Analysis of Mechanistic Pathways in the Treatment of Non-Alcoholic Steatohepatitis. Evidence from a Bayesian Network Meta-Analysis

Muthiah, Mark; Ng, Cheng Han; Xiao, Jieling; Chin, Yip Han; Lim, Gina; Lim, Wen Hui; Tay, Phoebe Wen Lin; Tan, Darren Jun Hao; Yong, Jie Ning; Pan, Xinliang; Koh, Jeffery Wei Heng; Chew, Nicholas; Syn, Nicholas; Tan, Eunice X.; Huang, Daniel Q.; Siddiqui, Mohammad Shadab; Loomba, Rohit; Sanyal, Arun J.; Noureddin, Mazen

doi:10.1101/2021.10.22.21265361

Cited by 2 publications

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References 71 publications

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“…This was a post hoc analysis of a previous data set examining the outcomes of NASH in clinical trials. [ 14 ] This meta‐analysis was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses statement. [ 15,16 ] A comprehensive search was conducted on Medline, EMBASE, and the Cochrane Central Register of Controlled Trials with assistance from a medical librarian on NASH RCTs since inception on October 1, 2021.…”

Section: Methodsmentioning

confidence: 99%

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Placebo effect on progression and regression in NASH: Evidence from a meta‐analysis

Xiao

Lim

et al. 2022

Hepatology

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Background and Aims The evaluation of the natural history of NASH has been limited. Currently, liver biopsy remains the gold standard in the assessment of NASH. Placebo‐controlled trials represent a controlled environment with paired biopsies for the evaluation of NASH. This meta‐analysis thus seeks to quantify the change severity of NASH over time, with patients on placebo arms from randomized controlled trials (RCTs) to examine the natural history of NASH. Methods A search was conducted to include NASH RCTs with placebo treatment arms. Primary outcomes were (1) the resolution of NASH without worsening of fibrosis, (2) two‐point reduction in NAFLD activity score without worsening of fibrosis, and (3) at least one‐point reduction in fibrosis. Generalized linear mix model was used to estimate pooled proportion and mean differences. Results This meta‐analysis of 43 RCTs included 2649 placebo‐treated patients. The pooled estimate of NASH resolution and two‐point NAFLD activity score reduction without worsening of fibrosis was 11.65% (95% CI: 7.98‐16.71) and 21.11% (95% CI: 17.24‐25.57). The rate of ≥1 stage reduction and progression of fibrosis was 18.82% (95% CI: 15.65‐22.47) and 22.74% (CI: 19.63‐26.17), respectively. Older age and African American ethnicity was associated with lower NASH resolution rate in placebo‐treated patients. Conclusions Despite the absence of any pharmacological interventions, a significant proportion of patients in the placebo arm demonstrated improvements in liver histology, highlighting the possibility that NASH is a disease that can not only progress but regress spontaneously over time. Additionally, histologic response in placebo‐treated patients is helpful in future design of phase 2B and phase 3 trials.

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Section: Methodsmentioning

confidence: 99%

“…This was a post hoc analysis of a previous data set examining the outcomes of NASH in clinical trials. [14] This meta-analysis was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. [15,16]…”

Section: Search Strategymentioning

confidence: 99%

Placebo effect on progression and regression in NASH: Evidence from a meta‐analysis

Xiao

Lim

et al. 2022

Hepatology

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Hypertension is prevalent in non-alcoholic fatty liver disease and increases all-cause and cardiovascular mortality

Wong

Chew

et al. 2022

Front. Cardiovasc. Med.

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Background and aimsHypertension (HTN) is a common comorbidity in non-alcoholic fatty liver disease (NAFLD) affecting up to 40% of individuals. However, the impact of HTN and its control on outcomes in NAFLD remains unclear. Therefore, we aimed to examine the impact of HTN on survival outcomes in a longitudinal cohort of NAFLD patients.MethodsThe analysis consisted of adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with data on socio-demographic characteristics and comorbidities. NAFLD was diagnosed with fatty liver index (FLI) and United States-FLI at a cut-off of 60 and 30, respectively in the substantial absence of alcohol use. A multivariate regression analysis was conducted to adjust for confounders.ResultsA total of 45,302 adults were included, and 27.83% were identified to have NAFLD. Overall, 45.65 and 35.12% of patients with NAFLD had HTN and uncontrolled HTN, respectively. A multivariate analysis with confounders demonstrated that hypertensive NAFLD had a significantly increased risk of all-cause mortality (HR: 1.39, CI: 1.14–1.68, p < 0.01) and cardiovascular disease (CVD) mortality (HR: 1.85, CI: 1.06–3.21, p = 0.03). Untreated HTN remained to have a significantly increased risk in all-cause (HR: 1.59, CI: 1.28–1.96, p < 0.01) and CVD mortality (HR: 2.36, CI: 1.36–4.10, p < 0.01) while treated HTN had a non-significant increased risk of CVD mortality (HR: 1.51, CI: 0.87–2.63, p = 0.14) and a lower magnitude of increase in the risk of all-cause mortality (HR: 1.26, CI: 1.03–1.55, p = 0.03).ConclusionDespite the significant burden of HTN in NAFLD, up to a fifth of patients have adequate control, and the lack thereof significantly increases the mortality risk. With the significant association of HTN in NAFLD, patients with NAFLD should be managed with a multidisciplinary team to improve longitudinal outcomes.

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Analysis of Mechanistic Pathways in the Treatment of Non-Alcoholic Steatohepatitis. Evidence from a Bayesian Network Meta-Analysis

Cited by 2 publications

References 71 publications

Placebo effect on progression and regression in NASH: Evidence from a meta‐analysis

Placebo effect on progression and regression in NASH: Evidence from a meta‐analysis

Hypertension is prevalent in non-alcoholic fatty liver disease and increases all-cause and cardiovascular mortality

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