Hepatitis C in Hemophilia

Hepatitis is a major cause of morbidity and mortality in patients with hemophilia. In our study with a follow-up of 35 years, we found that the risk for end-stage liver disease (liver failure, hepatocellular carcinoma, liver-related death) was 12% for HIV negative, and 35% for HIV coinfected patients. Although a significant proportion of hemophilia patients is at risk for long-term complications of hepatitis, many patients still have not been treated. In the Dutch hemophilia population, approximately 30-40% were not treated mainly due to fear of side effects, lack of clinical symptoms, and expected low efficacy of treatment. However, health-related quality of life was reduced in hemophilia patients with chronic hepatitis C. Thus providing an additional argument in favor of treatment, as health-related quality of life will improve after successful treatment for hepatitis C. Liver biopsies are rarely performed in hemophilia patients because of risk of bleeding, and high costs of clotting factor replacement. In order to assess liver fibrosis in the hemophilic population and identify patients eligible for antiviral therapy, we were the first to use a new, non-invasive device: the Fibroscan®. With this new technique we found an unexpected high proportion of patients with severe fibrosis or cirrhosis of approximately 35%. Many patients had significant liver damage that would not have been detected with the conventional methods like laboratory tests and ultrasonography. Based on the results of the Fibroscan® examination, approximately 25% of patients started antiviral therapy within three months. The majority of these patients had postponed antiviral therapy for years despite therapy had frequently been offered. These results indicate that the Fibroscan® may play an important role in persuading patients with significant fibrosis to start therapy. Furthermore, this technique may be used to follow patients in order to assess progression of fibrosis and determine prognosis. Conflicting data exist about the efficacy of IFN-based therapy in the hemophilic population. For many years, it was thought that patients with hemophilia would respond worse to IFN-based therapy than patients in the general population. Patients with hemophilia are often infected with HCV genotype 1, are predominantly male, have long-lasting infection, and have often high levels of viraemia. However, in our review of IFN-based therapies in the hemophilic population responses were similar to that seen in the general population. This was also corroborated in our pilot study of patients who were treated with Pegylated IFN combined with ribavirin. The sustained virological response for HIV negative and treatment naïve patients was 70%. This high response may be due to the high compliance to therapy in this population. The direct responses to antiviral therapy are precisely defined, but what are the long-term effects of this therapy? In a cohort study of approximately 300 patients, we found that all patients who achieved a sustained response after IFN-based therapy remained HCV RNA negative up to 15 years after treatment. Furthermore, none of the successfully treated patients developed liver failure or hepatocellular carcinoma. This was in contrast with patients who failed to eradicate HCV: the risk for developing end-stage liver disease was approximately 13%. In conclusion, these findings indicate that successful therapy postpones or may even prevent long-term complications of chronic hepatitis C during the first 10-15 years after therapy. However, longer follow-up is required to assess whether this favorable effect is sustained over the next decades