Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection

Authors

Jennifer R Kramer
Yumei Cao
Liang Li
Donna Smith
Jagpreet Chhatwal
Hashem B El-Serag
Fasiha Kanwal

Publication Date

11-1-2022

Journal

The American Journal of Gastroenterology

DOI

10.14309/ajg.0000000000001968

PMID

36327437

PMCID

PMC9641546

PubMedCentral® Posted Date

11-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Male, Carcinoma, Hepatocellular, Hepacivirus, Liver Neoplasms, Antiviral Agents, Retrospective Studies, Hepatitis C, Chronic, Incidence, Hepatitis C, Liver Cirrhosis, Risk Factors, Albumins, hepatitis C virus, hepatocellular carcinoma, risk factors, sustained viral response

Abstract

INTRODUCTION: There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection.

METHODS: We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status.

RESULTS: Among 92,567 patients (32% cirrhosis), 3,247 cases of HCC were diagnosed during a mean follow-up of 2.5 years. In patients with cirrhosis, male sex (hazard ratios [HR]: 1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HR: 1.71, 1.79, and 1.34), varices (HR: 1.73, 1.60, and 1.56), baseline albumin (HR: 0.48, 0.47, and 0.49), and change in albumin (HR: 0.82 and 0.90) predicted HCC risk at each landmark time. HCV genotype 3, previous treatment, bilirubin, smoking, and race influenced HCC risk at baseline, but their effects attenuated over time. In patients without cirrhosis, diabetes (HR: 1.54, 1.42, and 1.47) and hypertension (HR: 1.59, 1.65, and 1.74) were associated with HCC risk at all landmark times. Changes in fibrosis-4 scores over time were associated with HCC risk both in patients with and without cirrhosis.

DISCUSSION: Risk factors for HCC were different in patients with and without cirrhosis and some also evolved during follow-up. These factors can help with risk stratification and HCC surveillance decisions in patients with cured HCV.