Improvement of Liver Fibrosis in Patients with MASLD Undergoing Pioglitazone Treatment: An Update

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as steatotic liver disease with at least one cardiometabolic risk factor, in the absence of harmful alcohol intake, and includes a spectrum of conditions. These range from isolated liver steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma. Patients with MASLD and type 2 diabetes are at increased risk of developing MASH and significant/advanced fibrosis. The severity of fibrosis is a key determinant of long-term prognosis in MASLD. The most recent AASLD and EASL-EASD-EASO Guidelines on the Management of MASLD recommend a step-by-step approach to identify patients at higher risk of fibrotic progression. Recent epidemiological trends highlight the socioeconomic impact of MASLD and MASH, particularly in middle- and low-income countries. Given the high cost of new targeted therapies, implementing effective treatment strategies in low-resource settings is essential in managing MASLD and MASH patients. Pioglitazone is an oral antidiabetic agent of the thiazolidinedione class that targets peroxisome proliferator-activated receptors activated by fatty acids and derivatives or pharmacological agonists and involved in lipid metabolism, cell differentiation, and inflammation. Pioglitazone treatment is a potential cost-effective option, particularly for low-resource settings. This review examines recent epidemiological trends in MASLD and MASH, outlines the mechanisms of action of pioglitazone with an emphasis on its role in improving liver fibrosis, and summarizes clinical studies on fibrosis evaluation during pioglitazone treatment. The literature search focused on English-language studies from the past two years in the PubMed database.