NON-ALCOHOLIC fatty liver disease (NAFLD), now reclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), represents a growing global health concern. Often linked to obesity, diabetes, and dyslipidaemia, MASLD is the hepatic manifestation of metabolic syndrome. Its prevalence has soared, with Japanese data showing an increase from 12.9% in 1994 to 34.7% in 2000. While lifestyle modifications like diet and exercise are cornerstones of treatment, effective pharmacological options remain elusive.
Fibrates, specifically fenofibrate, have shown promise in managing MASLD when accompanied by hypertriglyceridaemia. However, limitations such as small sample sizes in studies and a lack of consensus on their efficacy have restricted widespread adoption. Enter pemafibrate, a selective PPARα modulator (SPPARMα) approved in Japan, Thailand, Singapore, and Malaysia, which offers a more targeted mechanism of action with potentially greater benefits.
Clinical trials suggest that pemafibrate improves liver function markers, reduces triglycerides, and enhances HDL-C levels. Notably, in a MASLD/MASH mouse model, pemafibrate reduced liver damage and improved markers of inflammation and fibrosis. Additionally, a randomised controlled trial demonstrated significant reductions in liver stiffness and ALT levels, indicating its potential as a therapeutic option.
This study examined the efficacy and safety of pemafibrate in 360 patients with MASLD and hypertriglyceridaemia. It highlighted the drug’s role in enhancing fatty acid β-oxidation and reducing triglyceride accumulation in the liver. Importantly, pemafibrate’s safety profile stood out, particularly for long-term use, even in patients with renal dysfunction.
While the study’s strengths include its multicentre approach and large sample size, it faced limitations such as an open-label design and the absence of liver biopsies. Despite these challenges, it lays the groundwork for future investigations, including histological assessments and evaluations of long-term outcomes.
MASLD/MASH presents a complex interplay of metabolic pathways. Pemafibrate shows significant promise in addressing this condition, offering hope for patients where effective treatment options remain scarce. Further research will determine its full potential as a transformative therapy for MASLD/MASH.
Reference
Iwaki M et al. Pemafibrate for treating MASLD complicated by hypertriglyceridaemia: a multicentre, open-label, randomised controlled trial study protocol. BMJ Open. 2024;14(11):e088862.
