Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection

Background: Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. Objective: To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. Methods: HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing. Results: Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either ade-fovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay. Conclusion: The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus. .

Efficacy of telbivudine in the treatment of chronic hepatitis B infection in population of Peshawar, Pakistan

To study the efficacy of telbivudine in 2 years treatment of chronic hepatitis B infection in local population of Peshawar. This study was conducted in Khyber Teaching Hospital, Peshawar from June 2007 to June 2012. 83 patients, 56 males and 27 females of chronic hepatitis B with no other liver problem like hepatitis C and D, alcoholic hepatitis, fatty liver, hepatocellular carcinoma etc were included in the study. HIV, pancreatitis and pregnancy was also ruled out before study was undertaken. Base line investigations of CBC, Liver and kidney profile, CPK, HBsAg, HBeAg, HBe antibody, HBV DNA, Ultra sound abdomen and upper GI endoscopy were conducted in the subjects. Each patient was given oral telbivudine 600mg/d for 2 years. Biochemical, serological, virological and clinical follow ups were conducted after one month of starting treatment and then every 3 months. Biochemical, serological and virological end points were observed beside adverse effects of telbivudine. Data was analyzed using SPSS version 15.0. Mean serum ALT was reduced from 36.9 iu/ml from first visit to 21.0 iu/ml [p value=0.001] after 24 months of treatment. The serum viral load decreased from 165277.82 iu/ml to 3.80 iu/ml from initial to final visit after 2 years of treatment. No viral breakthrough was reported during 24 months of treatment with telbivudine. The drug was well tolerated without any significant adverse effects. Treatment of chronic hepatitis B patients with telbivudine shows statistically significant reduction in viral load and serum ALT with no significant adverse effects

Modulation of thymidine kinase activity: a biochemical strategy to enhance the activation of antineoplastic drugs

Thymidine kinase is a key enzyme responsible for the activation of several anticancer and antiviral drugs. As the first enzyme in the salvage pathway of thymidine, it is regulated by the feedback inhibition exerted by the end-product of the pathway, namely thymidine 5'-triphosphate. 5'-Aminothymidine is a non-toxic analogue of thymidine capable of interfering with this regulatory mechanism. In fact, it has been shown that 5'-aminothymidine increases the cytotoxicity and metabolism of various thymidine analogues currently in use of the clinic as antineoplastic agents. This mini-review article focuses in the evidence supporting the role of 5'-aminothymidine as a potential prototype drug for a new class of anticancer agents: drugs which affect the regulation of key metabolic pathways that determine the efficacy of agents with cytotoxic activity. The mechanism of action, antineoplastic activities and basis for selectivity in tissue culture models are also described