Liver Fibrosis and MAFLD: From Molecular Aspects to Novel Pharmacological Strategies

Abstract

Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and this nomenclature MAFLD was proposed to renovate its former name, non-alcoholic fatty liver disease (NAFLD). MAFLD/NAFLD have shared and predominate causes from nutrition overload to persistent liver damage and eventually lead to the development of liver fibrosis and cirrhosis. Unfortunately, there is an absence of effective treatments to reverse MAFLD/NAFLD-associated fibrosis. Due to the significant burden of MAFLD/NAFLD and its complications, there are active investigations on the development of novel targets and pharmacotherapeutics for treating this disease. In this review, we cover recent discoveries in new targets and molecules for antifibrotic treatment, which target pathways intertwined with the fibrogenesis process, including lipid metabolism, inflammation, cell apoptosis, oxidative stress, and extracellular matrix formation. Although marked advances have been made in the development of antifibrotic therapeutics, none of the treatments have achieved the endpoints evaluated by liver biopsy or without significant side effects in a large-scale trial. In addition to the discovery of new druggable targets and pharmacotherapeutics, personalized medication, and combinatorial therapies targeting multiple profibrotic pathways could be promising in achieving successful antifibrotic interventions in patients with MAFLD/NAFLD.

Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions

“…Yamamura et al [ 67 ] compared the diagnostic accuracy of MAFLD and NAFLD in identifying individuals with significant hepatic fibrosis and clarified the influence of mild alcohol consumption (< 20 g/d) on the degree of the hepatic disease in a large cohort of 765 subjects clustered in two groups as NAFLD and MAFLD. Compared to NAFLD, MAFLD criteria provided careful detection of hepatic fibrosis, as reflected by the strong relationship between certain hepatic fibrosis markers and liver stiffness in patients diagnosed with MAFLD[ 67 ]. Given that, dysmetabolic patients at high risk of adverse hepatic outcomes were better identified through MAFLD than NAFLD criteria[ 12 , 21 ].…”

“…As the well-known relevance of alcohol intake on hepatic fibrosis risk development was not included in MAFLD definition, the authors also examined its influence on fatty liver severity[ 67 ]. Patients with MAFLD and alcohol intake of 1–59 g/d were more likely to be male and to have higher fasting blood glucose, serum liver enzymes, creatinine, and uric acid levels than those with MAFLD and no alcohol consumption[ 67 ]. Of note, there is no evidence on the potential negative effect of alcohol intake on renal damage risk in MAFLD individuals[ 67 ].…”

“…Patients with MAFLD and alcohol intake of 1–59 g/d were more likely to be male and to have higher fasting blood glucose, serum liver enzymes, creatinine, and uric acid levels than those with MAFLD and no alcohol consumption[ 67 ]. Of note, there is no evidence on the potential negative effect of alcohol intake on renal damage risk in MAFLD individuals[ 67 ]. Authors concluded that MAFLD presence was an independent risk factor for significant fibrosis (defined by FIB-4 index ≥ 1.3 and liver stiffness ≥ 6.6 kPa using Shear wave elastography), and both MAFLD and mild alcohol intake were associated with increased prevalence of significant fibrosis (25.0% vs 15.5%)[ 67 ].…”

Impact of NAFLD and its pharmacotherapy on lipid profile and CVD

“…As the most common chronic liver disease, nonalcoholic fatty liver disease (NAFLD) has a global prevalence of 25.24%, and its incidence is still rising [5,6]. Over one-third of patients with simple steatosis progress to a more severe form, nonalcoholic steatohepatitis (NASH), which largely increases the risk of developing liver fibrosis and cancer [7]. More importantly, the liver regulates systemic glucose and lipid metabolism, and its pathology enhances lipid dysregulation and IR [8].…”

Protective Mechanism of Polygonum perfoliatum L. Extract on Chronic Alcoholic Liver Injury Based on UHPLC-QExactive Plus Mass Spectrometry Lipidomics and MALDI-TOF/TOF Mass Spectrometry Imaging

“…While the majority of patients are affected by social, environmental and personal influences [ 5 ], maintaining a healthy lifestyle to improve the effect of liver steatosis is not obvious, only 30% of patients can be cured [ 6 ]. Up to now, although most drugs for liver injury have prominent therapeutic effects, they have certain side effects and repeatability [ 7 ]. Therefore, it is the general trend to develop corresponding liver protection products [ 8 ], especially the products with natural products as raw materials [ 9 ].…”