LACTOFERRIN INHIBITS HEPATITIS C VIRUS (HCV) VIREMIA IN CHRONIC HEPATITIS C PATIENTS WITH A HIGH VIRAL LOAD AND HCV GENOTYPE 1B

December 13, 2001

AASLD

November 2001

LACTOFERRIN INHIBITS HEPATITIS C VIRUS (HCV) VIREMIA

IN CHRONIC HEPATITIS C PATIENTS WITH A HIGH VIRAL LOAD

AND HCV GENOTYPE 1B - ABSTRACT 638

HCV infection frequently causes chronic hepatitis. It

is also frequently associated with the development of

liver cirrhosis and hepatocellular carcinoma. Bovine

lactoferrin, a milk protein of the iron transporter

family, is commercially available as a health food in

Japan. It has been reported that lactoferrin exerts

antiviral effect in cultured cells. Ikeda et al.

conducted a pilot study evaluating the effect of

lactoferrin in patients with chronic hepatitis C; they

showed that lactoferrin decreases serum HCV-RNA

concentrations in 3 out of 4 patients with a low viral

load.

The aim of the present study was to carry out a

double-blind trial for assessing the effect of

lactoferrin in chronic hepatitis C patients with a

high viral load and HCV genome subtype 1b.

Twenty-seven patients with chronic hepatitis C (16 men

and 11 women) were enrolled in the present study. The

inclusion criteria were as follows: (1) elevation of

alanine aminotransferase (ALT) levels above the upper

normal limit for 6 months or more; (2) positivity for

serum antibody to HCV; (3) high serum levels of

HCV-RNA [more than 100 KIU / ml as measured by Cobas

amplicor-HCV monitor version 2 (Roche Molecular

System, Tokyo, Japan)] and with serum HCV genotype 1b;

(4) absence of other causes of chronic hepatitis.

Among all patients, 18 had been treated with

interferon for more than 12 months before the

beginning of this study; none of them responded to

interferon therapy. Twenty-five patients orally

received a 6-month course of bovine lactoferrin

treatment. They were randomized into two groups: a

low-dose group of patients (n = 10) receiving 0.4 g of

lactoferrin per day, and a high-dose group (n = 15)

receiving 3.6 g of lactoferrin per day. The difference

between the mean of 2 variables was evaluated by the

Mann-Whitney U test. Comparison of the data obtained

before and after lactoferrin treatment was performed

by ANOVA.

There was no significant difference between the two

groups regarding age, sex, serum ALT and HCV-RNA

levels. No serious complications occurred during the

treatment, and all patients successfully completed the

study protocol. The serum concentration of HCV-RNA was

1627 ? 1397 KIU / ml at entry and 1049 ? 529 KIU / ml

after 6 months in the low-dose group; the decrease in

HCV-RNA copy was not significantly different. By

contrast, the serum concentration of HCV-RNA decreased

from 1106 ? 791 KIU / ml at entry to 733 ? 348 KIU /

ml after 2 months (p<0.05), to 632 ? 392 KIU / ml

after 4 months (p<0.01) and to 612 ? 234 KIU / ml

after 6 months (p<0.01) of treatment in the high-dose

group. The serum levels of aminotransferase, iron and

ferritin remained unchanged throughout the study in

both groups. Two months after cessation of lactoferrin

treatment, the serum HCV-RNA concentration was

significantly elevated.

In summary, Lactoferrin is believed to reduce serum

HCV-RNA level in patients with chronic hepatitis

patients by binding and neutralizing the activity of

HCV virion; this effect may prevent the viral

adsorption to hepatocytes. Lactoferrin is the first

substance other than interferon that shows anti-HCV

activity. Lactoferrin may be effective for the

treatment of chronic hepatitis C patients with a high

viral load when it is administered in combination with

interferon.

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December 13, 2001