests: The authors have none to declare.

Background: Hepatocellular carcinoma (HCC) has variable etiological risk factors. Radiofrequency ablation (RFA) and surgical resection (SR) are frequently used as curative treatment options. In the present study, we assessed the etiological factors and efficacy of RFA and SR in patients with unifocal HCC in a real-life setting., Methods: Of 870 patients with HCC seen over a period of nine years, 785 patients were assessed for stage and etiological risk factors. Of these, 110 (14%) patients with single HCC who were either treated with RFA (n = 72) or SR (n = 38) were evaluated for their outcomes in terms of overall survival (OS) and disease-free survival (DFS) over 3 years., Results: Of 785 patients [median age 60 (range 51-65) years, males (n = 685, 87.3%)] with HCC, viral hepatitis [HBV and HCV with or without alcohol = 502 (63.9%)] was the most common etiology; nonalcoholic steatohepatitis (NASH) and alcohol as an etiology showed increase over the years. About 677 (86.2%) patients had evidence of cirrhosis; NASH and HBV were predominant causes in noncirrhotic patients. Even though the groups were not matched, in 110 patients subjected to either RFA [mean tumor size, 2.2 (1.9-2.8) cm] or SR [mean tumor size, 7.1 (4.8-9.7) cm], tumor progression was observed in 49 (68%) and 16 (42%) patients in RFA and SR groups, respectively, with superior DFS in the SR group ( P < 0.01). Of total 31 deaths, 20 (27.8%) deaths were in the RFA group and 11 (28.9%) in the SR group with no difference in OS at 3 years., Conclusion: Viral hepatitis with or without alcohol is the commonest etiological factor for HCC in Northern India; NASH and alcohol are increasing over the years. In a real-life setting, in patients with unifocal HCC, there is no difference in overall 3-year survival subjected to SR or RFA with better DFS in the SR group., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. 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 and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting., Competing Interests: The authors have none to declare., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Percutaneous ablation is an important part of management strategy for liver tumors. While radiofrequency ablation and microwave ablation are the most widely used ablative techniques, cryoablation (CA) has several technical advantages but has been underused till recently. In this study, we report the initial experience with percutaneous CA of liver tumors., Methods: This was a retrospective evaluation of consecutive patients with liver tumors who underwent percutaneous CA between October 2018 and August 2019. The ablation procedures were performed under combined ultrasound and computed tomography guidance using argon-helium-based CA systems. The baseline tumor characteristics (including size and location), Barcelona Clinic Liver Cancer stage, and Child-Pugh score were recorded. Each patient underwent a follow-up after 1 month and at 3 months subsequently. Technical success, complete response, local tumor progression, and overall survival were evaluated., Results: Nine patients (mean age, 62.4 years, median age, 66 years, five men and four women) with 10 liver tumors (mean size, 2.22 cm) underwent CA. Seven (77.8%) patients had hepatocellular carcinoma (HCC), and 2 patients had solitary liver metastasis. One patient with HCC had two lesions, while the rest had only one lesion. Of the two metastatic lesions, one was from carcinoma of the cervix and the other was from jejunal neuroendocrine tumor. Five tumors were located adjacent to the gallbladder, two lesions were adjacent to the right portal vein, two lesions were subcapsular, and one lesion was adjacent to the stomach. Technical success was achieved in all the patients. Complete response was achieved in 7 (77.8%) patients. The median follow-up period was 7 months (range, 3-12 months). There was no local tumor progression and no death during the follow-up period. No procedure-related complication was seen., Conclusion: Percutaneous CA of hepatic tumors is technically feasible and is a safe and effective ablative technique., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aims: The objective of this study was to compare diagnostic accuracy of elastography point quantification (ElastPQ) with transient elastography (TE) and liver histology for measuring liver stiffness in patients with chronic viral hepatitis (CVH) and nonalcoholic fatty liver disease (NAFLD)., Methods: Thirty-two patients with chronic liver disease (CVH and NAFLD) were evaluated by ElastPQ and TE within 7 days of liver biopsy. Within the CVH group, subgroup analysis was carried out in patients with end-stage renal disease (ESRD) and without ESRD. Area under the receiver operating characteristic (AUROC) curves were calculated for ElastPQ and TE., Results: There were 15 patients with CVH and 17 patients with NAFLD. In the CVH group, there were 8 patients with ESRD and 7 patients without ESRD. Taking liver histopathology as the gold standard, liver stiffness measurement by ElastPQ (ρ = 0.826; P  < 0.0001) and TE (ρ = 0.649; P  < 0.0001) correlated significantly with the stage of fibrosis. AUROCs of ElastPQ and TE for the diagnosis of any fibrosis (F ≥ 1), significant fibrosis (F ≥ 2), and advanced fibrosis (F ≥ 3) were 0.907, 0.959, 0.926 and 0.870, 0.770, 0.881, respectively, in both CVH and NAFLD groups. However, the accuracy of both these techniques was poor in patients with CVH and ESRD (AUROCs for ElastPQ and TE of 0.667 and 0.167 for the diagnosis of significant fibrosis, respectively, and 0.429 and 0.143 for the diagnosis of advanced fibrosis, respectively). The diagnostic accuracy of both ElastPQ and TE for detecting significant fibrosis was excellent in patients with NAFLD (AUROC of 1.000 and 0.936, respectively). ElastPQ was superior to TE in the diagnosis of significant fibrosis in the combined analysis ( P  = 0.0149) and in the CVH group ( P  = 0.0391), while both modalities were comparable in patients of the NAFLD group ( P  = 0.2539)., Conclusion: ElastPQ may be equally accurate as Fibroscan, and large prospective studies are required to validate the same., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic coronavirus disease-19 (COVID-19) that began in Wuhan city, China, in December 2019. Till 14th April, 19,39,801 people have been affected by this virus, of whom 1,20,897 died. Though respiratory symptoms are the typical manifestation of this disease, gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, loss of taste sensation, diarrhea, abdominal pain, and discomfort have been reported. The pooled prevalence of GI symptom is 17.6% (95% confidence interval, 12.3%-24.5%), as indicated in a meta-analysis. A few studies suggested that the presence of GI symptoms is associated with poorer prognosis. The virus is excreted in feces during the acute disease, and even after, the nasopharyngeal swab has become negative for viral ribonucleic acid. Fecal viral excretion may have clinical significance because of possible feco-oral transmission of the infection. Nearly, 10.5%-53% of patients with COVID-19, particularly those with severe disease, have been shown to have an elevation of hepatic enzymes though biochemical and clinical jaundice are uncommon. Knowledge about this disease in general and GI involvement, in particular, is currently evolving., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors., Competing Interests: Dr Subrat K Acharya Has nothing to declare. This consensus statement was written by the members of the Task Force on Acute Liver failure (INASL-ALF Task Force), convened by Indian National Association for the Study of the Liver (INASL), India and was also supported by INASL, India., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background: Renal replacement therapy in the form of either dialysis or transplantation is the only option for end-stage renal disease (ESRD). Blood-borne infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are of special concern in these patients because of their high incidence. Although there are sufficient data from the developed world, there is scarcity of data from developing countries such as India., Methods: All newly diagnosed ESRD patients initiated on hemodialysis after attending the Department of Nephrology, PGIMER, Chandigarh between January 2015 and October 2015 were included in the study. All the subjects were initially screened for HCV and HBV serology status and subsequent HCV and HBV status on follow-up at the end of 6 months and evaluated by standardized precoded questionnaires and biochemical examinations. Univariate and multivariate analyses were done to identify the risk factors for seroconversion., Results: A total of 196 patients were recruited for the study after confirming seronegative status. At the end of 6 months, 61 patients lost to follow-up. Anti-HCV antibody had shown moderate association to HCV RNA testing at the end of 6 months by kappa test. Out of 135, 16.3% seroconverted to HCV RNA positive and 0.7% patient became hepatitis B surface antigen positive. Isolation of dialysis machine and nursing staff was associated with lower seroconversion., Conclusion: In a real-life scenario, HCV seroconversion is observed in 15% of the patients initiated on hemodialysis. Isolation of both dialysis machine and personnel was associated with lower seroconversion., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

[This corrects the article DOI: 10.1016/j.jceh.2019.07.005.]., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Cost-effectiveness analysis (CEA) provides information on how much extra do we need to spend per unit gain in health outcomes with introduction of any new healthcare intervention or treatment as compared to the alternative. This information is crucial to make decision regarding funding any new drug, diagnostic test or determining standard treatment protocol. It becomes even more important to consider this evidence in resource constrained low-income and middle-income country settings. Generating evidence on costs and consequences of a treatment or intervention could be performed in the setting of a randomized controlled trial, which is the perfect platform to evaluate efficacy or effectiveness. However, we argue that randomized controlled trial (RCT) offers an incomplete setting to generate comprehensive data on all costs and consequences for the purpose of a CEA. Hence, it is needed to use a decision model, either in combination with the evidence from RCT or alone. In this article, we demonstrate the application of decision model-based economic evaluation using 2 separate techniques - a decision tree and a Markov model. We argue that application of a decision model allows computation of health benefits in terms of utility-based measure such as a quality-adjusted life year or disability-adjusted life year which is preferred for a CEA, measure distal costs and consequences which are much more downstream to the application of intervention, allows comparison with multiple intervention and comparators, and provides opportunity of making use of evidence from multiple sources rather than a single RCT which may have limited generalizability. This makes the use of such evidence much more acceptable for clinical use and policy relevant., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Cirrhosis leads to considerable morbidity and mortality, compromises quality of life, and often necessitates assistance in activities of daily living. An informal caregiver bears the psychological burden of coping with the needs of the patient and the knowledge of morbid prognosis of a loved one. This aspect is rarely recognized and almost never addressed in a clinical practice., Methods: This cross-sectional study assessed the factors influencing psychological burden of cirrhosis on the caregivers in a predominantly lower-middle socioeconomic class Indian population. Patients underwent psychometric tests [Psychometric Hepatic Encephalopathy Score (PHES)], and questionnaires for quantifying caregiver burden [Perceived Caregiver Burden (PCB) and Zarit Burden Interview (ZBI)] and assessing depression [Beck Depression Inventory (BDI)] and anxiety [Beck Anxiety Inventory (BAI)] were administered., Results: One hundred patients with cirrhosis [70% male, 27% with past hepatic encephalopathy (HE), and 53% with minimal HE] and their caregivers (66% women, 81% spouse, 26.51 years of mean relationship) were evaluated. Caregiver burden scores were higher in patients with previous overt HE than in those without previous overt HE [PCB (74.63 vs . 66.15, P  = 0.001), ZBI (27.93 vs . 21.11, P  = 0.023), BDI (11.63 vs . 8.96, P  = 0.082), and BAI (11.37 vs . 8.12, P  = 0.027)]. Similarly, caregivers of patients with minimal HE had higher caregiver burden that those of patients who did not have minimal HE [PCB (70.74 vs . 65.85, P  = 0.027), ZBI (26 vs . 19.51, P  = 0.015)]. Burden scores correlated well with each other and with liver disease severity scores and negatively correlated with socioeconomic status. Repeated hospital admissions, alcohol as etiology, and lower socioeconomic status were the independent predictors of caregiver burden., Conclusion: Higher perceived burden is common in caregivers of patients with cirrhosis. Repeated hospital admissions, alcoholism, and lower socioeconomic status influence caregiver burden., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

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.)

Aim: The aim of this study was to compare the diagnostic adequacy of computed tomography (CT)-ultrasound (US) fusion image-guided fine needle aspiration (FNA) and US-guided FNA in patients with suspected hepatic metastases., Methods: Thirty consecutive patients of either sex with known or unknown primary malignancy suspected of having liver metastases on both US and CT, whose multiphasic contrast-enhanced computed tomography was performed using a 64-slice or a higher slice CT scanner, and who were referred for percutaneous FNA were included in this prospective study approved by the institutional review board of the study institute. CT-ultrasound fusion image-guided FNA of the largest lesion using electromagnetic tracking and with freehand ultrasound-guided FNA were performed in the same sitting. Value of fitness, which is a rough estimate of how well the fusion has been achieved, was recorded. Diagnostic adequacy of smears was assessed by a scoring system based on cellular material, background blood/clot, degree of cellular degeneration or trauma, and retention of architecture., Results: The size of the lesions ranged from 1 to 10 cm, and the depth of location of the lesions ranged from 1.4 to 9.3 cm. The fusion fitness values ranged from 1.2 to 10 mm. The scores of the smears did not correlate with lesion size, depth of location, and fusion fitness value. Diagnostic adequacy was seen in 90% and 93.3% of lesions sampled by fusion image guidance and ultrasound guidance, respectively (p = 0.655). All the lesions that yielded inadequate smears by fusion guidance were deep-seated lesions (>5 cm). All the lesions that yielded inadequate smears by ultrasound guidance were small lesions (<3 cm). No complications were encountered in any of the patients., Conclusion: Fusion image-guided FNA is a safe procedure with a high diagnostic adequacy rate. Fusion image-guided FNA is not better than US-guided FNA for conspicuous hepatic lesions; however, it may be useful in inconspicuous lesions., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second most common cause of cancer-related mortality worldwide. There are currently no universally accepted practice guidelines for the diagnosis of HCC on imaging owing to the regional differences in epidemiology, target population, diagnostic imaging modalities, and staging and transplant eligibility. Currently available regional and national guidelines include those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver, the Japan Society of Hepatology, the Korean Liver Cancer Study Group, Hong Kong, and the National Comprehensive Cancer Network in the United States. India with its large population and a diverse health infrastructure faces challenges unique to its population in diagnosing HCC. Recently, American Association have introduced a Liver Imaging Reporting and Data System (LIRADS, version 2017, 2018) as an attempt to standardize the acquisition, interpretation, and reporting of liver lesions on imaging and hence improve the coherence between radiologists and clinicians and provide guidance for the management of HCC. The aim of the present consensus was to find a common ground in reporting and interpreting liver lesions pertaining to HCC on imaging keeping LIRADSv2018 in mind., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background: The study aimed at assessing the prevalence and clinical profile of minimal hepatic encephalopathy (MHE) in patients with cirrhosis using neuropsychological assessment and at understanding the management practices of MHE in the Indian clinical setting., Methods: This cross-sectional, clinicoepidemiological study conducted at 20 sites enrolled liver cirrhosis patients with Grade 0 hepatic encephalopathy according to West-Haven Criteria. Patients were subjected to mini-mental state examination and those with a score of ≥24 were assessed using psychometric hepatic encephalopathy score. Short Form-36 questionnaire was administered to assess the impact on health-related quality of life., Results: Of the 1260 enrolled patients, 1114 were included in the analysis. The mean age was 49.5 years and majority were males (901 [81%]). The prevalence of MHE was found to be 59.7% (665/1114) based on the psychometric hepatic encephalopathy score of ≤-5. Alcohol-related liver disease was the most common etiology (482 [43.27%]) followed by viral infection (239 [21.45%]). Past smokers as well as those currently smoking were more likely to have MHE than nonsmokers. A significant association was found between tobacco chewing, smoking, alcohol consumption, diabetes, and the presence of MHE. Multivariable analysis revealed smoking as the only parameter associated with MHE. A total of 300 (26.9%) patients were on prophylaxis with lactulose/lactitol or rifaximin. These patients were less likely to have MHE as compared to those not on prophylaxis (odds ratio, 0.67; 95% confidence interval, 0.50-0.88; P  = 0.005)., Conclusion: The disease burden of MHE is quite substantial in patients with cirrhosis with no apparent cognitive defect. Smoking, whether past or current, has significant association with the presence of MHE. Although MHE has been shown to adversely affect quality of life, prophylaxis for MHE is not routinely practiced in the Indian setting.The study has been registered under clinical trials registry of India (CTRI/2014/01/004306).

Background: Majority of patients of hepatocellular carcinoma (HCC) in India present in advanced stages, when curative treatment options are limited. We undertook this study to assess the cost-effectiveness of treating advanced HCC patients with sorafenib compared with best supportive care (BSC)., Methods: A Markov model was parameterized to model the lifetime costs and consequences of treating advanced HCC patients with sorafenib versus BSC using a societal perspective. Cost of routine care, diagnostics, management of complications in both the arms and management of adverse effects of sorafenib treatment were considered. A probabilistic sensitivity analysis was undertaken to assess the effect of parameter uncertainty., Results: The incremental cost and benefit gained by treating HCC using sorafenib was Indian rupees 94,182 ($1459) and 0.19 quality adjusted life years (QALYs) per patient, implying an incremental cost of Indian rupees 507,520 ($7861) per QALY gained., Conclusions: Sorafenib is not cost-effective for use in advanced hepatocellular carcinoma treatment in India.

Background: Erectile dysfunction(ED) is common in patients with chronic liver disease(CLD). Although it significantly worsens the quality of life, caregivers and researchers often neglect it., Aim: Evaluating the prevalence of ED in patients with CLD, associated factors, and response to therapy with tadalafil, a phosphodiesterase-5 inhibitor., Methods: A total of 60 males with Child-Pugh score between 5 and 10 and no overt hepatic encephalopathy were studied. ED was assessed based on the 15-question International Index of Erectile Function (IIEF) questionnaire. Patients were classified as ED+ if score was <25. Patients with ED were given 10 mg of tadalafil for 4 weeks., Results: The mean age was 45.2 he 7.8 years. The mean Child-Turcotte-Pugh (CTP) score was 6.4 sc 1.7, and model for end-stage liver disease (MELD) score was 12.1 sc 4.5. Twenty-seven (45%) patients had compensated cirrhosis, and 45(75%) had alcohol as etiology. Twenty-five (42%) had an IIEF score <25, suggestive of ED. The IIEF score had significant correlation with the presence of ascites(r = -0.27, P 0.04) and serum creatinine (r -0.26, P  = 0.05); however, there was no correlation with CTP, MELD, or alcohol as etiology. Among ED group, IIEF scores improved significantly with 4 weeks of tadalafil therapy (15.1 ± 5.6 vs 22.0 ± 3.4, P  < 0.001), and 11(44%) had resolution of ED., Conclusion: ED is common in patients with cirrhosis. Tadalafil administration significantly improves ED in these patients.

Background: The selection of a low-risk blood donor involves a dialogue between the trained medical staff and the volunteer blood donor, and this is where the knowledge of the prospective blood donor with regard to the risk factors for acquiring hepatitis B and C and the mode of spread through a blood transfusion is of utmost importance. Therefore, the study was conducted to assess the knowledge and attitude on hepatitis B and C with regard to blood donation, in the existing and the potential donor base., Materials and Methods: This is a cross-sectional study conducted on 4000 participants, including 2000 blood donors and 2000 nondonors. The study tool was a pilot-tested, self-administered questionnaire, content and construct validated using Delphi methodology., Results: The mean age of the study participants was 25.12 ± 8.43 years ranging from 18 to 60 years; 24.64 ± 8.31 years in donors and 25.61 ± 8.55 years in non-donors. The study included 69.8% males and 30.2% females, with 87.5% males and 12.6% females in donors and 52.1% males and 47.9% females in non-donors. Overall knowledge score was 51.02%, being 51.21% in donors and 50.84% in non-donors. Overall attitude score was 47.93%, being 47.09% in donors and 48.77% in non-donors. There was a low degree of significant linear correlation between knowledge and attitude in the study participants., Conclusion: Based on the results obtained in the study, it is evident that neither the existing level of knowledge nor the attitude of both donors and nondonors towards hepatitis B and C is adequate for being able to select a low-risk blood donor.

Gallbladder Carcinoma (GBCA) is the most common biliary tract malignancy. As the disease is often diagnosed clinically in an advanced stage, the survival rates are dismal. Imaging studies allow for an early diagnosis of malignancy, though the findings may be indistinguishable from non-malignant disease processes affecting the gallbladder. Attempts have been made to make a specific diagnosis of GBCA at an early stage on imaging studies. Ultrasonography (US) is the most commonly employed technique for gallbladder evaluation. Gallbladder wall thickening is the most common finding of early GBCA and in this context, US is non-specific. Recently, contrast enhanced ultrasound has been shown to be effective in differentiating benign from malignant disease. Multidetector computed tomography represents the most robust imaging technique in evaluation of GBCA. It provides relatively sensitive evaluation of mural thickening, though it is not entirely specific and issues in differentiating GBCA from xanthogranulomatous cholecystitis do arise. Due to its superior soft tissue resolution, Magnetic Resonance Imaging (MRI) provides excellent delineation of gallbladder and biliary tree involvement. When coupled with functional MRI techniques, such as diffusion-weighted and perfusion imaging, it provides a useful problem solving tool for interrogating the malignant potential of nonspecific gallbladder lesions and detection of metastases. Positron emission tomography has a role in detection of distant metastases and following patients following treatment for malignancy. We review the current role of various imaging modalities in evaluating patients with GBCA.

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.

Approximately 700,000 people die of Hepatocellular Carcinoma (HCC) each year worldwide, making it the third leading cause of cancer related deaths. Rupture is a potentially life-threatening complication of HCC. The incidence of HCC rupture is higher in Asia and Africa than in Europe. In Asia approximately 10% of patients with a diagnosis of HCC die due to rupture each year. Spontaneous rupture is the third most common cause of death due to HCC after tumor progression and liver failure. The diagnosis of rupture in patients without history of cirrhosis or HCC may be difficult. The most common symptom of ruptured HCC is abdominal pain (66-100%). Shock at presentation can be seen in 33-90% of cases; abdominal distension is reported in 33%. Abdominal paracentesis documenting hemoperitoneum is a reliable test to provisionally diagnose rupture of HCC, it can be seen in up to 86% of clinically suspected cases. The diagnoses can be confirmed by computed tomography scan or ultrasonography, or both in 75% of cases. Careful pre-treatment evaluation is essential to decide the best treatment option. Management of ruptured HCC involves multi-disciplinary care where hemostasis remains a primary concern. Earlier studies have reported a mortality rate of 25-75% in the acute phase of ruptured HCC. However, recent studies have reported a significant decrease in the incidence of mortality. There is also a decrease in the incidence of ruptured HCC due to improved surveillance and early detection of HCC. Transarterial Embolization is the least invasive method to effectively induce hemostasis in the acute stage with a success rate of 53-100%. Hepatic resection in the other hand has the advantage of achieving hemostasis and in the same go offers a potentially curative resection in selected patients.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Background and Aims: There is sparse data on the prevalence of renal dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the presence of renal dysfunction in patients with NAFLD and correlate it with the severity of liver disease., Methods: One hundred nonalcoholic patients with ultrasound showing hepatic steatosis were enrolled into the study after exclusion of other causes. Presence of renal dysfunction was estimated by glomerular filtration rate and by evaluating 24 h urinary protein and microalbumin. Various risk factors including components of metabolic syndrome, severity of hepatic steatosis (as assessed on ultrasound), hepatic necro-inflammation (as assessed by hepatic transaminases) and hepatic fibrosis (as assessed by transient elastography) were correlated with the presence of renal dysfunction., Results: Twenty eight (28%) patients with NAFLD had evidence of impaired renal function with 5 (5%) having abnormal glomerular filtration rate, 18 (18%) having significant proteinuria and 5 (5%) having both. Presence of type 2 diabetes mellitus, raised hepatic transaminases and advanced fibrosis on transient elastography were found as independent predictors of impaired renal function with raised hepatic transaminases having the best sensitivity (89%) and presence of advanced fibrosis the best specificity (90%). A model comprising of these three parameters had good accuracy (AUROC = 0.763) in predicting impaired renal function in patients with NAFLD., Conclusions: Around one-third of patients with NAFLD have impaired renal functions. Prevalence of impaired renal function in patients with NAFLD is dependent on the severity of liver disease and presence of diabetes mellitus.