Predictors of Therapeutic Outcome to Nucleotide Reverse Transcriptase Inhibitor in Hepatitis B Patients.

Hepatitis B is a clinically important public health issue. Infection leads to hepatocellular carcinoma. Therefore, patients need antiviral therapy for prolonged period to prevent the complication of the disease. Data concerning chronic hepatitis B (CHB) patients with high hepatitis B virus (HBV) DNA are limited. The aim of the study was to check the efficacy of the nucleoside reverse transcriptase inhibitors (tenofovir) in terms of suppression of HBV DNA. The secondary end point in the study is to evaluate trends of predictive variables that predict outcome of treatment. In this specific study, we evaluated 140 CHB male and female patients, of these 110 completed 48 weeks of treatment. On the basis of hepatitis B e antigen (HBeAg), patients were stratified; HBV DNA and hepatitis B surface antigen (HBsAg) levels were measured along with liver function tests. All enrolled patients were given tenofovir disoproxil fumarate 300 mg daily before breakfast. Overall, 69.1% of patients showed virologic response. HBeAg-negative patient group showed 68% viral suppression and HBeAg-positive patient group showed 45.9% over 24 months of treatment, while at 48 months it was shown to be 76.7% and 54.1%, respectively. None of the patients suffered HBsAg loss during the 48 months. Baseline high HBV DNA level was found as a significant predictor of response (OR, 1.9; 95% CI = 1.23-3.9, p = 0.005). None of the patients observed had serious adverse events. Mutations in the RT region of polymerase gene are shown to be associated with resistance to antiviral drugs. Among patients suffering with chronic HBV infection, HBeAg-negative patient group have better virologic response as compared with HBeAg-positive group. Higher concentration of HBV DNA at baseline has negative prediction for sustained viral suppression. The A-B motif interdomain rtL122F mutation was found in nonresponder patients in our study. Another mutation rtN248H observed in E motif considered to have effect on DNA primer grip, which forms part of binding pocket.

Spectrum of hepatocellular carcinoma at Shifa International Hospital, Islamabad.

BACKGROUND: The aim of this study was to review etiological and clinical features of patients with hepatocellular carcinoma (HCC) at a tertiary care centre in past nine years. Relevant data on HCC in other parts of country and world were reviewed. METHODS: Patients who had biopsy proven HCC were reviewed retrospectively. Demographic features were noted and positivity for serology. presence of cirrhosis. level of alpha-fetoprotein, tumour size and distribution of liver lesions were noted. RESULTS: A total of 67 patients were found to have biopsy proven HCC. Mean age was 58.64 +/- 12.77 years. Males were 79%. Hepatitis B surface antigen was noted to be positive in 23% of the patients, who were tested and hepatitis C antibody was found to be positive in 67% of the patients who were tested. Alpha fetoprotein level was 632.09 +/- 1332.31. Cirrhosis was noted in 69% patients. Tumour size in patients with single lesion was 6.6 +/- 1.14 cm. Patients with single lesion had 70% time involvement of the left lobe and 30% times had involvement of the right lobe. Fifty one percent of the patients in this series had multilocular distribution. CONCLUSION: Hepatocellular carcinoma has become a common tumour in Pakistan and studies are showing that this cancer is related to hepatitis C virus infection in majority of the patients. A large number of them have underlying cirrhosis and are multifocal in origin and are presented in an advanced condition.