Very-Low-Dose Pegylated Interferon a2a Plus Ribavirin Therapy for Advanced Liver Cirrhosis Type C: A Possible Therapeutic Alternative without Splenic Intervention

Despite the recent progress in interferon (IFN) therapies for chronic hepatitis C, liver cirrhosis remains refractory. One of the major obstacles to successful IFN therapy is low platelet count. Currently, splenic interventions, such as partial splenic embolization (PSE) or surgical splenectomy, have been applied effectively and make standard IFN therapy possible. However, there may be a group of patients with low platelet counts who can be treated without splenic intervention. We here report two patients with advanced type C liver cirrhosis who were successfully treated using very-low-dose pegylated interferon a2a plus ribavirin. One patient had a very low platelet count (2.5 × 104/μl) due to splenomegaly before treatment. However, pretreatment serum HCV titers were low in both patients and early viral responses were obtained in both. Because PSE or splenectomy may still have some safety concerns, this attenuated IFN treatment protocol can be an alternative therapeutic option for patients with advanced type C liver disease, but good virological factors for sustained virological response

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture▿

To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients—β-carotene, vitamin D2, and linoleic acid—inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, β-carotene, vitamin D2, and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy

Anti-Dementia Drugs and Hepatotoxicity–Report of Two Cases

Summary: Two patients with Alzheimer's disease who developed hepatitis caused by anti-dementia drugs are presented. Case 1: An 84-year-old-woman was referred to our hospital with profound jaundice. The levels of liver enzymes and jaundice decreased after the cessation of memantine and yokukansan (herbal medicine approved for dementia in Japan). Case 2: An 82-year-old-man was referred because of elevated transaminases. Liver biopsy showed central necrosis typical for drug-induced liver injury. The levels of transaminases decreased after withdrawal of rivastigmine transdermal patch treatment. Anti-dementia drugs have been safely used in terms of hepatotoxicity. However, some cases might be missed because of the difficulty in recognizing signs and symptoms in elderly and dementia patients. Keywords: drug-induced liver injury, alzheimer's disease, anti-dementia drugs, elderl