Hepatitis C, systemic inflammation and oxidative stress: correlations with metabolic diseases

ABSTRACT

Introduction

Hepatitis C chronic infection has long been correlated with numerous systemic diseases, such as diabetes mellitus and hepatic steatosis. Recent studies have also revealed an association with atherosclerosis.

Areas covered

An analysis is presented on the mechanisms through which the hepatitis C viral infection can lead to a systemic increase in pro-inflammatory markers, especially tumor necrosis factor-a and interleukin-6. The immunological imbalance created may, through different mechanisms, act on the metabolic pathways that contribute to the development of insulin resistance, the accumulation of lipids in the liver, and even the formation of atherosclerotic plaques. Moreover, an additional contributing factor to the above-mentioned metabolic derangements is the unopposed oxidative stress observed in chronic hepatitis C viral infection. The virus itself contributes to the formation of oxidative stress, through alterations in the trace metal homeostasis and its effect on pro-inflammatory cytokines, such as tumor necrosis factor-a.

Expert opinion

The scope of this review is to emphasize the importance of the metabolic manifestations of hepatitis C viral infection and to elucidate the pathophysiological mechanisms behind their emergence.

KEYWORDS:

• Cardiovascular risk
• hepatitis C
• insulin resistance
• metabolic disease
• oxidative stress
• systemic inflammation

Article highlights

• Hepatitis C infection is associated with metabolic alterations due to the induction of reactive oxygen species, while metabolic disarrangements in turn inversely amplify the oxidative stress changes in the oxidation-reduction homeostasis in the liver.

• Increased hepatic iron and copper levels associated with chronic infection are hepatotoxic and further promote oxidative stress, while the observed zinc deficiency attenuates the systemic inflammatory response.

• Eradication of the hepatitis C virus beneficially influences the risk and course of insulin resistance, atherosclerosis and cardiovascular disease, and the overall extra-hepatic mortality.

• Treatment with direct-acting antivirals may be beneficial in reducing the incidence of metabolic alterations when achieving a sustained virologic response.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.