Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc

Abstract

The recently approved direct acting antivirals (DAA) agents are effective in terms of sustained virologic response (SVR) rates and are well tolerated in most hepatitis C virus (HCV) patients. This study aimed to analyze the association between serum zinc levels in patients who developed hepatocellular carcinoma (HCC) following HCV eradication after DAA treatment. The retrospective study included 769 HCV infected patients who achieved SVR after DAA treatment. We calculated the annual incidence rate of HCC and identified risk factors associated with HCC development. We also assessed serum zinc and clinical factors at both baseline and end of treatment (EOT). During follow up (median duration 35 months), HCC occurred in 18/769 (2.3%) patients. From the multivariate analysis, serum zinc <60 μg/dl [hazard ratio (HR) 5.936] and AFP ≥6.0 ng/dl (HR 5.862) at baseline, baseline zinc <60 μg/dl (HR 6.283), EOT serum zinc <63 μg/dl (HR 6.011), baseline AFP ≥6.0 ng/dl (HR 8.163), and EOT M2BPGi ≥2.5 (HR 12.194) at baseline and EOT were independently associated with increased HCC risk. In patients who achieved HCV eradication following DAA treatment, serum zinc levels before and at EOT could be a risk factor for developing HCC.

Serum α‐fetoprotein level at treatment completion is a useful predictor of hepatocellular carcinoma occurrence more than one year after hepatitis C virus eradication by direct‐acting antiviral treatment

“…The results of the present study demonstrated that the cumulative incidences of HCC were 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5 years, respectively, from EOT with DAAs. Previous studies have reported that the 3‐year cumulative incidence of HCC in patients who received DAA treatment was 2.4%–6.6%, consistent with our study 28–30 …”

“…According to the ROC value for HCC occurrence of multiple parameters at EOT in 561 patients, the cut-off values for parameters were set and are shown in HCV eradication by DAAs. 14,[28][29][30][31][32][33][34][35][36][37][38] The results of the present study demonstrated that the cumulative incidences of HCC were 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5 years, respectively, from EOT with DAAs. Previous studies have reported that the 3-year cumulative incidence of HCC in patients who received DAA treatment was 2.4%-6.6%, consistent with our study.…”

“…Previous studies have reported that the 3-year cumulative incidence of HCC in patients who received DAA treatment was 2.4%-6.6%, consistent with our study. [28][29][30] We revealed serum AFP level as a predictor of HCC occurrence ≥1 year after DAA treatment. Elevated AFP serum level is recognized as one of the common risk factors for HCC occurrence.…”

“…The increasing number of patients obtaining HCV clearance with DAAs and the continued risk of hepatocarcinogenesis even after SVR require the identification of patients at highest risk of developing HCC. Previous studies have demonstrated that serum AFP levels, age, FIB‐4 index and albumin bilirubin grade as risk factors for HCC occurrence following HCV eradication by DAAs 14,28–38 …”

Significance of zinc deficiency in patients with hepatocellular carcinoma undergoing hepatic resection

“…reported that, in patients who achieve HCV eradication after direct acting antiviral treatment, serum Zn concentrations before and at the end of antiviral treatment are a risk factor for developing HCC. 36 Miwa et have reported that Zn deficiency is likely to be a predictor of both the development of hepatic encephalopathy, and mortality in patients with liver cirrhosis and hepatic encephalopathy. 37 Imai et al…”