Non-alcoholic fatty liver disease is a risk factor for occurrence of hepatocellular carcinoma after sustained virologic response in chronic hepatitis C patients: A prospective four-years follow-up study

Dong Ji; Guo-Feng Chen; Xiao-Xia Niu; Mingjie Zhang; Cheng Wang; Qing Shao; Vanessa Wu; Yudong Wang; Gregory Cheng; Selwyn J Hurwitz; Raymond F Schinazi; George Lau

doi:10.1016/j.metop.2021.100090

Non-alcoholic fatty liver disease is a risk factor for occurrence of hepatocellular carcinoma after sustained virologic response in chronic hepatitis C patients: A prospective four-years follow-up study

Metabol Open. 2021 Mar 26:10:100090. doi: 10.1016/j.metop.2021.100090. eCollection 2021 Jun.

Authors

Dong Ji^{1

2}, Guo-Feng Chen^{1

2}, Xiao-Xia Niu^{1

2}, Mingjie Zhang³, Cheng Wang^{2

4}, Qing Shao^{1

2}, Vanessa Wu^{2

4}, Yudong Wang^{2

4}, Gregory Cheng^{3

4}, Selwyn J Hurwitz⁵, Raymond F Schinazi⁵, George Lau^{1

2

4}

Affiliations

¹ Department of Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
² Fifth Medical Center of Chinese PLA General Hospital-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre, Beijing, 100039, China.
³ Faculty of Health Science, Macau University, Taipa, Macau.
⁴ Humanity and Health Clinical Trial Center, Humanity & Health Medical Group, Hong Kong, China.
⁵ Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Abstract

Background and aim: The incidence of hepatocellular carcinoma (HCC) decreases significantly in chronic hepatitis C (CHC) patients with sustained virologic response (SVR) after pegylated-interferon plus ribavirin (PR) or direct-acting antiviral (DAAs) therapy. We follow-up a single cohort of CHC patients to identify risk factors associated with HCC development post-SVR.

Method: CHC patients with SVR in Beijing/Hong Kong were followed up at 12-24 weekly intervals with surveillance for HCC by ultrasonography and alpha-fetoprotein (AFP). Multivariate Cox proportional hazards regression analysis was used to explore factors associated with HCC occurrence.

Results: Between October 2015 and May 2017, SVR was observed in 519 and 817 CHC patients after DAAs and PR therapy respectively. After a median post -SVR follow-up of 48 months, HCC developed in 54 (4.4%) SVR subjects. By adjusted Cox analysis, older age (≥55 years) [HR 2.4, 95% CI (1.3-4.3)], non-alcoholic fatty liver diseases [HR 2.4, 95%CI (1.3-4.2), higher AFP level (≥20 ng/ml) [HR 3.4, 95%CI (2.0-5.8)], higher liver stiffness measurement (≥14.6 kPa) [HR 4.2, 95%CI (2.3-7.6)], diabetes mellitus [HR 4.2, 95%CI (2.4-7.4)] at pre-treatment were associated with HCC occurrence. HCC patients in the DAAs induced SVR group had a higher prevalence of NAFLD as compared with those in the PR induced SVR group, 62% (18/29) vs 28% (7/25), p = 0.026. A nomogram formulated with the above six independent variables had a Concordance-Index of 0.835 (95% CI 0.783-0.866).

Conclusion: Underlying NAFLD is associated with increased incidence of HCC in chronic HCV patients post-SVR, particularly in those treated with DAA.

Keywords: AFP, alpha-fetoprotein; ALT, alanine aminotransferase; ANGPTL, angiopoietin-like proteins; AST, aspartate aminotransferase; ASV, asunaprevir; BCLC, Barcelona-Clinic Liver Cancer Group; BMI, body mass index; CHC, chronic hepatitis C; CI, confidence intervals (CI); Chronic hepatitis C; DAAs, direct-acting antiviral agents; DCV, daclatasvir; FGF, fibroblast growth factor; HCC; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HR, Hazard Ratio; IFN, interferon; LDV, ledipasvir; LSM, liver stiffness measurement; NAFLD; PLT, platelet count; PR, Peg-IFN-α with RBV; Peg-IFN, Pegylated interferon; RBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response; Sustained virologic response; TBIL, total bilirubin; TNF, tumor necrosis factor; ULN, upper limit of normal.