Hepatitis: Murugavel KG

Shankar EM, Solomon SS, Vignesh R, Murugavel KG, Sundaram M, Solomon S, Balakrishnan P, Kumarasamy N. · YRG Centre for AIDS Research and Education (YRG CARE), Voluntary Health Services Hospital Campus, IT Corridor, Taramani, Chennai 600 113, India. · Trans R Soc Trop Med Hyg. · Pubmed #18513775 No free full text.

Abstract: The GB virus (GBV)/hepatitis G virus is a member of the Flaviviridae family and belongs to the hepatitis group of viruses transmitted parenterally, common among intravenous drug users. The strong association between GBV and HIV infection suggests that the two viruses may share similar epidemiological and transmission features. GBV infection is widely believed to prolong HIV disease progression as well as decreasing the HIV viral load and increasing the CD4(+) T-cell level. GBV-driven anti-E2 antibodies have been shown to inhibit HIV replication in vitro. Preliminary studies also suggest that GBV infection of peripheral blood mononuclear cells leads to increased production of beta-chemokines, which may explain the in vitro inhibitory effects and warrants further studies. With sufficient knowledge of resistance patterns studied in tropical south India, researchers are now keen to study the competitive interactions between GBV-induced chemokines and HIV ligands to bind CCR5.

Saravanan S, Velu V, Nandakumar S, Madhavan V, Shanmugasundaram U, Murugavel KG, Balakrishnan P, Kumarasamy N, Solomon S, Thyagarajan SP. · Department of Microbiology, Faculty of Medicine, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India. · J Microbiol Immunol Infect. · Pubmed #19597643 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection accounts for a substantial proportion of liver diseases worldwide. Although the exact prevalence is not known, these viral infections are common among patients with chronic liver disease (CLD). This study was performed to determine the prevalence of HBV and HCV dual infection among patients with CLD in Chennai, India. METHODS: 251 patients were tested for the presence of hepatitis B surface antigen (HBsAg), immunoglobulin (Ig)-M/IgG antibody to hepatitis B core antigen (anti-HBc) and anti-HCV antibodies, and HBV-DNA and HCV-RNA by qualitative polymerase chain reaction. RESULTS: Coinfection with HCV and HBV was detected in 15 patients (5.9%), 12 of whom (80.0%) were positive for HCV-RNA and IgG anti-HBc with no evidence of HBV-DNA, while 3 HBsAg-negative patients (20.0%) were positive for HBV-DNA in addition to HCV-RNA. Liver function test profiles were significantly altered for HCV-positive patients compared with HBV-positive and HBV/HCV coinfected patients (p = 0.001). Bilirubin and alanine aminotransferase levels were significantly raised in coinfected patients compared with non-HBV, non-HCV patients (p = 0.001). CONCLUSIONS: The results demonstrated that HBV was predominantly associated with underlying CLD among this group of patients in India and suggest that HBV coinfection in HCV-infected patients should not be excluded by negative HBsAg status alone.

Shanmugam S, Velu V, Nandakumar S, Madhavan V, Shanmugasundaram U, Shankar EM, Murugavel KG, Balakrishnan P, Kumarasamy N, Solomon S, Thyagarajan SP. · YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services, Chennai 600 113, India. · J Microbiol Biotechnol. · Pubmed #18955826 links to  free full text

Abstract: The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBeAg, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

Solomon SS, Srikrishnan AK, Mehta SH, Vasudevan CK, Murugavel KG, Thamburaj E, Anand S, Kumar MS, Latkin C, Solomon S, Celentano DD. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · J Acquir Immune Defic Syndr. · Pubmed #18845962 No free full text.

Abstract: OBJECTIVE: To estimate the prevalence of HIV and hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfections and current risk behaviors among HIV-positive and -negative injection drug users (IDUs) in Chennai, India. METHODS: Cross-sectional analysis of a convenience sample of 912 IDUs recruited between March 2004 and April 2005. Specimens were tested for HIV, HBV, and HCV. Adjusted prevalence ratios (PRs) were estimated using Poisson regression with robust variance estimates. RESULTS: The prevalence of HIV, hepatitis B surface antigen, and anti-HCV were 29.8%, 11.1%, and 62.1%, respectively. Among HIV-infected IDUs, prevalence of coinfection with anti-HCV and hepatitis B surface antigen/anti-HCV were 86% and 9.2%, respectively. In multivariate analysis, injecting at a dealer's place (PR: 1.57) and duration of injection drug use >or=11 years (PR: 3.02) were positively associated with prevalent HIV infection. Contrastingly, alcohol consumption >or=1 per week (PR: 0.55) was negatively associated with HIV. HIV-positive IDUs were as or more likely compared with HIV-negative IDUs to report recent high-risk injection-related behaviors. CONCLUSIONS: There is a high burden of HIV, HCV, and HBV among IDUs that needs to be addressed by improving access to therapies for these infections; furthermore, preventive measures are urgently needed to prevent further spread of HIV, HBV, and HCV in this vulnerable population.

Murugavel KG, Mathews S, Jayanthi V, Shankar EM, Hari R, Surendran R, Vengatesan A, Raghuram K, Rajasambandam P, Murali A, Srinivas U, Palaniswamy KR, Pugazhendhi T, Thyagarajan SP. · Infectious Diseases Laboratory, YRG Centre for AIDS Research & Education, VHS Hospital Campus, Taramani, Chennai 600 113, India. · Int J Infect Dis. · Pubmed #18658001 No free full text.

Abstract: OBJECTIVES: The prevalence of hepatitis B virus (HBV) is reportedly the main cause of hepatocellular carcinoma (HCC) in India, where hepatitis C virus (HCV)-associated HCC is believed to be relatively less prevalent. We verified the usefulness of alpha-fetoprotein (AFP) as a tumor marker and analyzed the influence of viral etiology on AFP levels in HCC. METHODS: Of a total of 1012 cases with liver disease, 202 were investigated for the presence of AFP (142 HCC cases, 30 cirrhosis cases, and 30 chronic liver disease (CLD) cases). In addition, serum samples from 30 healthy patients, 30 hepatitis B surface antigen (HBsAg) carriers, and 30 acute viral hepatitis cases were included as controls. AFP was quantitatively determined using a commercial ELISA (Quorum Diagnostics, Canada). Out of the 142 HCC cases screened for AFP, aflatoxin B1 (AFB1) detection was carried out in 38 HCC cases using an in-house immunoperoxidase test. RESULTS: In HBV and HCV co-infected HCC cases, the AFP positivity was 85.7%. In HBV alone-associated HCC, the positivity was 62.9%, and 54.5% of AFB1 positive HCC cases showed AFP positivity. In HBV and HCV negative HCC cases, the positivity was 20.5%, and in HCV-associated HCC it was 17.6%. The HBV/HCV co-infected group and HBV alone positive HCC cases had significantly elevated levels of AFP. When AFP positivity was analyzed based on the marker profile of HBV, 89.7% of AFP positive cases were HBV-DNA positive. CONCLUSIONS: The overall positivity pattern of AFP in HCC does indicate that higher levels of AFP are observed with hepatitis virus positivity, especially with HBV. Further studies must be carried out to correlate the serum levels of AFP with the size, number, and degree of differentiation of HCC nodules.

Saravanan S, Velu V, Kumarasamy N, Shankar EM, Nandakumar S, Murugavel KG, Balakrishnan P, Solomon S, Thyagarajan SP. · Indian Council of Medical Research Referral Centre for Chronic Hepatitis and Molecular Virology, Department of Microbiology, University of Madras, Chennai 600 113, India. · Trans R Soc Trop Med Hyg. · Pubmed #18556033 No free full text.

Abstract: Four hundred million people are carriers of hepatitis B virus (HBV) worldwide and approximately 5% of these are reportedly positive for hepatitis delta virus (HDV). Several reports indicate a declining trend in the occurrence of HDV infection in the north of tropical India. To our knowledge, no study has been conducted to evaluate whether a similar epidemiological change is occurring in southern India. Therefore we evaluated the seroprevalence of HDV among 153 individuals with HBV-related liver diseases in Chennai, and assessed any change in epidemiological pattern by comparing the results with seroprevalence figures reported previously. Of the 153 patients screened, nine (5.9%) were reactive to anti-delta antibodies, six (3.9%) presented an evidence of past infection (IgG anti-delta positive) and three (2.0%) showed anti-HDV IgM, suggestive of recent HDV infection. Alanine transaminase elevation was not significant in HDV-associated infection compared with HBV alone-infected acute viral hepatitis (AVH) (P=0.82) and chronic liver disease (P=0.77) patients. The anti-HDV positivity in AVH was considerably low (6.6%), compared with previous Indian reports varying from 10.7% to >30%. HDV infection was relatively low and seems to play a minor determining factor of liver diseases in the tropical south Indian population.

Saravanan S, Velu V, Kumarasamy N, Shankar EM, Nandakumar S, Murugavel KG, Balakrishnan P, Solomon SS, Solomon S, Thyagarajan SP. · Department of Microbiology, Faculty of Medicine, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai 600 113, India. · Int J Infect Dis. · Pubmed #18455943 No free full text.

Abstract: OBJECTIVE: Determining the identity of hepatitis C virus (HCV) genotypes in liver disease has key implications for ascertaining the duration of antiviral therapy and disease prognosis. We investigated the presence of various genotypes of HCV among 69 chronic liver diseased (CLD) patients with chronic HCV infection. METHODS: Sixty-nine consecutive subjects with underlying chronic hepatitis (n=28), cirrhosis (n=35), and hepatocellular carcinoma (n=6), diagnosed by clinical, biochemical, and histological means, were studied. Hepatitis B virus (HBV) and HCV diagnostic markers were used. HCV-RNA was extracted from sera of HCV-infected subjects and subsequently the HCV genotypes were determined using a commercial line probe assay (Inno-LiPA HCV II). RESULTS: Of the 69 CLD cases screened for possible markers of HBV and HCV infection, 39 (57%) were positive for HBV and 30 (43%) were HCV infected. The overall HCV-RNA positivity was 77% (23/30). Of these, the majority were genotype 1b (13/23, 57%), followed by 1a (6/23, 26%), mixed genotypes 3 and 4(3/23, 13%), and mixed pattern of 1a, 1b, and 4 (1/23, 4.3%). The genotype 1b infected subjects demonstrated significantly elevated transaminase (ALT) levels (p<0.05) as compared with the other non-1b HCV genotypes. CONCLUSIONS: The predominance of HCV genotype 1b among CLD patients could pose a major challenge for the efficient management of HCV disease and the development of effective therapeutic interventions in peninsular India.

Velu V, Saravanan S, Nandakumar S, Dhevahi E, Shankar EM, Murugavel KG, Kumarasamy T, Thyagarajan SP. · Department of Medical Microbiology, Dr ALM Post Graduate Institute of Basic Medical Sciences and National Referral Centre for Viral Hepatitis, University of Madras, Chennai, India. · Jpn J Infect Dis. · Pubmed #18219140 links to  free full text

Abstract: Hepatitis B virus (HBV) surface antigen mutations may lead to immune escape and eventually cause failure of immunization. In this report, we identified immune escape variants in immunized babies born to hepatitis B surface antigen (HBsAg) carrier mothers. A total of 68 babies were followed up for 2 years after the full course of vaccination; 2.9% (2/68) of babies were found to be infected with the variant HBV in spite of preexisting antibody to surface antigen (anti-HBs) at 24 months post immunization. Both infants were positive for HBV-DNA; sequencing results of the "a" determinant region of the surface gene revealed that both babies had point mutations at a different nucleotide position resulting in various amino acid substitutions. In addition, an intriguing variant having an addition-deletion mutation was observed in one of the babies. This is the first report to show the addition-deletion variant of HBV in India. However, the immunological significance of the above HBV variants needs to be further elucidated.

Murugavel KG, Naranatt PP, Shankar EM, Mathews S, Raghuram K, Rajasambandam P, Jayanthi V, Surendran R, Murali A, Srinivas U, Palaniswamy KR, Srikumari D, Thyagarajan SP. · Department of Microbiology, Faculty of Medicine, Dr ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India. · J Med Microbiol. · Pubmed #17965344 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death in the world. The incidence of HCC in India is reportedly low and varies from 0.2 to 1.9 %. Aflatoxins, secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus, are potent human carcinogens implicated in HCC. The prevalence of aflatoxin B1 (AFB1) as co-carcinogen was analysed using an in-house immunoperoxidase test in 31 liver biopsies and 7 liver-resection specimens from histopathologically proven HCC, and in 15 liver biopsies from cirrhosis patients (control group). Serum was tested for hepatitis B and C serological markers using commercial assays, and for AFB1 using an in-house ELISA with a sensitivity of approximately 1 ng ml(-1) for AFB1. In spite of positive AFB1 immunostaining in HCC cases, all serum specimens, from both HCC and the control groups, were AFB1-negative. There were 18 (58.1 %) HCC cases that revealed AFB1 in liver biopsies; 68.8 % (n=11) of non-B non-C hepatitis cases with HCC and 46.1 % (n=6) of the hepatitis B surface-antigen-positive subjects were positive for AFB1. Out of the two hepatitis B/hepatitis C virus co-infected cases, one was positive for AFB1. Of seven tumour-resection samples, six were positive for AFB1. Only one case revealed AFB1 in the non-tumour area of the resected material. Thus AFB1 staining was significantly associated with tumour tissue (P=0.03). Aflatoxins proved to have a significant association with HCC in this peninsular part of the subcontinent. The impact seems to be a cumulative process, as revealed by the AFB1 deposits in HCC liver tissue, even though the serum levels were undetectable.

Saravanan S, Velu V, Kumarasamy N, Nandakumar S, Murugavel KG, Balakrishnan P, Suniti S, Thyagarajan SP. · YRG Centre for AIDS Research and Education, VHS Campus, Taramani, Chennai 600 113, India. · World J Gastroenterol. · Pubmed #17854146 links to  free full text

Abstract: AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-RNA) using commercially available ELISA kits; HBsAg, HBeAg/anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV. RESULTS: HBV co-infection was detected in 45/500 (9%) patients and HCV co-infection in 11/500 (2.2%) subjects. Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55% (22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6 (54.5%) were anti-HCV and HCV RNA positive, while 3 (27.2%) were positive for anti-HCV alone and 2 (18%) were positive for HCV RNA alone. CONCLUSION: Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients. Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest.

Marx MA, Murugavel KG, Tarwater PM, SriKrishnan AK, Thomas DL, Solomon S, Celentano DD. · Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Clin Infect Dis. · Pubmed #12905135 No free full text.

Abstract: To determine the association between sexual exposure and hepatitis C virus (HCV) infection in urban Chennai, India, a random sample of adults who live in a slum community completed interviews and provided samples to test for HCV, herpes simplex virus type 2 (HSV-2), and other sexually transmitted infections (STIs). All analyses excluded recent and current injection drug users. HCV infection was not associated with the reported number of sex partners for men or women. Women were more likely to be HCV infected if they reported previous genital ulcer disease (adjusted odds ratio [AOR], 3.88; 95% confidence interval [95% CI], 0.94-16.0; marginally statistically significant). Men were more likely to be HCV infected if they were HSV-2 infected (AOR, 3.85; 95% CI, 1.18-12.6) or reported having had sex with men (AOR, 3.61; 95% CI, 1.00-13.1). Sexual transmission of HCV infection may be facilitated by ulcerative STIs and male-male sexual practices, but it appears to occur infrequently in this population.

Marx MA, Murugavel KG, Sivaram S, Balakrishnan P, Steinhoff M, Anand S, Thomas DL, Solomon S, Celentano DD. · Johns Hopkins Bloomberg School of Public Health, USA. · Am J Trop Med Hyg. · Pubmed #12641422 links to  free full text

Abstract: To determine whether health-care use was associated with prevalent hepatitis C virus (HCV) infection in Chennai, India, 1,947 adults from 30 slum communities were randomly selected to be interviewed about parenteral and sexual risks for HCV infection and to provide biological specimens for HCV and sexually transmitted infection (STI) testing. Prevalent HCV infection was detected in 2.4% of non-injection drug using (IDU) participants. Controlling for other associated factors, and excluding IDU, men who used informal health-care providers were five times as likely to be HCV infected as those who did not use informal providers (Adjusted Odds Ratio, AOR = 5.83; 95% confidence interval [CI]: 1.57, 21.6), a finding not detected in women. More research is needed to determine the extent to which HCV infection is associated with reuse of contaminated injection equipment in health-care settings in developing countries.

Mohan KV, Murugavel KG, Rajanikanth, Mathews S, Raghuram K, Rajasambandam P, Murali A, Srinivas U, Mathiazhagan, Palaniswamy KR, Panda SK, Thyagarajan SP. · Department of Microbiology, Dr ALMPGIBMS, Taramani, Chennai. · Indian J Gastroenterol. · Pubmed #10319537 No free full text.

Abstract: OBJECTIVES: To evaluate the efficacy of second-generation ELISA (ELISA-2), third-generation ELISA (ELISA-3) and third-generation recombinant immunoblot assay (RIBA 3.0) for detection of antibodies to hepatitis C virus (anti-HCV) in comparison with reverse transcriptase-polymerase chain reaction (RT-PCR) to detect HCV RNA for the diagnosis of hepatitis C. METHODS: Sera of 108 patients with chronic liver disease (CLD) were analyzed by ELISA-2, ELISA-3, RIBA 3.0 and RT-PCR in the first part of the study; in the second part, sera of 105 patients with non-chronic liver disease were evaluated with ELISA-3, RIBA 3.0 and RT-PCR. RESULTS: In the CLD group, anti-HCV was positive in 4.6%, 14.8% and 16.6% by ELISA-2, ELISA-3 and RIBA 3.0, respectively. Among these anti-HCV positive cases, HCV RNA was positive in 100%, 58.9% and 64%, respectively. ELISA-2 did not give false-positive results, but missed substantial number of anti-HCV positive cases (p < 0.001). In the second group, anti-HCV was positive in 76.3% by ELISA-3 and 68.6% by RIBA 3.0 (p:ns). HCV-RNA was positive in 88.7% of ELISA- and RIBA-positive cases; in 60% of ELISA-positive, RIBA-indeterminate cases; and in 46.4% of ELISA-negative, RIBA-negative cases. CONCLUSIONS: ELISA-2 is not a suitable assay for routine screening. ELISA-3 was at par with RIBA 3.0 and it can be recommended for routine screening for anti-HCV. RT-PCR for HCV is of value in detecting early viremic, anti-HCV negative cases; this may be of importance in the treatment of hepatitis C.