Long-Term Effect of Interferon Plus Ribavirin on Hepatitis B Surface Antigen Seroclearance in Patients Dually Infected with Hepatitis B and C Viruses

PLOS ONE, Jun 2011

Background Interferon-α/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg) seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV), but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-α/ribavirin combination therapy in HBV/HCV dually-infected patients. Methodology/Principal Findings Eighty-one patients who received interferon-α/ribavirin combination therapy for 24 weeks with a follow-up period of >24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-of-treatment, respectively. Fifteen (18.5%) patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5–5.1) years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR), 95% confidence intervals (CI) of 16.6, 1.8–153 and 9.2, 1.4–62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5–745). Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss. Conclusions We demonstrated that interferon-α/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCV-infected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were significant factors associated with HBsAg seroclearance.

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Long-Term Effect of Interferon Plus Ribavirin on Hepatitis B Surface Antigen Seroclearance in Patients Dually Infected with Hepatitis B and C Viruses

et al. (2011) Long-Term Effect of Interferon Plus Ribavirin on Hepatitis B Surface Antigen Seroclearance in Patients Dually Infected with Hepatitis B and C Viruses. PLoS ONE 6(6): e20752. doi:10.1371/journal.pone.0020752 Long-Term Effect of Interferon Plus Ribavirin on Hepatitis B Surface Antigen Seroclearance in Patients Dually Infected with Hepatitis B and C Viruses Ming-Lun Yeh 0 Chao-Hung Hung 0 Jee-Fu Huang 0 Chun-Jen Liu 0 Chuan-Mo Lee 0 Chia-Yen Dai 0 Jing-Houng Wang 0 Zu-Yau Lin 0 Sheng-Nan Lu 0 Tsung-Hui Hu 0 Ming-Lung Yu 0 Jia-Horng Kao 0 Wan-Long Chuang 0 Pei-Jer Chen 0 Ding-Shinn Chen 0 Man-Fung Yuen, The University of Hong Kong, Hong Kong 0 1 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital , Kaohsiung, Taiwan , 2 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan , 3 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, 4 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University , Kaohsiung, Taiwan , 5 Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital , Taipei, Taiwan , 6 Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan Background: Interferon-a/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg) seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV), but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-a/ ribavirin combination therapy in HBV/HCV dually-infected patients. Methodology/Principal Findings: Eighty-one patients who received interferon-a/ribavirin combination therapy for 24 weeks with a follow-up period of .24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-oftreatment, respectively. Fifteen (18.5%) patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5-5.1) years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR), 95% confidence intervals (CI) of 16.6, 1.8153 and 9.2, 1.4-62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5-745). Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss. Conclusions: We demonstrated that interferon-a/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCVinfected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were significant factors associated with HBsAg seroclearance. - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the two leading causes of chronic liver disease, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) [1,2]. Since both viruses share the same transmission routes, dual HBV/HCV infection is not uncommon, accounting for 1040% of patients with chronic hepatitis in Taiwan and Europe [3,4]. Previous studies also indicated that HBV/ HCV dually infected patients had a much higher risk of developing LC or HCC than those with HBV or HCV infection alone [5,6] Seroclearance of hepatitis B surface antigen (HBsAg) is a rare event in chronic hepatitis B (CHB) patients [7,8]. The estimated annual incidence of HBsAg seroclearance is 0.12.26% [9,10]. A recent study demonstrated the annual HBsAg seroclearance rate has quite differed in Hepatitis B e antigen (HBeAg) positive and negative populations (0.39 versus 2.61 per 100 person-years, P,0.001) [10]. HBsAg seroclearance usually confers a favorable outcome and is the optimal treatment goal. However, HBsAg seroclearance is very rarely observed in HBV infected patients receiving current antiviral agents, with an annual rate of 2.43.2% with interferon (IFN) or pegylated IFN therapy and only ,1% with nucleoside/nucleotide analogues [11,12] IFN is an antiviral agent approved for the treatment of CHB and chronic hepatitis C. Although IFN monotherapy has been Mean age (years), mean 6 SD Post-treatment follow-up period, year, mean 6 SD (range) Bas (...truncated)


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Ming-Lun Yeh, Chao-Hung Hung, Jee-Fu Huang, Chun-Jen Liu, Chuan-Mo Lee, Chia-Yen Dai, Jing-Houng Wang, Zu-Yau Lin, Sheng-Nan Lu, Tsung-Hui Hu, Ming-Lung Yu, Jia-Horng Kao, Wan-Long Chuang, Pei-Jer Chen, Ding-Shinn Chen. Long-Term Effect of Interferon Plus Ribavirin on Hepatitis B Surface Antigen Seroclearance in Patients Dually Infected with Hepatitis B and C Viruses, PLOS ONE, 2011, 6, DOI: 10.1371/journal.pone.0020752