Premashis Kar

Hepatitis E virus infection and fulminant hepatic failure during pregnancy.

Background and Aim:  Hepatitis E virus (HEV) infection leading to fulminant hepatic failure (FHF) and high mortality is a common feature in Indian women during the second and third trimesters of pregnancy. An altered status of hormones and immunity are observed during pregnancy but the actual cause of high mortality is still unknown. The present study was carried out to analyze CD3, CD4 and CD8 T cell counts and to assay the level of pregnancy‐related hormones such as estrogen, progesterone and β‐HCG in order to discover the role played by these factors.

Does Hepatitis E Viral Load and Genotypes Influence the Final Outcome of Acute Liver Failure During Pregnancy

BACKGROUND:Hepatitis E is a major health problem in developing countries including India. The incidence and mortality rate in pregnant women with fulminant hepatic failure (FHF) due to hepatitis E virus (HEV) has been reported to be significantly higher, specifically in Asian women. Pregnancy is usually associated with an altered status of sex steroid hormones and immunity. Steroid hormones directly influence the replication through their effects on viral regulatory elements. Moreover, pregnant women in Asia generally suffer from folate deficiency, which is known to cause reduced immunocompetence leading to greater risk of multiple viral infections and higher viral load.OBJECTIVES:To correlate and analyze the viral load and genotypes of HEV in acute liver failure with that of acute viral hepatitis among pregnant and nonpregnant women.MATERIALS AND METHODS: A total of 100 FHF and 150 acute viral hepatitis (AVH) patients (50, 75 pregnant and 50, 75 nonpregnant, respectively), were included in the study. These cases were evaluated on the basis of history, clinical examination, liver function profile, and serological test of hepatitis A, B, C, and E using commercially available ELISA kits. Quantification of HEV RNA-positive samples was carried out.RESULTS:Out of 100 FHF and 150 acute viral hepatitis (AVH) patients, 28 (56%) and 22 (29.3%) pregnant and 7 (14%) and 8 (16%) nonpregnant, respectively, were HEV RNA-positive. HEV viral load in FHF pregnant women was 5.87 × 104± 1.5 × 105μ L/mL as compared to AVH pregnant women 343.29 ± 216.44 μL/mL and FHF and AVH nonpregnant 199.2 ± 225.5 μL/mL and 13.83 ± 7.8 μL/mL, respectively. Sequencing data of all the positive samples of FHF and AVH pregnant and nonpregnant women showed genotype 1.CONCLUSION:HEV viral load was found to be significantly higher (P < 0.05) in pregnant patients compared to the nonpregnant. Pregnancy appears to be a risk factor for viral replication. The viral copies of HEV in FHF pregnant women were comparatively higher when compared to AVH pregnant women, which may be related to the severity of the disease in these patients. We could detect only one genotype (genotype 1) in our study population. Thus in the absence of other genotypes in this population, the impact of genotype could not be adequately assessed in this study.

Role of polymorphic N-acetyl transferase2 and cytochrome P4502E1 gene in antituberculosis treatment-induced hepatitis.

Background and Aim:  Antituberculosis drugs, isoniazid and rifampicin, in combination, are known to develop drug‐induced hepatotoxicity (DIH). A higher risk of DIH during antituberculosis treatment (ATT) has been reported in the Indian subcontinent compared to its Western counterparts. The role of genetic factors in a higher incidence of ATT hepatotoxicity in the Indian population is still unclear. The present study was aimed at investigating the role of the N‐acetyltransferase2 (NAT2) and cytochrome P4502E1 (CYP2E1) gene polymorphisms in ATT hepatotoxicity.

Prevalence of transfusion‐transmitted virus infection in patients on maintenance hemodialysis from New Delhi, India

Transfusion‐transmitted virus (TTV) has been reported from a number of hemodialysis (HD) units from various countries throughout the world. TTV has been associated with liver diseases, viral hepatitis B, and C. Clinical details and information regarding TTV prevalence from India are insufficient. The prevalence and clinical significance of TTV infection were studied in New Delhi, India in HD patients. Serum samples were derived from 75 patients on maintenance HD, and 75 age‐ and sex‐matched voluntary blood donors were examined for TTV viremia by nested polymerase chain reaction (PCR) using primers derived from UTR (A) region of the TTV genome. The prevalence of TTV DNA in patients on HD (83%) was significantly (p<0.05) higher than in blood donors (43%). Clinical background including the mean age, sex, mean duration of HD, and mean alanine aminotransferase (ALT) levels did not differ significantly between TTV DNA‐positive and ‐negative HD patients. Fifty‐four (72%) TTV‐positive HD patients and 7 (56%) TTV‐negative HD patients had blood transfusion histories (p>0.05). Among TTV‐positive patients, Hepatitis B virus (HBV) co‐infection was present in 14.2% cases while hepatitis C virus (HCV) co‐infection was absent. Persistent elevation of ALT levels was observed in 7(9.3%) HD patients; 3 (43%) of them were TTV positive and 4 (57%) were TTV negative (p>0.05). All 3 TTV‐positive patients with elevated ALT levels were co‐infected with HBV. Patients with TTV infection alone showed normal ALT levels. Prevalence of TTV infection is high in North Indian patients on maintenance HD. Also, none of the exclusively TTV DNA‐positive patients had clinical or biochemical signs of liver disease. TTV seems to spread through parenteral routes. More often, TTV seems to be associated with parenterally transmitted virus HBV, indicating a parenteral mode of TTV transmission. The pathogenicity of TTV remains unclear from the present study.

Role of hepatitis E and other hepatotropic virus in aetiology of sporadic acute viral hepatitis: a hospital based study from urban Delhi.

Major hepatotropic virus continues to be an important cause of acute viral hepatitis (AVH) in developing countries like India. While epidemics of AVH have been well studied few serious sporadic cases from developing countries have been reviewed. We studied prospectively 75 cases of sporadic AVH who reported to our hospital and were evaluated for the presence of various hepatotropic viruses. The seroprevalence of IgG anti-HEV antibodies was studied in the general population as a control. We found 53.3% (40/75) of sporadic AVH cases were due to hepatitis E virus while 11% (8/75) were due to hepatitis B virus. Hepatitis C virus was responsible for 8% (6/75) of the sporadic AVH cases and hepatitis A was found in 5% (4/75) of the cases. No causative agent was found in 23% (17/75) of the sporadic AVH cases. The sporadic AVH cases due to HEV were not clinically or biochemically not different from AVH due to other viruses. We found a high prevalence of IgG anti-HEV in 35.6% (178/500) among the general population of urban Delhi. The study suggested that hepatitis E was the most common cause of sporadic AVH in urban Delhi. High seroprevalence of IgG anti-HEV antibodies in the general population and amongst the sporadic AVH cases suggests that it is unlikely to be protective antibody. IgM anti-HEV positive serology is considered diagnostic of acute hepatitis E infection in India, where hepatitis E is endemic.

Evidence of extrahepatic replication of hepatitis E virus in human placenta.

The incidence and severity of hepatitis E virus (HEV) infection in pregnant women is high in developing countries. Transplacental transmission of HEV in the third trimester of pregnancy has been found to be associated with high fetal mortality. Based on this evidence and in the absence of reports on HEV replication in extrahepatic sites, this study was carried out to investigate if HEV replication occurs in the placenta of infected mothers. The study included 68 acute viral hepatitis (AVH) and 22 acute liver failure (ALF) pregnant patients. Viral RNA was extracted from blood and placenta. HEV replication in placenta was confirmed by a replicative negative-strand-specific reverse transcriptase PCR. Viral load was estimated by real-time PCR. Immunohistochemical studies were also carried out for in situ detection of HEV in placental tissue sections. Replicative HEV RNA was detectable only in the placenta in ALF and AVH cases and not in blood samples. Positive staining of placental tissue sections with HEV antibody against the viral structural protein ORF3 was observed. HEV replication in placenta also correlated with fetal and maternal mortality in ALF patients. It is demonstrated for the first time that HEV replication occurs in human placenta and that placenta may be a site of extrahepatic replication of HEV in humans.

Increasing trend of acute hepatitis A in north India: Need for identification of high-risk population for vaccination

Background and Aims:  Hepatitis A (HAV) is endemic in India and most of the population is infected asymptomatically in early childhood with lifelong immunity. Because of altered epidemiology and decreasing endemicity, the pattern of acute HAV infection is changing from asymptomatic childhood infection to an increased incidence of symptomatic disease in the 18–40 age group. The aims of the present study were to assess whether the proportion of adults with acute HAV infection has been increasing over the years and to analyze the seroprevalence of immunoglobulin G (IgG) anti‐HAV antibodies in young adults above the age of 15 years as well as in cases of chronic liver disease.

Hepatitis B virus BCP, Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India.

The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV‐related HCC cases and 136 HBV‐related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non‐HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patients age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto‐protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India. J. Med. Virol. 82: 1115–1125, 2010.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part I: Status Report of HCV Infection in India

Globally, around 150 million people are infected with hepatitis C virus (HCV). India contributes a large proportion of this HCV burden. The prevalence of HCV infection in India is estimated at between 0.5% and 1.5%. It is higher in the northeastern part, tribal populations and Punjab, areas which may represent HCV hotspots, and is lower in western and eastern parts of the country. The predominant modes of HCV transmission in India are blood transfusion and unsafe therapeutic injections. There is a need for large field studies to better understand HCV epidemiology and identify high-prevalence areas, and to identify and spread awareness about the modes of transmission of this infection in an attempt to prevent disease transmission.

Does high viral load of hepatitis E virus influence the severity and prognosis of acute liver failure during pregnancy

The incidence and mortality in pregnant women with acute liver failure caused by hepatitis E virus (HEV) is high. Data on the viral load of HEV during pregnancy are limited. The study was designed to determine the viral load of HEV and its association with the disease severity in patients with acute liver failure. A total of HEV related 163 patients with acute liver failure which included 105 pregnant, 46 non‐pregnant women and girls and 12 men and 730 patients with acute viral hepatitis which comprised of 220 pregnant women; 282 non‐pregnant women and girls and 228 men were included. Viral load was measured by real‐time PCR. Comparison was made between the pregnant and non‐pregnant women. HEV RNA was detectable in 265 patients (142 pregnant; 75 non‐pregnant and 48 men) and 104 patients with acute liver failure (64 pregnant, 34 non‐pregnant and 6 men). The viral load of HEV in pregnant women with acute liver failure and acute viral hepatitis was significantly higher 129,984.0 ± 103,104.17 and 768.92 ± 1,105.40 copies/ml, respectively compared to the non‐pregnant women which was 189.2 ± 225 and 12.73 ± 7.8 copies/ml (P < 0.0001). The viral load of HEV was also significantly higher in the pregnant patients with acute liver failure compared to the pregnant women with acute viral hepatitis and also men (P < 0.0001). High viral load of HEV during pregnancy could be one of the factors responsible for the severity of the infection during pregnancy. J. Med. Virol. 85:620–626, 2013.