 Persons infected with hepatitis C virus HCV suffer from multiple symptoms caused by both the disease and the current conventional treatment peginterferon alfa and ribavirin if they can tolerate the treatment or have no contraindications to taking it. Most HCV-infected individuals eventually develop chronic liver disease that may progress to complications such as hepatocellular carcinoma, hepatic decompensation, and cirrhosis. What is not known is whether or not modulation of the HCV disease using the standardized herbal formulation Sho-saiko-to SST, 3 capsules containing 700 mg of the SST herbal extractcapsule and 28 mg of the excipients, magnesium stearate and silicon dioxidecapsule 2 times a day, over 12 weeks might reduce or prevent the prevalence and severity of liver deterioration and symptoms. Thus, the objectives of this project are to: a demonstrate quantitatively in a sample of persons infected with HCV expected SST treatment-driven changes in serum levels of liver enzymes, viral load, and CD4 and CD8 T-cell counts by longitudinal statistical modeling, and to correlate these to the severity of individual symptoms, liver enzyme levels, and CD4 and CD8 T-cells as measured at screening, 4, 8, and 12 weeks; b examine in vitro the response of a line of HCV-infected cells to the standardized herbal formulation; and c assess the mechanism by which the herbal formulation may affect the HCV-infected cells in vitro. Taken together, the clinical and laboratory components of the study should provide a strong test of our primary hypothesis that compared to placebo a standardized combined herbal formulation, SST, will reduce viral load, liver enzymes, and improve CD4 and CD8 T-cell counts in persons infected with HCV who did not respond or have relapsed after peginterferon alfa and ribavirin or in those for whom this conventional therapy is contraindicated. Our long-term objectives are to identify the basic mechanisms underlying chronic HCV infection-related cytokines and immune mediators and to provide a rationale for mechanism-driven SST disease treatment. Confirming the effect of SST in chronic HCV infection will create a foundation for a potentially supportive approach to managing HCV disease-related and treatment-related symptoms. Ability to reduce liver damage or even prevent the side effects of conventional therapy through the use of a standardized herbal formula, SST, would be of potential benefit to thousands of persons infected with HCV by providing an herbal treatment when the current conventional therapy is not effective or is contraindicated. 