Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial

Harrison, Stephen A.; Abdelmalek, Manal F.; Neff, Guy; Gunn, Nadege; Guy, Cynthia D.; Alkhouri, Naim; Bashir, Mustafa R.; Freilich, B.; Kohli, Anita; Khazanchi, Arun; Sheikh, Muhammad Y.; Leibowitz, Mark; Rinella, Mary E.; Siddiqui, Mohammad Shadab; Kipnes, Mark; Moussa, Sam; Younes, Ziad; Bansal, Meena B.; Baum, Seth; Borg, Brian B.; Ruane, Peter; Thuluvath, Paul J.; Gottwald, Mildred D.; Khan, Mujib; Chen, Charles; Melchor‐Khan, Liza; Chang, Wei‐An; DePaoli, Alex M.; Ling, Lei; Lieu, Hsiao

doi:10.1016/s2468-1253(22)00017-6

Cited by 68 publications

(38 citation statements)

References 34 publications

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“…After the full-text screening, a total of 26 RCTs met the eligibility criteria and were included for further qualitative synthesis (Fig. 1) [23,28–52]. The characteristics of included studies are presented in Supplementary Table 1, Supplemental digital content 1, http://links.lww.com/EJGH/A794.…”

Section: Resultsmentioning

confidence: 99%

“…There was no head-to-head comparison of most therapies, so indirect comparison played a major role in our study. Among the 26 included studies, 25 were double-blind and randomized trials, which increased the reliability of our NMA results [23,28–35,37–52]. To our knowledge, this is the first NMA to provide a comparison regarding the safety of antifibrotic treatments for NAFLD.…”

Section: Discussionmentioning

confidence: 99%

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Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

Liu

Lei

et al. 2023

European Journal of Gastroenterology &Amp; Hepatology

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Several studies have found that antifibrosis treatment for nonalcoholic fatty liver disease (NAFLD) can cause a variety of side effects. No network meta-analysis (NMA) analyzes the adverse events of antifibrotic drugs for NAFLD. This NMA aimed to systematically compare the drug-related side effects when using different pharmacological agents for the treatment of liver fibrosis in NAFLD. PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched to select related studies published in English from the database inception until 30 June 2022. We conducted Bayesian fixed-effects NMA using data from randomized controlled trials (RCTs) to derive relative risks (RRs). The surface under the cumulative ranking (SUCRA) probabilities was used to assess ranking. A total of 26 RCTs with 19 interventions met the inclusion criteria. SUCRA analysis suggested that the lanifibranor group had the highest risk of diarrhea (SUCRA, 94), whereas the liraglutide group had the highest risk of constipation (SUCRA, 92.9). The semaglutide group showed the highest incidence of nausea (SUCRA, 81.2) and abdominal pain (SUCRA, 90.5), respectively. The cenicriviroc group showed the highest risk in the incidence of fatigue (SUCRA, 82.4). The MSDC-0602K group had the highest risk of headache (SUCRA, 76.4), whereas the obeticholic acid group had the highest risk of pruritus (SUCRA, 80.1). The risk of side effects significantly varied among different pharmacologic regimens, and evidence showed that lanifibranor, liraglutide, semaglutide, cenicriviroc, MSDC-0602K and obeticholic acid were the pharmacological interventions with the highest risk in patients with NAFLD. This study may guide clinicians and support further research.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

Liu

Lei

et al. 2023

European Journal of Gastroenterology &Amp; Hepatology

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“…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 . The most promising randomized controlled trials in the NAFLD arena were published since 2010 [ 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ].…”

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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“…Recently, their team conducted a randomized, double-blind, placebo-controlled, phase IIb clinical study, in which, they set up different doses of the drug groups, including 0.3 mg/d and 1 mg/d. The results showed that the treatment was generally well-tolerated; however, there was no significant difference between the different doses in improving fibrosis ( 173 ). Studies also showed that NGM282 could reduce liver fat, liver damage, and inflammation in NASH patients, but elevated cholesterol levels.…”

Section: Treatment Strategies Of Nafldmentioning

confidence: 99%

Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)

Zou

Wei

et al. 2023

Front. Endocrinol.

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Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the liver and is often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, and other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD in 2020 as metabolic (dysfunction) associated with fatty liver disease (MAFLD). The changes in diet and lifestyle are recognized the non-drug treatment strategies; however, due to the complex pathogenesis of NAFLD, the current drug therapies are mainly focused on its pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. There is still a lack of specific drugs. In clinical studies, the common NAFLD treatments include the regulation of glucose and lipid metabolism to protect the liver and anti-inflammation. The NAFLD treatments based on the enterohepatic axis, targeting gut microbiota, are gradually emerging, and various new metabolism-regulating drugs are also under clinical development. Therefore, this review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.

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Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial

Cited by 68 publications

References 34 publications

Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

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

Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)

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