Fatty Liver Contributes to Hepatocarcinogenesis in Cirrhotic Livers
Jacob Alexander, Michael Torbenson, Tsung-Teh Wu, Matthew M Yeh. University of Washington, Seattle, WA; Johns Hopkins University, Baltimore, MD; Mayo Clinic, Rochester, MN
Background: Some specific etiologies of hepatocellular carcinoma (HCC) are well known, such as viral hepatitis and cirrhosis. Diabetes and obesity, two conditions strongly associated with nonalcoholic fatty liver disease, have been established as independent risk factors for the development of HCC. Recent studies have suggested an association between non-cirrhotic fatty liver and risk of HCC. However, morphological data directly linking fatty liver to HCC in the setting of cirrhosis are lacking.
Design: All cirrhotic livers explanted in 3 tertiary centers in 2010-2011 were retrieved, including 131 cases with HCC and 162 cases without HCC. 85 HCC cases arising in non-cirrhotic liver resected during the same period were also compared. Slides of tumor and liver distant from tumor were reviewed and steatosis was scored according to NASH-CRN. Clinical data including metabolic profile were collated.
Results: The prevalence of significant steatosis (≥grade 1) in non-tumor (NT) liver in 54/131 (41%) cirrhotic cases with HCC was significantly higher than that in 29/162 (18%) cirrhotic cases without HCC (p<0.0001), but similar to 42/85 HCC cases (49%) arising in non-cirrhotic liver (p=0.2). NT liver steatosis was associated with obesity (p=0.04), dyslipidemia (p=0.02), but not diabetes (p=0.2) or hypertension (p=0.07). 33/96 (34%) cirrhotic cases with viable tumor slides available to review showed the steatohepatitic(SH)-HCC morphology, in which 18/33 (54%) cases had significant steatosis in NT liver, while 22/63 cases (35%) without SH-HCC morphology had significant steatosis in NT liver (p=0.06). 23/63 (36%) non-cirrhotic cases with viable tumor slides available to review showed the SH-HCC morphology, in which 14/23 (60%) had significant steatosis in NT liver, while 18/40 (45%) cases without SH-HCC morphology had significant steatosis in NT liver (p=0.2). There was no difference in the frequency of SH-HCC between cirrhotic and non-cirrhotic livers (34% vs 36%, respectively, p=0.78). Irrespective of background cirrhosis, cases with SH-HCC had a statistically significant association with higher BMI (29.9 vs. 27.5; p=0.01), but not with diabetes, hypertension, and dyslipidemia.
Conclusions: Steatosis in cirrhotic liver is strongly associated with the occurrence of HCC and metabolic risks. This multi-center and large cohort study highlights the role of hepatic steatosis and metabolic syndrome in hepatocarcinogenesis in cirrhotic liver. Further, the occurrence of SH-HCC does not differ between cirrhotic and non-cirrhotic livers.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 151, Tuesday Afternoon