Predicting who may be at highest risk of developing cirrhosis after undergoing a liver transplant may soon be easier, thanks to a special test described by doctors at the University of North Carolina. In a report published in the journal Liver Transplantation this month,¹ a group of hepatologists identified a unique laboratory test that appears to show that the activation of specialized liver cells, known as hepatic stellate cells, can serve as an indicator of higher cirrhosis risk.

No Tests to Predict Cirrhosis Currently
Cirrhosis is characterized by damage to liver cells beyond repair. As these cells are destroyed, scar tissue forms. When enough of this scar tissue builds up, blood can no longer flow through the liver properly. Normally, the liver filters toxins and wastes as blood flows through the organ. But when scar tissue blocks blood from moving through, these toxins and other substances can build up in the body, resulting in symptoms like mental confusion, agitation and shaking. In serious instances, people can die from this condition.²

Among those patients who undergo a liver transplant, about one-fifth will developed advanced cirrhosis, wrote Mark Russo, MD, an assistant professor of Medicine in the Division of Gastroenterology and Hepatology at UNC, and his colleagues. Using this test, however, Russo's group pointed out that doctors could ascertain who should receive therapy to save the transplanted liver from the condition.

"Right now, there are no reliable tests for identifying the group that's at high risk," Russo explained. "The reason you want to identify that group is because there are some people who will not go on to develop cirrhosis from hepatitis C after liver transplant, and the therapy has a lot of side effects and is also very expensive."

Additionally, the antiviral medication used in hopes of preventing cirrhosis, interferon and ribavirin, is effective only up to about one-third of patients. Side effects can also often be an issue, Russo and his colleagues noted.

Specialized Liver Cells May Provide Clues
The activation of hepatic stellate cells in the liver is "the earliest step" in the development of liver fibrosis, the research team wrote. "Although it seems intuitive that early hepatic stellate cell activation would be associated with the subsequent development of bridging fibrosis or cirrhosis, there are no studies reporting this association," they explained.

While these stellate cells are primarily responsible for storing vitamin A in the liver, they also produce collagen and other proteins that can lead to fibrosis in those infected with the hepatitis C virus (HCV).

In this study, Russo's team had two aims: to identify whether stellate cell activation measured soon after a transplant actually is linked with eventual advanced fibrosis, and whether a certain indicator of this cellular activation in the liver can better predict fibrosis development compared to examining liver tissue after biopsy, which can be more invasive. The test scrutinized in the study measures levels of alpha smooth muscle actin (alpha-SMA) in liver tissue.

Comparing Cell Activity Levels
The team focused on patients who had undergone liver transplants at the University of Florida over a four-year period. In all, 46 patients who had been diagnosed with hepatitis C were identified. They were then divided into two groups. The first comprised those who developed advanced fibrosis within two years of their transplant. The second group included patients who developed mild or no fibrosis during the same post-transplant period.

Biopsies were performed at three postoperative intervals. The researchers reported there were no differences between any of the patients, except for their individual fibrosis stage. Those with more advanced fibrosis had higher levels of alanine aminotransferase (ALT) compared to those with milder or no fibrosis. ALT is an enzyme that is released by the liver when it is damaged.³

After measuring stellate cell activity in the liver tissues of the patients in both groups, Russo's team found that the activity was significantly higher in those with more advanced fibrosis.

Subgroup Analysis
Patients with early-stage fibrosis were further divided between those who eventually developed advanced liver scarring versus those who did not within two years of their transplant. Stellate cell activation was measured in all these patients. The researchers also found that activation of this liver cell was somewhat higher in the majority of those who eventually went on to develop more aggressive fibrosis compared to those who did not.

In conclusion, Russo and his associates wrote that hepatic stellate activation predicted a one-and-a-half times greater risk of developing rapid fibrosis. Only a person's stage of fibrosis after transplant was a better predictor of developing more advanced fibrosis, they found. Those in this group with greater than 6% stellate cell activation four months after transplant were more than eight times more likely to develop aggressive fibrosis within two years postoperatively, on average, the researchers wrote. However, the odds of developing advanced fibrosis in the general population of transplant patients with early-stage liver scarring can vary widely, the researchers acknowledged.

Treating liver transplant patients whose hepatitis C recurs is "challenging", they added. Antiviral medications can worsen symptoms, and such patients are "vulnerable" when they are recovering from surgery and adjusting to side effects from immunosuppression therapy. 

However, "these findings have implications for identifying recipients early after liver transplantation at highest risk for developing advanced fibrosis and with the greatest need for antiviral therapy," the team wrote.

1. Russo MW, Firpi RJ, Nelson DR, Schoonhoven R, Shrestha R, Fried MW. Early hepatic stellate cell activation is associated with advanced fibrosis after liver transplantation in recipients with hepatitis C. Liver Transpl 2005 Oct;11(10):1235-41.
2. American Academy of Family Physicians. Cirrhosis and Portal Hypertension. What is Cirrhosis? Available at: http://familydoctor.org/188.xml. Accessed October 20, 2005.
3. The Merck Manual. Liver and Gallbladder Disorders. Diagnostic Tests for Liver and Gallbladder Disorders. Introduction: Biopsy of the Liver/Imaging Tests. Available at: http://www.merck.com/mmhe/sec10/ch134/ch134a.html. Accessed October 20, 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.