Which factors elevate HCC risk in patients with cured HCV infection?

Predictors of hepatocellular carcinoma (HCC) differ in patients with virologically cured hepatitis C virus (HCV) infection with and without cirrhosis, according to a study. However, changes in fibrosis-4 (FIB-4) scores over time are associated with HCC risk in both cohorts.

“[O]ur study provides evidence from a well-characterized cohort of virologically cured patients with HCV but free of cirrhosis that monitoring changes in FIB-4 might have clinical utility, especially in patients with coexisting diabetes and hypertension,” the researchers said. “In patients with cirrhosis, evolution of FIB-4 and other select markers of liver disease severity could refine risk stratification.”

A retrospective cohort study was carried out on patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals from 2014 to 2018, followed through 2021.

The researchers generated Cox proportional hazards models at three landmark times (baseline and 12 and 24 months after sustained virological response) to examine the associations of demographic, clinical, and behavioural factors with HCC risk, stratified by cirrhosis status.

A total of 92,567 patients were included, of whom 32 percent had cirrhosis, while 3,247 HCC cases had been diagnosed during a mean follow-up of 2.5 years. [Am J Gastroenterol 2022;117:1834-1844]

In patients with cirrhosis, the following factors correlated with HCC risk at each landmark time: male sex (hazard ratios [HRs], 1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HRs, 1.71, 1.79, and 1.34), varices (HRs, 1.73, 1.60, and 1.56), baseline albumin (HRs, 0.48, 0.47, and 0.49), and change in albumin (HRs, 0.82, and 0.90).

Likewise, HCV genotype 3, previous treatment, bilirubin, smoking, and race predicted HCC risk at baseline, but their associations weakened over time.

In patients free of cirrhosis, diabetes (HRs, 1.54, 1.42, and 1.47) and hypertension (HRs, 1.59, 1.65, and 1.74) influenced HCC risk at all landmark times. Notably, changes in FIB-4 scores over time significantly correlated with HCC risk both in patients with and without cirrhosis.

“Our study has three key findings: First, HCC risk factors differed in patients with and without cirrhosis,” the researchers said. “Second, changes in several risk factors over time, especially markers of liver fibrosis, could inform risk prediction in patients with virologically cured HCV.”

“Third, our data confirm previous reports that showed that the risk of HCC remains elevated in some groups of patients after SVR,” they noted. [Gastroenterology 2017;153:996-1005; Gastroenterology 2019;157:1264-1278; Hepatobiliary Pancreat Dis Int 2020;19:541-546; J Hepatol 2018;69:1088-1098]

Furthermore, smoking was found to contribute to an increased risk of HCC in patients with cirrhosis. Previous studies pointed to several constituents of tobacco smoke that promote hepatocarcinogenesis. [Liver Int 2018;38:1487-1494; Int J Epidemiol 2009;38:1497-1511; J Epidemiol 2013;23:115-121; J Hepatol 2011;54:753-759]

Low BMI and sarcopaenia also contributed to a higher risk of HCC, but the exact mechanism could not be explored in the current study. [Clin Nutr 2020;39:3132-3139]

“We believe risk assessment based on repeat measurements at 2 years is practical and can improve shared decision-making between patients and their physicians by providing a quantifiable personalized HCC risk assessment, including how it changes over time,” the researchers said.