By Liz Highleyman

Over the course of years or decades, people with chronic viral hepatitis may progress to advanced liver disease, including severe fibrosis or cirrhosis. Some studies indicate that this may occur faster in HIV positive patients coinfected with hepatitis B or C.

Successful treatment with nucleoside/nucleotide analogs for hepatitis B or interferon-based therapy for hepatitis C can slow or halt liver disease progression. However, such treatment is not always successful over the long term, and investigators have also studied therapies aimed at directly interfering with the fibrosis process.

Warfarin Tablets

The blood-thinning drug warfarin, used as an anticoagulant to reduce blood clotting, might play a role in limiting fibrosis, according to British study described in the August 2008 Journal of Thrombosis and Haemostasis.

As background, the study authors noted that there is evidence that activation of the coagulation system contributes to wound healing and promotes organ fibrosis, both of which involve production of collagen and other substances that make up scar tissue. Several epidemiological studies have shown that a pro-thrombotic state, including presence of the factor V Leiden mutation, is associated with rapid liver fibrosis progression.

The aim of the present study was to assess the effect of a pro-coagulant state on progression of liver fibrosis in a controlled laboratory environment, and to test whether an anticoagulant agent could reduce fibrogenesis.

The investigators analyzed the effects of coagulation status on fibrosis progression in a mouse model of chronic liver injury. Mice with the prothrombotic factor V Leiden mutation, "anticoagulated" mice, and control mice were exposed to carbon tetrachloride, which produces liver damage similar to that seen in people with drug-induced hepatotoxicity, excessive alcohol use, chronic viral hepatitis, and other liver conditions.

The researchers found that mice carrying the factor V Leiden mutation had significantly increased hepatic fibrosis. The anticoagulant warfarin significantly reduced fibrosis progression in wild-type (non-mutant) mice, but was less effective in mice with the profibrotic FV Leiden mutation. Changes in fibrosis scores were reflected in changes in liver hydroxyproline content and activation of hepatic stellate cells, which produce scar tissue material.

"These results demonstrate that coagulation status has a strong influence on hepatic fibrogenesis," the investigators concluded. "These results represent the first reported use of anticoagulation to slow hepatic fibrogenesis and suggest a potential novel anti-fibrotic therapeutic approach for the future."

Based on these findings, the investigators are starting a clinical trial of warfarin as an anti-fibrotic treatment for liver transplant recipients with hepatitis C, who are at risk for rapid fibrosis in the new liver due to HCV recurrence.

"If we have positive results from the new trial, we will have a potential treatment that is already available and very cheap, and which should be safe enough for people to take," said study coauthor Quentin Anstee in a media release issued by Imperial College London. "If we are successful in hepatitis C patients, we are hopeful that such treatment might benefit people with liver damage from other causes, and this is something we would be keen to study further."

Faculty of Medicine, Imperial College, London, UK; Southampton General Hospital, Southampton, UK; MRC Mammalian Genetics Unit, MRC Harwell, Oxfordshire, UK.

8/26/08

Reference
QM Anstee, RD Goldin, M Wright, and others. Coagulation status modulates murine hepatic fibrogenesis: implications for the development of novel therapies. Journal of Thrombosis and Haemostasis 6(8): 1336-1343. August 2008. (Abstract).

Other source
Imperial College London. Liver damage in hepatitis C patients could be treated with warfarin, says study. Press release. July 31, 2008.