Virus-host Interactions during Hepatitis C Virus Entry-Implications for Pathogenesis and Novel Treatment Approaches

Hepatitis C virus (HCV) is a member of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antibody-mediated virus neutralization. Following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has been markedly advanced. In this review we summarize recent developments in the molecular biology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.

Klatskin tumor treated by inter-disciplinary therapies including stereotactic radiotherapy: A case report

In view of the poor prognosis of patients with cholangiocarcinoma (CCC), there is a need for new therapeutic strategies. Inter-disciplinary therapy seems to be most promising. Radiotherapy is an effective alternative to surgery for hilar CCC (Klatskin tumors) if an adequate radiation dose can be delivered to the liver hilus. Here,we describe a patient for whom we used a stereotactic radiotherapy technique in the context of an inter-disciplinary treatment concept. We report a 45-year-old patient with a locally advanced Klatskin tumor. Explorative laparotomy showed that the tumor was not resectable. A metallic stent was implanted and the patient was treated by stereotactic radiotherapy using a body frame. A total dose of 48 Gy (3x4 Gy/wk) was administered. Therapy was well tolerated. After 32 mo, local tumor recurrence and a chest wall metastasis developed and were controlled by radio-chemotherapy. After more than 56 mo with a good quality of life, the patient died of advanced neoplastic disease. Stereotactic radiotherapy led to a long-term survival of this patient with a locally advanced Klatskin tumor. In the context of inter-disciplinary treatment concepts, this radiotherapy technique is a promising choice of treatment for patients with hilar CCC.

Molecular Therapy and Prevention of Liver Diseases

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.