Current status in the therapy of liver diseases.
Hepatic diseases, like viral hepatitis, autoimmune hepatitis, hereditary hemochromatosis, non-alcoholic fatty liver disease (NAFLD) and Wilson's disease, play an important role in the development of liver cirrhosis and, hence, hepatocellular carcinoma. In this review, the current treatment options and the molecular mechanisms of action of the drugs are summarized. Unfortunately, the treatment options for most of these hepatic diseases are limited. Since hepatitis B (HBV) and C (HCV) infections are the most common causes of liver cirrhosis and hepatocellular carcinoma, they are the focus of the development of new drugs. The current treatment of choice for HBV/HCV infection is an interferon-based combination therapy with oral antiviral drugs, like nucleos(t)ide analogues, which is associated with improving the therapeutic success and also preventing the development of resistances. Currently, two new protease inhibitors for HCV treatment are expected (deleobuvir, faldaprevir) and together with the promising drug, daclatasvir (NS5A-inhibitor, currently in clinical trials), adequate therapy is to be expected in due course (circumventing the requirement of interferon with its side-effects), while in contrast, efficient HBV therapeutics are still lacking. In this respect, entry inhibitors, like Myrcludex B, the lead substance of the first entry inhibitor for HBV/HDV (hepatitis D) infection, provide immense potential. The pharmacokinetics and the mechanism of action of Myrcludex B are described in detail.
Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. philipp.uhl@med.uni-heidelberg.de.
Philipp
P
Uhl
Ruprecht-Karls-University, Institute of Pharmacy and Molecular Biotechnology, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany. gert.fricker@uni-hd.de.
Gert
G
Fricker
Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. uwe.haberkorn@med.uni-heidelberg.de.
Uwe
U
Haberkorn
Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. walter.mier@med.uni-heidelberg.de.
Walter
W
Mier
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D004359:Drug Therapy, Combination; D006525:Hepatitis, Viral, Human / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D011480:Protease Inhibitors / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011480:Protease Inhibitors; D007372:Interferons