国际医讯 | 国外靠什么区分脓毒症相关性肝损伤or药物性肝损伤？

脓毒症相关性肝损伤（Sepsis-associated Liver Injury, SALI）在临床中具有高度复杂性，常与药物性肝损伤（DILI）表现相似，给及时准确的诊断带来了极大挑战。教授在肝损伤领域拥有丰富的临床和研究经验。肝胆相照平台特别专访教授，围绕脓毒症相关性肝损伤的临床特点、诊断要点、与DILI的鉴别要点进行了深入交流，并将精彩内容整理成文，以飨读者。

问题一：脓毒症相关性肝损伤主要临床特点

Question 1

肝胆相照：

脓毒症相关性肝损伤（sepsis-associated liver injury）的主要临床特点是什么？

What are the main clinical characteristics of sepsis-associated liver injury?

Bjornsson 教授：

脓毒症相关性肝损伤主要有两种临床表现。第一种是由于缺氧和低血压引起的肝细胞损伤，这类患者通常表现为血清转氨酶（AST 和 ALT）明显升高，且 AST 通常高于 ALT，这种现象在药物性肝损伤中并不常见。这种类型常见于明显的血流动力学异常背景下。

第二种是以胆汁淤积为主，表现为碱性磷酸酶（ALP）显著升高，可伴或不伴黄疸。这种类型的起病相对较缓，通常不伴有低血压或缺氧。

There are mainly two phenotypes of sepsis-associated liver injury. The first is linked to hypoxia and hypotension, typically showing very high AST and ALT levels, with AST usually being higher than ALT—a pattern that is rather uncommon in DILI. This occurs in the context of significant hemodynamic dysfunction.

The second phenotype is cholestatic, characterized by a significant elevation of alkaline phosphatase (ALP), with or without jaundice, and usually occurs without preceding hypotension or hypoxia. This form presents more gradually compared to the hypoxic type.

问题二：脓毒症相关性肝损伤or药物性肝损伤？

Question 2

肝胆相照：

如何在脓毒症相关性肝损伤与药物性肝损伤之间进行有效鉴别？

How can clinicians effectively differentiate between sepsis-associated liver injury and DILI?

Bjornsson 教授：

目前脓毒症相关性肝损伤与药物性肝损伤的鉴别并不容易。一个重要的参考因素是肝损伤的发展速度。脓毒症相关性肝损伤通常发生迅速，尤其是缺氧型，往往在 1-2 周内迅速恢复，甚至完全正常化。如果肝损伤持续存在或加重，应考虑其他可能性，例如病毒性肝炎、自身免疫性肝炎或药物性肝损伤。

尽管部分药物有明确的肝毒性，但在临床上，单凭病史和恢复速度往往难以完全排除药物性肝损伤。目前尚缺乏可用于区分这两种肝损伤的生物标志物或遗传学指标。

Distinguishing between sepsis-associated liver injury and DILI can be challenging. One key factor is the speed of liver injury progression. Sepsis-associated injury, especially the hypoxic type, tends to develop rapidly and often shows significant recovery within one to two weeks.

If liver injury persists or worsens, clinicians must consider other possibilities like viral hepatitis, autoimmune hepatitis, or DILI. Although some drugs are known to be hepatotoxic, we currently lack specific biomarkers or genomic factors that can reliably differentiate between these two conditions.

问题三：脓毒症相关性肝损伤具有价值的指标

Question 3

肝胆相照：

在脓毒症相关性肝损伤的诊断过程中，哪些实验室或影像学指标最具参考价值？

Which laboratory or imaging indicators are most valuable in diagnosing sepsis-associated liver injury?

Bjornsson 教授：

缺氧型脓毒症相关性肝损伤的显著特征是AST 和ALT显著升高，且AST通常高于ALT，这一点与药物性肝损伤不同。黄疸在两种肝损伤类型中可能都不明显，因此诊断时不能单纯依赖黄疸。

此外，转氨酶恢复的速度也是重要的鉴别依据。如果在 1-2 周内转氨酶迅速恢复，通常支持脓毒症相关性肝损伤的诊断。

In hypoxic sepsis-associated liver injury, very high AST and ALT levels are typical, with AST usually exceeding ALT—an uncommon pattern in DILI. Jaundice may not be a reliable differentiator as it can be absent in both conditions.

The recovery rate of liver enzymes within the first one to two weeks is a particularly valuable indicator supporting the diagnosis of sepsis-associated liver injury.

问题四：未来的研究方向

Question 4

肝胆相照：

未来在脓毒症相关性肝损伤和药物性肝损伤的鉴别诊断方面，您认为最需要突破的研究方向是什么？

What do you think is the most critical research direction for improving the differential diagnosis between sepsis-associated liver injury and DILI in the future？

Bjornsson 教授：

未来最重要的突破应来自于前瞻性研究，特别是在重症监护室（ICU）环境下，对明确有肝损伤的患者进行动态随访，排除其他可能的合并因素，系统性描述肝损伤的全过程。

同时，应重点关注脓毒症的病原学类型、炎症因子（如 IL-6、CRP、TNF-α）等生物标志物的变化，探索是否存在差异化的免疫炎症模式，这些可能为未来的鉴别诊断和个体化治疗提供新思路。

The most critical research direction would involve prospective studies in ICU settings, where clearly defined phenotypes of liver injury are carefully monitored over time, excluding other potential confounding factors.

It is also important to investigate the types of infections involved, along with biomarkers of systemic inflammation such as interleukin-6, CRP, and TNF-α, to determine whether distinct immuno-inflammatory patterns could help differentiate these liver injuries and guide more personalized treatment strategies.