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New drug targets for alcoholic liver disease.

ABSTRACT: Alcoholic liver disease (ALD) represents a spectrum of disorders, ranging from simple steatosis to severe alcoholic hepatitis and cirrhosis. The severe form of ALD comprises multiple problems in the liver, including inflammation, hepatocellular damage, fibrosis, and impaired liver regeneration, and likely requires combinational therapies. In this review, we discuss recently identified therapeutic targets that inhibit inflammation, ameliorate hepatocyte death, and promote liver repair in ALD, with a focus on our recent studies on the immunosuppressive drug prednisolone and the hepatoprotective cytokine interleukin-22. Clinical trials examining prednisolone plus interleukin-22 therapy for severe alcoholic hepatitis are currently under consideration.

SUBMITTER: Xu M

PROVIDER: S-EPMC5451265 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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New drug targets for alcoholic liver disease.

Xu Mingjiang M Chang Binxia B Mathews Stephanie S Gao Bin B

Hepatology international 20140308

Alcoholic liver disease (ALD) represents a spectrum of disorders, ranging from simple steatosis to severe alcoholic hepatitis and cirrhosis. The severe form of ALD comprises multiple problems in the liver, including inflammation, hepatocellular damage, fibrosis, and impaired liver regeneration, and likely requires combinational therapies. In this review, we discuss recently identified therapeutic targets that inhibit inflammation, ameliorate hepatocyte death, and promote liver repair in ALD, wit ...[more]

PMID: 26201327

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Project description:One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease (NAFLD), which is the most common form of liver disease in children. NAFLD is defined by hepatic fat infiltration > 5% hepatocytes, as assessed by liver biopsy, in the absence of excessive alcohol intake, viral, autoimmune and drug-induced liver disease. It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, which, in turn, can evolve into cirrhosis and end stage liver disease. Obesity and insulin resistance are the main risk factors for pediatric NAFLD. In fact, NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome, prediabetes and type 2 diabetes mellitus (T2D). In particular, it has been clearly shown in obese youth that the prevalence of metabolic syndrome, pre-diabetes and type 2 diabetes increases with NAFLD severity progression. Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition. Recently, a non-synonymous SNP (rs738409), characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene (PNPLA3), has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children. Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein. The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes, is aimed at acting upon specific targets involved in the pathogenesis. There are some therapeutic approaches that are being studied in children. This article reviews the current knowledge regarding the pediatric fatty liver disease, the new insights and the future directions.

Dataset Information

New drug targets for alcoholic liver disease.

Publications

New drug targets for alcoholic liver disease.

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