Pharmacotherapeutic efficacy on noninvasive fibrosis progression in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

Kovalic, Alexander J.; Gozar, Martin; Da, Ben L.; Bernstein, David

doi:10.1097/meg.0000000000002463

Cited by 8 publications

(6 citation statements)

References 34 publications

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“…Additionally, other FGF21 analogs besides PGBF may have different effects on improving NASH. A network metaanalysis evaluated the efficacy of PGBF compared to other drugs in treating NASH (38), and PGBF's treatment effect did not show particular advantages over other drugs in NASH treatment. However, this study only included indicators of liver fibrosis improvement, and there were differences in the liver function status of patients included in the studies, making it impossible to comprehensively evaluate the superiority or inferiority of PGBF in improving liver function compared to other drugs.…”

Section: Discussionmentioning

confidence: 99%

Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials

Lu,

Yu,

et al. 2024

Front. Med.

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BackgroundThe efficacy of Pegbelfermin (PGBF) in treating non-alcoholic steatohepatitis (NASH) remains controversial. Therefore, we conducted a dose-response meta-analysis to explore the effect and pattern of PGBF at different dosages and treatment durations on transaminase reduction in NASH patients.MethodsWe conducted searches on PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov, and supplemented the search with gray literature and manual searches. Randomized controlled trials (RCTs) evaluating the efficacy of PGBF in NASH patients were included. Risk of bias was assessed by Cochrane Risk of Bias Tool 2.0. We used random-effects models, generalized least squares regression, constrained maximum likelihood, and restricted cubic splines to explore the dose-response relationship. Egger's linear regression was employed to assess publication bias. The study is registered with PROSPERO, CRD42023448024.ResultsFour RCT studies from the period 2018–2023, involving 546 participants, were included. No participants discontinued PGBF treatment due to adverse events. High-dose PGBF treatment significantly reduced transaminase levels in NASH patients compared to the low-dose group (ALT %: MD = 14.94, 95% CI = 2.11–27.77; AST %: MD = 9.05, 95% CI = 3.17–14.92). Longer treatment duration further decreased transaminase levels (ALT%: MD = 8.81, 95% CI = 4.07–13.56; AST%: MD = 6.72, 95% CI = 2.62–10.81). Egger's test did not reveal significant publication bias (p > 0.05). Further investigation indicated a ceiling effect of PGBF dosage on transaminase reduction at 30 mg/week, and NASH patients experienced a rebound in transaminase levels after 28 weeks of continuous treatment.ConclusionThere is a positive correlation between PGBF dosage and transaminase reduction within a certain range, showing an overall non-linear dose-response relationship. This finding provides guidance for the clinical application of PGBF. Clinicians should be mindful of the dosage ceiling at 30 mg/week and monitor changes in transaminase levels after 28 weeks for timely adjustments in PGBF dosage.Systematic review registrationPROSPERO, CRD42023448024. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=448024

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Section: Discussionmentioning

confidence: 99%

Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials

Lu,

Yu,

et al. 2024

Front. Med.

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“…Finally, a meta-analysis conducted by Mantovani A et al confirmed the effectiveness of various GLP1 receptor agonist in reducing the percentage of hepatic fat [ 47 ]. Also Kovalic AJ et al in their meta-analysis proved that semaglutide is one of the most effective drugs to treat NAFLD, which was confirmed by elastography and non-invasive blood tests [ 48 ]. The same results were published in 2023 by Gu Y et al [ 49 ] Similar results to our study on FIB-4 decrease were obtained by Arai, T et al in their pilot study for oral semaglutide treatment [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Does Therapy with Glucagon-like Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes—Interventional Study

Hachuła,

Kosowski,

Basiak

et al. 2023

Pharmaceuticals

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Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) is associated with the excessive collection of lipids in hepatocytes. Over 75% of diabetes patients typically have MASLD, and, at the same time, the presence of MASLD increases the risk of diabetes by more than two times. Type 2 diabetes and MASLD are independent cardiovascular disease (CVD) risk factors. New diabetes treatment should also take into account pleiotropic effects that reduce cardiovascular risk. The aim of our study is to investigate whether analogs of GLP1 receptors have a pleiotropic metabolic effect and global impact to decrease cardiovascular risk, and also reduce the risk of hepatic fibrosis in patients with MASLD. This study involved 41 patients with diabetes and dyslipidemia who also had atherosclerotic plaque and hepatic steatosis verified by ultrasonography and who were eligible to begin one of the GLP1 receptor agonists treatments. We observed a statistically significant decrease in: BMI (p < 0.001) waist and hip circumference (p < 0.001), glycated hemoglobin (p < 0.001) and creatinine (p < 0.05). Additionally, we obtained a decrease in FIB-4 (p < 0.001) and in the De Ritis (AST/ALT aminotransferase ratio) (p < 0.05). The positive correlation between the FIB-4 value and BMI, WHR, waist circumference and the De Ritis index was observed. In conclusion, semaglutide and dulaglutide had a beneficial effect on metabolic and cardiovascular risk factors in patients with type 2 diabetes. These medications had a positive effect on MASLD biochemical markers.

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“…At the moment, though, it seems that semaglutide is not effective in resolving or ameliorating liver fibrosis once it is present [ 125 ], whereas it seems to decrease steatosis and liver inflammation in vivo in Ldrl −/− mice [ 126 ]. Comparative studies and meta-analyses are currently being carried out in order to identify the most effective drug and its posology, which seems to also vary according to the patients’ metabolic status and compliance [ 127 , 128 , 129 , 130 ].…”

Section: Possible Therapeutic Approachesmentioning

confidence: 99%

Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD

Vitulo

Gnodi

Rosini

et al. 2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD, including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH)) is a high-prevalence disorder, affecting about 1 billion people, which can evolve to more severe conditions like cirrhosis or hepatocellular carcinoma. NAFLD is often concomitant with conditions of the metabolic syndrome, such as central obesity and insulin-resistance, but a specific drug able to revert NAFL and prevent its evolution towards NASH is still lacking. With the liver being a key organ in metabolic processes, the potential therapeutic strategies are many, and range from directly targeting the lipid metabolism to the prevention of tissue inflammation. However, side effects have been reported for the drugs tested up to now. In this review, different approaches to the treatment of NAFLD are presented, including newer therapies and ongoing clinical trials. Particular focus is placed on the reverse cholesterol transport system and on the agonists for nuclear factors like PPAR and FXR, but also drugs initially developed for other conditions such as incretins and thyromimetics along with validated natural compounds that have anti-inflammatory potential. This work provides an overview of the different therapeutic strategies currently being tested for NAFLD, other than, or along with, the recommendation of weight loss.

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Pharmacotherapeutic efficacy on noninvasive fibrosis progression in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

Cited by 8 publications

References 34 publications

Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials

Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials

Does Therapy with Glucagon-like Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes—Interventional Study

Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD

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