[Importance of adherence for efficacy of hepatitis C combined therapy].

INTRODUCTION: Dual antiviral therapy with pegylated interferon alfa-2a and ribavirin leads do sustained elimination of hepatitis C virus infection in over 50% patients with genotypes 1 and 4 and in over 80% with genotypes 2 and 3. In addition to genotype, for predicting success of therapy, important factors are baseline HCV RNA level, age, sex, stage of fibrosis, insulin resistance, degree of fat in liver, and patient's weight and genetics. Also, adherence to therapy could be a very important factor associated with success of therapy. OBJECTIVE: The aim of this study was to assess importance of therapy adherence and reduced doses of pegylated interferon alfa-2a and ribavirin on sustained virological response. METHODS: One hundred and sixteen patients with chronic hepatitis C were analyzed. Sustained virological response was analyzed in relation to whether the patients received a full cumulative dose of pegylated interferon alfa-2a, a full cumulative dose of pegylated interferon alfa-2a and ribavirin, and a full cumulative dose of pegylated interferon alfa-2a and at least 60% the expected cumulative dose of ribavirin. RESULTS: At the end of the follow-up period, sustained virological response was achieved in 26 (96.3%) patients who received full cumulative dose of pegylated interferon alfa-2a and in 66 (74.2%) who did not (p < 0.05). Sustained virological response was achieved in 18 (94.7%) patients who received full cumulative dose of pegylated inteferon alfa-2a and ribavirin, and in 73 (76%) who did not (p < 0.05). Sustained virological response was achieved in 25 (96.2%) patients who received full cumulative dose of pegylated inteferon alfa-2a and at least 60% of cumulative dose of ribavirin and in 66 (74.2%) who did not (p < 0.05). CONCLUSION: These findings indicate that adherence to therapy for chronic hepatitis C is a very important factor for achieving sustained virological response.

[Efficacy and safety of peginterferon alfa-2a and ribavirin treatment of chronic hepatitis C in the Republic of Serbia].

INTRODUCTION: Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. Pegylated interferon alfa-2a or 2b (PEG IFN alfa-2a or 2b) and ribavirin (RBV) represent a standard treatment of chronic hepatitis C (CHC). Sustained virological response (SVR), defined as continued undetectable HCV RNA 24 weeks after completion of treatment, is universally considered as an indicator of treatment efficacy. OBJECTIVE: The aim of this study was to determine efficacy and safety of PEG IFN alfa-2a and RBV treatment in patients with CHC in Serbia. METHODS: One hundred seventy-six patients with CHC were included in this multicenter trial from 8 reference centers in Serbia. The patients were treated with standard PEG IFN alfa-2a and RBV protocol. We performed the following virological testing: anti-HCV (ELISA), HCV RNK (quantitative PCR), HCV genotype (type-specific PCR), HBsAg, anti-HBs, anti-HBc and anti-HIV (ELISA). Histological activity and the degree of fibrosis were determined according to the Metavir scoring system. Potential predictors for achieving SVR were evaluated using multivariable logistic regression analysis. RESULTS: Of the treated patients with CHC 65.9% were male, and 60.2% of them aged over 40 years. Of the treated patients 68.2% had infection over 5 years, 63% had HCV RNA >400.000 IU/mL, 76.1% had HCV G1/4, and 60.1% had a mild to moderate liver fibrosis. SVR was achieved in 78.9% of patients (G1/4 79.1%; G2/3 78.1%). The factors that indicated a poorer efficacy of the treatment were age >40 (p<0.05), high basal viremia (p=0.013), and the reduction of PEG IFN alfa-2a and RBV doses, with interruption of therapy (p<0.001). Of the treated patients 45.9% had adverse affects (G1/4 50.8%; G2/3 29.7%). CONCLUSION: Treatment of CHC with PEG IFN alfa-2a and RBV was efficient in 78.9% of patients. The safety profile of therapy was satisfactory. Longer therapy increases the possibility of the development of adverse affects. No life-threatening adverse effects were recorded in our patients.

Concurrent quantitation of the A and D genotypes of hepatitis B virus.

Hepatitis B virus (HBV) infection is a global health problem associated with severe liver disorders. Viral load and HBV genotype affect the clinical outcome, guide antiviral therapy and provide long term prognosis for HBV infected patients. Various types of detection and quantitation assays are currently in use with a different effectiveness. The aim of this study was to develop a method that would provide simultaneous identification and quantitation of genotypes A and D in a single-tube reaction. Sera from infected patients were analyzed by a TaqMan based real time PCR. Optimized reagents were used for HBV DNA quantitation while the genotypes A and D were quantified separately by our design of the assay. Multiplex real time PCR was achieved and was specific for HBV genotypes A and D within a single-tube reaction. Simulation of mixed virus populations was identified reproducibly in vitro. Quantitation of these individual genotypes was exceptionally reliable, so much so that the sum of individual genotypes was equal to the total viral load determined in a separate reaction. Therefore, a straightforward, conceptually simple and reliable approach to issues involving HBV genotypes A and D is submitted. Identity and exact titer of these genotypes in the Caucasian population can now be determined easily.

[Treatment of chronic hepatitis C with PEG-interferon]. / Lecenje hronicnog hepatitisa C peg-interferonom.

INTRODUCTION: Since the discovery of the hepatitis C virus, the etiology of chronic liver diseases has been revealed in great number of patients. However, the treatment of hepatitis C viral infection still hasn't been completely resolved. Antiviral and immunomodulatory effects of interferon, and antiviral effect on the nucleoside analogs were efficient only in small number of patients. Discovery of pegylated interferon brings progress in therapeutic success rates. MATERIAL AND METHODS: Combined therapy with peginterferon alfa-2a (Pegasys) 180 mg once a week plus Ribavirin 800 mg a day during a 24-week period was conducted in 20 patients (13 were previously treated with standard antiviral therapy). The aim of this study was to determine the safety and the efficacy of therapy in our patients. RESULTS AND DISCUSSION: Analysis of safety of the combined therapy was conduced in all 20 patients, and analysis of efficiency in 18 patients. Efficacy of the combined therapy was assessed regarding to biochemical response (normalization of aminotransferase activity at the end of therapy and at the end of 6-month follow-up) and virologic response (disappearance of RNA HCV in serum at the end of 6-month follow-up). 30% of treated patients experienced no troubles during treatment. Influenza-like symptoms, weight loss, depression, hair loss and reaction at the site of injection were mild and did not exclude patients from their usual activities in family, society and work place. Neutropenia, thrombocytopenia and anemia as well as elevated aminotransferase activity demanded periodical dose modification in 20% of patients. Unexpected unwanted effect emerged in one patient after cessation of therapy (pulmonary sarcoidosis). Good effects of combined therapy at the end of follow-up period showed biochemical and virologic response in 66% of patients. CONCLUSION: Combined therapy with Pegasys 180 mg/week and Ribavirin 80 mg/day is safe and well tolerated. Sustained biochemical and virologic response was achieved in 66% of patients.