Liver international : official journal of the International Association for the Study of the Liver
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Comparative Study
Strain dependence of diet-induced NASH and liver fibrosis in obese mice is linked to diabetes and inflammatory phenotype.
Obese Alms1 mutant (foz/foz) NOD.B10 mice develop diabetes and fibrotic NASH when fed high-fat(HF) diet. To establish whether diabetes or obesity is more closely associated with NASH fibrosis, we compared diabetic foz/foz C57BL6/J with non-diabetic foz/foz BALB/c mice. We also determined hepatic cytokines, growth factors and related profibrotic pathways. ⋯ In mice with equivalent genetic/dietary obesity, NASH development is linked to strain differences in hyperinsulinaemia and hyperglycaemia inversely related to lipid partitioning between adipose and liver. Diabetes-mediated CTGF-regulation of MMPs as well as cytokines/growth factors (Th-2 cytokine predominant, PDGFα, not TGF-β) mobilized in the resultant hepatic necroinflammatory change may contribute to strain differences in NASH fibrosis.
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Nonalcoholic fatty liver disease (NAFLD) is an insulin resistance-related hepatic disorder which can transform to cirrhosis. Insulin resistance deregulates hepatic lipid metabolism, leading to accumulation of cytotoxic lipids including ceramide and diacylglycerols. Myriocin, obtained from fungi traditionally used in Chinese medicine in an effort to attain eternal youth, is a potent pharmacological inhibitor of ceramide de novo synthesis. We examined whether inhibition of ceramide de novo synthesis with myriocin ameliorate hepatic lipid accumulation and reverse NAFLD. ⋯ Inhibition of ceramide de novo synthesis reduced hepatic lipid accumulation in rats with NAFLD, this led to amelioration of hepatic steatosis.
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Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). ⋯ Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.
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Inflammation and cardiac dysfunction plays an important role in the development of complications leading to increased mortality in patients with cirrhosis. Novel cardiac markers such as prohormone of ANP (proANP), copeptin and high-sensitivity troponin T (hs-TnT) and proinflammatory markers including soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP) are related to these complications. We aimed to investigate if cardiac and proinflammatory markers are related to severity of liver disease, cardiac and haemodynamic changes, and long-term survival. ⋯ Markers of cardiac dysfunction and inflammation are significantly associated with disease severity, degree of portal hypertension and survival in cirrhosis. In particular, hs-TnT and suPAR seem to contain prognostic information.
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Prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma (ICC) after curative resection were not clear. We aim to analyse prognostic factors after curative resection and evaluate adjuvant therapy and survival based on the new staging system. ⋯ The new staging system can predict the survival of ICC patients after R0 resection. High GGT level may be suggestive of biliary and vascular invasion and was an independent risk factor for OS after R0 resection. Adjuvant TACE may be indicated only for patients at advanced stages for better survival.