Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: November 2025 updates to AASLD Practice Guidance.

FDA-indication and Practice Recommendation: The Wegovy formulation, whose main ingredient is semaglutide, received accelerated FDA approval in August 2025 for treating MASH with moderate-to-advanced fibrosis (consistent with stages F2-F3 fibrosis), based on interim results of the phase 3 ESSENCE trial where 72 weeks of 2.4 mg/week subcutaneous injection resulted in achievement of both primary histologic endpoints: (1) resolution of MASH without worsening of fibrosis (62.9% vs. 34.3% placebo, p <0.001) and (2) ≥1 stage reduction in liver fibrosis without worsening of MASH (36.8% vs. 22.4% placebo, p <0.001); final approval awaits long-term outcomes.

FDA批准和实践建议：Wegovy配方的主要成分是semaglutide，于2025年8月获得了FDA的加速批准，用于治疗中度至重度纤维化的MASH（与F2-F3阶段纤维化一致），这是基于第三阶段ESSENCE试验的中期结果，其中每周2.4 mg皮下注射72周，实现了两个主要组织学终点：(1)在不加重纤维化的情况下解决MASH（62.9%对34.3%安慰剂，p<0.001）和(2)在不加重MASH的情况下，肝脏纤维化减少≥1级（36.8%对22.4%安慰剂，p<0.001）；最终批准有待长期结果。

Patient Selection: Candidates should have MASH with stage 2-3 fibrosis, identified using non-invasive tests (NITs) such as VCTE (8-15 kPa), MRE (3.1-4.4 kPa), or ELF (9.2-10.5), rather than liver biopsy, which is impractical and unnecessary for most patients.

患者选择：候选人应有2-3期纤维化的MASH，通过非侵入性测试（NITs）如VCTE（8-15 kPa）、MRE（3.1-4.4 kPa）或ELF（9.2-10.5）来识别，而不是肝活检，这对大多数患者来说不切实际且没有必要。

In those with VCTE (15-20 kPa), MRE (4.4-5 kPa), or ELF (10.5-11.3), an individualized decision to treat should be based on exclusion of cirrhosis with another confirmatory NIT, or cross-sectional imaging excluding nodular-appearing liver contour and signs of portal hypertension, or a platelet count of <150,000/mm 3 .

对于VCTE（15-20 kPa）、MRE（4.4-5 kPa）或ELF（10.5-11.3）的患者，治疗的个体化决策应基于排除肝硬化，通过另一项确认性的NIT，或排除结节状肝轮廓和门静脉高压迹象的横断面成像，或血小板计数<150,000/mm3。

While semaglutide is not approved to treat patients with MASH cirrhosis (VCTE >20 kPa, MRE>5.0 kPa, ELF>11.3, and/or evidence of portal hypertension), those with compensated cirrhosis who are receiving semaglutide for another FDA-approved indication should be monitored carefully.

尽管Semaglutide尚未被批准用于治疗MASH肝硬化（VCTE>20 kPa，MRE>5.0 kPa，ELF>11.3和/或门静脉高压的证据）患者，但那些因其他FDA批准的适应症而接受Semaglutide治疗的代偿性肝硬化患者应仔细监测。

Monitoring and Safety: Semaglutide showed a favorable hepatic safety profile in the ESSENCE trial, with no discontinuations due to liver enzyme elevations.

监测与安全性：在ESSENCE试验中，Semaglutide显示出良好的肝脏安全性，没有因肝酶升高而停药的情况。

Routine hepatic panels are recommended only as clinically indicated.

仅在临床指示的情况下推荐进行常规肝功能检查。

The most common adverse events were gastrointestinal (nausea, diarrhea, constipation, vomiting), generally mild and transient; patient education and dose titration help improve tolerance.

最常见的不良事件为胃肠道相关症状（恶心、腹泻、便秘、呕吐），通常程度较轻且为暂时性；通过患者教育和剂量滴定可改善耐受性。

Clinicians should monitor for rare but serious risks, including acute kidney injury (from dehydration), symptomatic gallbladder disease, pancreatitis, thyroid C-cell tumors, retinopathy progression, and lean mass loss.

临床医生应监测包括急性肾损伤（由脱水引起）、有症状的胆囊疾病、胰腺炎、甲状腺C细胞肿瘤、视网膜病变进展和瘦体重减少等罕见但严重的风险。

Treatment Response and Concomitant Therapy: Lifestyle modification remains the cornerstone of MASLD/MASH management alongside semaglutide.

治疗反应和联合治疗：生活方式的改变仍然是MASLD/MASH管理的基石，与semaglutide联合使用。

Combination use of resmetirom with semaglutide 2.4mg/week has not been studied.

尚未研究将resmetirom与每周2.4mg的semaglutide联合使用的疗效。

While no NITs reliably predict histologic response at the individual patient level, reductions from baseline to 72 weeks of treatment suggest significant improvement in MASH resolution (ALT ≥17 U/L or ≥20%) and fibrosis improvement (VCTE LSM ≥30%; MRE LSM ≥20%; ELF ≥0.5).

虽然没有可靠的NITs能够在个体患者层面预测组织学反应，但从基线到72周治疗期间的降低表明MASH消解（ALT≥17 U/L或≥20%）和纤维化改善（VCTE LSM≥30%；MRE LSM≥20%；ELF≥0.5）有显著改善。

Non-response may be suspected if ALT or NITs worsen.

如果ALT或NITs恶化，可能怀疑无反应。

The benefit is uncertain if a suboptimal response occurs, and may require an individualized approach and further follow-up.

如果出现次优反应，其益处不确定，可能需要个体化的方法和进一步的随访。