No abstract

Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma (CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA (HL-CCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliary-enteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.

Background and Aims: In a previous study, the authors found that reduced expression of peroxisome proliferator-activated receptor (PPAR)-a might play an important role in developing nonalcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the effects of PPAR-a and -g agonists on NAFLD and verify the mechanisms underlying the PPAR-a and -g agonist-induced improvements by evaluating the hepatic gene expression profile involved in fatty-acid metabolism, using the Otsuka-Long Evans-Tokushima fatty (OLETF) rat. Methods: Rats were assigned to a control group (group I), fatty liver group (group II), PPAR-a agonist treatment group (group III), or PPAR-g agonist treatment group (group IV). Fasting blood glucose, total cholesterol, and triglycerides were measured. Liver tissues from each group were processed for histological and gene expression analysis. mRNAs of enzymes involved in fatty-acid metabolism and tumor necrosis factor (TNF)-a were measured. Results: After 28 weeks treatment with PPAR-a or -g agonist, steatosis of the liver was improved in groups III and IV compared with group II. Fasting blood glucose levels were significantly lower in groups III and IV than in group II. In group III, mRNA expression of fatty-acid b-oxidation enzymes, such as fatty-acid transport protein (FATP), fatty-acid binding protein, carnitine palmitoyltransferase II, medium-chain acyl-CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase, and acyl-CoA oxidase, was significantly increased. However, the treatment-induced modulation of fatty-acid b-oxidation enzymes was confined to FATP and MCAD in group IV. TNF-a tended to be reduced in groups III and IV compared with group II. Conclusions: Treatment with PPAR agonists, especially a PPAR-a agonist, improved the histological and biochemical parameters in the OLETF rat model by inducing fatty-acid metabolic enzymes.