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RESEARCH PRODUCT

Persistent expression of hepatitis C virus genome in primary tumor and adrenal metastasis of a hepatocellular carcinoma developed in a non-cirrhotic liver

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To the Editor: There is increasing evidence that chronic infection with hepatitis C virus (HCV) is a risk factor for hepatocellular carcinoma (HCC) in patients seronegative for hepatitis B virus (HBV) surface antigen (HBsAg). In western countries, HCCs occur in anti-HCV positive patients mostly in association with cirrhosis, which can be considered as a precancerous condition (1). However, there are rare cases of HCC that were found in anti-HCV positive patients without pre-existing liver cirrhosis (2). We report here the detection of HCV RNA in a primary HCC derived from an HCV-infected patient with a non-cirrhotic liver and its persistent expression in an adrenal metastasis that developed 3 years later. In January, 1992, the 7 l-year-old symptomless patient was admitted to our hospital because of a solitary inhomogeneous tumor in the right lobe of the liver with a size of 5×4x3 cm. The serum aminotransferase levels were slightly increased not exceeding 3 times normal. All other liver function parameters were within normal range. The c~-fetoprotein (c~-FP) level was elevated to 86 ng/ml. The patient's serum was positive for antiHCV antibodies (Ab) as measured by second-generation immunoassay. He had no history of non-viral risk factors of liver disease. The tumor staging was free from metastases in other organs, so a right-sided hemihepatectomy was performed. The histological examination of tumor tissue showed a moderately differentiated, trabecular HCC. The surrounding nontumorous liver tissue showed no cirrhosis, but nodular regenerative hyperplasia. The postoperative ot-FP level returned to normal range. In March, 1995, an increase in ~-FP level to 50 ng/ml was observed. The tumor staging revealed a singular right adrenal mass that was completely resected. The histological examination of the tumor showed metastatic tissue of the previously described HCC. A liver biopsy was still free from cirrhosis and tumor reactivation. In 1992 and 1995, we found HCV RNA using reverse transcription polymerase chain reaction (RT-PCR) (3) in the patient's serum, lymphocytes, nontumorous liver tissue, primary HCC or adrenal metastasis, respectively. In contrast, the patient's serum and tumor were negative for HBV DNA using PCR assay performed as recently published by our group (4). Our case shows in a prospective manner that HCV RNA detected in a primary HCC without cirrhosis can be found again in an adrenal metastasis occurring 3 years later. This observation is in line with results of a retrospective study about HCV RNA expression in HCV-associated HCCs without cirrhosis previously reported by Brechot's group (5). In conclusion, these data support the view that HCV may exert a direct oncogenic effect during long-lasting infection, and, therefore, itself play an important role in the pathogenesis of HCCs arising in non-cirrhotic livers.