The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

BACKGROUND: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. METHODS: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. RESULTS: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. CONCLUSION: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

Clinical audit to determine efficacy of daily infusion of low dose of 20% albumin in combination with antibiotics in patients with spontaneous bacterial peritonitis.

AIM OF THE STUDY: The recommended high dose albumin treatment for spontaneous bacterial peritonitis (SBP) is not possible in the Indian setting due to financial constraints. Aim of the study was the retrospective audit to determine the outcome of patients with SBP on combination treatment of low dose albumin and appropriate antibiotics. MATERIAL AND METHODS: Patients undergoing abdominal paracentesis in the period 2016-2018 were included. Patient details including age, gender, co-morbidity profile, details of previous hospitalisation and antibiotics, MELD score, and ascitic fluid analysis were noted. Details of albumin use and antibiotics were retrieved. SBP was classified based on mode of acquisition of infection and severity risk based on laboratory parameters. Statistics - χ2 test, Mann-Whitney U test, relative risk calculation. A p value of < 0.05 was considered as significant. RESULTS: 24 (18.8%), 38 (29.7%) and 66 patients (51.5%) belonged to low, intermediate and high risk SBP groups, respectively. The median dose of albumin was 20 g/day for a median duration of 5 days (range 1-8). Between the 3 subgroups, there was no significant difference in the median age; the majority were men. Antibiotic escalation was necessary in intermediate and high risk cases (42.1% vs. 84.8%, p < 0.0001). The mortality rate in intermediate and high risk groups was 29% and 42%, respectively (p = 0.18). Between the 2 subgroups of intermediate risk, patients with serum bilirubin < 4 mg/dl and serum creatinine > 1 mg/dl were significantly older (54 vs. 49 years, p = 0.02), and had high mortality (40.7% vs. 0%). Cirrhosis-related complications (CRC; one or more in combinations) were more frequent in high risk and intermediate risk patients (p = 0.001) with a 7-8 times higher risk of mortality compared to those who had no CRC. CONCLUSIONS: Our protocol is associated with high mortality in intermediate and high risk SBP patients. Presence of one or more CRC increases the risk of mortality several fold.

Health-related quality of life in liver cirrhosis patients using SF-36 and CLDQ questionnaires.

AIM OF THE STUDY: To determine the factors that are likely to influence the domains of health-related quality of life (HRQOL) using SF-36 and CLDQ questionnaires in patients with liver cirrhosis. MATERIAL AND METHODS: Patients with liver cirrhosis were compared with age- and gender-matched healthy controls for physical and mental components of the SF-36 score. Effects of age, co-morbidity, namely diabetes, severity of liver disease and complications of liver cirrhosis on HRQOL using self-administered or by direct interview SF-36 and CLDQ questionnaires were studied. Statistical analysis: chi square test, ANOVA, Kruskal-Wallis test and stepwise linear regression analysis. A p value of < 0.05 was considered significant. RESULTS: Regarding SF-36 score, except for bodily pain, 149 patients had significantly low individual and composite domain scores (p value < 0.0001) compared to age/gender-matched controls. Patients below 45 years, the majority of whom belonged to Child-Turcotte-Pugh (CTP) class C with a high Model of End-Stage Liver Disease (MELD) and higher rates of complication had low SF-36 for bodily pain (KW p < 0.005) and those above 55 years for physical function (p < 0.05). Both the physical components had a major impact on mental composite score (MCS) (KW p < 0.05). The overall CLDQ score was also low in patients below 45 years old (p < 0.05). Diabetes with or without other co-morbid conditions had no effect on SF-36 or CLDQ scores, while non-diabetic co-morbid conditions did on physical domains (physical function, bodily pain and role physical) and the physical component score of SF-36 (KW p < 0.01 to < 0.0001). In linear regression, MELD had a direct and significant association with overall PCS, MCS and CLDQ. CONCLUSIONS: Age below 45 years, higher MELD and CTP score with the presence of ascites and hepatic encephalopathy affect the overall CLDQ scores.

von Willebrand Factor: A Tool to Predict Severity and Prognosis in Liver Disease.

Von Willebrand factor (vWF) is an adhesive and multimeric glycoprotein that has a central role in primary hemostasis. v W F levels correlate with thrombosis risk and inversely with bleeding risk within the apparently healthy population. Recently, numerous publications in Indian and western literature have focussed to its role in liver diseases like acute liver failure, chronic liver disease, non cirrhotic portal hypertension and tropical infections eg. dengue. The present review encapsulates the recent advances in this aspect.

Changing pattern of biliary complications in an evolving liver transplant unit.

Biliary complications (BCs) remain a significant cause of morbidity following liver transplantation (LT). This series of 640 LT recipients with a blend of living and deceased donor transplants was analyzed to determine the incidence, risk factors, management protocol, and outcomes in these patients. Review of a prospectively collected database of transplant recipients operated between August 2009 and June 2016 was performed. Patients were divided into those with and without BCs and data analyzed. The 640 LT recipients from both living (n = 481) and deceased donors (n = 159) were evaluated for BCs. The overall incidence of BCs was 13.7%. It reduced from 23% to 5% (P = 0.003) over a 6-year period. Risk factors for BCs on multivariate analysis were living donor liver transplantation, prolonged time to rearterialization, recipient age above 16 years, prolonged cold ischemia time (CIT) after deceased donor liver transplantation, and biliary reconstruction performed by anyone but the senior author. One-fifth of bile leaks progressed to strictures, and 40% of strictures followed leaks. Endoscopic therapy resolved 60% of the strictures. Surgical repair of strictures was successful in 90% of those in whom endoscopy failed, those who could not undertake the follow-up schedules endoscopic therapy entails, and those presenting with late strictures. BCs significantly prolonged hospital stay but did not alter survival after LT. BCs affect 1 in 7 recipients, although they are not associated with increased mortality. The frequency of these complications is influenced by potentially modifiable factors like evolving surgical expertise and CIT. Liver Transplantation 23 478-486 2017 AASLD.