Resmetirom is considered a comprehensive clinical
development for MASH – Karim Kammeruddin
PSIM’s 6th International Conference
KARACHI: MAFLD is the most common liver disease and it is also the second common reason for liver transplant. It has emerged as the leading indication for transplant in people under the age of fifty years and an important predisposing factor for primary liver cancer and it can occur even without cirrhosis. Majority of the people with MAFLD have normal liver enzymes. Management of MASLD needs a multidisciplinary approach and Resmetirom is considered comprehensive clinical development in MASH. These views were expressed by Prof.Karim Kmmeruddin, Prof. of Medicine at Baqai Medical University. He was making a presentation on “Resmetirom- a breakthrough for MASLD/MASH” in one of the scientific sessions during the recently concluded 6th International Conference of Pakistan Society of Internal Medicine held at Karachi from April 17th to April 20th 2025.
Prof. Karim Kammeruddin
Prevalence of MAFLD/NAFLD in various countries of the world ranges between 20-30%. He also discussed the cardio metabolic risk factors in MASLD. About 25% of normal liver suffer from isolated steatosis of which 20-25% have no fibrosis, a few develop Hepatocellular carcinoma while 30% develop fibrosis. Out of this up to 38% develop cirrhosis and again about 12% of these will develop Hepatocellular carcinoma, he remarked. Metabolomic changes, he pointed out, predict MASLD and stratify risk. Saturated and monounsaturated fatty acids, Glycolipids, free cholesterol increases wile polysaturated fatty acids and secondary bile acids decrease. The occurrence of co-morbidities increases with the progression from MASLD to MASH.
Speaking about screening for CKM syndrome, he suggested annual screening for overweight and obesity using age and sex specific CDC growth Charts, mental and behavioral health screening, annual Metabolomics changes blood pressure checkup, in case of positive family history of HLD start screening besides screening for glucose intolerance and monitor ALT. Factors associated with high risk of HCC occurrence of MASLD include presence and duration of Type-2 diabetes, obesity or both, older age, smoking and concurrent alcohol consumption. Patients suffering from MASLD, Prof. Karim Kammeruddin stated require multidisciplinary approach to management.
Prof. Zafar Chadhury VC Faisalabad Medical University alongwith Prof. Iftikhar Arain and Dr. M. Saleem Khan charing a scientific session durning PISM Conference.
He also discussed Life style management for MASLD and then highlighted. the safety and efficacy of Resmetirom and spoke about its pharmacokinetics in detail. It achieves plasma concentration within two to four hours after administration and its half-life is four and half hour. It ensures 99% plasma protein binding, about 67% excretion is via feces and 23% through urine. It is metabolized by liver and has no meal dependency. He also referred to the selection of patients for Resmetirom therapy like those suffering from MASLD. Studies have proved its safety and efficacy during twelve months of treatment with Resmetirom. Phase-III study published in New England Journal of Medicine showed that Resmetirom treated patients showed either MASH resolution of improvement in fibrosis. It also showed about 47% reduction in non-invasive test results. Patients on Resmetirom therapy also achieved 26% fibrosis reversal and no fibrosis progression. He also highlighted the drug interactions with some other medications.
Talking about the contraindications for the use of Resmetirom therapy he mentioned sever liver disease, pregnancy and lactation, strong CYP2CB inhibitors while its use should also be avoided in patients with decompensated cirrhosis. He also discussed the combined Resmetirom and GLP-Agonists approach to MASH treatment besides therapeutic landscape of metabolic dysfunction associated steatohepatitis.
