Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival.
BACKGROUND
Although cirrhosis is a major risk factor for development of hepatocellular carcinoma, no definitive prospective analyses have assessed the long-term efficacy of antiviral therapy in cirrhotic patients.


OBJECTIVE
To elucidate the role of antiviral therapy in the suppression of liver tumors and survival over a long-term follow-up period.


METHODS
Prospective cohort study.


METHODS
25 clinical centers.


METHODS
345 patients with chronic hepatitis C and cirrhosis enrolled in previous trials.


METHODS
271 patients received 6 to 9 million U of interferon 3 times weekly for 26 to 88 weeks; 74 received no treatment.


METHODS
Blood tests and abdominal ultrasonography were done regularly to detect hepatocellular carcinoma.


RESULTS
Hepatocellular carcinoma was detected in 119 patients during a 6.8-year follow-up: 84 (31%) in the interferon-treated group and 35 (47%) in the untreated group. Cumulative incidence of hepatocellular carcinoma among interferon-treated patients was significantly lower than in untreated patients (Cox model: age-adjusted hazard ratio, 0.65 [95% CI, 0.43 to 0.97]; P = 0.03), especially sustained virologic responders. A total of 69 patients died during follow-up: 45 (17%) in the treated group and 24 (32%) in the untreated group. Interferon-treated patients had a better chance of survival than the untreated group (Cox model: age-adjusted hazard ratio, 0.54 [CI, 0.33 to 0.89]; P = 0.02). This was especially evident in sustained virologic responders.


CONCLUSIONS
This was not a randomized, controlled study. Patients enrolled in the control group had declined to receive interferon treatment even though they were eligible for treatment.


CONCLUSIONS
Interferon therapy for cirrhotic patients with chronic hepatitis C, especially those in whom the infection had been cured, inhibited the development of hepatocellular carcinoma and improved survival.
Shiratori
Yasushi
Y
University of Tokyo, Japanese Red Cross Medical Center, Nippon University School of Medicine, and Tokyo Women's Medical College. shirato@cc.okayama-u.ac.jp <shirato@cc.okayama-u.ac.jp>
Ito
Yoichi
Y
Yokosuka
Osamu
O
Imazeki
Fumio
F
Nakata
Ryo
R
Tanaka
Naohide
N
Arakawa
Yasuyuki
Y
Hashimoto
Etsuko
E
Hirota
Katsutaro
K
Yoshida
Haruhiko
H
Ohashi
Yasuo
Y
Omata
Masao
M
D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000517:prevention & control* / Q000628:therapy; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008113:Liver Neoplasms / Q000175:diagnosis / Q000517:prevention & control* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012307:Risk Factors; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins