Zinc May Improve Current Hepatitis C Therapies

A great deal of current research in the area of hepatitis C virus (HCV) centers on the complex mechanisms by which to disrupt or prevent infection. Not surprisingly, the research and the resulting treatments are extremely costly.

Recently, Scott Read, PhD, a researcher at the Storr Liver Centre at The Westmead Institute for Medical Research in Australia, and several colleagues focused their attention instead on a much smaller target: liver cells and their components. Their research has the potential to add a less expensive adjunctive therapy to improve current HCV regimens.

Metallothioneins (MTs), the primary intracellular zinc-binding proteins, are responsible for zinc homeostasis and a number of intracellular functions, including heavy metal detoxification and scavenging of free radicals.

Researchers have documented the induction of MTs in response to numerous viruses, such as influenza, measles, and hepatitis C, but it remains unclear whether MTs merely modulate cellular stress or possess true antiviral activity.

A connection between HCV infection and MT expression has been previously established. While acute HCV infection has been noted to induce MT expression, chronic HCV infection has been linked to low serum zinc as well as low MT expression in liver cells. Read and colleagues set out to study the role of metallothioneins and zinc in HCV infection.

“Because MTs are potently induced in vitro and after localization following HCV infection, we hypothesized that MTs may play an antiviral role in response to infection,” researchers wrote.

Using needle biopsies from patients with untreated chronic HCV infection (genotype 1 and 3) or hepatitis B virus (HBV) infection and control samples from healthy liver tissue surrounding resected hepatocellular carcinoma, Read and colleagues carried out a series of experiments in vitro and in vivo to attempt to further elucidate the nature of the relationship among MTs, zinc, and HCV infection. The results of their research reinforced the findings of previous HCV studies in addition to adding new conclusions.

Read and colleagues determined that HCV facilitates intracellular MT expression and that MTs build up in the nucleus after HCV infection. They also demonstrated that MT induction is linked to antiviral activity against HCV and that this is tied to intracellular zinc levels.

The data collected by Read and colleagues also suggest that zinc plays a number of inhibitory roles in HCV. Zinc is believed to inhibit viral propagation or obstruct host factors used by HCV to infect, replicate, or assemble.

“Because hepatic zinc and MT expression decline in patients with chronic HCV infection, zinc supplementation could be a low-cost and safe addition to current therapies, particularly in patients with severe zinc deficiencies,” researchers wrote. “In combination with its immune-boosting effects, zinc can limit viral replication via MT-mediated mechanisms and reduce subsequent inflammation and liver damage associated with chronic infection.”

The study, “The Antiviral Role of Zinc and Metallothioneins in Hepatitis C Infection” was published last month in the Journal of Viral Hepatitis.

This article was originally published by MD Magazine.