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Hepatic and Extrahepatic Malignancies in Cirrhosis Caused by Nonalcoholic Steatohepatitis and Alcoholic Liver Disease


Reprint requests: Katsutoshi Tokushige, MD, Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo 162-8666, Japan; Tel.: 81 3 33535 8111; Fax: 81 3 5269 7435; E-mail:



To clarify the carcinogenic factors associated with steatohepatitis, we investigated the characteristic features of hepatic and extrahepatic malignancies in patients with cirrhotic nonalcoholic steatohepatitis (NASH-LC) and cirrhotic alcoholic liver disease (ALD-LC).


A total of 72 patients with NASH-LC and 85 with ALD-LC (both biopsy-proven steatohepatitis without hepatocellular carcinoma [HCC]) were assessed with regard to the development of hepatic and extrahepatic malignancies. Risk factors for HCC were analyzed.


During follow-up, 10 NASH-LC patients and 6 ALD-LC patients developed HCC. The 5-year HCC development rate was similar for these 2 groups, being 10.5% in the NASH-LC group and 12.3% in the ALD-LC group. After adjusting for age and gender, the HCC development rates were also similar. Risk factors for HCC in the NASH-LC group were older age, higher γ-GTP level, and higher Child–Pugh score as determined by Cox hazards analysis. Regarding risk factors in the ALD-LC group, no risk factor was found by Cox hazards analysis, although diabetes mellitus led to a significantly higher HCC rate by log-rank test (p = 0.013). Regarding extrahepatic cancer, only 1 NASH-LC patient (1.4%) developed endometrial cancer. In contrast, 7 ALD-LC patients (8.2%) had other cancers (p = 0.052).


Comparison between NASH-LC and ALD-LC revealed similar HCC development curves. However, the risk factors for HCC and extrahepatic malignancies differed between the 2 diseases. In ALD-LC, the incidences of HCC and extrahepatic cancer are similar. When treating LC patients with NASH or ALD, the risk factors and extrahepatic malignancies associated with ALD-LC should be assessed.

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