HO-1 Protects Remnant Liver against Dysfunction after Major Hepatectomy in Humans

Abstract

Objective

During major resection of liver carcinoma, liver regeneration (LR) is induced by various clinical and biological factors. Heme oxygenase (HO)-1 has been found as a key inducer of LR in preclinical trial. The clinical evidence for the role of HO-1 in liver dysfunction (LD) including LR is still unknown and has been included in this study.

Methods

Therefore, plasma HO-1 were monitored during perioperative period in 65 patients with hepatectomy, with 35 training and 30 validation cohorts. LD were evaluated by liver function serum markers and calculation of regeneration indices, respectively.

Results

In the training setting, HO-1 levels were remarkably reduced after liver resection (P < 0.001) and gradually recovered within 7 days after surgery. Preoperative HO-1 specifically predicted LD during the first week after surgery (AUC: 0.757; P = 0.01). In patients with LD and complications after surgery, HO-1 levels decreased throughout the perioperative period. In addition, we had also confirmed that low levels of HO-1 (<169 ng/ml) before surgery were associated with an increase in the incidence of postoperative LD and morbidity (P = 0.007, P = 0.045), and decrease of liver regeneration (P = 0.005). And HO-1 was an independent predictor for poor clinical outcome.

Conclusions

We had provided the first clinical data verifying that human HO-1 was related to LD. Consequently, HO-1 levels can be used as effective clinical indicators to predict LD and clinical outcome, and can be used as intervention target before liver resection.

Keywords:

• liver carcinoma
• Heme oxygenase (HO)-1
• liver regeneration (LR)
• liver dysfunction (LD)
• volume measurement

This article refers to:

Prometheus Unbound: The Allure of Hepatic Regeneration

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the [National Natural Science Foundation of China #1] under Grant [number 81900595; and [Innovative Research Groups of National Natural Science Foundation of China #2] under Grant [number 81721091].