Swastik Agrawal

Probiotic VSL#3 Reduces Liver Disease Severity and Hospitalization in Patients With Cirrhosis: A Randomized, Controlled Trial

BACKGROUND & AIMS Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.

Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome

AIM To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF. METHODS Consecutive patients of cirrhosis with acute decompensation were prospectively included. They were grouped into ACLF and no ACLF groups as per CLIF-SOFA and APASL criteria. Patients were followed up for 3 mo from inclusion or mortality whichever was earlier. Mortality at 28-d and 90-d was compared between no ACLF and ACLF groups as per both criteria. Mortality was also compared between different grades of ACLF as per CLIF-SOFA criteria. Prognostic scores like CLIF-SOFA, Acute Physiology and Chronic Health Evaluation (APACHE)-II, Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were evaluated for their ability to predict 28-d mortality using area under receiver operating curves (AUROC). RESULTS Of 50 patients, 38 had ACLF as per CLIF-SOFA and 19 as per APASL criteria. Males (86%) were predominant, alcoholic liver disease (68%) was the most common etiology of cirrhosis, sepsis (66%) was the most common cause of acute decompensation while infection (66%) was the most common precipitant of acute decompensation. The 28-d mortality in no ACLF and ACLF groups was 8.3% and 47.4% (P = 0.018) as per CLIF-SOFA and 39% and 37% (P = 0.895) as per APASL criteria. The 28-d mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) as per CLIF-SOFA criteria was 8.3%, 18.2%, 42.9% and 76.9% (χ(2) for trend, P = 0.002) and 90-d mortality was 16.7%, 27.3%, 78.6% and 100% (χ(2) for trend, P < 0.0001) respectively. Patients with prior decompensation had similar 28-d and 90-d mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P = NS). AUROCs for 28-d mortality were 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE-II, Child-Pugh and MELD scores respectively. On multivariate analysis of these scores, CLIF-SOFA was the only significant independent predictor of mortality with an odds ratio 1.538 (95%CI: 1.078-2.194). CONCLUSION CLIF-SOFA criteria is better than APASL criteria to classify patients into ACLF based on their prognosis. CLIF-SOFA score is the best predictor of short-term mortality.

Non-alcoholic Fatty Liver Disease: East Versus West.

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West.

Simple organ failure count versus CANONIC grading system for predicting mortality in acute-on-chronic liver failure.

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.

Clinical Practice GuidelinesIndian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.

Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy

OBJECTIVES:Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis.METHODS:Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG).RESULTS:Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.CONCLUSIONS:This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE.

Portal Cavernoma Cholangiopathy – History, Definition and Nomenclature

Biliary changes secondary to portal hypertension, especially in portal cavernoma secondary to extrahepatic portal vein obstruction have long been described in literature under different names by various authors. Most of the times these changes are asymptomatic and discovered on imaging, but can occasionally cause obstructive jaundice. There is no consensus on the appropriate nomenclature and definition of this entity. This article reviews the history of portal hypertensive biliopathy and the Indian Association for the Study of Liver Working Party consensus definition and nomenclature for it.

Answers to multiple choice questions.

7. A Choice B: Intervals don’t give us any information about the percentage of specific population observations are contained in them. Choice C: This specific interval taken from only one sample doesn’t speak to the long-term success rate of the method. Choice D: Avoid the word – or in this case the symbols – for “probability” because once the interval is set, it has either captured the true parameter (probability = 1) or it hasn’t (probability = 0).

A Case of Acute-on-Chronic Liver Failure (ACLF) Due to An Uncommon Acute And Chronic Event

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.

Hepatobiliary Quiz–12 (2014)

Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) has been described by various terminologies such as idiopathic portal hypertension, non-cirrhotic portal fibrosis (NCPF), nodular regenerative hyperplasia (NRH), incomplete septal cirrhosis, partial nodular transformation of the liver, benign intrahepatic portal hypertension and hepatoportal sclerosis. Although, these diseases differ in some details in their description and defining criteria, they are believed to represent variations in appearance of a single pathological entity. The basic pathology of NCIPH is narrowing or occlusion of 3rd/4th order portal vein radicles. Small portal vein radicles are obliterated or thrombosed with portal vein sclerosis and/or portal angiomatosis, peri-sinusoidal fibrosis and sinusoidal dilatation suggestive of obliterative portal venopathy (OPV). In advanced stages thrombosis of the medium and large portal vein branches may be seen. The various morphological patterns of NRH, NCPF, incomplete septal fibrosis etc. may be histological spectrums of different stages of a single clinical entity cumulating in NCIPH. While NCIPH is more common in developing countries it has been reported from all parts of the world. It is reported to be associated with low socio-economic groups. The disease is relatively rare in the West and even in developing countries there is a decline in its incidence in parallel with improving in living standards and hygienic conditions.