QUANTITATIVE ASSESSMENT OF HEPATIC FUNCTION IN CHRONIC HEPATITIS C

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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. An evaluation of the usefulness of certain tests of the liver function and liver blood circulation; an ancillary study to the HALT-C trial. It is estimated that 8,000 to 10,000 patients in the U.S. died in 1998 and 30,000 will die annually by the year 2010, as a direct result of advanced liver disease from chronic hepatitis C (HCV). Patients with advanced histologic stages of hepatitis C, bridging fibrosis and cirrhosis, are at greatest risk of developing clinical evidence of hepatic decompensation, need for liver transplantation, liver cancer, and death from liver disease. The hypothesis for the National Institutes of Health Trial of HCV nonresponders with fibrosis or cirrhosis is that long-term use of antiviral therapy (maintenance treatment) will slow the progression of liver disease. In noncirrhotic patients who have significant fibrosis, effective maintenance therapy is expected to slow or stop histologic progression to cirrhosis. Standard endpoints for effective response to maintenance therapy in cirrhotic patients are prevention of clinical decompensation, (ascites [the accumulation of fluid in the abdomen], variceal hemorrhage[bleeding from enlarged veins], encephalopathy [degenerative diseases of the brain]), and stabilization of liver function as measured clinically by Childs-Turcott-Pugh (CTP) score. However, clinical endpoints are insensitive parameters of disease progression. HALT-C treatment is long-term therapy with interferon plus ribavirin. Testing will be done three times during this study. First, at baseline, before the beginning of the HALT-C medications, and two and four years after the first six months of treatment. Each testing period will be the same. Patients will be admitted to the CRC for one day. Diets will be caffeine free three days before and three days after the tests and there will be a pre-admit overnight fast. Saliva samples will be collected at home twice a day for two days after testing and then brought to the CRC. At the time of testing , there will be an intravenous catheter placed into the arm to draw blood and administer test compounds. Six saliva samples will be collected over three days. Three compounds will be given by vein and three will be given orally. Blood will be drawn to see how the liver clears these compounds. After the tests are complete, the patient will eat a normal meal. Two hours later a SPECT Scan will be done to allow measurement of hepatic function.