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A structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH).

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is a chronic, progressive disease, that can advance to fibrosis, cirrhosis, and hepatocellular carcinoma. Despite being a leading cause of liver transplantation, there are no approved pharmacological treatments. Our aim was to identify literature on management options in NASH. Our structured review of interventions treating NASH patients from English language publications between 1 January 2007 and 25 September 2017 elicited 48 eligible references. Lifestyle management was identified as the mainstay of NASH therapy. Vitamin E and pioglitazone reported reductions in steatosis; however, although recommended for some, no therapies are indicated in NASH. Multiple investigational treatments reported efficacy in mild-to-moderate fibrosis in Phase II/III NASH trials. Lifestyle management, although the focus of clinical guidelines, is insufficient for patients progressing to advanced fibrosis. With no clear guidelines for patients requiring interventions beyond lifestyle modification, long-term outcomes data are needed, particularly in patients with moderate-to-severe fibrosis.

SUBMITTER: Povsic M

PROVIDER: S-EPMC6536401 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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A structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH).

Povsic Manca M Oliver Louisa L Jiandani Neha Raju NR Perry Richard R Bottomley Juliana J

Pharmacology research & perspectives 20190527 3

Nonalcoholic steatohepatitis (NASH) is a chronic, progressive disease, that can advance to fibrosis, cirrhosis, and hepatocellular carcinoma. Despite being a leading cause of liver transplantation, there are no approved pharmacological treatments. Our aim was to identify literature on management options in NASH. Our structured review of interventions treating NASH patients from English language publications between 1 January 2007 and 25 September 2017 elicited 48 eligible references. Lifestyle m ...[more]

PMID: 31149341

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Project description:BackgroundThere is limited data on the comparative economic and humanistic burden of non-alcoholic steatohepatitis (NASH) in the United States. The objective was to examine the burden of disease comparing NASH to a representative sample of the general population and separately to a type 2 diabetes mellitus (T2DM) cohort by assessing health-related quality of life (HRQoL) measures, healthcare resource use (HRU) and work productivity and activity impairment (WPAI).MethodsData came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey conducted in the United States. Respondents with physician-diagnosed NASH, physician-diagnosed T2DM, and respondents from the general population were compared. Humanistic burden was examined with mental (MCS) and physical (PCS) component summary scores from the Short-Form (SF)-36v2, concomitant diagnosis of anxiety, depression, and sleep difficulties. Economic burden was analysed based on healthcare professional (HCP) and emergency room (ER) visits, hospitalizations in the past six months; absenteeism, presenteeism, overall work impairment, and activity impairment scores on WPAI questionnaire. Bivariate and multivariable analysis were conducted for each outcome and matched comparative group.ResultsAfter adjusting for baseline demographics and characteristics, NASH (N = 136) compared to the matched general population cohort (N = 544), reported significantly lower (worse) mental (MCS 43.19 vs. 46.22, p = 0.010) and physical (PCS 42.04 vs. 47.10, p < 0.001) status, higher % with anxiety (37.5% vs 25.5%, p = 0.006) and depression (43.4% vs 30.1%, p = 0.004), more HCP visits (8.43 vs. 5.17), ER visits (0.73 vs. 0.38), and hospitalizations (0.43 vs. 0.2) all p's < 0.05, and higher WPAI scores (e.g. overall work impairment 39.64% vs. 26.19%, p = 0.011). NASH cohort did not differ from matched T2DM cohort (N = 272) on mental or work-related WPAI scores, but had significantly worse physical status (PCS 40.52 vs. 44.58, p = 0.001), higher % with anxiety (39.9% vs 27.8%, p = 0.043), more HCP visits (8.63 vs. 5.68, p = 0.003) and greater activity impairment (47.14% vs. 36.07%, p = 0.010).ConclusionThis real-world study suggests that burden of disease is higher for all outcomes assessed among NASH compared to matched general controls. When comparing to T2DM, NASH cohort has comparable mental and work-related impairment but worse physical status, daily activities impairment and more HRU.

Project description:Nonalcoholic fatty liver disease (NAFLD), representing a clinical spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), is rapidly evolving into a global pandemic. Patients with NAFLD are burdened with high rates of metabolic syndrome-related comorbidities resulting in polypharmacy. Therefore, it is crucial to gain a better understanding of NAFLD-mediated changes in drug disposition and efficacy/toxicity. Despite extensive clinical pharmacokinetic data in cirrhosis, current knowledge concerning pharmacokinetic alterations in NAFLD, particularly at different stages of disease progression, is relatively limited. In vitro-to-in vivo extrapolation coupled with physiologically based pharmacokinetic and pharmacodynamic (IVIVE-PBPK/PD) modeling offers a promising approach for optimizing pharmacologic predictions while refining and reducing clinical studies in this population. Use of IVIVE-PBPK to predict intra-organ drug concentrations at pharmacologically relevant sites of action is particularly advantageous when it can be linked to pharmacodynamic effects. Quantitative systems pharmacology/toxicology (QSP/QST) modeling can be used to translate pharmacokinetic and pharmacodynamic data from PBPK/PD models into clinically relevant predictions of drug response and toxicity. In this review, a detailed summary of NAFLD-mediated alterations in human physiology relevant to drug absorption, distribution, metabolism, and excretion (ADME) is provided. The application of literature-derived physiologic parameters and ADME-associated protein abundance data to inform virtual NAFLD population development and facilitate PBPK/PD, QSP, and QST predictions is discussed along with current limitations of these methodologies and knowledge gaps. The proposed methodologic framework offers great potential for meaningful prediction of pharmacological outcomes in patients with NAFLD and can inform both drug development and clinical practice for this population.

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A structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH).

Publications

A structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH).

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