Metabolic factors affecting hepatocellular carcinoma in steatohepatitis

Abstract

Background & Aims: With the rising prevalence of alcoholism, obesity and metabolic syndrome, steatohepatitis will become the leading cause of end-stage liver disease and hepatocellular carcinoma in the United States by 2025. Patients with non-alcoholic steatohepatitis and alcoholic liver disease have similar clinical and histopathological presentations, whether these similarities persist in non-alcoholic steatohepatitis and alcoholic liver disease patients with hepatocellular carcinoma remains unknown. Methods: A retrospective analysis of the clinical features of adult patients from a large transplant center who underwent liver transplantation for steatohepatitis due to non-alcoholic steatohepatitis and alcoholic causes (alcoholic liver disease) between 1/1/02 and 1/1/12 was performed. Clinical features, explant histopathology, and clinical outcomes were compared. Results: Hepatocellular carcinoma was present in 80 of 317 patients, who underwent liver transplantation for steatohepatitis with equivalent distribution in non-alcoholic steatohepatitis and alcoholic liver disease patients (24% vs 26%; P = 0.8). On multivariate analysis, significant predictors of hepatocellular carcinoma included age, ethnicity (Hispanic), and diabetes, but not BMI, hypertension or smoking. A lower risk of hepatocellular carcinoma was associated with a clinical history of hyperlipidemia. Clinical parameters were similar between patients with alcoholic liver disease-hepatocellular carcinoma and non-alcoholic steatohepatitis-hepatocellular carcinoma, except sex and presence of metabolic syndrome. non-alcoholic steatohepatitis-hepatocellular carcinoma livers retained histopathological features of non-alcoholic steatohepatitis such as ballooning and Mallory bodies, while alcoholic liver disease-hepatocellular carcinoma livers did not. There were no significant differences in hepatocellular carcinoma recurrence rates or post-transplant overall survival. Conclusions: We report the largest single-center study evaluating clinical, histopathological and outcome measures of patients undergoing liver transplantation for steatohepatitis. Older patients, diabetics, and Hispanics may warrant more frequent cancer screening due to increased risk of hepatocellular carcinoma.

Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease

“…(8) A recent singlecenter, retrospective, cross-sectional study showed an independent association between diabetes and HCC in patients with NASH cirrhosis who underwent LT. BMI, hypertension, or smoking was not associated with the risk of HCC. (37) The cross-sectional study design that measures risk factor and outcome simultaneously prevented the researchers from addressing the potential temporal causal relationship between diabetes and HCC among patients with NASH cirrhosis. (38) In addition to older age and diabetes, a low albumin level was independently associated with the risk of HCC.…”

Racial Disparities in Diagnosis and Prognosis of Nonalcoholic Fatty Liver Disease

“…A systematic review done in south Texas and another large, retrospective analysis of patients undergoing liver transplant showed Hispanics experienced greatest burden of NAFLD‐related HCC compared with other ethnicities 29,30 . Non‐US‐born Hispanics are at lower risk for HCC compared with US‐born Hispanics, whereas foreign‐born Asians are at increased risk for HCC compared with US‐born Asians 31 .…”

Hepatocellular carcinoma in non-alcoholic fatty liver disease with and without cirrhosis

“…Other related variables are attributed to difficulties in access to adequate health care [31] . Patients with NAFLD-related HCC are older, have a shorter survival time, have more cardiovascular diseases and diabetes and are more likely to die from their HCC than other patients [41][42][43] . It has been demonstrated that curative treatment for HCC and serum albumin level > 3.7 g/dL suggest best prognostic profile for NAFLD-related HCC [44] .…”