HBsAg positive subjects were selected from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin Effect in Chronic hepatitis C Treatment (KIPECT) study which evaluated the treatment efficacy and safety of peginterferon plus ribavirin therapy in 758 CHC patients.14 A total of 18 HBsAg positive patients among the 758 subjects were retrospectively included from eight university hospitals. In KIPECT study, CHC patients with detectable serum HCV RNA and/or elevated serum alanine aminotransferase levels for more than 6 months, age ≥18 years, and treated with peginterferon alfa plus ribavirin from January 2000 to September 2008 were included. Exclusion criteria were acute hepatitis C patients, history of prior exposure to interferon or peginterferon, and no available data on genotype of HCV. The study protocol was approved by the Institutional Review Board of each hospital and was conducted in accordance with the principles of the Declaration of Helsinki.

The study patients were treated with either pegylated interferon alfa-2a plus ribavirin or pegylated interferon alfa-2b plus ribavirin. Initial dosage and dose modification of the treatment drug was determined based on the current guideline suggested by the Korean Association for the Study of the Liver.15 Duration of the treatment was planned as 24 weeks for genotype 2/3 infection and 48 weeks for non genotype 2/3 infection.15

Baseline clinical and virologic characteristics were obtained by retrospective review of medical records, and when available, histologic data before the treatment were also recorded. HCV RNA values measured in copies/mL were converted into IU/mL using conversion factor according to the used assay in each hospital.2 Serum HCV RNA levels were determined using the COBAS TaqMan HCV test (Roche Molecular System Inc., Branchburg, NJ, USA) in five institutes, Cobas Amplicor HCV Monitor V2.0 (Roche Molecular System Inc., Branchburg, NJ, USA), Abbott RealTime (Abott Diagnostics, Abbott Park, Illinois, USA), and Artus HCV RG RT-PCR Kit (Qiagen, Valencia, CA, USA) in one institute, respectively. Pre-and post-treatment hepatitis B e antigen (HBeAg), anti-hepatitis e antibody, HBV DNA values, and history of other treatment modalities used for HBV infection were recorded. Baseline histologic data concerning steatosis and fibrosis were collected. Hepatic steatosis was assessed as either presence or none, and the degree of hepatic fibrosis was classified as recommended by Korean Study Group for the Pathology of Digestive Disease: grade 0, no fibrosis; grade 1, portal fibrosis; grade 2, periportal fibrosis; grade 3, septal fibrosis; grade 4, cirrhosis.16 Data collection was performed using an case record form in the charge of doctors in the individual hospital from April 2009 to December 2009.

The early virologic response (EVR), end of treatment response (ETR) and sustained virologic response (SVR) were used to investigate the treatment response of CHC proposed by The Korean association for the study of the liver.15 Quantitative HCV RNA values were recorded which were determined at baseline, at 12 week after the treatment, and at the time of the treatment termination for HCV of genotype 1. Based on the level of HCV RNA value at 12 week, the presence of EVR was judged as either complete (HCV RNA negative) or partial (reduction in HCV RNA level more than 2 log compared to baseline HCV RNA level). For CHC patients infected with genotype 2/3 HCV, quantitative HCV RNA levels of baseline and at the time of treatment termination were recorded. Regardless of genotype, ETR was defined as HCV RNA negativity at the end of treatment. SVR was defined as HCV RNA negativity measured at 24 weeks after cessation of treatment in all genotype.

The mean±standard deviation (SD) was used to describe continuous variables and categorical variables were presented as the number with a percent. Comparison of continuous variables was performed with a student's t-test and Fisher's exact test was used to compare categorical variables. P-values less than 0.05 were considered to be statistically significant. All data were analyzed using SPSS (version 15.0; Chicago, IL, USA).

Eighteen out of 758 CHC patients in the KIPECT study were positive for HBsAg. The prevalence of HBV-HCV coinfection was 2.37%. The mean age of the subjects was 44.1 years and males constituted 66% of the total. When categorized by the age in detail, 1 patient (5.6%) was younger than 30 years, 5 patients (27.8%) were between 30 and 40 years, 8 patients (44.4%) were between 40 and 50 years, and 4 patients (22.2%) were older than 50 years. One patient had a history of intravenous drug use and another patient had a history of transfusion. None were coinfected with human immunodeficiency virus. Histologic data was available in 5 patients and all had fibrosis of stage 2 and no steatosis. There was no patient with clinical or histologic evidences of liver cirrhosis. Other detailed baseline characteristics of the study subjects are presented in Table 1.

Genotype 1b was found in eight patients (44%) and was the most common HCV genotype. Genotype 2a/c was present in 5 (28%) and was the second most common. Genotype 2 unclassified and 1a was seen in 3 (17%) and 2 (11%) patients, respectively. Mean value of baseline HCV RNA was 8.79×10⁶±1.45×10⁷ IU/mL and 11 patients (61.1%) had HCV RNA level more than 600,000 IU/mL. Sixteen of the 18 patients (88.8%) were negative for HBeAg and 15 (83.3%) patients had HBV DNA level less than 2,000 IU/mL. Other data concerning HBV infection are detailed in Table 2. Serum HCV RNA levels were compared between patients with and without detectable serum HBV DNA. HCV RNA level was 4.9×10⁶±6.7×10⁶ IU/mL in patients with detectable HBV DNA and 1.6×10⁷±2.1×10⁷ IU/mL in patients without detectable DNA, although there was no statistical significance (P=0.257). HCV RNA levels were also compared according to HBeAg status. It was 2.4×10⁷±2.7×10⁷ IU/mL in HBeAg positive patients and 5.7×10⁷±8.4×10⁷ IU/mL in HBeAg negative patients (P=0.367). The proportion of CHC patients with high viral load (HCV RNA > 600,000 IU/mL) was not significantly different according to detectable serum HBV DNA (P=1.000) and HBeAg status (P=1.000).

Overall, fourteen out of the 18 patients (77.8%) showed EVR and 16 patients (88.9%) had ETR. Thirteen patients showed SVR (72.2%) regardless of the genotype. Treatment responses according to HCV genotype are presented in Figure 1. The SVR rate was 60% in genotype 1 and 87.5% in genotype 2 (Fig. 1).

Peginterferon alfa is also approved for the treatment of CHB.13 In this study, no one developed seroclearance or seroconversion of HBsAg or HBeAg after the completion of treatment. Post-treatment HBV DNA values were available in 16 patients. The change of serum HBV DNA levels before and after treatment of CHC is presented in Figure 2. Three patients had a baseline HBV DNA value exceeding 2,000 IU/mL and HBV DNA was undetectable in 2 of these 3 patients after the treatment. Two of the 3 patients with a baseline HBV DNA level under 2,000 IU/mL exhibited increase of HBV DNA level more than 1 log from the baseline. A 44-year-old male patient with genotype 1b infection had undetectable baseline HBV DNA (limit of detection 12 IU/mL) and was negative for HBeAg before treatment of CHC. Serum HCV RNA level was 9,340,000 IU/mL at baseline. He achieved ETR and subsequently showed SVR after the treatment with peginterferon plus ribavirin for 48 weeks, however, serum HBV DNA was increased to 4,444 IU/mL. Biochemical breakthrough or reversion of HBeAg was not observed and no additional therapy for HBV infection was administered. The clinical course of another patient who developed flare-up of CHB is presented in detail (Fig. 3A). A 38-year-old man infected with HCV genotype 1b additionally received entecavir for HBV infection after treatment of CHC. Baseline HBeAg was positive and serum HBV DNA was 1,552 IU/mL. After the 48 week treatment of peginterferon plus ribavirin, serum aspartate aminotransferase and alanine aminotransferase levels were elevated with achievement of the ETR. When other potential etiologies of acute hepatitis were surveyed, it was absent. Serum HBV DNA level increased to 153,844,063 IU/mL and 0.5 mg/day of entecavir was prescribed to manage flare-up of CHB. HCV RNA was positive at 24 weeks after the treatment and SVR was not observed in this patient (Fig. 3B).