A key liver protein was the focus of a new study by excited Belgium scientists last month. The substance can potentially protect the liver from inflammation and the death of liver cells, according to the researchers from Ghent University in Belgium. This discovery, they say, could form the basis for an eventual treatment against  hepatitis.

Their findings were published in the August issue of the journal Hepatology.¹

The promising protein is known as ABIN-1, and is responsible for neutralizing another protein that plays a role in the inflammation and eventual death of liver cells.

"We originally identified two ABINs (ABIN-1 and ABIN-2), and tested both" for their ability to protect the liver from the negative effects of HCV infection, explained the study's chief investigator, Rudi Beyaert, PhD, in the department of Molecular Biomedical Research at the university, in an interview. "However, only ABIN-1 showed protection."

The Path to Liver Inflammation
The inflammation of the liver in people who have hepatitis involves many factors. One of these is a substance known as Tumor Necrosis Factor, or TNF. TNF is a pro-inflammatory cytokine, a biologic factor in the body that is produced in minute amounts, but has a very powerful ability to create inflammatory conditions. This is because TNF helps mediate the response by immune system cells to injury caused by disease-causing organisms in the body.² In this case, hepatitis is causing injury to the liver. Excessive TNF amounts in the liver can lead to inflammation, as well as the death of liver cells.

Additionally, TNF stimulates a protein known as nuclear factor-KB (NF-KB), which also helps inflame the liver during the course of hepatitis infection. The NF-KB protein is produced when TNF is present in high amounts in liver cells. But NF-KB is a paradoxical protein. It not only helps mediate inflammation in the liver, but it also helps block the death of liver cells. Thus, using potential medications that block NF-KB activity may be toxic, the Belgium investigators pointed out. "This dual function of NF-KB emphasizes the need for therapeutics that can inhibit both TNF-induced NF-KB activation and cell death," wrote Beyaert and his colleagues.

The Efficacy of a Protective Protein
For their analysis, Beyaert and his team artificially introduced liver disease in the mice, and then gave each animal doses of TNF, which helped increase liver inflammation. They then divided the animals into two groups: one group received doses of the protective ABIN-1 protein, and the other group did not. The differences at the end of the study were striking. Mice given ABIN-1 survived and showed no signs of disease, whereas those rodents not given the protein subsequently died, the research team reported.

When all the animals' liver tissue was analyzed, Beyaert's group saw more significant differences. The mice given ABIN-1 had better preserved livers, but those without the protein had obvious liver damage. "The marked difference between the two groups of mice could also easily be appreciated on macroscopic [observed by the naked eye] examination of the liver," wrote the researchers. Those not given ABIN-1 in the study had black livers due to massive hemorrhage, whereas the livers of mice given the protein "had a normal appearance," the scientists wrote.

Additional inflammatory cells of the immune system had infiltrated the livers of the mice without ABIN-1, but the opposite was true in the other group of animals.

The scientists also looked for evidence of liver cell death, and found that ABIN-1 livers had less of it than those without the protein. The researchers conducted several other liver damage tests, including measurements of the liver enzyme alanine aminotransferase  (ALT), and found the same results.

Protein Circumvention
Given the well-known influence of the NF-KB protein in preventing liver cell death, the researchers didn't understand how blocking the activity of NF-KB (by suppressing TNF) in the liver through ABIN-1 also prevented liver cell death.

So, they conducted additional experiments, and found that the ABIN-1 protein has a protective effect on liver cells that is independent of NF-KB suppression. "The prophylactic effect of ABIN-1 is a result of both its NF-KB inhibiting and anti-apoptotic (survival of hepatocytes) effect," Beyaert explained. "However the latter effect seems to be dominant."

So far, why the ABIN-1 protein is protective isn't known, Beyaert's group stated.

Based on their discovery, "strategies that increase the … activity of ABIN-1 might have a therapeutic potential for the treatment of inflammatory liver disease," the scientists wrote.

Beyaert said that ABIN-1 is an intracellular protein that does not enter cells if it was given systemically to a patient, so it needs to be delivered therapeutically so that it is taken up by cells.

He says there are further research plans for he and his team. One of those includes "testing the effect of ABIN-1 against liver damage in response to virus infection (instead of TNF)," Beyaert said.

1. Wullaert A, Wielockx B, Van Huffel S et al. Adenoviral gene transfer of ABIN-1 protects mice from TNF/glactosamine-induced acute liver failure and lethality. Hepatology 2005 Aug;42(2):381-9.
2. The Merck Manual of Diagnosis and Therapy. Immunology: Allergic Disorders. Biology of the Immune System. Available at: http://www.merck.com/mrkshared/
mmanual/section12/chapter146/146a.jsp. Accessed September 22, 2005.

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