Hepatitis C Infection: Can It Cause Hepatocellular Carcinoma in Non-Cirrhotic Livers?
M Torbenson, HD Daniel, MM Yeh. Johns Hopkins Univ, Baltimore, MD; Univ of Washington, Seattle, WA
Background: Chronic hepatitis C viral (HCV) infection can lead to cirrhosis and hepatocellular carcinoma (HCC). It is generally believed that HCV is not oncogeneic per se, but that the presence of cirrhosis determines the increased risk for HCC. To date there is little data on HCC arising in HCV infected, but non-cirrhotic livers.
Design: To further study HCCs arising in this setting, we searched our files from 1982-2008 for HCCs resected for curative intent. Cases with clinical or serologic evidence of HBV coinfection were excluded. All remaining cases were tested for occult HBV by PCR in formalin-fixed, paraffin embedded tissues. The tumors were further tested for CTNNB1 (beta catenin) exon 3 mutations. TP53 was also tested for codon 249 mutations, a characteristic mutation strongly linked to aflatoxin exposure.
Results: 18 non-cirrhotic HCC cases arising in HCV were identified. All were negative for occult HBV infection. Average age at resection was 58 years (M:F=14:4), including 9 Whites, 5 Blacks, 2 Asians, and 2 Egyptians. Only 1 had additional risk factors for fibrosis (iron overload and significant alcohol use). The cases were not enriched for unusual HCV genotypes:1A,1B,2B,3A,4, unavailable (n=3,3,2,1,2,7, respectively). HCV viral loads averaged 6.48 log IU/ml (available in 7 cases). Only 3 had serum AFP greater than 30 ng/ml: 5188, 2329, 2303 (available in 15 cases). 4 showed bridging fibrosis while 7 showed portal fibrosis; none were cirrhotic. The average tumor size was 5.9 cm and tumors were unifocal in 9 cases and multifocal in 9 cases. AJCC staging was: T1 (n=6), T2 (n=8), T3 (n=4). Histology of tumors (not available in 1 case due to necrosis) showed typical HCCs, with Edmonson-Steiner grades 1 (n=2), 2 (n=5), 3 (n=7), and 4 (n=3) and showed pseudoglandular (n=6), solid (n=9), or mixed (n=2) patterns. No mutations were seen in exon 3 of CTNNB1 or in TP53.
Conclusions: Our results clearly demonstrate that HCC can arise in livers chronically infected with HCV but without cirrhosis. The HCCs had typical histology with no enrichment for unusual growth patterns. In this cohort, occult HBV was not detected and there was no molecular evidence for aflatoxin exposure. These findings raise the possibility that in some cases HCV can be directly oncogeneic. It is also possible that established cirrhosis may have regressed in some cases. Regardless of the mechanism, these findings highlight an important and previously under-recognized risk for HCC in HCV infected individuals who do not have cirrhosis.
Category: Liver & Pancreas
Monday, March 9, 2009 2:45 PM
Platform Session: Section E, Monday Afternoon