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肝静脉压力梯度可预测 MASLD 患者肝性失代偿和与肝脏相关死亡率的风险。

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium; Laboratory of Experimental Medicine and Pediatrics (LEMP), Division of Gastroenterology-Hepatology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.

出版信息

J Hepatol. 2024 Nov;81(5):827-836. doi: 10.1016/j.jhep.2024.05.033. Epub 2024 May 31.

DOI:10.1016/j.jhep.2024.05.033
PMID:38823501
Abstract

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD).

METHODS

This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest.

RESULTS

A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001).

CONCLUSION

HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both.

IMPACT AND IMPLICATIONS

While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

摘要

背景与目的

代谢相关脂肪性肝病(MAFLD)相关性肝失代偿性脂肪性肝病(MASLD-cACLD)是导致晚期慢性肝病(ACLD)的主要原因。门脉高压是导致肝失代偿的主要原因,最好通过肝静脉压力梯度(HVPG)测量来诊断。在此,我们研究 HVPG 在 MASLD-cACLD 中的预后价值。

方法

这项欧洲多中心研究纳入了基线 HVPG 存在的 MASLD-cACLD 患者。肝性失代偿(静脉曲张出血/腹水/肝性脑病)和肝脏相关死亡率是主要研究终点。

结果

共纳入 340 例 MASLD-cACLD 患者(56.2%为男性;中位年龄 62 [55-68] 岁,中位 MELD 8 [7-9],71.2%患有糖尿病)。209 例患者存在临床显著的门脉高压(CSPH:即 HVPG≥10mmHg)。在中位随访 41.5(27.5-65.8)个月后,65 例患者出现肝性失代偿,其中 MASLD-cACLD 合并 CSPH 的患者在 2 年(2Y)和 5 年(5Y)的累积发生率分别为 10.0%和 30.7%,而无 CSPH 的患者分别为 2.4%和 9.4%。无 CSPH 时不会发生静脉曲张出血。CSPH(亚分布危险比[SHR]5.13;p<0.001)与肝失代偿风险增加相关,多变量模型中 HVPG 仍然是独立的危险因素(每 mmHg 调整后的 SHR:1.12,p<0.001)。37 例患者发生肝脏相关死亡,CSPH 患者的累积发生率分别为 2Y 时 3.3%和 5Y 时 21.4%。无 CSPH 时,5Y 时的发生率为 0.8%。因此,较高的 HVPG 也与肝脏相关死亡的风险增加独立相关(每 mmHg 调整后的 SHR:1.20,p<0.001)。

结论

HVPG 测量在 MASLD-cACLD 中具有较高的预后价值。在无 CSPH 的 MASLD-cACLD 患者中,短期内发生失代偿的风险非常低,肝脏相关死亡率罕见,而 CSPH 的存在则显著增加了两者的风险。

影响和意义

虽然代谢相关脂肪性肝病(MAFLD)引起的代偿性晚期慢性肝病(cACLD)的发病率在全球范围内呈上升趋势,但对于临床显著门脉高压(CSPH)对 MASLD-cACLD 中肝脏相关事件风险的影响仍知之甚少。基于这项纳入 340 例 MASLD-cACLD 患者的欧洲多中心研究,我们可以发现,HVPG 值的升高和特别是 CSPH 的存在与首次肝失代偿和肝脏相关死亡率的风险显著增加相关。相比之下,无 CSPH 的 MASLD-cACLD 患者在短期内发生肝失代偿的发生率较低,肝脏相关死亡率仍可忽略不计。因此,HVPG 测量可为 MASLD-cACLD 的个体化风险分层提供重要的预后信息,并可能有助于研究 MASLD 的新的有前途的治疗方法。

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