Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C–Related Advanced Fibrosis and Cirrhosis

Abstract

Background and Aim Existing data are controversial regarding the incidence of hepatitis C (HCV)–related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). Methods Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. Results The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×10 3 /mL, and high AFP were independent risk factors of developing HCC. Conclusion Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

Magnetic resonance imaging‐based risk factors of hepatocellular carcinoma after direct‐acting antiviral therapy: A multicenter observational study

“…Other factors, including γglutamyltranspeptidase, platelet count, total bilirubin, and α-fetoprotein, were also found to be independent risk factors, although their associations with hypervascular HCC development have shown inconsistencies in previous studies. 5,[13][14][15]17 Notably, α-fetoprotein did not emerge as a significant risk factor for the hypervascularization of HBP hypointense nodules without APHE in a recent meta-analysis involving patients with HCC. 33 Other discrep- F I G U R E 6 Cumulative rates of hypervascular hepatocellular carcinoma (HCC) development according to the signal pattern of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement.…”

“…[9][10][11][12] Previous investigations have identified several risk factors associated with HCC development after DAA therapy, including older age, sex, albumin levels, γ-glutamyltranspeptidase activity, fibrosis-4 index, platelet count, total bilirubin, hyaluronic acid levels, liver stiffness, α-fetoprotein levels, history of HCC treatment, and pretreatment fibrosis stage. 5,[13][14][15][16][17] Recently, attention has been drawn to hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) as potential indicators of hypervascular HCC development in patients with chronic liver disease. 18,19 HBP hypointense nodules without APHE are defined as hepatic nodules that do not show hyperenhancement during the arterial phase and display low signal intensity during the HBP on gadoxetic acid-enhanced magnetic resonance imaging (MRI).…”

“…Although chronic HCV infection can promote hepatocarcinogenesis, and its eradication may decrease the risk of HCC, the impact of viral eradication through DAA therapy on HCC development remains contentious. Some studies have reported a decrease in HCC incidence after DAA therapy, 5–8 whereas others have found no significant change 9–12 . Previous investigations have identified several risk factors associated with HCC development after DAA therapy, including older age, sex, albumin levels, γ ‐glutamyltranspeptidase activity, fibrosis‐4 index, platelet count, total bilirubin, hyaluronic acid levels, liver stiffness, α ‐fetoprotein levels, history of HCC treatment, and pretreatment fibrosis stage 5,13–17 .…”

The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt

“…Similarly, Kilany et al found a low incidence of HCC in patients with HCV treated with DAA with advanced fibrosis and cirrhosis. The factors associated with a high risk of HCC were decompensated cirrhosis, metabolic syndrome, failure to obtain SVR, and a baseline AFP level of ≥ 10 ng/dL [ 32 ]. In the current study, post-IFN HCC tended to be solitary tumors, while tumor necrosis was significantly observed in post-DAA HCC.…”

Therapeutic Vaccines against Hepatocellular Carcinoma in the Immune Checkpoint Inhibitor Era: Time for Neoantigens?

“…These risk factors vary from region to region, with HBV infection predominating in Asia, and HCV in Egypt, Japan, Western Europe, and North America, whereas obesity is becoming a relevant factor in Western societies [3]. Despite implementation of vaccination programs against HBV [4] and the use of antiviral drugs in HCV infection [5] to curb virus-induced HCC, this tumor continues to rise, mainly because of the increasing incidence of obesity, which leads to non-alcoholic fatty liver disease [6].…”