A Markov Model Unveiling the Impact of Resmetirom on the Natural History of MASLD Patients: A Sistematic Review and Meta-Analysis

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-03-11 DOI:10.1111/liv.70056

Grazia Pennisi, Gabriele Di Maria, Marco Enea, Marco Vaccaro, Ciro Celsa, Michela Antonucci, Giacinta Ciancimino, Carlo Ciccioli, Giuseppe Infantino, Claudia La Mantia, Adele Tulone, Vito Di Marco, Calogero Cammà, Salvatore Petta

{"title":"A Markov Model Unveiling the Impact of Resmetirom on the Natural History of MASLD Patients: A Sistematic Review and Meta-Analysis","authors":"Grazia Pennisi, Gabriele Di Maria, Marco Enea, Marco Vaccaro, Ciro Celsa, Michela Antonucci, Giacinta Ciancimino, Carlo Ciccioli, Giuseppe Infantino, Claudia La Mantia, Adele Tulone, Vito Di Marco, Calogero Cammà, Salvatore Petta","doi":"10.1111/liv.70056","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aim</h3>\n \n <p>The MAESTRO-NASH phase 3 trial reported that a 52-week treatment of Resmetirom is effective in improving fibrosis and metabolic dysfunction-associated steatohepatitis (MASH) in patients with MASH and F2 or F3 fibrosis, while data on the impact on 5-year and long-term clinical outcomes are still lacking. We simulated the transition probabilities of disease progression in MASLD patients with F2 or F3 fibrosis and the effect of Resmetirom treatment on clinical outcomes.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A meta-analysis of literature data formed transition matrices for fibrosis stages and complications, defined as compensated (CC) and decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and mortality—liver-related mortality (LR-M), cardiovascular mortality (CV-M) and extra-hepatic cancer mortality (EHC-M). Markov model was developed to depict the F2 and F3 fibrosis stage progression towards the complications and to evaluate the effect of Resmetirom treatment on the natural history of MASLD.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We estimated the 5-year probability of Resmetirom-treated and untreated MASLD patients with baseline F2 fibrosis of developing CC (5.16% vs. 6.82%, respectively), DC (0.25% vs. 0.3%, respectively), HCC (0.25% vs. 0.32%, respectively) and mortality (0.15% vs. 0.16% for LR-M; 1.02% vs. 1.1% for CV-M; 1.07% vs. 1.2% for EHC-M, respectively). Similarly, we estimated the five-year probability of Resmetirom-treated and untreated MASLD patients with baseline F3 fibrosis of developing CC (17.12% vs. 21.34%, respectively), DC(1.1% vs. 1.47%, respectively), HCC (1.21% vs. 1.73%, respectively) and mortality (0.59% vs. 0.91% for LR-M, 1.92% vs. 2.14% for CV-M and 1.04% vs. 1.14% for EHC-M, respectively). Life Years Gained (LYG) of Resmetirom-treated patients were 0.45 and 0.63 in MASLD patients with F2 and F3 fibrosis, respectively, and the model was sensitive to changes in Resmetirom efficacy and transition probabilities.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Resmetirom decreases the 5-year and lifetime Markov-model estimated risk of CC, DC, HCC and liver-related mortality in patients with MASLD and F2 or F3 fibrosis.</p>\n </section>\n </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 4","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70056","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.70056","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and Aim

The MAESTRO-NASH phase 3 trial reported that a 52-week treatment of Resmetirom is effective in improving fibrosis and metabolic dysfunction-associated steatohepatitis (MASH) in patients with MASH and F2 or F3 fibrosis, while data on the impact on 5-year and long-term clinical outcomes are still lacking. We simulated the transition probabilities of disease progression in MASLD patients with F2 or F3 fibrosis and the effect of Resmetirom treatment on clinical outcomes.

Methods

A meta-analysis of literature data formed transition matrices for fibrosis stages and complications, defined as compensated (CC) and decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and mortality—liver-related mortality (LR-M), cardiovascular mortality (CV-M) and extra-hepatic cancer mortality (EHC-M). Markov model was developed to depict the F2 and F3 fibrosis stage progression towards the complications and to evaluate the effect of Resmetirom treatment on the natural history of MASLD.

Results

We estimated the 5-year probability of Resmetirom-treated and untreated MASLD patients with baseline F2 fibrosis of developing CC (5.16% vs. 6.82%, respectively), DC (0.25% vs. 0.3%, respectively), HCC (0.25% vs. 0.32%, respectively) and mortality (0.15% vs. 0.16% for LR-M; 1.02% vs. 1.1% for CV-M; 1.07% vs. 1.2% for EHC-M, respectively). Similarly, we estimated the five-year probability of Resmetirom-treated and untreated MASLD patients with baseline F3 fibrosis of developing CC (17.12% vs. 21.34%, respectively), DC(1.1% vs. 1.47%, respectively), HCC (1.21% vs. 1.73%, respectively) and mortality (0.59% vs. 0.91% for LR-M, 1.92% vs. 2.14% for CV-M and 1.04% vs. 1.14% for EHC-M, respectively). Life Years Gained (LYG) of Resmetirom-treated patients were 0.45 and 0.63 in MASLD patients with F2 and F3 fibrosis, respectively, and the model was sensitive to changes in Resmetirom efficacy and transition probabilities.

Conclusions

Resmetirom decreases the 5-year and lifetime Markov-model estimated risk of CC, DC, HCC and liver-related mortality in patients with MASLD and F2 or F3 fibrosis.

Abstract Image

查看原文本刊更多论文

揭示雷司替罗对MASLD患者自然史影响的马尔可夫模型：系统回顾和荟萃分析

背景和目的MAESTRO-NASH 3期试验报道，52周的瑞斯替罗姆治疗可有效改善MASH和F2或F3纤维化患者的纤维化和代谢功能障碍相关脂肪性肝炎（MASH），但对5年和长期临床结果的影响数据仍然缺乏。我们模拟了伴有F2或F3纤维化的MASLD患者疾病进展的转移概率，以及瑞司替康治疗对临床结果的影响。方法对文献数据进行荟萃分析，形成纤维化分期和并发症的过渡矩阵，定义为代偿性（CC）和失代偿性肝硬化（DC）、肝细胞癌（HCC）和死亡率-肝脏相关死亡率（LR-M）、心血管死亡率（CV-M）和肝癌外死亡率（EHC-M）。建立马尔可夫模型，描述F2和F3纤维化阶段向并发症的进展，并评估雷司替龙治疗对MASLD自然病程的影响。结果：我们估计了接受瑞司替龙治疗和未接受治疗的基线F2纤维化MASLD患者发生CC（分别为5.16%对6.82%）、DC（分别为0.25%对0.3%）、HCC（分别为0.25%对0.32%）和死亡率(rr - m为0.15%对0.16%；1.02% vs. CV-M 1.1%；EHC-M分别为1.07%和1.2%)。同样，我们估计了接受瑞司替龙治疗和未接受治疗的基线F3纤维化MASLD患者发生CC（分别为17.12%对21.34%）、DC（分别为1.1%对1.47%）、HCC（分别为1.21%对1.73%）和死亡率的5年概率（LR-M为0.59%对0.91%，CV-M为1.92%对2.14%，EHC-M为1.04%对1.14%）。在F2和F3纤维化的MASLD患者中，雷司替龙治疗的患者获得的生命年（LYG）分别为0.45和0.63，该模型对雷司替龙疗效和过渡概率的变化敏感。雷司替罗降低了MASLD合并F2或F3级纤维化患者的5年和终生markov模型估计的CC、DC、HCC风险和肝脏相关死亡率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.