PEG-IFN-α Plus Ribavirin in Elderly Chronic Hepatitis C 1. Background Hepatitis C virus (HCV) infection is one of the main etiologies of chronic liver disease, with a global preva- lence of 3 % (1). It is estimated that approximately 85 % of patients with a HCV infection go on to develop chronic disease and up to 20 % will eventually develop cirrhosis, which may lead to liver failure, hepatocellular carcinoma (HCC), and death (2, 3). In Korea, the prevalence of HCV infection in the general population is approximately 1 % and this number increases with age peaking at 60 years or older (4). The prevalence in older patients has been increasing in Korea, and this will become an impending problem in other countries where viral spread has oc- curred more recently as well. Thus, the care of aging pa- tients with chronic hepatitis C (CHC) is one of the most important issues confronted by physicians. The current standard of care for CHC is a combination of pegylated- IFN-α (PEG-IFN-α) and ribavirin (5-7). In pivotal clinical tri- als for the registration of PEG-IFN-α and ribavirin therapy, sustained virologic response (SVR), defined as an unde- tectable HCV RNA level 24 weeks after treatment comple- tion, was achieved in 46 % of patients infected with HCV genotype 1, and in 82 % of cases with HCV genotypes 2 and 3 (8, 9). In those studies, older age was associated with a poorer response to treatment. However, it is not known whether the rate of response in persons older than 65 years is the same as or worse than that for persons 40–65 years of age, because these studies excluded patients > 65 years old. A few reports concerning PEG-IFN-α-based com- bination treatment in elderly CHC patients have been published, and these found slightly different treatment outcomes (10-13). 2. Objectives The aim of this study was to investigate the treatment response and tolerability of PEG-IFN-α plus ribavirin com- bination therapy in elderly patients with CHC. We also as- sessed the factors associated with SVR in elderly patients. 3. Patients and Methods 3.1. Study Population and Study Design We reviewed the medical records of CHC patients who had been treated with PEG-IFN-α plus ribavirin between May 2004 and December 2010, at the Chonbuk National University Hospital in Korea. Treatment-naïve adults of both sexes aged 18 years or more that met the following conditions were considered eligible; seropositivity for the HCV antibody (anti-HCV), quantifiable serum HCV RNA identified by real-time polymerase chain reaction (PCR) (COBAS AmpliPrep/COBAS TaqMan HCV test; Roche Molecular Systems, USA), and compensated liver disease. Exclusion criteria included; decompensated liver dis- ease, uncontrolled depressive illness, drug or alcohol abuse within six months of study commencement, prior organ transplantation, positivity for hepatitis B virus or Hepat Mon. 2012 Kim HI et al. human immunodeficiency virus, pregnant status or an unwillingness/inability to comply with adequate contra- ception, untreated hyperthyroidism, autoimmune hepa- titis, a hemoglobin level ≤ 10 g/dL, an absolute neutrophil count (ANC) ≤ 750/mm3, and a platelet count ≤ 50 000/ mm3. Patients with known hypersensitivity to drugs used to treat HCV were also excluded. We recruited 191 patients who fulfilled the above criteria. Of these 191 patients, 10 patients who were undergoing current combination treatment or did not show any obvious effects of the anti- viral treatment were also excluded. The data from the re- maining 181 patients were finally analyzed. Study subjects received once weekly subcutaneous injections of either PEG-IFN-α-2a (Pegasys, Hoffmann-La Roche Ltd., Basel, Switzerland) 180 μg (79 patients) or PEG-IFN- α-2b (PegIn- tron, Shering Plough Corp., Kenilworth, NJ, USA) 1.5 μg/ kg (for 24 weeks for HCV genotype 2, 3 or for 48 weeks for HCV genotype 1). In addition, all 181 participants received daily oral ribavirin; 800 mg/day for genotype 2 and 3 and 1 000 mg/day (body weight < 75 kg) or 1 200 mg/day (body weight ≥ 75 kg) for genotype 1. Patients aged ≥ 65 years were defined as the elderly group, and patients aged < 65 years were defined as the non-elderly group. Treatment response and adverse events were retrospectively com- pared between the two groups by an independent inves- tigator unaware of study or treatment details. Informed consent was obtained from all study patients. This study was conducted in compliance with the World Medical As- sociation Declaration of Helsinki and was approved by the Institutional Review Board at the Chonbuk National University Hospital. 3.2. Laboratory Tests Baseline clinical and demographic characteristics, ad- verse events during treatment, and serum assay values (especially alanine aminotransferase (ALT), serum HCV RNA level, and HCV genotype) were stored in a database. HCV RNA was amplified by RNA PCR and hybridization methods (COBAS Amplicor HCV test, version 2.0; Roche Molecular Systems, Branchburg, NJ, USA; lower limit of detection 50 IU/mL), and the serum concentration of HCV-RNA was measured by real-time PCR (COBAS Am- pliPrep/COBAS TaqMan HCV test; Roche Molecular Sys- tems, USA). HCV genotyping was performed by reverse hybridization (INNO-LiPAHCV, Innogenetics, and Ghent, Belgium). A liver biopsy was not mandatory. In this study, liver cirrhosis was diagnosed mainly by ultrasonography (i.e., a coarse liver architecture, a nodular liver surface, and blunt liver edges) and evidence of hypersplenism (i.e., splenomegaly on ultrasonography and a platelet count of < 100 000/ mm3). 3.3. Treatment Response and Safety Assessments Patients that received at least one dose of study medica- tion were entered in the analysis, which was conducted on an intention-to-treat basis. The following variables 431