Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

Fasiha Kanwal,Jennifer R Kramer,Srikar Mapakshi,Yamini Natarajan,Maneerat Chayanupatkul,Peter A Richardson,Liang Li,Roxanne Desiderio,Aaron P Thrift,Steven M Asch,Jinna Chu,Hashem B El-Serag

doi:10.1053/j.gastro.2018.08.024

Abstract

There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to estimate the risk of incident HCC among patients with NAFLD. We conducted a retrospective cohort study from a total of 130 facilities in the Veterans Health Administration. Patients with NAFLD diagnosed between January 1, 2004 and December 31, 2008 were included and followed until HCC diagnosis, death, or December 31, 2015. We also identified a sex- and age-matched control cohort without NAFLD. We ascertained all new HCC cases from the Central Cancer Registry and manual chart reviews. We calculated incidence rates for HCC by NAFLD status, as well as in subgroups of NAFLD patients. We used competing risk models to compare the risk of HCC in patients with NAFLD vs those without NAFLD. We reviewed electronic medical records of all HCC cases that developed in NAFLD patients without cirrhosis. We compared 296,707 NAFLD patients with 296,707 matched controls. During 2,382,289 person-years [PYs] of follow-up, 490 NAFLD patients developed HCC (0.21/1000 PYs). HCC incidence was significantly higher among NAFLD patients vs controls (0.02/1000 PYs; hazard ratio, 7.62; 95% confidence interval, 5.76-10.09). Among patients with NAFLD, those with cirrhosis had the highest annual incidence of HCC (10.6/1000 PYs). Among patients with NAFLD cirrhosis, HCC risk ranged from 1.6 to 23.7 per 1000 PYs based on other demographic characteristics; risk of HCC was thehighest in older Hispanics with cirrhosis. In medical record reviews, 20% of NAFLD patients with HCC had no evidence of cirrhosis. Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.

Highlights

There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD)
Risk of HCC was higher in NAFLD patients than that observed in general clinical population
The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis

Summary

Introduction

There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Recent studies reported the absence of any of these known major risk factors in a large proportion (20–40%) of patients with HCC.[4] Some, if not all, of these HCC cases are speculated to have non-alcoholic fatty liver disease (NAFLD) as the underlying etiological risk factor. NAFLD has become the leading cause of chronic liver disease in the U.S.5 It is posited as the hepatic manifestation of the metabolic syndrome, and is closely associated with diabetes and obesity. Coinciding with large increases in metabolic syndrome, the prevalence of NAFLD in the general population has doubled in the past 2 decades with estimates as high as 30%.6,7. NAFLD is often a non-progressive hepatic steatosis associated with few, if any, hepatic complications. NAFLD is the fastest growing cause of cirrhosis in the U.S.9–a concerning trend given the possible association between NAFLD related cirrhosis and HCC. 10 HCC has been reported to arise in patients with NAFLD in the absence of cirrhosis.[11]

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