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Incidence and clinical characteristics of hepatocellular carcinoma associated with nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis
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Clinical and Lab Clues to HCC Without Cirrhosis or Advanced Fibrosis
AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
Incidence (new diagnoses) of hepatocellular carcinoma (HCC) without cirrhosis or advanced fibrosis was low in a US study of 47,000 people with nonalcoholic fatty liver disease (NAFLD) [1]. Noncirrhotic people with NAFLD and HCC (versus those with NAFLD without HCC) tended to have lower body mass index (BMI), lower albumin and serum iron, and higher alkaline phosphatase and platelet count.
Estimated incidence of HCC in people with NAFLD-related cirrhosis and advanced fibrosis stands above 1%, and HCC surveillance usually begins when HCC risk exceeds 1.5%, noted University of Pittsburgh researchers who conducted this study. But they cited large cohort studies showing that HCC can develop in people with NAFLD who do not have cirrhosis. The Pittsburgh team undertook this study to estimate incidence of HCC in NAFLD patients with or without cirrhosis or advanced liver fibrosis.
This retrospective case-control analysis involved everyone in a big US healthcare system identified by ICD-9/10 codes as having NAFLD between 2004 and 2018. The investigators also used ICD-9/10 codes to identify cohort members with cirrhosis or HCC. And they used FIB-4 score at HCC diagnosis to segregate advanced fibrosis from less severe fibrosis (FIB-4 below 1.30 is the lower threshold to rule out advanced fibrosis; FIB-4 above 2.67 is the upper threshold to rule in advanced fibrosis). Poisson regression analysis compared HCC incidence with versus without cirrhosis and in different FIB-4 groups.
The research team identified 47,165 people with NAFLD between the ages of 40 and 89 in the years 2004-2018. During an average 3.5 years of follow-up, HCC developed in 981 (2.1%) of these people. Among people with newly diagnosed HCC, 842 (85.8%) had cirrhosis and 139 (14.2%) did not. Annual HCC incidence in the whole group came to 0.60%, compared with 2.36% in people with cirrhosis and 0.11% in people without cirrhosis (P < 0.001 for cirrhosis vs no cirrhosis). Annual HCC incidence rose with each higher FIB-4 score:
- 0.07% for FIB-4 below 1.30
- 0.12% for FIB-4 between 1.30 and 2.67 (P < 0.05 vs lower group)
- 0.28% for FIB-4 above 2.67 (P < 0.001vs two lower groups)
- 0.22% for FIB-4 unknown
Age was significantly younger in the 43 NAFLD patients with HCC without cirrhosis and FIB-4 below 1.3 than in the 868 people with HCC with cirrhosis or FIB-4 above 2.67 (59.3 vs 68.6 years, P < 0.001). Diabetes proved less likely in the NAFLD-HCC group without cirrhosis than in those with cirrhosis (41.9% vs 60%, P = 0.018). Variables that did not differ significantly between people with HCC with versus without cirrhosis were gender, white race, ever smoking, hypertension, abnormal lipids, and body mass index.
More than a half-dozen lab values differed significantly between people with NAFLD-HCC without cirrhosis and FIB-4 below 1.3 versus those with cirrhosis or FIB-4 above 2.67. Values significantly lower in the group without cirrhosis were aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, international normalized ratio (INR), bilirubin, and FIB-4 score. Values significantly higher in people with HCC and without cirrhosis were platelet count and albumin.
Among demographic variables and clinical parameters, body mass index was significantly lower in NAFLD patients with HCC than in those without HCC (31.5 vs 34.3 kg/m2, P = 0.013).
Among noncirrhotic people with NAFLD, those with versus without HCC had higher alkaline phosphatase (126.6 vs 85.4 U/L, P < 0.001) and platelet count (318.5 vs 268.6 x 1000 mL, P < 0.001) and lower albumin (3.68 vs 3.92 g/dL, P = 0.013) and serum iron (52.8 vs 76.5 mcg/dL, P = 0.010).
The researchers stressed that many people with NAFLD and incident HCC without cirrhosis had high FIB-4 scores indicating advanced fibrosis. They speculated that clinical traits of NAFLD-HCC patients without cirrhosis or advanced fibrosis "suggest possible differences in underlying disease etiology."
Reference
1. Behari J, Wang R, Luu HN, et al. Incidence and clinical characteristics of hepatocellular carcinoma associated with nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis. The Liver Meeting, November 12-15, 2021. Parallel session 20: Hepatobiliary Neoplasia.
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