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