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

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.

Predictive Factors for Hepatocellular Carcinoma Development after Direct-Acting Antiviral Treatment of HCV

“…Similarly, a recent study revealed that patients with higher post-treatment AFP had a high risk of recurrence of HCC [37]. In line with these findings, several other studies have confirmed AFP as a circulating biomarker associated with HCC development after DAA treatment [38][39][40].…”

“…Peleg et al identified liver steatosis as a major risk factor of all-cause mortality and HCC in HCV patients who achieved a sustained virological response following DAA treatment, regardless of the stage of liver fibrosis [46]. Similarly, a recent study revealed that the underlying NAFLD is strongly associated with higher incidence of HCC in HCV patients after DAA treatment [38]. Indeed, growing evidence suggests that successful DAA treatments may cause modulations in lipid profile, ameliorate hepatic steatosis, reduce the incidence of metabolic alterations, including diabetes mellitus and insulin resistance, and improve the risk of cardiovascular disease [47].…”

The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments

“…Consequently, HCV-infected patients who either have advanced fibrosis at treatment initiation or steatosis should be closely monitored for liver-related complications. Underlying NAFLD has, therefore, been associated with increased incidence of HCC in CHC patients following a SVR by DAAs [52]. A reduction in liver steatosis was also reported by Kobayashi et al in a study involving 57 patients with CHC who achieved a SVR following DAA treatment [122].…”

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region

“…77,78 Co-existing fatty liver is also a risk factor for Kawaguchi T et al P. 8 HCC after cure in patients with HCV infection. 79,80 Furthermore, Peleg et al demonstrated that fatty liver is a major predictor of all-cause mortality in patients who achieve a sustained virological response following DAA treatment, regardless of fibrosis stage. 81 Thus, MAFLD should be treated and managed on its own merits, even in patients with cured HCV infection.…”

“…[19][20][21][22][102][103][104][105][106] Moreover, co-existing fatty liver is a risk factor for HCC in patients with HBV/HCV infection. 69,70,79,107,108 Recently, Pfister et al performed a meta-analysis and demonstrated that non-viral HCC is less responsive to immunotherapy. 109 Non-viral HCC does not equal MAFLDrelated HCC.…”