Meta‐analysis: analysis of mechanistic pathways in the treatment of <scp>non‐alcoholic</scp> steatohepatitis. Evidence from a Bayesian network <scp>meta‐analysis</scp>

Ng, Cheng Han; Muthiah, Mark; 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:10.1111/apt.16808

Cited by 22 publications

(17 citation statements)

References 83 publications

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“…While lifestyle modifications serve as a forefront in the care of NAFLD ( 8 , 42 ) and HTN, these interventions are often unsuitable ( 43 , 44 ). Instead, ACE inhibitors may be considered for use in individuals with NAFLD due to the multifactorial benefits they present where aside from regulation of blood pressure ( 45 ), ACE inhibitors have been found to reduce decompensation ( 46 ), hepatic fibrosis ( 47 ), and steatosis ( 48 ) in NAFLD and may also provide protection against CKD ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Many excellent review articles have recently been published on emerging drug approaches for the treatment of NAFLD (see, for example, among others [ 108 , 109 , 110 , 111 , 112 ]). Although a detailed discussion of the recent developments in pharmacotherapy for NAFLD/NASH is beyond the scope of our review, they are briefly summarized in Table 2 .…”

Section: Discussionmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications

Lonardo

Mantovani

Targher

et al. 2022

IJMS

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Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide, affecting up to ~30% of adult populations. NAFLD defines a spectrum of progressive liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, which often occur in close and bidirectional associations with metabolic disorders. Chronic kidney disease (CKD) is characterized by anatomic and/or functional renal damage, ultimately resulting in a reduced glomerular filtration rate. The physiological axis linking the liver and kidneys often passes unnoticed until clinically significant portal hypertension, as a major complication of cirrhosis, becomes apparent in the form of ascites, refractory ascites, or hepatorenal syndrome. However, the extensive evidence accumulated since 2008 indicates that noncirrhotic NAFLD is associated with a higher risk of incident CKD, independent of obesity, type 2 diabetes, and other common renal risk factors. In addition, subclinical portal hypertension has been demonstrated to occur in noncirrhotic NAFLD, with a potential adverse impact on renal vasoregulation. However, the mechanisms underlying this association remain unexplored to a substantial extent. With this background, in this review we discuss the current evidence showing a strong association between NAFLD and the risk of CKD, and the putative biological mechanisms underpinning this association. We also discuss in depth the potential pathogenic role of the hepatorenal reflex, which may be triggered by subclinical portal hypertension and is a poorly investigated but promising research topic. Finally, we address emerging pharmacotherapies for NAFLD that may also beneficially affect the risk of developing CKD in individuals with NAFLD.

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“…The classification of treatments was conducted as previously described in our previous network analysis. 19 Briefly, NASH treatments of the included articles were classified into four major groups, (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. Treatments were classified according to these groups based on the pathophysiology of disease and mechanism of action of drugs, which could in turn give rise to insights regarding disease pathways.…”

Section: Classification Of Treatmentsmentioning

confidence: 99%

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia

Xiao¹,

Ng²,

Chin³

et al. 2022

J Clin Transl Hepatol

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Background and Aims: Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation. Methods: Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups:(1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA). Results: Fortyfour RCTs were included in the analysis. Bile acid modulating treatments (MD: 0.05, Crl: 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD: 0.03, Crl: 0.02-0.04) and fibrosis (MD: 0.01, Crl: −0.12 to 0.14) compared with placebo. The top three treatments for reduction in triglycerides were treatments modulating energy (MD: −0.46, Crl: −0.49 to −0.43), bile acids (MD: −0.22, Crl: −0.35 to −0.09), and inflammation (MD: −0.08, Crl: −0.13 to −0.03) compared with placebo. SUCRA found treatment modulating fibrosis (MD: −1.27, Crl: −1.76 to −0.79) was the best treatment for reduction in low-density lipid (LDL) cholesterol followed by treatment modulating inflammation (MD: −1.03, Crl: −1.09 to −0.97) and energy (MD: −0.37, Crl: −0.39 to −0.34) compared with placebo, but LDL cholesterol was worsened by treatments modulating bile acids. Conclusions: Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of atherogenic dyslipidemia. Future studies are required to evaluate the cardiovascular outcomes.

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Meta‐analysis: analysis of mechanistic pathways in the treatment of non‐alcoholic steatohepatitis. Evidence from a Bayesian network meta‐analysis

Cited by 22 publications

References 83 publications

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

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

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia

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