Nargis Begum

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.

Association of maternal periodontal health with adverse pregnancy outcome

Aim:  The present study aims to determine the association of periodontal disease (identified early in pregnancy) and adverse pregnancy outcomes in a North Indian population.

Latent celiac disease in reproductive performance of women

OBJECTIVE To investigate the prevalence of positive serologic findings for celiac disease in Indian women with poor reproductive performance. DESIGN Cross-sectional except that the women with intrauterine growth restriction were followed prospectively until delivery. SETTING Department of Obstetrics and Gynecology of a tertiary teaching hospital, New Delhi. PATIENT(S) Eight hundred ninety-three women (104 women with idiopathic recurrent abortion, 104 women with unexplained stillbirth, 230 cases of unexplained infertility, 150 pregnant women with idiopathic intrauterine growth restriction, 305 control cases). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The presence of antigliadin IgA and IgG, anti-tissue transglutaminase IgA by ELISA, and IgA antiendomysium antibody by indirect immunofluorescence microscopy. RESULT(S) The seroprevalence of transglutaminase IgA was 6.70% in the group with recurrent abortion, 5.70% in the group with stillbirth, 5.65% in the group with infertility, 9.33% in the group with intrauterine growth restriction, and 1.30% in the control group. Rates of previous preterm births, low-birth-weight infants, and cesarean section were higher in seropositive women compared with seronegative subjects. CONCLUSION(S) Women having poor reproductive performance had subclinical celiac disease. The serology for celiac disease can be considered in idiopathic cases.

Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial.

OBJECTIVE To study the impact of administration of dydrogesterone in early pregnancy on pregnancy outcome and its correlation with Th1 and Th2 cytokine levels. DESIGN Double-blind, randomized, placebo-controlled study. SETTING A medical college and its associated hospital. PATIENT(S) Women with either: [1] a history of idiopathic recurrent pregnancy loss (RPL), in either a dydrogesterone group or a placebo group, or [2] no history of miscarriage. INTERVENTION(S) Dydrogesterone 20 mg/day from confirmation of pregnancy to 20 weeks of gestation. MAIN OUTCOME MEASURE(S) Occurrence of another pregnancy loss and concentrations of T-helper (Th)1 (interferon-γ and tumor necrosis factor-α) and Th2 (interleukin (IL)-4 and IL-10) cytokines in serum at recruitment (4-8 weeks of gestation) and at abortion or 20 weeks of gestation, using commercially available ELISA kits. RESULT(S) Occurrence of another abortion after 3 consecutive abortions was significantly higher (29 of 173; 16.76%) in women with RPL compared with healthy pregnant controls (6 of 174; 3.45%). Risk of occurrence of miscarriage after 3 abortions was 2.4 times higher in the placebo group vs. the treatment group (risk ratio=2.4, 95% CI=1.3-5.9). Mean gestational age at delivery (excluding those aborted before 20 weeks of gestation) increased significantly in the dydrogesterone group (38.01±1.96 weeks) compared with the placebo group (37.23±2.41 weeks). Baby weight was significantly lower in the placebo group (2421.4±321.6 g) compared with the healthy pregnant controls (2545.3±554.3 g). At recruitment, serum IL-4 and tumor necrosis factor-α levels were significantly lower in the RPL group compared with the healthy pregnant controls. However, serum interferon-γ level was significantly higher in the RPL group (8.87±0.72 pg/mL) compared with the healthy pregnant controls (8.08±1.27 pg/mL). CONCLUSION(S) The present study supports the use of dydrogesterone in women with recurrent abortions to improve pregnancy outcome, such as a reduction in abortions and improved gestational age and baby weight at delivery. However, these outcomes were not modulated by Th1 and Th2 cytokine production. CLINICAL TRIAL REGISTRATION NUMBER CTRI/2010/091/000373.

IL-10, TNF-α & IFN-γ: potential early biomarkers for preeclampsia.

The present study was designed to evaluate levels of IL4, IL10, TNF-α & IFN-γ at early second trimester and 24h from delivery to assess potential correlation of cytokine variation with preeclampsia. A total of 176 consecutive healthy, normotensive primigravidas with uncomplicated singleton pregnancies were recruited at 14-18weeks of gestation. Serum cytokine levels were estimated at recruitment and 24h from delivery. In present study, 14(7.95%) women developed preeclampsia. Levels of IL-10, TNF-α and IFN-γ (Mean±SE) at recruitment were statistically significantly lower in preeclamptic group (39.21±9.46pg/mL, 73.57±13.37pg/mL and 0.70±0.20pg/mL, respectively) than non-preeclamptic group (86.02±4.55pg/mL, 601.37±63.54pg/mL and 1.67±0.08pg/mL, respectively) (p<0.05). In preeclamptic group, IL-4 and TNF-α levels (Mean±SE) were significantly higher 24h from delivery (5.35±0.95pg/mL and 381.21±43.28pg/mL, respectively) than at recruitment (2.39±0.71pg/mL and 73.57±13.37pg/mL) (p=0.019 and 0.0001, respectively) while IL-10 and IFN-γ levels decreased after delivery but the change was not statistically significant. Therefore, the levels of IL-10, TNF-α and IFN-γ between 14 and 18weeks of gestation may act as potential early biomarkers in the diagnosis of preeclampsia.

Diagnostic utility of hepatitis C virus core antigen in hemodialysis patients

BACKGROUND Patients undergoing hemodialysis are at high risk for Hepatitis C virus infection. Anti-HCV antibody detection is widely used for screening this infection but is not sensitive for window period detection. An ELISA to detect the HCV Core Antigen has recently become available. OBJECTIVES To investigate the utility of the HCV core Antigen ELISA in the detection of HCV infection in hemodialysis patients and to compare with 3rd generation ELISA validated by real-time PCR. METHODS Two hundred fifty hemodialysis patients were included in the study. Anti-HCV antibodies and Total HCVcAg was determined by third generation ELISA kits. HCV RNA was determined using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and sensitivity of the two assays was confirmed by estimating viral load using real-time PCR. RESULTS Forty-three out of 250 (17.2%) patients were positive for anti-HCV antibodies and HCVcAg. 13/250 (5.2%) were positive for HCVcAg but anti-HCV negative, which is statistically significant (P<0.05). All 13 were confirmed viremic by in-house nested RT-PCR leading to specificity of 100%. Viral load of 49,258+/-28,682 copies/mL were detected in HCVcAg positive cases in comparison to 239,383+/-107,805 copies/mL in the only anti-HCV positive group (P<0.001). False negative cases for HCVcAg assay accounted for 2/250 (0.8%) in which the viral load was 306+/-461 copies/mL which was significantly lower in comparison to HCVcAg positive group (P<0.001, t-test=9.982). CONCLUSIONS Total HCVcAg ELISA is an accurate serological marker for early identification of HCV infection, than is possible by currently used serological assay. It will be useful for patients undergoing hemodialysis who have a longer window period due to immunosuppressed state. It is both a cost-effective and a less labor-intensive alternative to PCR, enhancing its clinical utility.

Duration of hepatitis E viremia in pregnancy

To investigate the duration of hepatitis E virus (HEV) infection in pregnant and non‐pregnant women with acute viral hepatitis (AVH) or fulminant hepatic failure (FHF).

Prevalence of Hepatitis B Virus Genotype D in Precore Mutants Among Chronic Liver Disease Patients from New Delhi, India

Hepatitis B is one of the most important causes of chronic viral hepatitis world wide. Mutations in the precore region of the hepatitis B virus (HBV) genome are frequently found in hepatitis B envelope antigen-negative cases. Data from India on the HBV genotype-associated distribution of precore mutations are limited. Our objective in this study was to genotype and detect the precore mutant with a point mutation from G to A at nucleotide 1896 using ligase chain reaction (LCR) and direct sequencing. A total of 115 cases of chronic liver disease were screened. The cases were evaluated on the basis of history, clinical examination, liver function profile, and serological test for HBV infection, which includes HBsAg, anti HBcIgG, HBeAg using commercially available ELISA kits. The cases, which were HBeAg+, HBeAg–, and HBV DNA+, were subjected to LCR and confirmed by direct sequencing. Of 115 chronic liver disease cases, 50 (43.5%) cases were HBV DNA positive. All cases were subjected to LCR; 11 (22%) cases confirmed the presence of precore mutants, while the remaining 39 (78%) were classified as the wild form of the virus. HBV genotyping by direct sequencing revealed that genotype D was predominant in both wild and mutant forms of the virus. We conclude that the HBV genotype distribution was not significantly different between precore mutants and the wild form of the virus (P>0.05). North Indian patients with genotype D were more likely to have persistent HBV infection with precore mutants. HBV genotypes correlate with the clinical outcome of chronic HBV infection.

Role of cytokines in development of pre‐eclampsia associated with periodontal disease – Cohort Study

AIM The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. MATERIALS AND METHODS A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. RESULTS The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p < 0.001). Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). CONCLUSION Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia.

Corrigendum to “Diagnostic utility of hepatitis C virus core antigen in hemodialysis patients” [Clin Biochem 41 (2008) 447–452]

Corrigendum Corrigendum to “Diagnostic utility of hepatitis C virus core antigen in hemodialysis patients” [Clin Biochem 41 (2008) 447–452] Subhash Medhi ⁎, Sai K. Potukuchi , Sunil K. Polipalli , Shyam S. Swargiary , Purabi Deka , Anis Chaudhary , Nargis Begum , Zahid Hussain , R.S. Ahlawat , Premashis Kar a a PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College and Lok Nayak Hospital, University of Delhi, New Delhi-110002, India b Department of Biotechnology, Gauhati University, Guwahati-781014, Assam, India c Human Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India