LETTER
Interferon-
in Chronic Hepatitis C
Savino Bruno, MD;
Mauro Borzio, MD; and
Pier Maria Battezzati, MD
1 June 1998 | Volume 128 Issue 11 | Page 956
TO THE EDITOR:
Marcellin and colleagues' study [1] suggests that patients with chronic hepatitis C showing sustained response to interferon-
have a low risk for development of hepatocellular carcinoma. We are following a cohort of 23 long-term responders (5 with cirrhosis) who received interferon-2a in a randomized clinical trial [2] and were observed for a mean (±SD) of 77 ± 20 months (range, 50 to 114 months) after discontinuation of treatment. Sustained response was defined as persistently normal alanine aminotransferase levels at monthly determinations during the first 12 months after discontinuation of interferon-2a and every 3 months afterward. Hepatitis C virus (HCV) RNA was quantitatively and qualitatively measured by nested polymerase chain reaction (as described by Manzin and colleagues [3]) at the end of treatment and at 6-month intervals thereafter. Patients with cirrhosis underwent abdominal ultrasonography twice yearly. For all patients, liver histologic findings were available at baseline and 1 year after discontinuation of interferon-2a therapy.
Hepatitis C virus RNA had become undetectable in both serum and liver tissue at the time of post-treatment liver biopsy in two patients with cirrhosis. These patients showed no biochemical or virologic relapse during further follow-up. However, in one male patient (63 years of age at entry; genotype 2a/c; negative for hepatitis B surface antigen; no history of alcohol abuse; histologic activity index score, 13 ± 4 at baseline and 7 ± 4 after treatment), an 18-mm focal lesion was detected by ultrasonography 54 months after discontinuation of interferon-2a therapy. Intralesional histologic assessment confirmed the presence of hepatocellular carcinoma.
We conclude that hepatocellular carcinoma may occur in cirrhotic patients even when HCV RNA clearance and histologic improvement have been achieved. Efficacy of interferon-2a therapy in preventing neoplastic evolution is far from being established in this population, and careful ultrasonographic monitoring aimed at early recognition of hepatocellular carcinoma should not be discarded.
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Author and Article Information
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School of Medicine Ospedale S. Paolo; 20142 Milan, Italy
1. Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Castelnau C, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon- therapy. Ann Intern Med. 1997; 127:875-81.
2. Battezzati PM, Podda M, Bruno S, Zuin M, Crosignani A, Camisasca M, et al. Factors predicting early response to treatment with recombinant interferon -2a in chronic non A, non B hepatitis. Preliminary report of a long-term trial. Ital J Gastroenterol. 1992; 24:481-4.
3. Manzin A, Bagnarelli P, Menzo S, Giostra F, Brugia M, Francesconi R, et al. Quantitation of hepatitis C virus genome molecules in plasma samples. J Clin Microbiol. 1994; 32:1939-44.
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