TY - JOUR
T1 - Hepatitis C-associated hepatocellular carcinomas in non-cirrhotic livers
AU - Yeh, Matthew M.
AU - Daniel, Hubert Darius J.
AU - Torbenson, Michael
N1 - Funding Information:
This work was supported by R01DK078686 (MT).
PY - 2010/2
Y1 - 2010/2
N2 - Chronic hepatitis C viral infection can lead to cirrhosis and hepatocellular carcinoma. It is generally believed that hepatitis C infection is not oncogeneic per se, but that the presence of cirrhosis determines the increased risk for hepatocellular carcinoma. However, a search of surgical pathology files from two large tertiary care centers for the years 2001-2008 identified a total of 18 hepatocellular carcinomas in non-cirrhotic livers with chronic hepatitis C infection. In six cases the background livers showed bridging fibrosis, while the remainder showed lower stages of fibrosis. Cases were negative for clinical and serological evidence of hepatitis B co-infection, and occult hepatitis B test was negative by PCR of formalin-fixed, paraffin embedded tissues. The tumors were also negative for TP53, exon 7, codon 249 mutations, a characteristic mutation strongly linked to aflatoxin exposure. The hepatocellular carcinomas had typical histology with no enrichment for unusual growth patterns or histological features. Among all resected hepatocellular carcinomas in non-cirrhotic livers over this time period, the prevalence of 16% with HCV infection was significantly greater than that expected by chance. In conclusion, these results demonstrate that hepatocellular carcinomas can arise in livers chronically infected with hepatitis C but without cirrhosis. These findings raise the possibility that in some cases hepatitis C infection and inflammation 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 hepatocellular carcinoma in HCV-infected individuals who do not have cirrhosis.
AB - Chronic hepatitis C viral infection can lead to cirrhosis and hepatocellular carcinoma. It is generally believed that hepatitis C infection is not oncogeneic per se, but that the presence of cirrhosis determines the increased risk for hepatocellular carcinoma. However, a search of surgical pathology files from two large tertiary care centers for the years 2001-2008 identified a total of 18 hepatocellular carcinomas in non-cirrhotic livers with chronic hepatitis C infection. In six cases the background livers showed bridging fibrosis, while the remainder showed lower stages of fibrosis. Cases were negative for clinical and serological evidence of hepatitis B co-infection, and occult hepatitis B test was negative by PCR of formalin-fixed, paraffin embedded tissues. The tumors were also negative for TP53, exon 7, codon 249 mutations, a characteristic mutation strongly linked to aflatoxin exposure. The hepatocellular carcinomas had typical histology with no enrichment for unusual growth patterns or histological features. Among all resected hepatocellular carcinomas in non-cirrhotic livers over this time period, the prevalence of 16% with HCV infection was significantly greater than that expected by chance. In conclusion, these results demonstrate that hepatocellular carcinomas can arise in livers chronically infected with hepatitis C but without cirrhosis. These findings raise the possibility that in some cases hepatitis C infection and inflammation 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 hepatocellular carcinoma in HCV-infected individuals who do not have cirrhosis.
KW - Hepatitis C virus
KW - Hepatocellular carcinoma
KW - Non-cirrhotic liver
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U2 - 10.1038/modpathol.2009.174
DO - 10.1038/modpathol.2009.174
M3 - Article
C2 - 19935643
AN - SCOPUS:76349089552
VL - 23
SP - 276
EP - 283
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 2
ER -