Abstract

Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15–0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17–0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59–58.82) and high BMI (OR = 1.19, 95% CI 1.07–1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p < 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC.

Highlights

  • Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers

  • NAFLD can lead to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC)3

  • In an unadjusted bivariate analysis comparing clinical factors associated with cirrhosis, we identified that being of non-Hispanic ethnicity (OR = 0.07, p = 0.0001), having dyslipidemia (OR = 0.321, p = 0.0268) and a lower body mass index (BMI) (p = 0.00065) were associated with non-cirrhosis in the NAFLD HCC group

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. We compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Current society guidelines only recommend HCC screening in patients with cirrhosis or those with high risk features of chronic hepatitis B (HBV) infection22 This creates a clinical dilemma given the number of patients with NAFLD, the increase in HCC incidence and the potential for cancer in non-cirrhosis population not currently targeted for screening. We aimed to study the overall and recurrence-free survival rates of NAFLD-associated HCC in cirrhosis and non-cirrhosis patients and compared their overall and recurrence-free survival outcomes to chronic viral etiologies of HCC in a large, diverse liver transplantation center in Los Angeles

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