Diabetes is a risk factor for the progression of liver fibrosis and development of hepatocellular carcinoma in chronic hepatitis C. However, the impact of diabetes on the long-term prognosis and the synergistic interactions of various host factors for diabetes to the progression of liver fibrosis are unknown. In the present study, we examined the host factors associated with the progression of hepatitis C in 68 patients with a posttransfusion hepatitis (PTH) and analyzed the relationships. Multivariate analysis showed that age of PTH, being male, and type 2 diabetes mellitus were risk factors for the progression of liver fibrosis. By the Kaplan-Meier method, the cirrhosis-free survival rates after the onset of PTH were significantly lower in the diabetic group than in the nondiabetic group (P < .01). Diabetes also had a great impact on the long-term prognosis of chronic hepatitis C by reducing the time from PTH to the occurrence of hepatocellular carcinoma (P < .01) and to liver-related death (P < .05). Coexistence of obesity (body mass index > or =25 kg/m(2)) or hypertriglyceridemia (> or =150 mg/dL) with diabetes had a synergistic effect on liver fibrosis progression in patients with chronic hepatitis C. Thus, the treatment of diabetes, obesity, and hypertriglyceridemia may hold the key to improving the prognosis of chronic hepatitis.