Zinc supplementation improves the outcome of chronic hepatitis C and liver cirrhosis

Abstract

We treated patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) with polaprezinc and determined prospectively the effect on long-term outcome. 62 patients were enrolled. Of these, 32 were administered 1.0 g polaprezinc and the remainder were not administered polaprezinc. We measured the serum zinc concentrations using conventional atomic absorption spectrometry and conducted a prospective study to determine the long-term outcome of the polaprezinc therapy. Changes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the polaprezinc administration group were significantly lower than those of the untreated group. The decrease in platelet count was clearly less than that of the untreated group. The factors that inhibited increases in serum zinc concentrations following administration of polaprezinc included low serum zinc concentration states. Furthermore, the reductions of AST and ALT levels in the low zinc group were significantly greater than those of the high zinc group. When the patients who were administered polaprezinc were divided into two groups whose zinc concentrations increased (zinc responders) or remained stable or decreased (zinc non-responders), the zinc responders had a clearly lower cumulative incidence of HCC than the zinc non-responders. We conclude zinc supplementation improved the long-term outcome in C-viral CH and LC patients.

Keywords: chronic hepatitis C; hepatocellular carcinoma (HCC); liver cirrhosis; polaprezinc; zinc supplementation.

Fig. 1

Changes in serum zinc concentrations in patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC), with and without zinc administration. The median serum zinc concentration in the group of patients who had been administered polaprezinc was significantly higher than that of the untreated group (p = 0.0036).

Fig. 2

The changes in the serum zinc levels were compared according to the quantity of polaprezinc administered per kg body weight. In the group administered less than 0.6 mg/kg zinc, the serum zinc level increased above that before the start of administration during the early stage of administration, but decreased later. However, in the group administered more than 0.6 mg/kg, the serum zinc level increased continuously from one year after the start of administration.

Fig. 3

Comparison of changes of serum zinc concentrations in the polaprezinc administration group between the low zinc group, whose serum zinc concentrations were below 64 µg/dl, and the high zinc group, whose serum zinc concentrations were above 64 µg/dl. The change of serum zinc concentrations in the low zinc group was significantly greater than that of the high zinc group (p = 0.0002).

Fig. 4

When the polaprezinc administration group was divided into two, the high zinc group and the low zinc group, the reductions of AST levels and ALT levels in the low zinc group were significantly greater than those of the zinc high group (p = 0.0008, p = 0.0193).

Fig. 5

The cumulative incidence of HCC was compared between the responders and the non-responders, based on changes in serum zinc concentrations between the initial and final examinations. The cumulative incidence of HCC over four years was 24.9% in the zinc non-responders and 0% in the zinc responders. The cumulative incidence of HCC over four years in the zinc responders was clearly less than that in the zinc non-responders.

Fig. 6

Changes of serum zinc concentration in patients with or without HCC development in the polaprezinc administration group and control group. The changes of serum zinc concentrations were significantly lower in the patients who developed HCC than those who did not (a). However, the changes of serum zinc concentrations in the control group did not differ significantly between those who developed HCC and those who did not (b).