Chronic Liver Disease In India Research Articles

ASPARTATE PLATELET RATIO INDEX AS A PREDICTOR OF SEVERITY OF FIBROSIS IN CHRONIC HEPATITS C

Introduction: Hepatitis C is an important emerging cause for chronic liver disease in India, with high risk for chronicity and hepatocellular carcinoma. Chronic hepatitis C (CHC) is the most common cause for chronic liver disease and cirrhosis, and liver transplantation. Liver biopsy is the gold standard for evaluation of fibrosis - however it remains fraught with drawbacks and limitations. The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability is a promising non-invasive alternative to liver biopsy for detecting hepatic fibrosis in CHC. Objectives: (1) The objectives of the study were to determine the association between APRI and severity of fibrosis in Hepatitis C (2) and to describe the clinical profile of patients with Hepatitis C. Methods: A cross-sectional descriptive study in 60 patients diagnosed with hepatitis C for more than 6 months admitted to the General Medicine and Medical Gastroenterology Departments of Govt Medical College, Kottayam. Data were collected with a structured pro forma and analyzed using SPSS. Results: 35 of 60 patients belonged to METAVIR F3 (severe fibrosis) and F4 (cirrhosis). An APRI of 0.5 was associated with a finding of F3 or F4 with a sensitivity of 97.14% and a specificity of 88%. 31 of the 60 patients belonged to F4. An APRI of 1.5 or more was a predictor for cirrhosis with a sensitivity of 93.1% and specificity of 96.77%. The positive predictive value of cirrhosis APRI threshold >1.5 is 96.4%.

Correlation of APRI Index with Metavir Index in Children with Neonatal Cholestasis Without Biliary Atresia

Introduction and aim. Neonatal cholestasis constitutes for 19 to 33% of all chronic liver disease in India. Cholestasis leads to fibrosis of liver and ultimately cirrhosis. There are various methods of diagnosis of fibrosis of liver like fibroscan, aspartate transaminase to platelet ratio index (APRI) index, FIB-4, fibro index, forns index, heap score, magnetic elastography. Here we are comparing APRI index with METAVIR index in patients with neonatal cholestasis without biliary atresia and determining whether APRI index can be used as a tool to determine fibrosis in these patients.Material and methods. Patients with neonatal cholestasis without biliary atresia were included in the study. This retrospective analysis was done between 2009 and 2015. All patients underwent a liver biopsy and METAVIR index was calculated. APRI at the time of liver biopsy was determined.Results. Forty-eight patients were included in this study with mean age of 3.5 ± 2.8 months with a male: female ratio of 35:13. Metavir Index F0 was seen in was 32 (66.67%) patients, F1 in 6(12.5%), F2 in 4(8.33%), F3 in 0 and F4 in 6(12.5%) patients respectively. Mean APRI for F0-F3 was 1.38 and for F4 was 3.74 respectively. With an APRI of 1.38, the sensitivity and specificity to detect fibrosis/cirrhosis was 100% and 21.43% respectively.Conclusion. APRI is not an effective tool to measure fibrosis or cirrhosis in patients with non-BA neonatal cholestasis in Indian children.

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

Translation and validation of the Hindi version of chronic liver disease questionnaire (CLDQ) for the assessment of health related quality of life in patient with chronic liver disease in India

Chronic liver disease questionnaire (CLDQ) is an established disease specific tool to assess the health related quality of life (HRQOL) in patients with CLD irrespective of the etiology and severity. The objective of the study was to develop the Hindi language version of CLDQ and to assess the validity of the Hindi CLDQ. CLDQ was adapted into Hindi language by following a standard method of forward and back-translation by two bilingual translators, revision by expert panel and formulation of a consensual version followed by pilot testing and appropriate modifications before final administration. Hindi CLDQ along with short form 36 (SF-36) were administered in 494 patients with chronic liver disease (CLD) and 103 healthy controls (HC). To assess reproducibility, Hindi CLDQ was re-administered in a subsample of 20 patients. Internal consistency was assessed by Cronbach’s alpha coefficient. Structural validity was assessed by exploratory factor analysis and construct validity was assessed with help of correlation of SF-36 scores and CLDQ pattern across disease severity groups. The Cronbach’s alpha coefficient was 0.93 and intra class coefficient correlation was 0.88 for the average CLDQ score, suggestive of good reliability. An inverse relationship of the average CLDQ score with the disease severity (CLDQ score of Child A vs. B vs. C = 5.2±1.10 vs. 4.73±1.24 vs. 4.15±1.19 respectively; p<0.001) and good correlation with SF-36 scores (average CLDQ score with PCS & MCS; r=0.63 & 0.55; p<0.001) was suggestive of good validity of Hindi CLDQ. The factor analysis identified 6 domains accounting for 62% of variability. The derived cut-off of 6 for the average CLDQ had the AUC of 0.826 with a sensitivity of 76.7. Hindi version of CLDQ is found to be a reliable and a valid tool comparable to the original English version. The HRQOL of patients with CLD is lower than healthy controls and HRQOL decreases with increase in disease severity.

Genetic variants of TNFα, IL10, IL1β, CTLA4 and TGFβ1 modulate the indices of alcohol-induced liver injury in East Indian population

Alcohol induced liver disease or alcoholic liver disease (ALD), a complex trait, encompasses a gamut of pathophysiological alterations in the liver due to continuous exposure to a toxic amount of alcohol (more than 80g per day). Of all chronic heavy drinkers, only 15–20% develops hepatitis or cirrhosis concomitantly or in succession. Several studies revealed that inter-individual as well as inter-ethnic genetic variation is one of the major factors that predispose to ALD. The role of genetic factors in ALD has long been sought for in ethnically distinct population groups. ALD is fast emerging as an important cause of chronic liver disease in India; even in populations such as “Bengalis” who were “culturally immune” earlier. While the genetic involvement in the pathogenesis of ALD is being sought for in different races, the complex pathophysiology of ALD as well as the knowledge of population level diversity of the relevant alcohol metabolizing and inflammatory pathways mandates the need for well designed studies of genetic factors in ethnically distinct population groups. An array of cytokines plays a critical role as mediators of injury, inflammation, fibrosis and cirrhosis in ALD. We, therefore, studied the association of polymorphisms in five relevant cytokine genes with “clinically significant” ALD in an ethnic “Bengali” population in Eastern India. Compared with “alcoholic” controls without liver disease (n=110), TNFα −238AA genotype, IL1β −511CC genotype, TGFβ1 −509CC genotype and IL10 −592AA genotype were significantly overrepresented in ALD patients (n=181; OR=2.4 and 95% CI 1.2–5.5, Pgenotype=0.042, Pallelic=0.008; OR=2.7 and 95% CI 1.2–5.9, Pgenotype=0.018, Pallelic=0.023; OR=4.7 and 95% CI 1.7–13.1, Pgenotype=0.003, Pallelic=0.014; and OR=2.2 and 95% CI 1.1–4.8, Pgenotype=0.04, Pallelic=0.039 respectively). Moreover a cumulative genetic risk analysis revealed a significant trend for developing ALD with an increase in the number of risk alleles on IL10 and TGFβ1 loci among alcoholics. The risk genotype of IL1β and TGFβ1 also influences the total bilirubin, albumin and alanine aminotransferase levels among alcoholic “Bengalis”. The present study is the first case–control study from Eastern India that comprehensively identified polymorphic markers in TNFα, IL10, IL1β and TGFβ1 genes to be associated with ALD in the Bengali population, accentuating the significance of genetic factors in clinical expressions of ALD.

Comparative Study of Terlipressin, Somatostatin and Octreotide in Acute Esophageal Variceal Bleed: A Prospective Randomized Study

© 2011, INASL 13 CIRRHOSIS AND ITS COMPLICATIONS Comparative Study of Terlipressin, Somatostatin and Octreotide in Acute Esophageal Variceal Bleed: A Prospective Randomized Study CK Adarsh, KS Prasanna, H Devarbhavi, D Karanth, Mallikarjuna, B Girisha Department of Gastroenterology, St. Johns Medical College Hospital, Bangalore Background and Aims: Terlipressin, somatostatin and octreotide are known to reduce portal pressures and hence used as adjuvant therapy to endoscopic management of acute variceal bleed. However head to head comparison of above drugs has not been carried out. We evaluated the efficacy of these drugs with respect to control of acute variceal bleed, rebleed and mortality at 6 weeks. Methods: A total of 210 cirrhotic patients with esophageal variceal bleed were randomized to receive either somatostatin (group A = 73), terlipressin (group B = 69), or octreotide (group C = 68) prior to the endoscopic therapy. The drug was continued for 48 hours after endotherapy. Failure to control bleeding and rebleeding were defined according to Baveno-IV criteria. Results: Baseline characteristics of the three groups were comparable with respect to age, gender, etiology, Child-Pugh class, MELD score, duration of hospital stay, serum creatinine, serum sodium, active bleed seen during endoscopy and ascites. No significant difference was seen in failure to control bleed (group A vs. group B vs. group C: 15.1% vs. 18.8% vs. 25% p > 0.05), in hospital mortality (2.7% vs. 2.9% vs. 2.9%), rebleed at 6 weeks (13.7% vs. 15.9% vs. 26.5%, p > 0.05) and mortality at 6 weeks (13.7% vs. 10.1% vs. 17.6%, p > 0.05) among the three groups. On multivariate analysis, presence of portal hypertensive gastropathy, number of units of blood transfused and serum creatinine levels were independent predictors of failure to control bleed. Etiology of liver disease (ethanol and hepatitis C) and active bleed during endoscopy were independent predictors of mortality at 6 weeks. Child-Pugh class and serum sodium levels were independent predictors of rebleed at 6 weeks. Conclusion: The efficacy of somatostatin, terlipressin and octreotide as an adjuvant therapy for the control of acute esophageal variceal bleed, in-hospital survival, rebleed at 6 weeks and mortality at 6 weeks was comparable. Conflict of Interest: None A Study on Seroprevalence of Hepatitis A Antibody (IgG Anti-HAV) in Cirrhotic Patients DJ Payeng*, AK Das** *PGT, **Professor, Department of Medicine, Assam Medical College, Dibrugarh, Assam Background: Hepatitis A virus (HAV) vaccination is recommended in worldwide for cirrhotic patients to prevent decompensation due to superinfection with HAV. The prevalence of pre-existing antibodies against HAV due to subclinical exposure to the virus in childhood among cirrhotic patients may be high and, therefore, vaccination may not be needed. However, little data are available on the prevalence of HAV antibody among patients with chronic liver disease in India, especially in North East part of our country. Aims: To evaluate the seroprevalence of Hepatitis A virus anti-body (IgG anti-HAV) in cirrhotic patients and necessity of uniform vaccination against hepatitis A in these patients. Methods: Eighty cirrhotic patients attended in Department of Medicine, Assam Medical College and Hospital, during the period of 1 year were tested for the presence of IgG anti-HAV antibody (using a commercial ELISA kit). In addition, 100 apparently healthy subjects without liver disease were tested for the presence of IgG anti-HAV antibody in their sera. Results: Mean age of these cirrhotics and healthy group was 48.07 and 33.08 years and 67 (84%) and 70 (70%) of them were males, respectively. The seroprevalence of anti-HAV in two groups were 95% and 89%, respectively. In apparently healthy group, lower seroprevalence was observed in young adult (70%) than the rest. The prevalence of anti-HAV positivity was similar among patients with various etiologies. Conclusion: As there is a very high prevalence of pre-existing antibodies in these patients, uniform vaccination is not required. However those with negative anti-HAV are increased risk especially in young adult for developing fulminant hepatic failure should be vaccinated rendering cost effectiveness of vaccine. Conflict of Interest: None 03_JCEH-Abstract.indd 13 3/18/2011 11:13:03 AM

A Study on Seroprevalence of Hepatitis A Antibody (IgG Anti-HAV) in Cirrhotic Patients

© 2011, INASL 13 CIRRHOSIS AND ITS COMPLICATIONS Comparative Study of Terlipressin, Somatostatin and Octreotide in Acute Esophageal Variceal Bleed: A Prospective Randomized Study CK Adarsh, KS Prasanna, H Devarbhavi, D Karanth, Mallikarjuna, B Girisha Department of Gastroenterology, St. Johns Medical College Hospital, Bangalore Background and Aims: Terlipressin, somatostatin and octreotide are known to reduce portal pressures and hence used as adjuvant therapy to endoscopic management of acute variceal bleed. However head to head comparison of above drugs has not been carried out. We evaluated the efficacy of these drugs with respect to control of acute variceal bleed, rebleed and mortality at 6 weeks. Methods: A total of 210 cirrhotic patients with esophageal variceal bleed were randomized to receive either somatostatin (group A = 73), terlipressin (group B = 69), or octreotide (group C = 68) prior to the endoscopic therapy. The drug was continued for 48 hours after endotherapy. Failure to control bleeding and rebleeding were defined according to Baveno-IV criteria. Results: Baseline characteristics of the three groups were comparable with respect to age, gender, etiology, Child-Pugh class, MELD score, duration of hospital stay, serum creatinine, serum sodium, active bleed seen during endoscopy and ascites. No significant difference was seen in failure to control bleed (group A vs. group B vs. group C: 15.1% vs. 18.8% vs. 25% p > 0.05), in hospital mortality (2.7% vs. 2.9% vs. 2.9%), rebleed at 6 weeks (13.7% vs. 15.9% vs. 26.5%, p > 0.05) and mortality at 6 weeks (13.7% vs. 10.1% vs. 17.6%, p > 0.05) among the three groups. On multivariate analysis, presence of portal hypertensive gastropathy, number of units of blood transfused and serum creatinine levels were independent predictors of failure to control bleed. Etiology of liver disease (ethanol and hepatitis C) and active bleed during endoscopy were independent predictors of mortality at 6 weeks. Child-Pugh class and serum sodium levels were independent predictors of rebleed at 6 weeks. Conclusion: The efficacy of somatostatin, terlipressin and octreotide as an adjuvant therapy for the control of acute esophageal variceal bleed, in-hospital survival, rebleed at 6 weeks and mortality at 6 weeks was comparable. Conflict of Interest: None A Study on Seroprevalence of Hepatitis A Antibody (IgG Anti-HAV) in Cirrhotic Patients DJ Payeng*, AK Das** *PGT, **Professor, Department of Medicine, Assam Medical College, Dibrugarh, Assam Background: Hepatitis A virus (HAV) vaccination is recommended in worldwide for cirrhotic patients to prevent decompensation due to superinfection with HAV. The prevalence of pre-existing antibodies against HAV due to subclinical exposure to the virus in childhood among cirrhotic patients may be high and, therefore, vaccination may not be needed. However, little data are available on the prevalence of HAV antibody among patients with chronic liver disease in India, especially in North East part of our country. Aims: To evaluate the seroprevalence of Hepatitis A virus anti-body (IgG anti-HAV) in cirrhotic patients and necessity of uniform vaccination against hepatitis A in these patients. Methods: Eighty cirrhotic patients attended in Department of Medicine, Assam Medical College and Hospital, during the period of 1 year were tested for the presence of IgG anti-HAV antibody (using a commercial ELISA kit). In addition, 100 apparently healthy subjects without liver disease were tested for the presence of IgG anti-HAV antibody in their sera. Results: Mean age of these cirrhotics and healthy group was 48.07 and 33.08 years and 67 (84%) and 70 (70%) of them were males, respectively. The seroprevalence of anti-HAV in two groups were 95% and 89%, respectively. In apparently healthy group, lower seroprevalence was observed in young adult (70%) than the rest. The prevalence of anti-HAV positivity was similar among patients with various etiologies. Conclusion: As there is a very high prevalence of pre-existing antibodies in these patients, uniform vaccination is not required. However those with negative anti-HAV are increased risk especially in young adult for developing fulminant hepatic failure should be vaccinated rendering cost effectiveness of vaccine. Conflict of Interest: None 03_JCEH-Abstract.indd 13 3/18/2011 11:13:03 AM

Hepatitis B e antigen negative chronic hepatitis in Indian patients : A reality

Background: Hepatitis B e antigen negative chronic hepatitis (e − CHB) with detectable levels of hepatitis B virus DNA (HBV DNA) in serum has been reported in cases from Asia. This study was undertaken to find out prevalence e −CHB and to correlate its presence with the clinical status and severity of the illness in cases of chronic liver disease in India. Methods: All patients of infective hepatitis, who were hepatitis B surface antigen (HBsAg) positive by enzyme-linked immunosorbent assay (ELISA), were evaluated with liver function tests and HBeAg and antiHBe antibody studies. Polymerase chain reaction (PCR) test was carried out to detect HBV DNA qualitatively. Result: Out of 2064 samples tested by ELISA, 429 (20.78%) were HBsAg positive. HBV DNA (qualitative) was performed on all 429 patients and 74 (17.2%) were HBV DNA positive. Of these only 42 (56.75%) tested positive for HBeAg. Overall, 8.3% of HBeAg negative patients (32/384) were viraemic with evidence of chronic liver disease/clinical cirrhosis and alteration of transaminase levels, while three cases (0.84%) HBeAg positive cases did not show presence of HBV DNA. Conclusion: This study shows e −CHB prevalence rate of 8.3% in patients with HBV infection in India. Since HBeAg negative patients had detectable levels of HBV DNA as seen in HBeAg positive patients, benefit of antiviral therapy should be given to them. Population studies on e − CHB cases are needed to determine its true prevalence, natural course and response to therapy.

Hepatitis D Is an Important Cause of Decompensation in HBV Related Chronic Liver Disease in India

Purpose: To study the extrinsic causes and methods of decompensation in hepatitis B related chronic liver disease. Methods: 78 patients of CLD-B; 13 compensated and 65 recently (< 3 months) decompensated were included. ACLF was defined as acute deterioration in liver function over a period of 2–4 weeks in a pre-existing patient of CLD. Patients with alcohol intake > 20 g/day, concomitant HCC, chronic liver disease due other causes, HIV positivity or severe co-morbid conditions were excluded. Serological tests including IgM anti HAV, IgM anti HEV, HBsAg, HBeAg, Anti HBe, IgM anti HBc, Anti -HCV, IgM Anti-delta, HIV 1&2. HBV DNA was quantified. Results: 68 patients were followed-up; 56 were ACLF and 12 were compensated liver disease. Patients with ACLF presented alone or in combination as jaundice, ascites or variceal bleed in 78%, 61% and 11% patients respectively. ACLF patients had higher AST, ALT, bilirubin, CPT score and lower serum albumin than compensated CLD patients. IgM anti HBc was significantly higher in ACLD (p < 0.001) but median HBV DNA was comparable to compensated CLD patients {(12 (0.5–1129) vs. 1.7 (0.5–3809) pg/ml)}. The most common extrinsic causes of decompensation were Hepatitis E in 17.8% of patients followed by Hepatitis D in 14.2% cases. Hepatitis A in 3.5% and Hepatitis C in 1.8% were other minor causes of decompensation. Reactivation of HBV was the cause in about 63% patients. Conclusions: Besides reactivation of HBV, and superinfection by Hepatitis E, Hepatitis D infection is an important cause of recent decompensation and acute-on chronic liver failure in India.

Genotypes of GB virus C and hepatitis C virus in hepatitis patients in India, Iran and Slovenia

RNA of GB virus C (GBV-C) was detected in 12 of the 99 (12%) patients with chronic liver disease in India, including two of 11 (18%) with antibody to hepatitis C virus (HCV), as well as in six of the 21 (29%) patients with anti-HCV in Iran and 16 of the 54 (30%) patients with anti-HCV in Slovenia. Of the 99 patients in India, 47 were without serological markers of hepatitis B or C virus infection and four (9%) of them were positive for GBV-C RNA. Genotypes of GBV-C in the 34 samples from the three countries were invariably G2 that is prevalent in Europe and the United States. In contrast, the distribution of HCV genotypes were much different among them with 2c, 4d and 5a detected locally, in addition to I/1a, II/1b and V/3a. These results indicate frequent GBV-C infection with genetic divergence much less than that of HCV in patients with chronic liver disease in India, Iran and Slovenia.

Seroreactivity and Genomic Amplification Profile of Hepatitis C Virus From Patients With Chronic Liver Disease in India

Patients with chronic liver disease were screened initially for antibodies to the hepatitis C virus using commercially available assay systems. Positive sera were tested for amplification of the 5' noncoding region, and putative structural and nonstructural genomic regions of hepatitis C virus by reverse transcription-polymerase chain reaction. Eight out of 22 patients who were seropositive showed presence of viral RNA by amplification from genomic regions. Sera from four subjects showed amplification of the 5' noncoding region, a different serum showed amplification of the capsid region, and three other sera showed amplification of the nonstructural genomic region of the virus. An amplification profile of the RNA-positive samples suggests genomic sequence divergence of hepatitis C virus circulating among Indian patients.

Hepatitis C virus antibodies in acute and chronic liver disease in India

The prevalence of serum antibodies to hepatitis C virus was assessed by an enzyme-linked immunosorbent assay in patients with epidemic non-A, non-B hepatitis (14), sporadic non-A, non-B hepatitis (42), chronic hepatitis (14) and cirrhosis (26). None of the patients with epidemic non-A, non-B hepatitis (14) and acute self-limiting sporadic non-A, non-B hepatitis without prior parenteral exposure (38) tested positive for hepatitis C virus antibody. Based on epidemiologic features, hepatitis E virus is presumably the etiologic agent for both these entities. Hepatitis C virus (HCV) antibody was positive in none of the patients with cryptogenic chronic hepatitis (11) and in 2(8%) patients with cryptogenic cirrhosis (25). It was concluded that cryptogenic chronic hepatitis and cirrhosis in India may be caused by alternative viral agents of the non-A, non-B type or by hepatotoxins to which the population may be exposed. Of 8 patients with prior parenteral exposure (transfusions 6, needle pricks 2) 5 (62.5%) patients tested positive for HCV antibody. HCV antibody was detected in 1 (25%) patient with acute self-limiting, parenterally transmitted non-A, non-B hepatitis and in 4 (100%) patients with chronic parenterally transmitted non-A, non-B hepatitis.

Herbal medicines and veno-occlusive disease in India

Six cases are described of veno-occlusive disease (VOD) after medicinal herb ingestion. The herb Heliotropium eichwaldii, taken by three patients, was found to contain the toxic pyrrolizidine alkaloid, heliotrine. Two patients presented with fulminant hepatic failure while the other four patients had a clinical picture suggestive of decompensated cirrhosis. The medical use of this herb may possibly be responsible for a significant proportion of acute and chronic liver disease in India, making it of public health importance.