Early viral kinetics on treatment with combination of pegylated interferon-α and ribavirin in chronic hepatitis C virus infection

• Main Authors: Ching-Sheng Hsu, 許景盛
• Other Authors: 高嘉宏
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/07223598229778448811

碩士 === 國立臺灣大學 === 臨床醫學研究所 === 93 === Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma in the western world. In Taiwan, 80% to 90% of chronic liver diseases are caused by hepatitis B virus infection and HCV is the second common cause of these diseases. Combination therapy with pegylated interferon and ribavirin is the current standard treatment for chronic hepatitis C and able to eradicate virus in more than 40% of genotype 1 infected patients and more than 76 % of non-genotype 1 patients. Due to the expense and the adverse events of combination therapy, identification of patients who will not respond is desirable in order to stop the treatment and save money. Western studies have suggested that early viral kinetics following initiation of antiviral therapy may be worthwhile and remain a milestone to assess the need for continued treatment. Pilot studies in Taiwan have suggested that Taiwanese patients with chronic hepatitis C virus infection respond better than white patients. Thus we designed this study to examine the early viral kinetic response of hepatitis C virus (HCV) in Taiwanese chronic hepatitis C patients receiving pegylated interferon alfa and ribavirin combination therapy for 6 months. Methods: Six chronic hepatitis C patients were prospectively collected from the outpatient clinic of the National Taiwan University Hospital. They all received peginterferon alfa in combination with ribavirin for 24 weeks, and were follow-up for another 24 weeks. Serum HCV RNA levels were checked quantitatively and frequently during the first day after initiation of peginterferon alfa therapy. The viral loads were then monitored quantitatively everyday for 3 days, every week for 4 weeks, every 2 weeks for 4 weeks and every month for 3 months. After 24 weeks of follow-up, serum HCV RNA level was qualitatively assayed to determine the sustained virological response. The kinetic parameters (ε, treatment effectiveness at inhibiting viral production; δ, loss rate of virus-producing cells) were estimated from the viral load decay profiles by using a mathematical model. Results: There were 4 patients infected with HCV genotype1 and 3 with genotype 2. Mixed infection with both genotype 1 and 2 was found in one patient. All of there serum HCV RNA levels became undetectable at week 12 and only one patient relapsed at week 33. The ε was between 0.4128 to 0.9904 and δ was between 0.0019 to 0.1245. The differences in viral load between day 7 and 14 were observed in three patients, and the log values of the differences were 0.15, 0.66 and 1.21 respectively. Half of the patients’ serum ALT levels returned to normal range at week 24 and only one still had abnormal ALT level at week 40. Conclusions: This is the first early HCV kinetic study on chronic hepatitis C patients with pegylated interferon-based therapy in Taiwan. Although no significant differences were found between our kinetic parameters and previous reports, the viral decline pattern and viral negativity rates at early viral kinetic stage of Taiwanese patients seems to be different from Caucasian patients. This study gave us some clues about the possible underlying mechanisms of the differences between races, and let us more close to the goal of ideal therapy for chronic hepatitis C.