Ribavirin and Interferon Is Effective for Hepatitis C Virus Clearance in Hepatitis B and C Dually Infected Patients
Liu CJ, Chen PJ, Lai MY, Kao JH, Jeng YM, Chen DS
Hepatology. 2003;37(3):568-576
Is combination interferon (IFN) and ribavirin therapy effective in the management of patients coinfected with hepatitis B and C?
In areas where infection is endemic, it is not uncommon to find individuals who are dually infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). It is important to note that patients coinfected with HBV and HCV have been shown to have a higher risk of developing cirrhosis or hepatocellular carcinoma than patients infected with either HBV or HCV alone.
Combination treatment with IFN and ribavirin is shown to eradicate HCV in approximately 30% to 60% of patients who have chronic hepatitis C. However, because the current trials and therapeutic targets exclude individuals who are coinfected with hepatitis B, the issue remains of whether this regimen is effective in clearing virus in the setting of dual infection. Studies of IFN monotherapy have not convincingly demonstrated efficacy in clearing HCV in patients dually infected with HBV. Because the combination of IFN and ribavirin has shown enhanced effectiveness vs IFN monotherapy in clearing HCV in patients with only hepatitis C, Liu and colleagues conducted this open but not randomized trial to assess the utility of this combination regimen in the setting of HBV and HCV coinfection.
This study involved 24 consecutively enrolled patients who were positive for both serum anti-HCV antibody and hepatitis B surface antigen (HBsAg) for more than 6 months. Patients were stratified by group: patients who were seropositive for HCV RNA comprised Group 1; those who were negative for serum HCV RNA comprised Group 2 (n = 3). Seventeen of 21 patients in Group 1 were HBV DNA positive; all patients in Group 2 were HBV DNA positive. All subjects received the same regimen: 1200 mg of ribavirin daily for 6 months plus IFN alfa-2a thrice-weekly for 12 weeks, and then 3 MU IFN alfa-2a for another 12 weeks. A group of 30 patients with chronic hepatitis C infection alone served as controls. Serum HCV RNA, HBV DNA, and alanine aminotransferase (ALT) levels were measured in all patients for 12 months.
The primary aims of the study were to assess the biochemical response (defined as the normalization of serum ALT level), the HCV clearance (defined as the persistent disappearance of serum HCV RNA), and the degree of histologic improvements in patients coinfected with hepatitis B and C after treatment with the combination regimen. Sustained virologic response was defined as the sustained disappearance of serum HCV RNA or HBV DNA at week 24 posttreatment.
Overall, results showed that combination treatment with IFN and ribavirin cleared serum HCV in 43% of patients with hepatitis C viremia who were dually infected with HCV and HBV (Group 1 patients). This finding was comparable to that seen in controls (ie, patients with chronic hepatitis C alone). Normalization of serum ALT levels occurred in 43% of Group 1 patients and 0% of Group 2 patients 24 weeks after the end of treatment. Disappearance of serum HBV DNA was achieved in 30% of patients who had hepatitis B viremia, but this was not accompanied by loss of HBsAg. The difference in the histologic changes in disease grading and staging was not statistically significant for those patients in whom paired liver biopsy specimens had been obtained.
Based on these findings, the study authors conclude that combination treatment with IFN and ribavirin has utility in achieving a sustained HCV clearance rate in patients dually infected with HBV and HCV that is comparable to that achieved in patients infected with HCV alone. However, it is important to note that, in this study, the patients' hepatic activity was more likely due to hepatitis C rather than hepatitis B disease. For those patients coinfected with HBV and HCV in whom HBV is the dominant infection, alternative therapeutic strategies may be required.
