Genes, RNAs & the Future of Liver Disease

Recent key publications

Long Non-Coding RNAs in Non-Alcoholic Fatty Liver Disease; Friends or Foes?
Cell Biochem Biophys 2025; 83:279-294. Soltanieh SK, Khastar S, Kaur Iet al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39377981

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a global health crisis affecting about 25% of the world's population, with increasing rates tied to obesity and metabolic syndrome. Long non-coding RNAs (lncRNAs) play crucial roles in MAFLD development by influencing lipid buildup, inflammation, and insulin resistance. Recent research shows these molecules have significant potential as diagnostic markers and treatment targets, offering new perspectives on disease mechanisms. This review examines current findings on lncRNAs in MAFLD, presenting a comprehensive framework for understanding their functions and clinical applications.

Global burden of MAFLD, MAFLD related cirrhosis and MASH related liver cancer from 1990 to 2021. 
Sci Rep 2025; 15:7083. Guo Z, Wu D, Mao Ret al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=40016310

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major global health threat, affecting over 1.27 billion people in 2021, with numbers expected to climb, especially in lower-income countries. Growing rates of obesity, metabolic syndrome, and type 2 diabetes are driving MAFLD and its serious complications—cirrhosis and liver cancer—which now significantly impact global mortality and disability-adjusted life years. Concerning trends show MAFLD increasingly affecting lower socioeconomic populations, highlighting critical healthcare access disparities. This analysis uses the Global Burden of Disease 2021 database to map regional inequalities, track trends, and forecast future patterns, providing essential insights for targeted public health strategies.

A class of MicroRNAs as diagnostic biomarkers and therapeutic strategies in non-alcoholic fatty liver disease: A review.Clin Res Hepatol Gastroenterol 2025; 49:102547. Mahdizadeh F, Sobhi P, Banaei S.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39924053

Non-alcoholic fatty liver disease (NAFLD) continues to be a major global health challenge, affecting roughly 25% of the population with risks of progressing to cirrhosis and liver cancer. Recent research reveals microRNAs (miRNAs) as crucial diagnostic markers and treatment targets, creating promising opportunities for early detection and intervention. This review examines cutting-edge findings on important miRNAs—including miR-122, miR-34a, and miR-33—and their roles in NAFLD development through effects on fat metabolism, inflammation, and scarring. Insights into these molecular pathways could transform NAFLD management, helping meet the pressing need for non-invasive testing and targeted treatments.

Global Epidemiological Impact of PNPLA3 I148M on Liver Disease. 
Liver Int 2025; 45:e16123. Kozlitina J, Sookoian S.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39373119

The PNPLA3 -148M variant (rs738409) stands as the most important genetic risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), affecting disease progression across different populations. Its frequency varies worldwide—reaching about 50% in Latin America while only about 12% in Africa—contributing significantly to regional differences in MASLD prevalence and severity. Recent research reveals its wide-ranging effects, including interactions with obesity and immune-related characteristics, highlighting its broader metabolic significance. This review examines the latest evidence on PNPLA3 -148M's population-level impact, molecular mechanisms, and potential clinical uses, providing valuable insights for precision medicine approaches to liver disease.

Integrating PNPLA3 into clinical risk prediction. 
Liver Int 2025; 45:e16103. Chen VL, Vespasiani-Gentilucci U.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39282715

The genetic risk factor PNPLA3 -148M variant (rs738409) is considered one of the most significant genetic risk factor for metabolic associated steatotic liver disease (MASLD), though experts still debate its practical value in predicting risk. Recent research shows it may improve risk assessment in high-prevalence populations, especially when combined with intermediate Fibrosis-4 scores or conditions like type 2 diabetes. New findings also highlight its importance in predicting liver cancer, particularly in patients with cirrhosis, although its added value beyond existing clinical models needs further confirmation. This review examines how PNPLA3 genotyping could be incorporated into diagnostic and predictive protocols, addressing current limitations and opportunities for precision medicine in MASLD care.

Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. 
N Engl J Med 2024; 391:299-310. Loomba R, Hartman ML, Lawitz EJet al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=38856224

Metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver condition connected to obesity and type 2 diabetes, represents a growing worldwide health challenge with few treatment options. Recent progress with dual GIP and GLP-1 receptor agonists like tirzepatide shows potential for improving both metabolic and liver-related outcomes. This phase 2 trial evaluates tirzepatide's effectiveness and safety in patients with MASH and moderate-to-severe scarring, showing notable improvements in tissue healing and fibrosis reduction. As MASH becomes more common and continues to cause serious liver complications, these results provide valuable insights into possible drug treatments that deserve further investigation in larger, longer-term studies.

EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). 
J Hepatol 2024; 81:492-542. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=38851997

The 2024 joint European clinical practice guidelines from liver, diabetes, and obesity associations provide a thorough update on diagnosing, assessing risk, and managing MASLD, focusing on evidence-based approaches to reduce liver-related and cardiometabolic complications. Recent progress, including the approval of targeted treatments like resmetirom, highlights the importance of early detection and personalized care strategies. This guideline combines current evidence to improve clinical outcomes and tackle the expanding public health impact of MASLD.