There are effective treatments for liver disease available today. But some patients fail to respond to them. In the end, they may need a liver transplant if their disease progresses to an advanced stage. Statistics show that about half of people with chronic HCV genotype 1 fail antiviral therapy, as well as about 20% of those with genotypes 2 and 3.¹

As such, experts say there is a need to develop other kinds of drugs that target different mechanisms in the body related to liver disease. "Therapeutic approaches that either inhibit immune-mediated mechanisms or directly inhibit liver cell damage are promising and might enter into the clinic," wrote Christian Trautwein, MD, in the department of Gastroenterology, Hepatology, and Endocrinology at Hannover Medical School in Germany, and his co-investigators.

Targeting Immune System Causes
Armed with the knowledge that many acute and chronic liver diseases are driven by immune-mediated processes, Klein's team set out to investigate whether alternative liver disease treatment might be able to target these processes effectively in some fashion.

In the March 3 online edition of the Journal of Clinical Investigation,² Klein's group identified these potential therapeutic candidates for people with liver disease.

There has been growing evidence that a protein known as interleukin-6 plays a key role in many physiological processes in the liver. Among other things, the protein possesses cell protection functions. According to Klein and his fellow researchers, interleukin-6 promotes liver regeneration, protects the liver from the damaging effects of alcohol, prevents the cellular suicide known as apoptosis (ap-ahp-TOE-sis), and has shown positive effects in livers undergoing ischemia/reperfusion—the process of blocking then reintroducing blood flow to the organ during a transplant procedure.

A Protein Pathway
In order for interleukin-6 to protect liver cells from damage, a process that leads to the production of two other proteins—KC and SAA2—in liver cells is necessary.

It is these two proteins, Klein and his colleagues stressed, that might be effective targets for future medications for people with liver disease. The effect of such medications would be the protection of liver cells when viral hepatitis strikes.

Blocking The Proteins Caused Liver Damage
To better understand these mechanisms, the researchers induced a form of experimental liver disease caused by activation of T-cells in the immune system in a group of mice. They learned that blocking a series of processes that leads to the production of KC and SAA2 in liver cells in the animals made them "more susceptible to injury" in the liver.

In fact, the experimental disease in the mice was more pronounced when the investigators deleted a protein that normally leads to activation of KC and SAA2 in liver cells.

In conclusion, the researchers noted that "both proteins are potent inhibitors of [experimental] hepatitis and might also be of interest in the treatment of immune-mediated liver diseases in humans."

1. Craxi A, Licata A. Clinical trial results of peginterferons in combination with ribavirin. Semin Liver Dis 2003;23 Suppl 1:35-46.
2. Pawlotsky JM. Mechanisms of antiviral treatment efficacy and failure in chronic hepatitis C. Antirviral Res 2003 Jun;59(10):1-11.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.