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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.

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 (

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.

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.

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

BACKGROUND Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P

Background and aims Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality in those with hepatic encephalopathy (HE). Polyethylene glycol (PEG) 3350 electrolyte solution can ensure rapid gut catharsis, which may resolve HE more effectively than lactulose. In this open-label-randomized trial, we compared PEG+lactulose versus lactulose alone in ACLF with HE grade ≥2 for efficacy and outcome. Patients and methods Patients were randomized to receive PEG (2 L q12 h) followed by lactulose (30 mL q8 h) or standard medical treatment [SMT, lactulose (titrated 30 mL q8 h)]. Endpoints were HE grade improvement at 24 hours, 48 hours, and 7 days using hepatic encephalopathy scoring algorithm (HESA), ammonia reduction, HE resolution, and survival benefit. Results Of 60 patients, 29 were randomized to PEG+lactulose arm and 31 to SMT. In the PEG arm, early reduction in HESA score was noted in more persons [18 (62.1%) vs. 10 (32.2%); P=0.021] with a shorter median time to HE resolution [4.5 (3 to 9) d vs. 9 (8 to 11) d; P=0.023]. On multivariate analysis, age [hazard ratio (HR),1.06 (1.00 to 1.13); P=0.03], HESA score [HR, 6.01 (1.27 to 28.5); P=0.024], and model for end-stage liver disease [HR, 1.26 (1.01 to 1.53); P=0.022] were predictors of mortality at 28 days. Ammonia level or reduction did not correlate with HE grades. Adverse events included excessive diarrhea (20.6% vs. 9.6%) in the PEG and SMT arms, albeit without dyselectrolytemia or worsened renal function. In the PEG versus SMT arm, survival at 28 days were 93.1% versus 67.7% (P=0.010) and at 90 days was 68.9% versus 48.3% (P=0.940), respectively, with fewer persons relapsing with HE in the PEG arm. Conclusions PEG resulted in early and sustained HE resolution with improved short-term survival making, it a suitable and safe drug in patients with acute HE in ACLF.

Background and Aim Innate immune disarray is a key component in the development and progression of acute on chronic liver failure (ACLF) and predisposition to infections. We evaluated the neutrophil dysfunction and its impact on outcomes in patients with ACLF. Methods Forty patients with acute decompensation of cirrhosis (10 each of grades 0, 1, 2, and 3 ACLF) and 10 healthy controls were prospectively evaluated for neutrophil immunophenotype (NP), neutrophil phagocytic capacity (NPC), and oxidative burst (OB) in both resting and stimulated conditions. The patients were followed up for 90 days or until death or transplant, whichever was earlier. Results NP was normal (in %) and NPC (in mean fluorescence intensity [MFI]) was better in controls compared to patients with ACLF (83.74 ± 12.38 vs 63.84 ± 22.98; P = 0.007 and 98.33 ± 130.60 vs 18.73 ± 17.88, P = 0.001, respectively). Resting OB was higher in patients with ACLF compared to controls (97 ± 4.9% vs 91 ± 9%; P = 0.034), but it failed to increase further after stimulation, suggesting an immune exhaustion. NP was normal (in %) and NPC (in MFI) was better in 90‐day survivors compared to nonsurvivors (78 ± 11.9 vs 62.2 ± 24.11, P = 0.02 and 33.3 ± 22.7 vs 16.36 ± 13.3; P = 0.004, respectively). Phenotypically normal neutrophils >71.7% had 78.6% sensitivity and 65.4% specificity with an area under receiver operating curve (AUROC) of 0.70 (95% confidence interval [CI]: 0.55–0.90); P = 0.017, and NPC >17.32. MFI had 71.4% sensitivity and 69.6% specificity with an AUROC of 0.73 (95% CI: 0.54–0.86), P = 0.035, in predicting 90‐day survival. Conclusion Neutrophils have impaired bactericidal function in patients with ACLF compared to healthy adults. Neutrophil phenotype and phagocytic capacity may be used to predict 90‐day survival in patients with ACLF., Neutrophils have impaired bactericidal function in patients with ACLF as compared to healthy adults. Neutrophil phenotype and phagocytic capacity may be used to predict 90‐day survival in patients with ACLF.

Aim of the study Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encepha-lopathy (HE). We compared the usefulness of the Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) for the diagnosis of MHE and the prediction of the development of overt episodes of HE. Material and methods 103 consecutive patients with liver cirrhosis without overt HE were subjected to PHES and ANT evaluation. The receiver-operating characteristic curve was used to determine the optimum cut-off of the ANT value for the diagnosis of MHE. Results Thirty-seven (35.9%) patients had MHE as assessed by altered PHES. ANT (< 14) was positive in 36 (34.95%) patients with MHE with a sensitivity of 89.19% and specificity of 95.7%, positive predictive value (PPV) of 91.67%, negative predictive value (NPV) of 94.03% and diagnostic accuracy of 93.20%. The area under the curve for diagnosis of MHE was 0.978 (95% CI: 0.954-1.0). MHE patients had significantly lower ANT as compared to non-MHE patients and controls (10.81 ±0.324 vs. 15.27 ±0.147 vs. 15.78 ±0.192, respectively, p = 0.01). ANT correlated with PHES (r = 0.752, p = 0.001) and also with Child-Pugh (r = –0.408, p = 0.001) and MELD (r = –0.318, p = 0.001) scores. During follow-up, 14 patients in the MHE group and 4 in the non-MHE group developed overt episodes of HE (p = 0.001). Conclusions ANT is simple and accurate for the diagnosis of MHE and prediction of overt episodes of HE in patients with cirrhosis and correlates well with the Child-Pugh and MELD scores.

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.

Background and aim The aim of this study is to evaluate the epidemiology and impact of bacterial infections at admission in patients with acute decompensation (AD) of cirrhosis. Methods A cohort with AD of cirrhosis (European Association for the Study of the Liver criteria) admitted at a tertiary center was evaluated between 2013 and 2014 for the presence of bacterial infections at admission. Clinical, demographic, and microbiological data were collected prospectively till death, transplant, or 90 days. Results Of 179 patients with AD, 102 (56.9%) had bacterial infections at admission. The commonest infections were spontaneous bacterial peritonitis (SBP) (n = 65; 63.7%), spontaneous bacteremia (n = 10; 9.8%), pneumonia (n = 9; 8.8%), urinary tract infection (n = 8; 7.8%), spontaneous bacterial empyema (n = 4; 3.9%), and cellulitis (n = 2; 1.9%). The commonest source was community acquired (n = 85; 83.3%). Serum albumin and sodium levels were lower in infected as compared with non-infected cohort (P = 0.015; for both). Escherichia coli was the commonest organism isolated from SBP (n = 14; 21.5%), urinary tract infection (n = 5; 45.5%), and bacteremia (n = 3; 20%). There was a trend toward higher 28-day mortality in infected cohort as compared with non-infected cohort (48 [52.7%] vs 28 [32%]; P = 0.152). Multidrug-resistant organisms (MDROs) were isolated in 63% of all culture-positive infections. The presence of MDRO was an independent predictor of 28-day mortality. Conclusions Infections are the leading reason for the occurrence of AD; SBP is the most common infection, and E. coli is the commonest microorganism based on this single-center study of Indian patients with AD of cirrhosis. There is a high prevalence of MDROs among culture-positive infections that independently predict 28-day mortality in AD of cirrhosis.

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: 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

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.

OBJECTIVES We assessed the efficacy of decentralized public health services and safety of direct-acting antiviral agents (DAAs) in the treatment of pediatric chronic hepatitis C (CHC) in the Mukh-Mantri Punjab Hepatitis C Relief Fund, a public-health initiative for prevention and control of CHC in Punjab, India. METHODS Consecutive children with CHC [age ≥12 to

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.

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.

Background & aims There is emerging data on the use of Sofosbuvir-based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with end-stage renal disease (ESRD) on maintenance haemodialysis (MHD). We evaluated the safety and efficacy of Sofosbuvir plus Velpatasvir fixed-dose combination in CHC patients with ESRD on MHD. Methods Fifty-one CHC patients with ESRD on MHD were included in a real-life prospective study. All patients irrespective of genotype; presence of cirrhosis; treatment naive or experienced status were treated with full-dose Sofosbuvir (400 mg) plus Velpatasvir (100 mg) fixed-dosed combination given daily for 12 weeks. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12 weeks after the end of treatment (ETR). Side effects if any were recorded in all patients. Results The median HCV RNA level in 51 CHC patients [Males 41 (80.4%), mean age 42.8 ± 14.6 years] was 2.0 × 106 IU/mL. HCV genotype was available in 19 patients with predominant genotype 1 in 15 (79%) patients. Ten (19.6%) patients had evidence of cirrhosis (defined as LSM ≥ 12.5 kPa on Transient Elastography), and 8 (15.6%) patients were treatment experienced. Testing for ETR was done in 36 patients and all 36 (100%) patients achieved ETR, and 49 patients (96%) achieved SVR 12. All 51 patients tolerated the Sofosbuvir + Velpatasvir combination, with none of the patients reporting any serious adverse event. Conclusion Sofosbuvir plus Velpatasvir fixed-dose combination is safe and effective in treating CHC in patients with ESRD on MHD.

Background: Many international guidelines on psoriasis management have emphasized upon the need to identify risk factors for liver fibrosis and that the risk may be increased after a certain total cumulative dose of methotrexate. Methods: Consecutive patients with moderate-to-severe psoriasis were assessed for liver fibrosis using transient elastography and noninvasive scores. Based on the presence of significant liver fibrosis, the Odds ratio associated with various factors was calculated using logistic regression analysis. Receiver operating characteristic curves were calculated to find maximal cutoff values of noninvasive tests to detect fibrosis. Results: In this cross-sectional study, 134 patients completed the study. Significant fibrosis (liver stiffness measurement ≥7, corresponding to F2 fibrosis or higher) was seen in 33 (24.6%) patients. Neither methotrexate exposure nor total cumulative dose of ≥1.5 was associated with significant fibrosis. Female sex (P = 0.024) and the presence of metabolic syndrome (P = 0.034) were the two variables associated with significant liver fibrosis. On logistic regression analysis, the odds ratio for the female gender and metabolic syndrome was estimated to be 2.51 (95% confidence interval - 1.09–5.81) and 2.33 (95% confidence interval - 1.03–5.27), respectively. Aspartate transaminase to platelet ratio index, nonalcoholic fatty liver disease score and the fibrosis-4 index had low sensitivity in comparison to transient elastography. Limitations: These included small sample size, small number of patients with a total cumulative methotrexate dose of >3–4.5 g, and lack of control group consisting of healthy persons. Another is the absence of liver biopsies considered as the gold standard in the diagnosis of liver fibrosis. Conclusions: Metabolic syndrome and female sex are associated with the development of significant liver fibrosis in patients with psoriasis. Methotrexate exposure does not seem to be significantly associated with significant liver fibrosis.

Aims The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. Aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. Methods A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty-two patients received Sofosbuvir and Ledipasvir and twelve patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data was analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. Results The median baseline HCV RNA concentration in the whole group was 7.38 x 106 IU/ml (1.23 x 104- 6.36 X 107). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0-F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in 5 (10.64%) patients. The only serious adverse effect was anemia observed in 8 (57%) patients in the Sofosbuvir and Ribavirin group. Conclusion DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients.

There is sparse data on the use of Sofosbuvir based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2. We evaluated the safety and efficacy of low-dose Sofosbuvir plus full-dose Daclatasvir in CHC patients with CKD. Sixty-five CHC patients with CKD with eGFR less than 30 mL/min/1.73 m2 [54 (83%) patients with ESRD on hemodialysis] were included. All patients irrespective of genotype were treated with half-dose Sofosbuvir [200 mg (half tablet of 400 mg)] plus full-dose Daclatasvir (60 mg) given daily for either 12 or 24 weeks given in patients with genotype 3 cirrhosis. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12 weeks after the end of treatment (ETR). The median HCV RNA level in 65 patients (Males 40, mean age 42.9 ± 13 years) was 1.65 × 106 (1.2 × 103–1.73 × 108) IU/mL with 42 (64.6%) patients having HCV genotype 1, followed by genotype 3 and 2 in 22 (34%) and 1 (1.4%) patients, respectively. Twenty-one (32%) patients had evidence of cirrhosis, and ten (15.4%) patients were treatment experienced. Sixty-four (98.5%) patients achieved ETR, and 65 (100%) patients attained SVR12. All patients tolerated the DAAs well with none of the patients reporting any serious adverse events. Minor side effects noted were nausea seen in five (7.7%) patients, insomnia and headache in four (6.2%) patients each, and pruritus in one (1.5%) patient. Low-dose Sofosbuvir and full-dose Daclatasvir are safe and effective in treating CHC in patients with CKD with eGFR less than 30 mL/min/1.73 m2.

Idiosyncratic drug-induced liver injury (DILI) is ranked among the top most common etiologies of acute liver failure (ALF). It carries poor transplant-free survival. Pirfenidone is an anti-inflammatory and antifibrotic drug that is commonly used for the treatment of idiopathic pulmonary fibrosis (IPF). Hepatotoxicity due to pirfenidone is rare and generally manifests as a mild rise in serum aminotransferases. In this mini-review, we report an unusual case of idiosyncratic DILI due to pirfenidone presenting as ALF, with emphasis on the definition, classification, diagnostic criteria, histopathology, molecular markers, and treatment options for DILI and related ALF. A 77-year-old man with known Parkinson's disease and IPF presented with jaundice for 7 days and altered mental status for 4 days. His long-term medications included a levodopa/carbidopa combination with a recent addition of pirfenidone over the previous 1 month; there was no monitoring of liver function tests. The evaluation suggested features of acute liver failure with grade III hepatic encephalopathy, acute kidney injury, and metabolic acidosis. The diagnostic workup ruled out viral, toxic, ischemic, and other etiologies for acute liver failure. Based on a Roussel Uclaf Causality Assessment Method score of 7 and possible DILI-ALF, pirfenidone was withdrawn. He was evaluated for liver transplantation but was declined. Despite all supportive measures in intensive care, organ failure progressed and he succumbed to the illness on day 4. Postmortem liver biopsy revealed findings consistent with DILI (final Roussel Uclaf Causality Assessment score, 10). Conclusion: DILI-ALF carries poor prognosis, and liver transplantation should be considered early in the course. Characterization, reporting, monitoring, and labeling of pirfenidone-related hepatotoxicity is vital given its common use in IPF. (Hepatology Communications 2018;2:142-147).

Background and Aim Deficiency of vitamin D may be related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the effect of vitamin D supplementation in patients with NAFLD. Methods A total of 81 patients with NAFLD with normal or raised (n = 47) serum alanine aminotransferase (ALT) having vitamin D deficiency were randomized prospectively. Group 1 (n = 51) received lifestyle modifications and a single injection of vitamin D (600 000 U) (standard medical treatment [SMT] + vitamin D) and group 2 (n = 30) received lifestyle modifications (SMT) for 6 months. The primary objective of this study was to assess the improvement in insulin resistance (IR) and serum ALT (in patients with raised ALT) and the secondary objective was to assess the change in cytokine profile in the SMT + vitamin D group. Results After 6 months, significant improvement in serum levels of ALT was observed in the SMT + vitamin D group when compared to the SMT group (ALT [87 ± 48 and 59 ± 32 IU/mL, P < 0.001] vs [64 ± 35 and 62 ± 24 IU/mL, P = 0.70]). Mean insulin levels and homeostasis model assessment-IR remained unchanged at 6 months in the SMT + vitamin D group while there was a significant increase in mean insulin and homeostasis model assessment-IR in the SMT group. SMT + vitamin D group had significant increase in mean serum levels of adiponectin (836 ± 309 and 908 ± 312 (pg/mL), P = 0.018) compared with the baseline; tumor necrosis factor-α levels decreased from baseline but the change was not significant. Conclusion Patients with NAFLD given vitamin D in addition to lifestyle modifications have significant improvement in serum ALT and serum adiponectin levels.

The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD).Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE.Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8-23.1] vs. 11.2 [95% CI 8.8-13.7] kPa, p 0.001), with a mean LSM reduction of 7.2 [95% CI 5.25-9.19] kPa. On stratification in two groups by net ultrafiltration during HD (or 2.5 liters [L]), change in LSM was substantially higher in patients when total fluid removed was 2.5 L (8.6 [95% CI 5.7-11.5] vs. 5.1 [95% CI 2.9-7.5], p = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46-0.97], versus 0.64 [95% CI 0.38-0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively.LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis.

Background and Aims The nature of cerebral edema in acute-on-chronic liver failure (ACLF) is not well studied. We aimed to characterize cerebral edema in ACLF using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Methods Forty-six patients with cirrhosis and acute decompensation were included. Patients were divided into groups A (no cerebral failure, n =39) and B (cerebral failure, n =7). Group A was subdivided into no-ACLF ( n =11), grade 1 ( n =10), grade 2 ( n =9) and grade 3 ( n =9) ACLF as per CANONIC study. MRI brain and plasma TNF-alpha, IL-1beta and IL-6 were measured at baseline and 7–10 days after admission. Ten age- and sex-matched healthy controls were also included. Results Mean diffusivity (MD) values, an MRI marker of water content, progressively increased from controls to no-ACLF to ACLF grade 1, 2 and 3 in group A in frontal white matter (FWM) and basal ganglia ( P 8×10 −9 M 2 /s) in FWM were independent predictors of 90-day mortality. There was no significant difference in clinical and MRI parameters between group A and B. Conclusion Cerebral edema increases with severity of ACLF. Correlation between MD values and IL-6 levels suggests pathogenic role of inflammation in cerebral edema. Patients with grade 3 ACLF have cerebral edema irrespective of presence of clinically evident cerebral failure. MELD score and cerebral edema have prognostic significance in ACLF.

Background and Aim Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our “real life” experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. Methods A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. Results Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. Conclusions Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

Acute on Chronic Liver Failure (ACLF) is an acute worsening of patients with chronic liver disease resulting in liver failure. Usually these patients have cirrhosis as the underlying liver disease with alcohol being the most common etiology. Common hepatitic illnesses causing acute worsening in Indian patients of ACLF include alcoholic hepatitis, acute viral hepatitis related to hepatitis E virus and acute flare in chronic hepatitis B. We report an adult case of ACLF due acute viral hepatitis related to hepatitis A virus infection superimposed on nonalcoholic steatohepatitis without cirrhosis.

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 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.

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.

ObjectivePharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still evolving. Probiotics could be a promising treatment option, but their effectiveness needs to be established. The present study aimed to evaluate the efficacy of a high potency multistrain probiotic in adult patients with NAFLD.MethodsThirty-nine liver biopsy-proven patients with NAFLD were randomised in a double-blind fashion to either lifestyle modifications plus an oral multistrain probiotic (675 billion bacteria daily, n=19) or identical placebo (n=20) for 1 year. Lifestyle modifications included regular exercise for all and control of overweight/obesity (with additional dietary restrictions), hypertension and hyperlipidaemia in those with these risk factors. Primary objective of the study was the histological improvement in NAFLD activity score (NAS) and its components and secondary objectives were improvement in alanine transaminase (ALT) and cytokine profile.ResultsThirty (76.9%) out of 39 patients with NAFLD completed the study with 1 year of follow-up. A repeat liver biopsy at 1 year could be done in 10 patients (52.6%) in probiotic group and five patients (25%) in placebo group. In comparison to baseline, hepatocyte ballooning (p=0.036), lobular inflammation (p=0.003) and NAS score (p=0.007) improved significantly at 1 year in the probiotic group. When compared with placebo, the NAS score improved significantly in the probiotic group (p=0.004), along with improvements in hepatocyte ballooning (p=0.05) and hepatic fibrosis (p=0.018). A significant improvement in levels of ALT (p=0.046), leptin (p=0.006), tumour necrosis factor-α (p=0.016) and endotoxins (p=0.017) was observed in probiotic group in comparison to placebo at 1 year. No significant adverse events were reported in the study.ConclusionPatients with NAFLD managed with lifestyle modifications and multistrain probiotic showed significant improvement in liver histology, ALT and cytokines.Trial registration numberThe clinical trial is registered with CLINICAL TRIAL REGISTRYINDIA (CTRI);http://ctri.nic.in, No. CTRI/2008/091/000074

Background & Aims We aimed to synthesize evidence for most effective treatments for minimal hepatic encephalopathy (HE) and prevention of overt HE in patients with cirrhosis. Methods We performed a systematic search of the PubMed, EMBASE, OvidSP, and Cochrane Central Register of Controlled Trials databases through July 26, 2018, for randomized controlled trials evaluating treatments for minimal HE in patients with cirrhosis, with primary outcomes of reversal of minimal HE or prevention of overt HE. We conducted a meta-analysis and then used network meta-analysis and surface under cumulated ranking (SUCRA) to pool the direct and indirect estimates and rank the different treatments. We appraised study quality using the Grading of Recommendations Assessment, Development and Evaluation system. Results Our meta-analysis and network meta-analysis included 25 trials, comprising 1563 participants. Agents found to be effective in reversing minimal HE compared with placebo or no treatment included rifaximin (odds ratio [OR], 7.53; 95% predictive interval [PrI], 4.45–12.73; SUCRA, 89.2%; moderate quality), lactulose (OR, 5.39; 95% PrI, 3.60–8.0; SUCRA, 67.2%; moderate quality), the combination of probiotics and lactulose (OR, 4.66; 95% PrI, 1.90–11.39; SUCRA, 52.4%; low quality), L-ornithine L-aspartate (OR, 4.45; 95% PrI, 2.67–7.42; SUCRA, 47.2%; low moderate quality), and probiotics (OR, 3.89; 95% PrI, 2.52–6.02; SUCRA, 34.1%; low quality). Agents found to be effective in preventing episodes of overt HE compared with placebo or no treatment included L-ornithine L-aspartate (OR, 0.19; 95% PrI, 0.04–0.91; SUCRA, 75.1%; high moderate quality), lactulose (OR, 0.22; 95% PrI, 0.09–0.52; SUCRA, 73.9%; moderate quality), and probiotics (OR, 0.27; 95% PrI, 0.11–0.62; SUCRA, 59.6%; low quality). Conclusions In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis. L-ornithine L-aspartate and lactulose are most effective in the prevention of overt HE. Lactulose was the only agent that was effective in reversing minimal HE, preventing overt HE, reducing ammonia, and improving quality of life, with tolerable adverse effects. International prospective register of systematic reviews ID: 107003.

Background & Aims The prevalence of anti-hepatitis C virus antibody in Punjab, India is 3.6%, with 728,000 people estimated to have viremic chronic hepatitis C (CHC). The Mukh-Mantri Punjab Hepatitis C Relief Fund, launched on 18th June 2016, provides no-cost generic direct-acting antivirals (DAAs) with sofosbuvir + ledipasvir ± ribavirin or sofosbuvir + daclatasvir ± ribavirin with the goal of eliminating CHC from Punjab. We assessed the safety and efficacy of decentralized treatment of CHC in a public health care setting. Methods Primary care providers from 3 university and 22 district hospitals were trained to provide algorithm-based DAA treatment and supervised by telehealth clinics conducted fortnightly. The diagnosis of cirrhosis was based on clinical and radiological evidence, including aspartate aminotransferase-to-platelet ratio index (APRI ≥2.0) and FIB-4 score (>3.25), or on liver stiffness measurement ≥12.5 kPa on Fibroscan®. Results We enrolled 48,088 individuals with CHC (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhosis; 69.9% genotype [GT] 3) between 18th June 2016 to 31st July 2018. While 36,250 (75.4%) patients completed treatment, 5,497 (11.4%) had treatment interruptions and 6,341 (13.2%) patients are currently ongoing treatment. Sustained virological response at 12 weeks after treatment completion (SVR12) was achieved in 91.6% of patients per protocol, 67.6% in intention-to-treat (ITT) analysis, where all interruptions were treated as failures, and 91.2% in a modified ITT analysis where all patients with successful SVR12 in the interruptions arm were included as cured. SVR12 rates in patients with and without cirrhosis and GT3 versus non-GT3 were comparable. The SVR12 rate was 84.4% in patients who had treatment interruptions. Conclusion Decentralized care of patients with CHC using generic all-oral DAA regimens is safe and effective regardless of genotype or presence of cirrhosis. ClinicalTrials.gov number: NCT01110447. Lay summary We assessed the safety and efficacy of public health care using no-cost all-oral generic direct-acting antiviral drugs against hepatitis C in the state of Punjab, India. The goal is elimination of chronic hepatitis C (CHC) by 2030 and involves primary care providers at 25 sites in the state. We enrolled 48,088 individuals (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhotic; 69.9% genotype 3) between 18th June 2016 to 31st July 2018. Cure was achieved in 91.6% of patients, demonstrating that decentralized care of CHC with generic all-oral regimens is safe and effective.

Background: Many international guidelines on psoriasis management have emphasized upon need to identify risk factors for liver fibrosis and the risk may be increased after a certain total cumulative dose of methotrexate. Materials and Methods: Consecutive patients with moderate to severe psoriasis were assessed for liver fibrosis using transient elastography and non-invasive scores. Based on the presence of significant liver fibrosis, Odd's ratio associated with various factors was calculated using logistic regression analysis. Receiver Operating Characteristic (ROC) curves to be calculated to find maximal cut-off values of non-invasive tests to detect fibrosis. Results: Of 159 patients, 134 patients completed the study. Significant fibrosis (LSM ≥7, corresponding to F2 fibrosis or higher) was seen in 33 (24.6%) patients. Neither methotrexate exposure nor total cumulative dose of ≥1.5 was associated with significant fibrosis. Male sex (p=0.024) and presence of MS (p=0.034) were the only variables associated with significant liver fibrosis. On logistic regression analysis, O.R. for male gender and metabolic syndrome was estimated to be 2.51 (95% CI - 1.09-5.81) and 2.33 (95% CI - 1.03-5.27) respectively. APRI, NAFLD score and Fib-4 index had low accuracy in comparison to transient elastography. Conclusion: MS and male sex are the most important risk factors for development of significant liver fibrosis in psoriasis patients. Methotrexate exposure does not seem to predict presence of liver fibrosis. Funding Statement: The authors declare: "None." Declaration of Interests: The authors declare: "None." Ethics Approval Statement: The study was initiated after taking approval from the Institute’s ethics committee (NK/978/Res/351). In addition, a STROBE checklist is included.

Background and aim The aim of this study was to analyze etiologies and frequency of hepatic and extrahepatic organ failures (OFs) and outcome of acute-on-chronic liver failure (ACLF) at 10 tertiary centers in India. Methods In this retrospective study (2011-2014), patients satisfying Asian Pacific Association for the Study of the Liver definition of ACLF were included. Etiology of acute precipitating insult and chronic liver disease and outcomes were assessed. Occurrence and severity of OF were assessed by chronic liver failure-sequential organ failure assessment score. Results The mean (±SD) age of 1049 consecutive ACLF patients was 44.7 ± 12.2 years; Eighty-two percent were men. Etiology of acute precipitants included alcohol 35.7%, hepatitis viruses (hepatitis A, hepatitis B, and hepatitis E) 21.4%, sepsis 16.6%, variceal bleeding 8.4%, drugs 5.7%, and cryptogenic 9.9%. Among causes of chronic liver disease, alcohol was commonest 56.7%, followed by cryptogenic and hepatitis viruses. Predictors of survival were analyzed for a subset of 381 ACLF patients; OF's liver, renal, coagulation, cerebral, respiratory, and failure were seen in 68%, 32%, 31.5%, 22.6%, 14.5%, and 15%, respectively. Fifty-seven patients had no OF, whereas 1, 2, 3, 4, and 5 OFs were recorded in 126, 86, 72, 28, and 12 patients, respectively. The mortality increased progressively with increasing number of OFs (12.3% with no OF, 83.3% with five OFs). During a median hospital stay of 8 days, 42.6% (447/1049) of patients died. On multivariate analysis by Cox proportional hazard model, elevated serum creatinine (hazard ratio [HR] 1.176), advanced hepatic encephalopathy (HR 2.698), and requirement of ventilator support (HR 2.484) were independent predictors of mortality. Conclusions Alcohol was the commonest etiology of ACLF. Within a mean hospital stay of 8 days, 42% patients died. OFs independently predicted survival.

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.

AIMS To study the prevalence, risk factors, role of serum biomarkers for diagnosis and impact of invasive fungal infections (IFIs) in patients with acute-on-chronic liver failure (ACLF). METHODS An analysis of IFI in patients with ACLF (EASL criteria) was conducted retrospectively. The diagnosis of IFI in clinically suspected patients was based on EORTC/MSG criteria. The demographical, clinical, laboratory details and outcomes were analysed. RESULTS Out of 264 patients with ACLF, 54 (20.4%) patients with suspicion of IFI were evaluated and IFI was diagnosed in 39 (14.7%). Invasive candidiasis was documented in 25 (64.1%) and invasive aspergillosis in 14 (35.8%). The most common source of infection was respiratory (n = 13) followed by renal (n = 7) and spontaneous fungal peritonitis (n = 6). On univariate analysis, diabetes mellitus, hemodialysis, prior antibiotic use, cerebral and respiratory organ failures, Chronic Liver Failure Consortium (CLIF-OF and CLIF-C ACLF) scores were predictors for development of IFI (P

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.

Background and aim The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial. There is sparse literature on the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor (TLR) signaling in NAFLD. The present study evaluated the relationship of SIBO with expression of TLR signaling genes in patients with NAFLD. Methods A total of 142 subjects composed of NAFLD (n = 60, mean age 38.7 ± 10.4 years), chronic viral hepatitis (CVH) (n = 32, mean age 39.5 ± 10.6 years), and healthy volunteers (n = 50, mean age 36.56 ± 4.2 years) were enrolled in the study. Duodenal fluid was taken endoscopically in 32 prospective patients with NAFLD for evaluation of SIBO. Hepatic mRNA expression of TLR4, CD14, TLR2, NF-κβ, and MD2 and protein expression of TLR4 and TLR2 were studied in 64 patients (NAFLD = 32, CVH = 32) by RT-PCR and immunohistochemistry, respectively. Serum levels of TNF-α, adiponectin, insulin, and endotoxins were also evaluated. Results Small intestinal bacterial overgrowth was present in 12 (37.5%) out of 32 patients with NAFLD with Escherichia coli as the predominant bacterium. In comparison with those without SIBO, patients with SIBO had significantly higher endotoxin levels and higher CD14 mRNA, nuclear factor kappa beta mRNA, and TLR4 protein expression. Patients with NASH had significantly higher endotoxin levels and higher intensity of TLR4 protein expression in comparison with patients without NASH. Serum levels of TNF-α, endotoxins, and insulin were significantly higher and of adiponectin lower in NAFLD in comparison with CVH and healthy volunteers. Conclusions Our study provides the first direct evidence of role of SIBO and endotoxemia and its relation with TLR signaling genes and liver histology in patients with NAFLD.

The association of obstructive sleep apnea (OSA) with nonalcoholic fatty liver disease (NAFLD) has only been studied in selected subgroups such as the morbidly obese. We aimed to determine the prevalence and effect of OSA on NAFLD and vice versa in unselected patients attending the outpatient department. OSA was diagnosed by polysomnography, done in patients having symptoms of OSA, in patients with NAFLD attending the liver clinic. Polysomnography-proven patients with OSA attending the chest clinic were evaluated for NAFLD by ultrasonography. Anthropometry, liver function tests, metabolic syndrome evaluation and transient elastography were performed in all patients. Three (3 %; 95 % CI 1.03–8.45 %) out of 100 patients with NAFLD (mean age 41 ± 11 years) had symptomatic OSA. Of 23 patients with OSA (mean age 46 ± 12 years,), 3 (13 %) had mild, 5 (22 %) moderate and 15 (65 %) severe OSA. Twenty-one (91.3 %; 95 % CI 73.2–97.6 %) patients with OSA had NAFLD, while raised hepatic transaminase levels were seen in seven (30.4 %; 95 % CI 15.6–50.9 %). Body mass index (OR 1.21, 95 % CI 1.02–1.44) and male gender (OR 4.79, 95 % CI 1.12–20.48) were significant independent predictors of OSA in NAFLD. The apnea-hypopnea index (OR 1.084, 95 % CI 1.002–1.172), a marker of OSA severity, was the only significant independent predictor of significant fibrosis in patients with NAFLD. Prevalence of symptomatic OSA in patients with NAFLD is low and is predicted by male gender and obesity. Prevalence of NAFLD in patients with OSA is very high. Significant hepatic fibrosis in patients with NAFLD is predicted by OSA independent of obesity and metabolic syndrome.

Background and Aim This study assessed the utility of a simple organ failure count (SOFC) in predicting the in-hospital mortality in patients with acute-on-chronic liver failure (ACLF) compared with Chronic Liver Failure Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) ACLF grading system. Methods Consecutive patients of ACLF were included prospectively from 2012 to 2013. The diagnosis was based on Asian-Pacific Association for the Study of the Liver (APASL) criteria except for the inclusion of non-hepatic insults as acute events. Organ failures were defined as per the Chronic Liver Failure–Sequential Organ Failure Assessment system. SOFC was calculated as the simple number of organ failures from 0 to 6. In-hospital mortality was recorded. Results Majority (92[87%]) of the 106 patients included were males, had alcohol (76[72%]) as the etiology of cirrhosis, and alcoholic hepatitis (58[55%]) as the acute precipitating event. Overall, 51(48%) patients died in-hospital. In-hospital mortality in patients with SOFC of 0 (n = 9), 1 (n = 39), 2 (n = 24), 3 (n = 24), 4 (n = 7), and 5 (n = 3) was 0%, 26%, 58%, 71%, 100%, and 100% respectively (P

Type 2 diabetes mellitus (T2DM) is a major risk factor associated with hepatocellular carcinoma (HCC). However, the association of T2DM with liver cirrhosis and therapy response in HCC patients is not clear. Hence, in this study, we have evaluated the influence of T2DM on liver cirrhosis severity of HCC and sorafenib response. HCC patients were divided in two groups: T2DM (n = 20) and non-T2DM (nT2DM; n = 50). We found significantly higher number of patients in T2DM group had decompensated liver disease with Child–Turcotte–Pugh score ≥ 7. Additionally, 71.4% patients were observed to be sorafenib sensitive in T2DM group which was significantly higher as compared to 30% in nT2DM group. This study has highlighted the predisposition of HCC patients with T2DM toward more severe liver disease who were found to be better respondents of sorafenib. Impact statement We have explored the association of type 2 diabetes mellitus (T2DM) on liver cirrhosis severity along with response toward sorafenib in hepatocellular carcinoma (HCC). Most HCC patients exhibit prior history of liver cirrhosis that results following long span of chronic liver disease. T2DM constitutes as an important risk factor for HCC development which is known to elevate its incidence. Further, sorafenib is the FDA approved therapy for HCC whose therapeutic outcome is not investigated in HCC patients with T2DM till date. This observation-based study has unveiled a positive association between T2DM and severity of liver cirrhosis as well as sorafenib response in HCC as examined in a clinical setting.

Background Acute exacerbation of Autoimmune Hepatitis (AIH) poses a significant challenge for diagnosis as it can mimic acute viral hepatitis especially in absence of autoantibodies and hypergammaglobulinemia. Aim To determine the clinical, laboratory, histopathological characteristics and response to treatment in AIH patients with acute exacerbation. Methods A retrospective analysis of 16 patients with acute exacerbation of AIH diagnosed over a period of eight years (2008–2016). Results Out of the 111 patients diagnosed with AIH, acute exacerbation of AIH was diagnosed in 16 (14.4%) patients. All patients were females with median age of 35 years. Nine patients (56%) had Type 1 AIH and seven (44%) patients were diagnosed with seronegative AIH. All 16 (100%) patients had acute viral hepatitis like illness at presentation. The median bilirubin was 4.2 mg/dl (range, 2.2–20), aspartate transaminase was 568 IU/L (range, 390–908), alanine transaminase was 430 IU/L (range, 257–1026) and serum alkaline phosphatase was 395 IU/L (range, 112–890) during symptomatic period. The histopathological examination showed underlying chronic hepatitis in 10 (71.4%) patients, only fibrosis in 2 (14.2) patients and cirrhosis with activity in 2 (14.2%). All 16 (100%) patients were treated with a combination of steroids and azathioprine. Thirteen (81%) patients achieved complete biochemical remission and three (19%) patients achieved partial remission out of which one (6%) patient succumbed to illness because of the complications of cirrhosis. Conclusion A suspicion of acute exacerbation of AIH should be considered in patients with unexplained acute hepatitis mimicking acute viral hepatitis in the absence of positive viral markers. Through evaluation with immunoserological markers and liver biopsy can clinch the diagnosis of acute exacerbation of AIH in such cases.