2025年11月7日，美国肝病研究学会(AASLD)年度大会 The Liver Meeting 2025 在美国•华盛顿会议中心正式召开。会议汇聚肝病研究领域的最新科研硕果与前沿探索方向，为全球参会者精心构筑一个深化肝病理论认知、拓展专业视野边界的学术交流殿堂。

为助力广大读者精准捕捉会议的学术精髓，及时洞悉领域前沿动态，肝胆相照平台特别甄选会议摘要中的热点研究内容，本篇专题报道聚焦“肝硬化”这一关键领域，为广大同仁提供最新研究进展。

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与去甲肾上腺素相比，特利加压素可降低失代偿期肝硬化患者的死亡率和肝脏相关并发症发生率：多国回顾性分析

THE USE OF TERLIPRESSIN IS ASSOCIATED WITH LOWER MORTALITY AND LIVER-RELATED COMPLICATION EVENTS COMPARED TO THE USE OF NOREPINEPHRINE IN PATIENTS WITH DECOMPENSATED CIRRHOSIS: A MULTINATIONAL ANALYSIS

作者：Christina Lee¹、Donghyun Ko²、Do Han Kim³、Paul Kroner⁴、Raffi Karagozian¹

¹Tufts Medical Center, ²Yale New Haven Health/Bridgeport Hospital, ³Mount Sinai Morningside & West Hospital, ⁴Riverside Health System

背景

 在失代偿期肝硬化患者中，特利加压素通过诱导内脏血管收缩、降低门静脉高压并改善肾脏灌注，相较去甲肾上腺素（NE）在改善肝肾综合征（HRS）方面更具疗效。既往研究提示，特利加压素还可减少腹水和静脉曲张出血，但对其他并发症的影响仍存在争议。本研究旨在基于多国患者队列，比较特利加压素与去甲肾上腺素在失代偿性肝硬化多种并发症中的作用差异。

Background：Terlipressin improves hepatorenal syndrome (HRS) outcomes more effectively than norepinephrine (NE) in patients with decompensated cirrhosis by inducing splanchnic vasoconstriction, reducing portal hypertension, and improving renal perfusion. Previous data also suggest terlipressin may decrease ascites and variceal bleeding in these patients; however, evidence regarding other complications remains inconsistent. This study aimed to investigate the broader impact of terlipressin versus NE on various complications of decompensated cirrhosis in a multinational cohort.

方法

本研究为回顾性队列分析，纳入TriNetX全球数据库中确诊的958例失代偿性肝硬化患者。根据治疗方案分为特利加压素组（n=479）和去甲肾上腺素组（n=479），两组通过倾向评分匹配，平衡年龄、性别、种族/民族、合并症（包括但不限于食管或胃静脉曲张、慢性肝功能衰竭、HRS、肝肺综合征、腹水、自发性细菌性腹膜炎、肝移植状态、高血压、2型糖尿病、慢性肾脏病）、药物使用（卡维地洛）及MELD评分相关实验室参数。匹配后，评估患者在30天和90天内的主要临床结局，包括全因死亡率、肝功能失代偿、主要不良肝脏事件（MALO）、腹水、肝性脑病（HE）、静脉曲张出血、SBP、肝移植及穿刺放液。采用Cox比例风险模型计算风险比（HR）。

Methods：This retrospective cohort study included 958 patients with decompensated cirrhosis identified in the TriNetX global database. A total of 479 patients treated with terlipressin and 479 treated with NE were matched based on age, sex, race/ethnicity, comorbidities (including but not limited to esophageal/gastric varices, chronic hepatic failure, HRS, hepatopulmonary syndrome, ascites, spontaneous bacterial peritonitis, liver transplant status, hypertension, diabetes mellitus type II, chronic kidney disease), medications (carvedilol), and MELD-related laboratory parameters. After matching demographic and clinical features, primary clinical outcomes were assessed at 30 and 90 days: all-cause mortality, hepatic decompensation, major adverse liver outcomes (MALO), ascites, hepatic encephalopathy (HE), variceal bleeding, spontaneous bacterial peritonitis (SBP), liver transplantation, and paracentesis (Table 1). The Cox proportional hazards model was applied to calculate hazard ratios (HRs) comparing terlipressin and NE.

 结果

与去甲肾上腺素相比，特利加压素治疗在30天及90天内均显著降低了全因死亡率（HR分别为0.531和0.589）、肝性脑病发生率（HR分别为0.594和0.721）及穿刺放液频率（HR分别为0.527和0.545）。此外，特利加压素组在腹水发生率方面亦较低（30天HR 0.920；90天HR 0.934），但差异无统计学意义。

Results：Within both 30 and 90 days after treatment, terlipressin use was associated with a statistically significant reduction in all-cause mortality (HR 0.531 and 0.589), hepatic encephalopathy (HR 0.594 and 0.721), and paracentesis frequency (HR 0.527 and 0.545), respectively. Terlipressin also reduced ascites incidence at both 30 and 90 days (HR 0.920 and 0.934), though these differences were not statistically significant.

结论

本多国回顾性研究显示，特利加压素较去甲肾上腺素在失代偿性肝硬化患者中显著改善临床结局，表现为更低的死亡率、更少的肝性脑病发作以及更少的穿刺放液需求。穿刺放液频率的下降可能与腹水控制改善有关。总体而言，特利加压素可减少多数失代偿性肝硬化相关并发症，支持其作为此类患者中优于去甲肾上腺素的首选血管加压药物。

Conclusion：This multinational retrospective study demonstrated that terlipressin significantly improved clinical outcomes in patients with decompensated cirrhosis, showing lower all-cause mortality, fewer episodes of hepatic encephalopathy, and reduced need for paracentesis compared to norepinephrine. The decreased requirement for paracentesis likely reflects improved ascites control. Overall, terlipressin reduced the majority of complications related to decompensated cirrhosis, supporting its preferential use over norepinephrine in this patient population.

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肝硬化患者中 ACEI/ARB 的安全性

The Safety of ACEI/ARBs in Patients with Cirrhosis

作者：Nirmal Desai¹，Christine Son¹，Vineela Appalaneni¹，Irena Helenowski¹，Jonah Rubin¹

¹Loyola University Medical Center

研究背景

美国肝病学会（AASLD）建议在合并腹水的失代偿性肝硬化患者中避免使用血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）。然而，最新研究显示，在代偿期肝硬化患者中，ACEI/ARB 的使用与肝相关不良事件风险降低有关。本研究旨在通过回顾性队列研究，评估 ACEI/ARB 在代偿期及失代偿期肝硬化患者中的潜在益处与风险。

Background：The AASLD recommends against using ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in patients with decompensated cirrhosis with ascites. However, recently published data suggest that ACEI/ARB use is associated with a lower risk of liver-related adverse events in patients with compensated cirrhosis. We aimed to conduct a retrospective cohort study to assess the potential benefits and harms associated with ACEI/ARB use in both compensated and decompensated cirrhosis.

研究方法

这是一项单中心回顾性队列研究，比较 ACEI/ARB 使用组与未使用组的结局。主要研究终点为无移植生存率（TFS）和总体生存率（OS）；次要终点包括失代偿事件发生率、肾功能及住院次数。通过 1:1 倾向评分匹配（propensity score matching）控制混杂因素。连续变量采用 Wilcoxon 秩和检验，分类变量采用 Fisher 精确检验。生存分析采用 Kaplan-Meier 法，多变量 Cox 回归模型用于评估 OS 和 TFS 的复合终点。

Methods：This was a single-center retrospective cohort study evaluating the effect of ACEI/ARB exposure compared to a non-exposed cohort. The primary outcomes were transplant-free survival (TFS) and overall survival (OS). Secondary outcomes included the rate of decompensation, renal function, and hospitalizations. Demographic and clinical variables were 1:1 propensity score matched to minimize confounding. Significant differences were assessed using the Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. Kaplan–Meier estimates were used for survival analysis, and a multivariable Cox regression model was applied to evaluate the composite outcome of OS and TFS.

 研究结果

倾向评分匹配后，ACEI/ARB 组与对照组各纳入 300 例患者。单变量分析显示，ACEI/ARB 组的无移植生存率显著提高（P = 0.003），失代偿事件显著减少（P < 0.001）。多变量 Cox 回归分析进一步证实，ACEI/ARB 组的 OS/TFS 显著改善（HR 0.65；95% CI, 0.49–0.87）。

代偿期肝硬化患者亚组分析显示，ACEI/ARB 组失代偿事件较少（P = 0.005）；然而，Cox 回归分析显示差异无统计学意义（HR 0.81；95% CI，0.46–1.41）。在失代偿期肝硬化患者中，ACEI/ARB 组的 OS/TFS 显著改善（HR 0.61；95% CI，0.43–0.88）。在腹水患者中，ACEI/ARB组的OS/TFS 无显著差异（HR 0.72；95% CI，0.48–1.07）。

Results：After propensity score matching, 300 patients were included in both the ACEI/ARB cohort and the control group. Patients in the ACEI/ARB group had significantly higher transplant-free survival (p = .003) and fewer decompensation events (p < .001) in univariate analysis. Multivariable Cox regression demonstrated a significant improvement in OS/TFS in the ACEI/ARB group (HR 0.65; 95% CI, 0.49–0.87).

Subset analysis of patients with compensated cirrhosis revealed fewer decompensation events in the ACEI/ARB group (p = .005); however, Cox regression analysis showed no significant difference (HR 0.81; 95% CI, 0.46–1.41). In patients with decompensated cirrhosis, there was a significant improvement in OS/TFS in the ACEI/ARB group (HR 0.61; 95% CI, 0.43–0.88). Among patients with ascites, ACEI/ARB exposure showed no significant difference in OS/TFS (HR 0.72; 95% CI, 0.48–1.07).

研究结论

在所有肝硬化患者中，ACEI/ARB 的使用与无移植生存率及总体生存率的显著改善相关。在伴有腹水的失代偿期肝硬化患者中，ACEI/ARB 并未增加不良结局风险。因此，ACEI/ARB 在肝硬化患者中使用是安全的，并可能带来潜在益处。

Conclusion：ACEI/ARB use was associated with a significant improvement in transplant-free and overall survival among all cirrhotic patients. In those with decompensated cirrhosis and ascites, ACEI/ARB exposure did not worsen outcomes. Therefore, ACEI/ARB therapy appears to be safe for use in cirrhotic patients and may provide clinical benefits.

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失代偿性肝硬化患者再代偿的发生率及临床结局：系统综述与Meta分析

Prevalence and Clinical Outcomes of Recompensation in Decompensated Cirrhosis: A Systematic Review and Meta-Analysis

作者：Xin En Goh¹、May Xuan Goh²、Vincent L. Chen³、Guadalupe Garcia-Tsao⁴、Juan Gonzalez-Abraldes⁵、Yu Jun Wong⁶

¹Yong Loo Lin School of Medicine, National University of Singapore, Singapore; ²Yong Loo Lin School of Medicine, NUS; ³Division of Gastroenterology & Hepatology, University of Michigan, Ann Arbor, Michigan, USA; ⁴p of Digestive Disease, Yale University School of Medicine, New Haven, USA; ⁵Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Canada; ⁶Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore

背景

在有效的病因学治疗后，失代偿性肝硬化患者可能出现“再代偿”（recompensation）。然而，获得再代偿患者的发生率及其临床结局尚不明确。本研究进行了一项系统综述与Meta分析，以评估失代偿性肝硬化患者达到再代偿的比例及其临床结局。

Background：Patients with decompensated cirrhosis may experience recompensation following effective etiological cure. However, the prevalence and clinical outcomes of decompensated patients who achieve recompensation remain unclear. We performed a systematic review and meta-analysis to determine the prevalence and clinical outcomes in decompensated patients who achieved recompensation.

方法

我们系统检索了PubMed和EMBASE数据库，纳入所有关于失代偿性肝硬化患者实现再代偿的研究。分析了再代偿的发生率及临床结局（尤其是死亡和肝细胞癌），并与未实现再代偿的患者进行比较。主要结局为再代偿的合并发生率，次要结局包括HCC发生率和死亡率。为提高预后分析的精确性，我们采用了严格的再代偿定义：需满足病因学治愈，且一年内无肝功能失代偿事件，并至少随访两年。

Methods：We systematically searched PubMed and EMBASE from inception to include all studies of patients with decompensated cirrhosis who achieved recompensation. We evaluated the prevalence of clinical outcomes—specifically death and hepatocellular carcinoma (HCC)—and compared them with patients who did not achieve recompensation. The primary outcome was the pooled prevalence of recompensation; secondary outcomes included HCC occurrence and death. To improve the precision of our prognostic analysis, we applied a strict definition of recompensation, requiring both etiological cure and absence of liver decompensating events for one year, with a minimum follow-up of two years.

 结果

共纳入26项研究，包含8261例失代偿性肝硬化患者。总体再代偿的合并发生率为32%（95% CI：24–41%）。其中，病毒性肝硬化患者的再代偿率最高（46%，95% CI：37–55%），其次为酒精性肝硬化（21%，95% CI：15–28%）和其他病因（15%，95% CI：2–37%）。

在中位MELD评分较低（<15）及样本量较小的研究中，再代偿发生率更高（P<0.05）；而发表类型和偏倚风险对结果无显著影响。 在再代偿后中位随访2–8年期间，再代偿患者的HCC发生风险（OR：0.60，95% CI：0.40–0.91，6项研究）及死亡风险（OR：0.34，95% CI：0.19–0.61，5项研究）均显著低于未再代偿者。使用标准Baveno-VII标准与扩展标准的研究间，其临床获益无显著差异。尽管实现了再代偿，仍有13%（95% CI：5–23%）的患者再次发生失代偿事件。

Results：A total of 26 studies encompassing 8,261 patients with decompensated cirrhosis were analyzed. The overall pooled prevalence of recompensation was 32% (95% CI: 24–41%). Recompensation prevalence was highest among viral-related cirrhosis (46%, 95% CI: 37–55%), followed by alcohol-related cirrhosis (21%, 95% CI: 15–28%) and other etiologies (15%, 95% CI: 2–37%). The pooled prevalence of recompensation was also higher in studies with lower median MELD scores (<15) and smaller sample sizes (p<0.05), but was not influenced by publication type or risk of bias. Over a median follow-up ranging from 2 to 8 years after recompensation, patients achieving recompensation had lower odds of HCC occurrence (OR: 0.60, 95% CI: 0.40–0.91, 6 studies) and death (OR: 0.34, 95% CI: 0.19–0.61, 5 studies). The clinical benefit of recompensation did not significantly differ between studies using the standard versus the expanded Baveno-VII criteria. Despite achieving recompensation, further decompensating events occurred in 13% (95% CI: 5–23%).

结论

在接受病因学控制的失代偿性肝硬化患者中，约有四分之一可实现再代偿。再代偿的实现与死亡风险及可能的HCC风险显著降低相关，提示“再代偿”可作为评估失代偿性肝硬化患者病因学治疗效果的重要临床终点。

Conclusion： Recompensation occurred in approximately one-quarter of decompensated cirrhosis patients who achieved etiological control. Recompensation was associated with a lower risk of death and possibly HCC, suggesting that recompensation could represent a clinically meaningful endpoint in patients with decompensated cirrhosis undergoing etiological treatment.

 

Tags： 2025 AASLD | 肝硬化治疗的最新热点与挑战