With Hepatitis C Virus on the Run, Meet the New Challenge: Hepatocellular Carcinoma

Digestive Disease Week (DDW) 2017

William F. Balistreri, MD


July 26, 2017

HCC in Fatty Liver Disease

Another candidate group for targeted surveillance is the obese, especially those with the associated hepatic consequence of nonalcoholic fatty liver (NAFLD). Despite the fact that this disease has risen to epidemic proportions, there is a lack of information on the risk for HCC in patients with NAFLD.

A longitudinal study presented by Kramer and colleagues[4] included a large number of geographically and ethnically diverse patients with NAFLD (N= 237,683) with sufficient follow-up to quantify this risk.

Study subjects were identified through the Veterans Affairs Health Care System between 2004 and 2008. NAFLD was defined as two or more determinations of serum ALT values > 40 IU/mL (> 31 IU/mL for women) obtained more than 6 months apart but within 2 years of each other, with no evidence of hepatitis B virus and HCV or alcohol abuse. The researchers also identified 237,683 matched controls.

Patients with NAFLD were significantly more likely than controls to be obese, Hispanic, and have diabetes, hypertension, dyslipidemia, and cirrhosis.

During a mean follow-up of 9 years, 469 patients with NAFLD developed HCC (an incidence rate of 0.21 per 1000 patient-years), compared with 54 from the control group (a rate of 0.03 per 1000 patient-years); therefore, the relative risk of developing HCC was higher in patients with NAFLD than in controls (HR, 6.65).

Among patients with NAFLD, the risk for HCC was highest in those with cirrhosis and a high FIB-4 score. The risk for HCC was intermediate in patients who had cirrhosis with a low FIB-4 score and in those with a high FIB-4 score but no cirrhosis. Absence of cirrhosis combined with a low FIB-4 score was associated with a negligible risk for HCC.

Advanced Fibrosis Prevalence in NAFLD

Lapid and colleagues[5] sought clinical predictors of advanced fibrosis among US adults with NAFLD using the 2011-2014 National Health and Nutrition Examination Survey (NHANES). The presence of advanced fibrosis among individuals with NAFLD was evaluated via the NAFLD fibrosis score (NFS) and the AST to Platelet Ratio Index (APRI).

Overall, the prevalence of NAFLD was significantly higher in women compared with men (31% vs 15%; P < .01). There was no significant race/ethnicity-specific difference in the prevalence of NAFLD. Increasing age was associated with increasing NAFLD prevalence, with individuals 60 years of age or older having an overall prevalence of 47%. Concurrent diabetes mellitus (OR, 3.1; P < .001) or obesity (OR, 2.7; P < .001) were both associated with an increased risk for NAFLD.

The prevalence of advanced fibrosis among individuals with NAFLD ranged from 9.7% when using a cutoff value of the NFS of > 0.676, to 23.8% when using an APRI cutoff value of > 0.7. On multivariate regression, obesity (OR, 9.10; P = .001) and concurrent diabetes (OR, 18.2; P < .001) were associated with significantly greater odds of advanced fibrosis among individuals with NAFLD.

The investigators therefore concluded that the prevalence of advanced fibrosis among US adults with NAFLD ranges from 10% to 24%, representing 7.3-17.9 million individuals, exceeding the prevalence of all US adults with chronic HCV and chronic hepatitis B virus combined.

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