Oral Zinc Supplementation Decreases the Risk of HCC Development in Patients With HCV Eradicated by DAA.

We have reported that the plasma zinc concentration gradually decreases with the progression of fibrosis and is related to hepatocellular carcinoma (HCC) development. The aim of this study was to examine the impact of the zinc concentration on HCC development (study 1) and the relationship between zinc intake and HCC development (study 2) in patients with hepatitis C virus (HCV) eradicated by direct-acting antivirals (DAAs). A total of 599 sustained virological response (SVR) patients treated with DAAs without a history of HCC were retrospectively analyzed in this study. Eighty patients received supplemental zinc (Zn treatment group), and 519 patients did not receive zinc (no Zn treatment group). In study 1, the cumulative incidence rate of HCC was compared between the Zn treatment group and the no Zn treatment group. In study 2, the risk factors for HCC development were examined in the no Zn treatment group. In study 1, in the Zn treatment group, HCC did not develop during follow-up, and the cumulative risk of HCC was significantly lower in the Zn treatment group than in the no Zn treatment group (P = 0.048). In study 2, the 1-year and 3-year cumulative incidence rates of HCC were 1.8% and 5.6%, respectively. The risk factors for HCC identified by multivariate analysis were male sex, cirrhosis, low platelet count before treatment, and low serum zinc concentration 12 weeks after the end of DAA therapy. Conclusion: The Zn concentration is related to HCC development in patients with HCV eradicated by DAA therapy. Oral zinc supplementation is recommended as a means of suppressing HCC development in patients who have achieved SVR.

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL.