Interferon Appears to Slow Progression, cancer & death in this Japanese Study of Patients with Compensated Cirrhosis
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Lancet Volume 357, Number 9251 20 January 2001

Abstract:
In a prospective randomized controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN- gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN- versus symptomatic treatment decreased by 0250 for progression to Child-Pugh grade B, 0256 for detection of hepatocellular carcinoma, and 0135 for a fatal outcome.

HCV RNA "disappeared" in 7/45 (16%) IFN treated patients and in none of the 45 controls.

Maximum, minimum, and mean follow-ups were 11.8, 2.6, and 8.2 years, respectively,for controls, and 12.0, 4.4, and 9.2 years for patients given IFN-. The two groups were well balanced for the major prognostic factors of chronic hepatitis C and cirrhosis.

During follow-up, 25 (56%) of the controls and 13 (29%) of the patients given IFN- were rated grade B or worse (p=0018).

IFN- decreased the cumulative incidence of worsening of the Child-Pugh score (figure)

Hepatocellular carcinoma was detected in 33 (73%) of the 45 controls and 12 (27%) of the 45 patients given IFN- (p<0001)

For patients with mean ALT 80 IU during this trial, these numbers were 23 (79%) of 29 controls and 10 (33%) of 30 patients given IFN- (p=0033).

26 (58%) of the controls and 5 (11%) patients in the IFN- group died during follow-up (p<0001);

the cumulative proportion of overall survival was higher in the group given IFN-a.

This means less risk for progression carcinoma and death for those receiving IFN:
By univariate analysis, the risk ratios of IFN- versus symptomatic treatment were 0302 (95% CI 0156-0583) for progression to Child-Pugh B, 0244 (0126-0475) for development of hepatocellular carcinoma, and 0169 (0065-0440) for death, respectively. By multivariate analysis, the risk ratios of treatment were 0250 (0124-0505) for progression to Child-Pugh B, 0256 (0125-0522) for development of hepatocellular carcinoma, and 0135 (0049-0372) for death, respectively (table).

The effects of IFN- on liver function, hepatocarcinogenesis, and survival rate are still controversial. The disagreement seems to be related to the annual rate of hepatocarcinogenesis in patients with type C cirrhosis being much greater in Japan than in the USA;2 in countries with low rates, much larger groups of patients are needed for the same statistical power. A second possible explanation is the difference in the patients' backgrounds: factors in addition to hepatitis C virus (HCV) infection (eg, occult hepatitis B virus [HBV] infection3) and predisposing characteristics involving race or life-style (such as alcohol intake). Japan has a high rate of HBV carriers; occult HBV infection in patients with type C cirrhosis may contribute to their high rate of hepatocarcinogenesis. A third explanation may be the different treatments used.

Hepatocellular carcinoma was detected in only two (13%, 2-40%) of our 15 patients with a complete response to IFN-(HCV RNA disappeared) or partial response (mean ALT <80 IU); the relative risk was 012 (003-048). In ten (33%, 17%-53%) of the 30 patients who did not respond to IFN-(ALT remained 80 IU), carcinoma was detected; the proportion was smaller than for the controls (23 [79%] of 29 patients; p=0033), but inhibition of carcinogenesis by IFN-was weak. Some part of such inhibition by IFN- seems to involve its
lessening of hepatic inflammation.