[1717] Fatty Liver Contributes to Hepatocarcinogenesis in Non-Cirrhotic Livers

Jacob Alexander, Michael Torbenson, Tsung-Teh Wu, Sanjay Kakar, Dhanpat Jain, Matthew Yeh. Univ Washington, Seattle; Johns Hopkins Univ, Baltimore; Mayo Clinic, Rochester; Univ California, San Francisco; Yale Univ, New Haven

Background: While many specific etiologies of hepatocellular carcinoma (HCC) are well known, such as viral hepatitis and cirrhosis, the exact mechanisms of hepatocarcinogenesis remain unclear, particularly in non-cirrhotic livers. Diabetes and obesity have been established as independent risk factors for HCC. Oxidative stress has also been suggested in carcinogenesis. As steatosis is a common hepatic manifestation of these conditions, we studied the prevalence of hepatic steatosis in non-cirrhotic livers with HCC.
Design: All resected HCC cases arising in non-cirrhotic livers from 2001-2010 in 3 tertiary centers in US were searched. All resected cholangiocarcinoma (CC) cases in non-cirrhotic livers from 2001-2010 were used as control. After excluding all etiologies such as hepatitis B and/or C, hemochromatosis, α-1 antitrypsin deficiency, liver adenoma, etc, there were 157 HCC and 120 CC cases. Slides of liver distant from tumor were reviewed and steatosis was scored according to NASH-CRN. Tumor slides were reviewed in a subset of cases. Clinical data including metabolic profile were collated.
Results: As shown in the Table, the prevalence of significant steatosis (at least grade 1) in non-tumor (NT) liver in 85/157 (54%) HCC cases was greater than in 32/120 (26%) CC cases (p<0.0001). NT hepatic steatosis was associated with obesity (p=0.003) in HCC and with obesity (p=0.002) and diabetes (p=0.04) in CC. NT steatosis was associated with obesity (p<0.0001) and diabetes (p=0.006) in HCC and CC cases altogether. NT steatosis was not associated with age or alcohol use. In 40 HCC cases with tumor slides available, 18 showed the recently described steatohepatitic(SH)-HCC morphology, in which 16 had significant steatosis in NT liver, while 11 of the 22 without SH-HCC pattern had significant steatosis in NT liver (p=0.016). NT steatosis was not associated with steatosis in HCC.

Grade of steatosis in non-tumor liver

	0	1	2	3
HCC (n=157)	72 (46%)	56 (36%)	22 (14%)	7 (4%)
CC (n=120)	88 (73%)	21 (17%)	10 (8%)	1 (1%)

Conclusions: The prevalence of steatosis in NT liver was higher in HCC than in CC. The latter is similar to the general US population with hepatic steatosis. Obesity and diabetes were associated with hepatic steatosis in both HCC and CC. Hepatic steatosis was also associated with SH-HCC morphology. This multi-center and large cohort study underlines the role of hepatic steatosis and metabolic syndrome in hepatocarcinogenesis in non-cirrhotic liver.
Category: Liver

Monday, March 19, 2012 1:15 PM

Platform Session: Section E, Monday Afternoon