According to a study, the predictors of hepatocellular carcinoma (HCC) differ in patients with virologically cured hepatitis C virus (HCV) infection with and without cirrhosis. However, changes in fibrosis-4 (FIB-4) scores over time are associated with HCC risk in both cohorts.
“[O]Our study provides evidence from a well-characterized cohort of virologically cured patients with HCV but free of cirrhosis that monitoring changes in FIB-4 could have clinical utility, especially in patients with coexisting diabetes and hypertension,” the researchers said. “In patients with cirrhosis, the evolution of FIB-4 and other select markers of liver disease severity could refine risk stratification.”
A retrospective cohort study was conducted in patients with HCV who achieved sustained virologic response to direct-acting antivirals from 130 Veterans Administration hospitals from 2014 to 2018 followed through 2021.
The researchers generated Cox models for proportional risks at three key time points (baseline and 12 and 24 months after sustained virologic response) to examine the associations of demographic, clinical and behavioral factors with HCC risk, stratified by cirrhosis status.
A total of 92,567 patients were enrolled, 32 percent of whom had cirrhosis, while 3,247 HCC cases were 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 key time point: male gender (hazard ratios [HRs]1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HRs, 1.71, 1.79, and 1.34), varicose veins (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).
Similarly, HCV genotype 3, prior treatment, bilirubin, smoking and race predicted baseline HCC risk, but their associations weakened over time.
In cirrhosis-free patients, diabetes (HRs, 1.54, 1.42, and 1.47) and hypertension (HRs, 1.59, 1.65, and 1.74) influenced HCC risk at all key time points . In particular, changes in FIB-4 scores over time correlated significantly with HCC risk, both in patients with and without cirrhosis.
“Our study has three important findings. First, HCC risk factors differed in patients with and without cirrhosis,” the researchers said. “Second, changes in several risk factors over time, particularly markers of liver fibrosis, may inform risk predictions in patients with virologically cured HCV.”
“Third, our data confirm previous reports showing that the risk of HCC remains elevated in some patient groups 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]
In addition, smoking was found to contribute to an increased risk of HCC in patients with cirrhosis. Previous studies pointed to several components 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 sarcopenia also contributed to a higher risk of HCC, but the exact mechanism could not be investigated in the current study. [Clin Nutr 2020;39:3132-3139]
“We believe that repeated measures risk assessment beyond 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,” said the researchers.