This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A test of the hypothesis that tacrolimus, an immunosuppressive drug, is well tolerated and inhibits hepatic inflammation and reduces evidence of bile duct injury in subjects with Primary Biliary Cirrhosis (PBC). PBC is a progressive disorder of the liver where there is a stoppage of bile flow and can cause end-stage liver disease requiring liver transplantation in many cases. Its cause is believed to be an immunologically mediated injury to medium sized bile ducts within the liver. Retention of bile, over time, injures hepatocytes causing deposition of fibrous tissue and eventual development of cirrhosis. It is believed that PBC is a slowly progressive disorder which progresses to cirrhosis over a period of 15-20 years. PBC is an immunologically mediated disease. Therefore, it appears reasonable to consider immunosuppressive therapy to slow down or arrest this condition. Tacrolimus is a potentially attractive treatment for PBC. Other drugs have been used but are limited in success because of a high toxicity level. Therefore, the need for an immunosuppressive agent that is more tolerable and has less side effects than steroids and cyclosporine is apparent. Tacrolimus is an effective immunosuppressive drug which is widely used for those who have undergone an orthotopic liver transplant. Tacrolimus has shown to reverse the injury in those who develop early signs of rejection after transplant. In this prospective, longitudinal study, each of the twenty patients will serve as his or her own control. Informed consent will be signed. History and physical exam will be done. Medical tests will be done. A liver biopsy will be done. At the entry visit, more tests will be done. A dose of tacrolimus will be administered and subjects will be supplied with the drug to be taken for 16 weeks. Patients will be seen at particular intervals and have tests done. The duration of the study will be 24 months.
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