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We present clinical cases, which underline some difficulties in diagnosis and treatment of hepatitis C virus (HCV) infection. Case report #1 shows a patient who avoided clinical follow-up for HCV until the development of hepatocellular carcinoma. In this patient, non-invasive procedures did not allow to make a differential diagnosis between hydatidosis and hepatocellular carcinoma but diagnosis was only made with liver biopsy.In the case report #2, 24-week treatment with peg-interferon α2 and ribavirin was successfully administered to a HCV genotype-1b infected patient. Shortening HCV treatment did not impair sustained virological response, probably because HCV RNA was low (< 200,000 IU/l) at baseline.Lastly, a case series of patients (#3-6) with hemoglobinopathies is described. Sustained virological response after peg-interferon α2 and ribavirin was achieved in 2 out of 4 patients. While no severe treatment limiting hematological effects were encountered, patients needed more frequent blood transfusions. Thus, new anti-HCV schemes without peg-interferon and ribavirin are urgently needed.