Metabolic syndrome instead of aflatoxin-related tp53 r249s mutation as a hepatocellular carcinoma risk factor

Abstract

Background: Hepatocarcinogenesis has a variety of risk factors. In Mexico City, autopsies found 14% of hepatocellular car¬cinomas (HCCs) without cirrhosis. Objective: The objective of the study was to explore if HCCs carry the TP53 R249S mutation that has linked them to aflatoxin exposure and describe the associated risk factors. Methods: A retrospective review of consecutive cases of HCC was performed. Exposure to hepatotropic viruses, alcoholism, metabolic diseases, diabetes mel- litus, and hypertension, as well as episodes of ascites, portal hypertension, and body mass index were retrieved. Slides were re-reviewed, macrodissected and DNA was extracted. TP53 exon 7 was amplified, purified, and used as a template for se¬quencing. Results: In 14 years, 74 HCCs were identified in 1863 (4%) consecutive liver biopsies. No data were available in five excluded patients; the rest was submitted to exon 7 screening. Patients had a median age of 62 years, and 46 (67%) were male. Stage 4 fibrosis was observed in 46 patients (67%) and their associated risk factors were hepatitis C virus (39%, 18/46), alcoholism (20%, 9/46), hepatitis B virus (2%, 1/46), and 18 were cryptogenic. Fibrosis stage 3 or lower was ob¬served in 23 (33%) patients without demonstrated liver disease; 8/23 had diabetes and 6/23, systemic hypertension. Ste- atohepatitic variants of HCC were observed in 4 and in 5, the remnant liver had steatohepatitis. A 238-bp fragment was obtained in each tumor without the expected TP53 R249S mutation. Conclusions: There was no evidence of aflatoxin ex¬posure in HCCs, with and without the known "classical" risk factors. One-third of non-cirrhotic HCCs had steatohepatitis or conditions associated to metabolic syndrome. (REV INVEST CLIN. 2020;72(5):316-22).