Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.
OBJECTIVE
The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication.


METHODS
The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis; 227 (34 hepatitis B virus and 193 hepatitis C virus related) were treated with alpha-interferon and 120 (28 hepatitis B virus and 92 hepatitis C virus) did not receive this treatment, in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma. In all patients, the cirrhosis was well compensated (Child A).


RESULTS
Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus, 20/347 patients (6/62 hepatitis B virus and 14/285 hepatitis C virus) developed hepatocellular carcinoma. The risk of developing this tumor was significantly greater in males (p < 0.007) and in patients not treated with alpha-interferon (p < 0.01). The Relative Risk of developing hepatocellular carcinoma increased significantly (p < 0.0002) with each passing year. In patients with hepatic cirrhosis secondary to hepatitis B virus infections, the risk did not seem to be modified by alpha-interferon treatment, even though a greater, but not significant risk (Relative Risk = 4.9; p = 0.3) was calculated for untreated patients; in contrast, in hepatitis C virus-related cirrhosis, this risk was reduced by a factor of 4.0 (p = 0.04). The tumor developed only in non-responder patients regardless of virus type. After adjustment for confounding factors (sex, age, alcohol consumption, cigarette smoking), a statistically significant (p < 0.025) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls, but not when responders were compared with non-responders.


CONCLUSIONS
These results show that, in addition to its ability to halt the progression of viral-induced liver disease, alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma.
Cattedra di Gastroenterologia, University of Bologna, Chieti, Italy.
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G
Mazzella
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E
Accogli
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S
Sottili
D
D
Festi
M
M
Orsini
A
A
Salzetta
V
V
Novelli
A
A
Cipolla
C
C
Fabbri
A
A
Pezzoli
E
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Roda
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D005069:Evaluation Studies as Topic; D005260:Female; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D018570:Risk Assessment
D016898:Interferon-alpha