Zinc supplementation therapy improves the outcome of patients with chronic hepatitis C

Abstract

We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase (AST) and alanine aminotaransferase (ALT) levels decreased, and platelet counts increased, significantly in the group with increased serum zinc concentrations. We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma (HCC). We administered polaprezinc to 32 patients, randomly selected for zinc therapy (treatment group), while another 30 formed the control group. We measured the serum zinc and albumin concentrations and conducted a prospective study to determine long-term outcomes. The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and +0.302 ± 0.30% in the treatment group and 56.7 ± 12.4 µg/dl and +0.033 ± 0.21% in the control group and had increased significantly (p = 0.0002, p = 0.0036). Progression of liver disease seemed to vary, depending on serum albumin concentrations. In the group with baseline serum albumin concentrations of 4.0 g/dl or more, the change and rate of change of serum zinc concentrations increased significantly, and the cumulative incidence of HCC tended to decrease, in the treated group. According to multivariate analysis, the factors that contribute to a reduction in the incidence of HCC are zinc therapy (risk ratio: 0.113, 95% CI: 0.015–0.870, p = 0.0362), and platelet counts (0.766, 0.594–0.989, 0.0409). Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC.

The status of zinc in the development of hepatocellular cancer

“…Some studies have indicated the potential effectiveness of oral zinc supplement to increase the zinc levels of the hypozincemia resulting from cirrhosis, which might also suppress the development of the associated HCC. 41,54 Thus, the rationale exists in support of the potential zinc therapeutic approach for HCC.…”

Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: A multicenter randomized controlled trial

“…In addition, a decrease in serum zinc levels is known to predict the development of HCC and poor prognosis in HCV-infected patients (8,9). Moreover, decreased risks of hepatocarcinogenesis and mortality have been observed in HCV-infected patients with increased serum zinc levels owing to zinc supplementation (8,9). The data reported here indicate that the zinc-enriched supplement has the potential to suppress the onset of HCC and improve prognosis in HCV-infected patients.…”

“…Thus, the supplement tested here may be beneficial for patients with hyperammonemia. In addition, a decrease in serum zinc levels is known to predict the development of HCC and poor prognosis in HCV-infected patients (8,9). Moreover, decreased risks of hepatocarcinogenesis and mortality have been observed in HCV-infected patients with increased serum zinc levels owing to zinc supplementation (8,9).…”

“…In patients with chronic liver disease, serum zinc levels decrease as the severity of liver disease increases (7), and low serum zinc levels are known to be associated with the development of HCC and poor prognosis in hepatitis C virus (HCV)-infected patients (8,9). Thus, serum zinc levels are a significant metabolic prognosticator in HCV-infected patients.…”

“…BCAAs and zinc are pharmacological nutrients that exert diverse biological effects (1). A decreased risk of hepatocarcinogenesis and mortality has been reported in patients with chronic liver disease treated with BCAA (4,10,11) or zinc (8,9) supplementation. Therefore, a supplement containing both BCAAs and zinc may have the potential to improve prognostic factors in patients with chronic liver disease.…”