Zinc Supplementation to Improve Prognosis in Patients With Compensated Advanced Chronic Liver Disease.

Zinc Supplementation to Improve Prognosis in Patients With Compensated Advanced Chronic Liver Disease: A Multicenter, Randomized, Double-blind, Placebo Controlled Clinical Trial

Zinc homeostasis could play a role in advanced chronic liver disease (cACLD) and its supplementation has been linked with improvement in liver function, decrease of hepatic complications and reduction in hepatocellular carcinoma (HCC) incidence. cACLD encompasses a heterogeneous group of patients with a variable risk of clinically significant portal hypertension (CSPH) and clinical events. The ANTICIPATE model is a validated model for stratifying these risks. Our aim is to demonstrate that the administration of zinc can reduce the rate and risk of presenting clinical events (first decompensation, HCC, death and liver transplantation). This study protocol describes an ongoing phase III, national, multicentre, randomized, double-blind clinical trial that will enroll 300 patients to receive either the trial treatment (zinc acexamate) or placebo. An inclusion period of 42 months is planned, with a minimal duration of follow up of 2 years. Our principal hypothesis is that zinc could modify the natural history of cACLD patients, with an overall improvement in prognosis

Inclusion Criteria:

• Patients of both sexes with diagnosed compensated advanced chronic liver disease (cACLD) determined by hepatic stiffness on transient elastography >15 kPa.
• Age between 18 and 80 years, inclusive.
• Absence of prior or current decompensation.
• For women of childbearing age, a possible pregnancy will be ruled out by a pregnancy test prior to the start of the study. Following the test, the woman must use an effective contraceptive method during sexual intercourse (see Appendix I) in the days leading up to the start of treatment, and continue to use it throughout the treatment period, as well as for several days after its completion.
• Signing of informed consent.

Exclusion Criteria:

• History or current presence of hepatocellular carcinoma.
• Concomitant systemic disease with a short-term poor prognosis.
• Pregnancy, breastfeeding, or refusal to use contraceptive measures during participation in the study.
• Patients with compensated advanced chronic liver disease (cACLD) due to hepatitis B virus (HBV) under antiviral treatment, and those with cACLD due to hepatitis C virus (HCV) cured with antiviral treatment.