Hepatitis: Balakrishnan P

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.

Kumarasamy N, Balakrishnan P, Venkatesh KK, Srikrishnan AK, Cecelia AJ, Thamburaj E, Solomon S, Mayer KH. · YRG Centre for AIDS Research and Education, Voluntary Health Service, Chennai, India. · AIDS Patient Care STDS. · Pubmed #18627276 No free full text.

Abstract: Sexually transmitted infections (STIs) have been identified as cofactors of HIV transmission. Greater understanding of local STI burdens can assist in the development of more effective STI and HIV prevention strategies. The aim of this study is to determine the prevalence and incidence of STIs among South Indian men and women identified to be at increased risk for HIV infection. Individuals at increased risk for HIV infection were enrolled in a prospective longitudinal study in Chennai, India (n = 480) between August 2002 and December 2003. Participants were enrolled from patients seeking services at an sexually transmitted disease (STD) clinic and a confidential HIV testing and counseling program. The most common prevalent STIs were herpes simplex virus (HSV)-2 (50% of women, 29% of men), syphilis (11% of women, 8% of men), and Trichomonas vaginalis (6% of women). At enrollment, women, participants with no schooling, participants with greater than four sex partners, and single participants were found to be at increased risk for HSV-2 infection (p < 0.05). The two most common incident STIs at 12 months were HSV-2 with 12% of men and 8% of women testing positive and hepatitis B with 2% of men and 5% of women testing hepatitis B surface antigen (HBsAg) positive. In this cohort of South Indian men and women with a high background prevalence of HSV-2, suppressive therapy against herpes replication may have a substantial impact in reducing both HSV-2 transmission and HIV acquisition. With the high incidence of STIs, targeted prevention and clinical management strategies among individuals practicing high risk behaviors may help to slow the continued spread of HIV in India.

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.

Kumarasamy N, Venkatesh KK, Cecelia AJ, Devaleenal B, Lai AR, Saghayam S, Balakrishnan P, Yepthomi T, Poongulali S, Flanigan TP, Solomon S, Mayer KH. · YRG Centre for AIDS Research and Education, VHS, Chennai, India. · AIDS Patient Care STDS. · Pubmed #18422462 No free full text.

Abstract: To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.

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, 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.