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  • Georg Thieme Verlag KG  (2)
  • 1
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2022
    In:  Seminars in Liver Disease Vol. 42, No. 03 ( 2022-08), p. 379-400
    In: Seminars in Liver Disease, Georg Thieme Verlag KG, Vol. 42, No. 03 ( 2022-08), p. 379-400
    Abstract: Nonalcoholic steatohepatitis (NASH) is a burgeoning global health crisis that mirrors the obesity pandemic. This global health crisis has stimulated active research to develop novel NASH pharmacotherapies targeting dysregulated inflammatory, cellular stress, and fibrogenetic processes that include (1) metabolic pathways to improve insulin sensitivity, de novo lipogenesis, and mitochondrial utilization of fatty acids; (2) cellular injury or inflammatory targets that reduce inflammatory cell recruitment and signaling; (3) liver–gut axis targets that influence bile acid enterohepatic circulation and signaling; and (4) antifibrotic targets. In this review, we summarize several of the therapeutic agents that have been studied in phase 2 and 3 randomized trials. In addition to reviewing novel therapeutic drugs targeting nuclear receptor pathways, liver chemokine receptors, liver lipid metabolism, lipotoxicity or cell death, and glucagon-like peptide-1 receptors, we also discuss the rationale behind the use of combination therapy and the lessons learned from unsuccessful or negative clinical trials.
    Type of Medium: Online Resource
    ISSN: 0272-8087 , 1098-8971
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2022
    detail.hit.zdb_id: 2063686-6
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  • 2
    In: Digestive Disease Interventions, Georg Thieme Verlag KG, Vol. 04, No. 02 ( 2020-06), p. 223-234
    Abstract: Background Nonalcoholic steatohepatitis (NASH) and alcoholic liver disease (ALD) are now the most common indications for liver transplantation (LT) in the United States. A subset of patients have both alcoholic and nonalcoholic steatohepatitis (BASH). This study characterizes patients with BASH requiring LT and assesses changes in the prevalence of BASH as an indication for LT. Methods The United Network for Organ Sharing database was analyzed for all patients ≥ 18 years of age who received their first deceased donor LT from 2002 to 2016 for ALD, NASH, or BASH. Baseline demographics, clinical parameters, and LT outcomes were compared between groups. Results Since 2002, 85,448 patients underwent LT:15,327 had ALD, 9,971 had NASH, and 2,779 had BASH. The prevalence of BASH as an indication for LT increased from 0.5% in 2002 to 5% in 2016. Compared with patients with NASH, those with BASH were significantly more likely to be male (85.6 vs. 57%), younger (mean 56.4 vs. 58.6 years), and Hispanic (22.2 vs. 13.6%) (p  〈  0.001 for all). While indication for transplant was not significantly associated with transplant outcomes on multivariable analysis, patient and graft survival curves do differ significantly by indication for transplant, with worse outcomes for patients with BASH (patient survival at 5 years: NASH 78.1%, ALD 77.2%, BASH 73.5%, p = 0.013; graft survival at 5 years: NASH 75.3%, ALD 74.0%, BASH 70.8%, p = 0.046). Conclusions BASH is a rising indication for LT, especially for Hispanic males, due to the increasing prevalence of ALD and NASH in the United States.
    Type of Medium: Online Resource
    ISSN: 2472-8721 , 2472-873X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2020
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