High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study.
BACKGROUND
Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naive Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues.


METHODS
We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001.


RESULTS
There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5-5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25-9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test).


CONCLUSIONS
We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis.
Yu
Ming-Lung
ML
Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Kaohsiung 807, Kaohsiung, Taiwan. d780178@kmu.edu.tw
Dai
Chia-Yen
CY
Chen
Shinn-Cherng
SC
Lee
Li-Po
LP
Hsieh
Ming-Yen
MY
Lin
Zu-Yau
ZY
Hsieh
Ming-Yuh
MY
Wang
Liang-Yen
LY
Tsai
Jung-Fa
JF
Chang
Wen-Yu
WY
Chuang
Wan-Long
WL
D000328:Adult; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis; D008297:Male; D008875:Middle Aged; D013624:Taiwan; D013997:Time Factors; D019562:Viral Load
D016898:Interferon-alpha