Vijayakumar Velu

The prevalence of hepatitis B virus and hepatitis C virus infection among patients with chronic liver disease in south India.

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.

Functional role of mucosal-associated invariant T cells in HIV infection.

MAIT cells represent an evolutionarily conserved, MR1‐restricted, innate‐like cell subset that express high levels of CD161; have a canonical semi‐invariant TCR iVα7.2; and may have an important role in mucosal immunity against various bacterial and fungal pathogens. Mature MAIT cells are CD161hiPLZFhiIL‐18Rα+iVα7.2+γδ‐CD3+CD8+ T cells and occur in the peripheral blood, liver, and mucosa of humans. MAIT cells are activated by a metabolic precursor of riboflavin synthesis presented by MR1 and, therefore, respond to many bacteria and some fungi. Despite their broad antibacterial properties, their functional role in persistent viral infections is poorly understood. Although there is an increasing line of evidence portraying the depletion of MAIT cells in HIV disease, the magnitude and the potential mechanisms underlying such depletion remain unclear. Recent studies suggest that MAIT cells are vulnerable to immune exhaustion as a consequence of HIV and hepatitis C virus infections and HIV/tuberculosis coinfections. HIV infection also appears to cause functional depletion of MAIT cells resulting from abnormal expression of T‐bet and EOMES, and effective ART is unable to completely salvage functional MAIT cell loss. Depletion and exhaustion of peripheral MAIT cells may affect mucosal immunity and could increase susceptibility to opportunistic infections during HIV infection. Here, we review some of the important mechanisms associated with depletion and functional loss of MAIT cells and also suggest potential immunotherapeutic strategies to restore MAIT cell functions, including the use of IL‐7 to restore effector functions in HIV disease.

Transmission of hepatitis C virus infection from asymptomatic mother to child in southern India

BACKGROUND Little information is available on the mother-to-child transmission of hepatitis C virus (HCV) in India, and no interventions to decrease transmission rates have been identified. Hence, we performed a long-term prospective study in infants born to HCV-positive mothers, with the aim of evaluating vertical transmission of HCV and correlated risks factors. METHODS Three thousand one hundred and fifteen healthy asymptomatic pregnant women were included in the study. We used third-generation (Murex anti-HCV) ELISA and HCV RNA reverse transcription PCR (RT-PCR) for screening, and the commercial line probe assay (Inno-LiPA) and direct sequencing HCV genotyping assays were performed to confirm the transmitted HCV genotypes. RESULTS Of the total 3115 healthy asymptomatic pregnant women, 18 (0.6%) were positive for anti-HCV. Of the 18 anti-HCV-positive women, eight (44.4%) were positive for HCV RNA RT-PCR. HCV transmission was observed in two of the eight babies born to eight HCV RNA-positive mothers who were followed up for 12 months. HCV genotyping of the mother/child pairs revealed the persistent presence of mixed genotypes 1a and 4 throughout the follow-up period. None of the non-viremic (HCV RNA-negative) mothers transmitted HCV infection to their baby. In our study approximately 25% of vertical/perinatal transmission of HCV was observed among HCV RNA-positive antenatal women. CONCLUSIONS This study is of importance as it is the first report from India of a successful attempt to analyze the rate of vertical/perinatal transmission of HCV from infected mothers to their children by a prospective longitudinal follow-up study, and to characterize the pattern of genotype(s) of HCV present in the infected mother/baby pairs, so as to confirm the source of HCV acquired by the newborn babies.

Seroprevalence of hepatitis delta virus infection among subjects with underlying hepatic diseases in Chennai, southern India

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.

High Prevalence of Hepatitis Delta Virus among Patients with Chronic Hepatitis B Virus Infection and HIV-1 in an Intermediate Hepatitis B Virus Endemic Region

We conducted a study to investigate HIV and hepatitis delta virus (HDV) coinfection among patients with chronic hepatitis B virus (HBV) infection and the triple infection’s (HIV/HBV/HDV) clinical implications in India, an intermediate HBV endemic region, with an estimated HIV-positive population of 2.5 million. A total of 450 patients (men: 270; women: 180) with chronic HBV infections and 135 healthy volunteers were screened for HIV and HDV. The incidence of the triple infection was low (4 [0.8%]) compared with dual infections of HIV-1/HBV (7 [1.5%]) and HBV/HDV (22[4.8%]). Among 21- to 40-year-olds, HBV/HDV coinfection (45.8%) and HBV/HDV/HIV-1 triple infection was predominant (75%). Among 11 patients coinfected with HIV-1/HBV, 4 (36%) were tri-infected and were also associated with chronic hepatitis and cirrhosis. The HDV coinfection was higher among patients coinfected with HBV/HIV-1, despite the declining trend in HDV infection among HIV-negative patients, as previously reported. Thus, it is important to assess the impact of HIV, chronic HBV, and HDV tri-infection in India.

Cold agglutinins in HIV-seropositive participants and diagnosis of respiratory disease due to Mycoplasma pneumoniae.

Objectives. Cold agglutinin (CA) titers are one among the first pathological indicators for diagnosing Mycoplasma pneumoniae disease. We prospectively studied the prevalence of CAs in 300 HIV-positive and 75 HIV-negative individuals with respiratory disease in Chennai, India. Methods. The cold agglutination test was used and retrospectively compared with the results of a particle agglutination test. Results. While CAs were positive in 51 HIV cases, particle agglutination test detected anti-M pneumoniae antibodies from 43 cases with HIV disease (P = .001). The seroprevalence of CAs was 2.6% (n = 2) among HIV-negative participants. The mean CD4 count in CApositive and -negative HIV cases was 107.4 + 121.2 and 259.2 + 247.2 cells/µL (P = .001), respectively. Conclusion. Our report suggests a basis for the existence of CAs in HIV-positive cases. Definitive diagnosis may be done only when CA detection is used in conjunction with a specific test.