Clinical Studies A 24-week course of high-dose interferon-a plus ribavirin for Taiwanese chronic hepatitis C patients with persistently normal or near-normal alanine aminotransferase levels Ming-Lung Yu 1,2 , Chia-Yen Dai 2,3 , Li-Po Lee 1 , Nei-Jen Hou 4 , Ming-Yen Hsieh 1 , Jee-Fu Huang 4 , Zu-Yau Lin 1,2 , Shinn-Cherng Chen 1,2 , Ming- Yuh Hsieh 1,2 , Liang-Yen Wang 1,2 , Wen-Yu Chang 1,2 and Wan-Long Chuang 1,5 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 Department of Occupational Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan, 4 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan, 5 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Yu M-L, Dai C-Y, Lee L-P, Hou N-J, Hsieh M-Y, Huang J-F, Lin Z-Y, Chen S-C, Hsieh M-Y, Wang L-Y, Chang W-Y, Chuang W-L. A 24-week course of high-dose interferon-a plus ribavirin for Taiwanese chronic hepatitis C patients with persistently normal or near normal alanine aminotransferase levels. Liver International 2006: 26: 1187–1195. r 2006 The Authors. Journal compilation r 2006 Blackwell Munksgaard Abstract: Background/Aims: We aimed to evaluate the efficacy, advantage, and safety of a 24-week regimen with high-dose interferon-a (INF-a;6 million units thrice weekly) plus ribavirin (1000–1200 mg/day) combination therapy for 46 Taiwanese chronic hepatitis C (CHC) patients with persistently normal or near-normal alanine aminotransferase (PNALT) levels. Methods: Ninety-two age- and sex-matched CHC patients with elevated ALT levels (42 times the upper limit of normal range) with a ratio of 1:2, treated with the same regimen, served as a control. Results: The sustained virologic response (SVR) rate was comparable between PNALT (67.4%) and elevated ALT (65.2%) groups (intention-to-treat analysis). The two groups had similar rates of discontinuation and incidence of adverse effects. Viral genotype 1b, baseline viral loads, body mass index, and age were significant factors negatively associated with SVR. Further decline of ALT levels throughout the follow-up period was observed in sustained responders of the PNALT group. None of the eight patients with ALT flares developed icteric hepatitis. The virologic efficacy was sustained in a 3-year extended follow-up period. Conclusion: high-dose INF-a with ribavirin combination therapy is effective, safe, and well tolerated in CHC patients with PNALT levels. The ALT assay might not be used as a single biochemical marker for determination of treatment consideration. Key words: HCV – IFN – persistently normal ALT – ribavirin Wan-Long Chuang, MD, PhD, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung 807, Taiwan. Tel: 1886 7 3121101 ext. 7475 Fax: 1886 7 3234553 e-mail: fishya@ms14.hinet.net; fish6069@ gmail.com Received 11 January 2006, accepted 24 June 2006                                                                                                           Serum levels of alanine aminotransferase (ALT) are frequently used as the sole biochemical mar- ker of liver injury in chronic hepatitis C (CHC). Over one-third of patients with CHC have persis- tently normal ALT levels (1, 2) and another 40% have ALT levels that are less than twice the upper limit of the normal range (ULN) (3). However, a poor correlation exists between the degree of ALT elevation and hepatic injury assessed per liver biopsy (4). Persistently normal and/or near- normal ALT (PNALT) levels are typically de- fined as serial normal and/or near-normal serum ALT levels, at least three times, over a period of 6 months (5–7). A significant number of CHC patients with PNALT levels have moderate to severe fibrosis, and few have cirrhosis (7, 8). Liver International 2006; 26: 1187–1195 r 2006 The Authors Journal compilation r 2006 Blackwell Munksgaard DOI: 10.1111/j.1478-3231.2006.01358a.x 1187