MASH clinical trials and drugs pipeline: An impending tsunami.

In the more advanced stage, metabolic dysfunction-associated steatohepatitis (MASH) may lead to fibrosis, a gateway to cirrhosis, liver cancer, and liver failure.

在更高级阶段，代谢功能障碍相关脂肪性肝炎（MASH）可能导致纤维化，这是肝硬化、肝癌和肝衰竭的门户。

Despite extensive research and exploration of various drug mechanisms, the anticipation for the inaugural approved drug to materialize by 2024 is palpable, marking a significant milestone.

尽管进行了广泛的研究和探索各种药物机制，但人们对于首个批准药物在2024年实现的期待是显而易见的，这标志着一个重要的里程碑。

Numerous pathways have been investigated for MASH treatment, exploring thyroid hormone receptors, glucagon-like peptides 1, peroxisome proliferator-activated receptors, and agents influencing hepatic steatosis synthesis, inflammatory pathways, genetic components, fibrosis mechanisms, and an array of other avenues.

已经探索了多种途径用于MASH（代谢相关脂肪性肝病）的治疗，包括研究甲状腺激素受体、胰高血糖素样肽1、过氧化物酶体增殖物激活受体，以及影响肝脂肪合成、炎症途径、遗传成分、纤维化机制和其他多种途径的药物。

Over time, key regulatory directions have crystallized, now manifesting in 2 primary endpoints under investigation: resolution of steatohepatitis without worsening fibrosis and/or improvement of fibrosis stage without worsening of steatohepatitis, especially used in phase 3 clinical trials, while alternative noninvasive endpoints are explored in phase 2 trials.

随着时间的推移，关键的监管方向已经明确，现在主要体现在两项正在研究的主要终点：在不加重纤维化的情况下解决脂肪性肝炎，和/或在不加重脂肪性肝炎的情况下改善纤维化阶段，特别是在III期临床试验中使用，而在II期试验中探索替代的非侵入性终点。

The prospect of proving efficacy in clinical trials opens doors to combination therapies, evaluating the ideal combination of drugs to yield comprehensive benefits, extending beyond the liver to other organs.

在临床试验中证明疗效的前景为联合疗法打开了大门，评估药物的理想组合以产生全面的益处，超越肝脏延伸到其他器官。

Certain combination drug trials are already underway.

目前，一些联合药物试验正在进行中。

In this review, we discuss the forefront of MASH drug research as of 2023/2024, illuminating mechanisms, outcomes, and future trajectories.

在本综述中，我们将讨论截至2023/2024年的MASH药物研究前沿，阐明其机制、结果和未来的发展方向。

Furthermore, we tackle the challenges confronting MASH trials and propose potential strategies for surmounting them.

此外，我们应对MASH试验面临的挑战，并提出可能的克服策略。