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Angeli P.,University of Padua | Sanyal A.,Virginia Commonwealth University | Moller S.,Copenhagen University | Alessandria C.,University of Turin | And 4 more authors.
Liver International | Year: 2013

Advanced cirrhosis is often complicated by a multi organ failure syndrome which involves many different organs besides the liver. The high morbidity and mortality secondary to this clinical setting is often related to renal dysfunction, either alone or, more frequently, in combination with other organ dysfunction. A clear defintion of renal dysfunction, an accurate differential diagnostic process of its different phenotypes as well as of full understanding of its pathophysiological mechanisms are crucial to the development of strategies for the management of this complication. This article is based either on the more recent knowledge on renal dysfunction in advanced cirrhosis or current opinions among the members of the International Club of Ascites (ICA) on the management of this complication, obtained through a survey and discussed during the EASL-ICA Joint Meeting in Berlin in March 2011. It reviews critically our current knowledge and it outlines future perspectives, on the management of renal dysfunction in patients with cirrhosis. © 2012 John Wiley & Sons A/S.


Mishra S.R.,G B Pant Hospital | Sharma B.C.,G B Pant Hospital | Kumar A.,Institute of Liver and Biliary science ILBS | Sarin S.K.,G B Pant Hospital | Sarin S.K.,Institute of Liver and Biliary science ILBS
Journal of Hepatology | Year: 2011

Background & Aims:: Gastric variceal bleeding is severe and is associated with high mortality. We compared the efficacy of cyanoacrylate injection and beta-blockers in primary prophylaxis of gastric variceal bleeding. Methods: Cirrhotics with large gastroesophageal varices type 2 with eradicated esophageal varices or large isolated gastric varix type 1, who had never bled from gastric varix, were randomised to cyanoacrylate injection (Group I, n = 30), beta-blockers (Group II, n = 29) or no treatment (Group III, n = 30). Primary end-points were bleeding from gastric varix or death. Results: The actuarial probability of bleeding from gastric varices over a median follow-up of 26 months was 13% in Group I, 28% in Group II (p = 0.039), and 45% in Group III (p = 0.003). The actuarial probability of survival was higher in the cyanoacrylate compared to the no-treatment group (90% vs. 72%, p = 0.048). The median hepatic venous pressure gradient (HVPG) was increased in Group I (14-15 mm Hg, p = 0.001) and III (14-16 mm Hg, p = 0.001) but decreased in Group II (14 to 12 mm Hg, p = 0.001) during follow-up. Size of gastric varix >20 mm, a MELD score ≥17, and presence of portal hypertensive gastropathy predicted 'high risk' of first bleeding from gastric varices. Conclusions: Primary prophylaxis is recommended in patients with large and high risk gastric varices to reduce the risk of first bleeding and mortality. Cyanoacrylate injection is more effective than beta-blocker therapy in preventing first gastric variceal bleeding. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Garg H.,GB Pant Hospital | Garg H.,Institute of Liver and Biliary science ILBS | Sarin S.K.,GB Pant Hospital | Sarin S.K.,Institute of Liver and Biliary science ILBS | And 7 more authors.
Hepatology | Year: 2011

Spontaneous reactivation of chronic hepatitis B (CHB) is an important cause of acute-on-chronic liver failure (ACLF). Antiviral drugs may help reduce the high morbidity and mortality in such patients, especially in places where liver transplant is not available. The aim was to evaluate the efficacy of tenofovir and to determine the predictors of mortality in patients with spontaneous reactivation of CHB with ACLF. Consecutive patients of ACLF due to spontaneous reactivation of CHB were randomized to receive either tenofovir or placebo. The primary endpoint was survival at 3 months. Of the 90 patients with ACLF of different etiologies, 27 (26%) were due to reactivation of CHB and were enrolled. The median baseline hepatitis B virus (HBV) DNA level was 9 × 10 5 IU/mL. Fourteen patients received tenofovir and 13 placebo. At 3 months the probability of survival was higher in the tenofovir than the placebo group (8/14 [57%] versus 2/13 [15%], respectively; P = 0.03). The cause of death in the 15 patients was progressive liver failure leading to multiorgan failure. Liver transplantation could not be offered due to its nonavailability. In the surviving patients, there was a significant improvement in the Child-Turcotte Pugh (CTP) and model for endstage liver disease (MELD) scores and significant decline in the HBV DNA levels in the tenofovir group, whereas these parameters did not change significantly in the placebo group. More than 2 log reduction in HBV DNA levels at 2 weeks was found to be an independent predictor of survival. Conclusion: Tenofovir significantly reduces HBV-DNA levels, improves CTP and MELD scores, and reduces mortality in patients with severe spontaneous reactivation of CHB presenting as ACLF. Reduction in HBV-DNA levels at 2 weeks should be a desirable goal and is a good predictor of survival. © 2011 American Association for the Study of Liver Diseases.


Maiwall R.,Institute of Liver and Biliary science ILBS | Maras J.S.,Institute of Liver and Biliary science ILBS | Nayak S.L.,Institute of Liver and Biliary science ILBS | Sarin S.K.,Institute of Liver and Biliary science ILBS
Hepatology International | Year: 2014

Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients. © 2014, Asian Pacific Association for the Study of the Liver.


Saha B.,Institute of Liver and Biliary science ILBS | Saha B.,University of Massachusetts Medical School | Choudhary M.C.,Institute of Liver and Biliary science ILBS | Sarin S.K.,Institute of Liver and Biliary science ILBS
AIDS | Year: 2013

Objective: Hepatitis C virus (HCV)/HIV coinfection is associated with rapid progression of hepatic fibrosis and liver disease. T-cell response has been implicated in the pathophysiological outcome of the disease. Design: This study sought to evaluate the role of memory T-cell exhaustion in enhancing immune dysfunction during coinfection. Methods: Sixty-four patients were included in the study; HCV monoinfected (n=21), HIV monoinfected (n=23), HCV/HIV coinfected (n=20), and healthy controls (n=20). Peripheral blood mononuclear cells (PBMCs) were isolated; immunophenotyped and functional assays were performed. Results: A significant increase in the naive T cells and central memory T cells and a marked reduction in effector memory T cells (TEM) were observed with coinfection as compared to monoinfection. Inhibitory markers programmed death 1 (PD-1) and T-cell immunoglobulin and mucin domain containing molecule 3 (TIM3) were highly upregulated on TEM in coinfection and functionally, these TEM cells displayed lowered proliferation. Increased expression of PD-1 and TIM3 correlated with decreased levels of CD8+CD107a + TEM cells in coinfection. Pro-inflammatory cytokines interferon-g and interleukin-2 (IL-2) secretion by TEM cells were also reduced during chronic viral infection. Secretion of IL-10, a human cytokine synthesis inhibitory factor, was significantly upregulated in CD4 + TEM with HCV/HIV coinfection in comparison to HCV monoinfection. Conclusion: TEM cells play an important role during viral infection and enhanced expression of inhibitory markers is associated with decreased proliferation and cytotoxicity and increased IL-10 production, which was pronounced in HCV/HIV coinfection. Thus, decreased TEM functionality contributes to diminished host immune responses during HCV/HIV coinfection as compared to HCV or HIV monoinfection. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Gupta N.,Gb Pant Hospital | Kumar A.,Institute of Liver and Biliary science ILBS | Sharma P.,Institute of Liver and Biliary science ILBS | Garg V.,Gb Pant Hospital | And 2 more authors.
Liver International | Year: 2013

Background: Probiotics, by altering gut flora, may favourably alter portal haemodynamics in patients with cirrhosis. Aim: To investigate the effect of probiotics on portal pressure in patients with cirrhosis. Methods: Randomized double-blind placebo-controlled trial conducted in G.B. Pant Hospital, New Delhi. A total of 94 cirrhotic patients having large oesophageal varices without history of variceal bleeding were randomized to three treatment groups and given 2 months' treatment with propranolol plus placebo, propranolol plus antibiotics (norfloxacin 400 mg BD) or propranolol plus probiotic (VSL#3, 900 billion/day) randomly assigned in 1:1:1 ratio. Outcome measures were change in Hepatic venous pressure gradient (HVPG): Response rate (Percentage of patients having a decrease from baseline of ≥20% or to ≤12 mm Hg) and changes from baseline; biochemical markers of inflammation: changes from baseline. Results: Adjunctive probiotics increased the response rate compared with propranolol alone (58% vs. 31%, P = 0.046), similar to adjunctive antibiotics (54%). The mean fall in HVPG was greater with either adjunctive probiotics (3.7 mm Hg vs. 2.1 mm Hg, P = 0.061) or adjunctive antibiotics (3.4 mm Hg) than with propranolol alone. Both adjunctive therapies were associated with greater decreases in TNF-α levels (in both peripheral and hepatic venous blood) that resulted from propranolol-only treatment. No clinically relevant between-group differences were observed in the type or frequency of adverse events. Conclusions: Adjunctive probiotic (VSL#3) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis. Adjunctive probiotic therapy merits further study for reduction in portal pressure. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Bhatia V.,Institute of Liver and Biliary science ILBS
Journal of Clinical and Experimental Hepatology | Year: 2012

A large part of portal venous system and the paragastric and para-esophageal collateral circulation is within the reach of endoscopic ultrasound (EUS). The EUS is more sensitive than gastroscopy for the detection of gastric varices (GV), and can accurately distinguish GV from thickened gastric folds. Gastric varices are depicted by serpiginous, anechoic, Doppler-positive mural channels, with larger collateral channels visible outside the gastric wall. The EUS has also been used to monitor the completeness of GV obturation after glue injection. There are limited data that this strategy may be clinically beneficial to prevent GV re-bleed. The EUS has been used to deliver glue injections under real-time monitoring into the vascular channels, with or without steel coils as scaffolding for the glue. The potential advantages of this technique include a straight scope position, lack of hindrance from pooled blood in gastric fundus, smaller glue volume requirements, and precise intra-vascular placement of glue with avoidance of intramural injections, and reduced embolic complications. © 2012 INASL.


Kumar R.,Institute of Liver and Biliary science ILBS
Hepatology International | Year: 2013

Non-alcoholic fatty liver disease (NAFLD), once regarded as an innocuous condition, is now considered to be the most common cause of chronic liver disease worldwide. Evidence suggests a strong association between NAFLD and other potentially life-threatening diseases. A significant proportion of these patients develops progressive liver injury leading to cirrhosis and hepatocellular carcinoma. Unrecognized NAFLD constitutes a substantial proportion of patients with cryptogenic cirrhosis. Several large community-based studies have found increased mortality in NAFLD patients compared to the expected mortality of the general population of the same age and sex. Cardiovascular disease is an important cause of morbidity and mortality in patients with NAFLD and accounts for up to 30 % of overall death. Cardiovascular mortality does not seem to differ between simple steatosis and non-alcoholic steatohepatitis. NAFLD is associated with increased risk of both hepatic and extra-hepatic malignancy. Malignancy is among the most important causes of death in NAFLD patients. NAFLD is a risk factor for liver cancer even without cirrhosis. The steatotic liver has poor ability to regenerate after volume loss, which may lead to the development of liver failure and increased mortality after extended liver resection. Also, transplantation of steatotic liver results in an increased rate of poor graft function, primary graft non-function, and poorer outcome. There is a high recurrence rate of fatty liver disease in patients transplanted for NASH. © 2013 Asian Pacific Association for the Study of the Liver.


Bhatia V.,Institute of Liver and Biliary science ILBS
Journal of Clinical and Experimental Hepatology | Year: 2014

Portal cavernoma cholangiopathy (PCC) refers to a constellation of secondary changes in the biliary tree in patients with chronic portal vein (PV) thrombosis and portal cavernoma formation. These findings of PCC are seen in the extra-hepatic bile duct(s), with or without involvement of the 1st or 2nd degree intra-hepatic bile ducts.Of all patients with chronic PV thrombosis, cholangiographic features of PCC are found in 80%-100%. The biliary changes are symptomatic in a smaller proportion of 5%-38% patients. Choledocholithiasis and hepatolithiasis occur in 5%-20%, independent of the occurrence of cholelithiasis. We review the published literature on cholangiographic description of PCC. We also propose standardized nomenclature for the cholangiographic findings, namely: extrinsic impressions/indentations, shallow impressions, irregular ductal contour, stricture (s), upstream dilatation, filling defects, bile duct angulation, and ectasia. © 2013 INASL.


Gupta E.,Institute of Liver and Biliary science ILBS | Pandey P.,Institute of Liver and Biliary science ILBS | Pandey S.,Institute of Liver and Biliary science ILBS | Sharma M.K.,Institute of Liver and Biliary science ILBS | Sarin S.K.,Institute of Liver and Biliary science ILBS
Journal of Clinical Virology | Year: 2013

Background: Demonstration of active viral replication is important in serologically confirmed cases of hepatitis E virus (HEV) infection to assess prognosis. Detection of HEV RNA by reverse transcriptase polymerase chain reaction (rtPCR) is the gold standard for demonstration of active viremia. Objectives: The present study was designed to compare the diagnostic utility of HEV antigen (Ag) with HEV IgM and HEV rtPCR in detecting the active viral replication. Study design: Blood samples from 156 probable cases of acute viral hepatitis (AVH) were collected. Screening for hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti HCV), IgM antibody to hepatitis A virus (HAV IgM) was done on the Architect platform (Abbott Laboratories, IL, USA). HEV IgM ELISA (Wantai Biological, Beijing, China), HEV-Ag ELISA (Wantai Biological, Beijing, China) and HEV rtPCR were done on all the samples. Results: Out of 156 AVH cases in 56 (35.8%) a diagnosis of HEV was confirmed. Positivity being; anti-HEV IgM 44/56, HEV RNA 20/56, and HEV antigen 17/56 in established cases. Male to female ratio was 3:1. The median age was 40 (range 14-71) years. HEV Ag showed a good concordance with HEV RNA (k=0.635, p<. 0.001). However HEV IgM did not show any concordance with HEV RNA (k=0.14). Conclusion: HEV antigen assay can be used as an additional diagnostic marker to confirm active viral replication in serologically positive samples. © 2013 Elsevier B.V.

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