Systematic Review with Meta-analysis: HIF-1α Attenuates Liver Ischemia-reperfusion Injury

Ischemia-reperfusion injury (IRI) induces inevitable complications in liver transplantation. Many studies have demonstrated that hypoxia-inducible factor 1α (HIF-1α) plays an important role in IRI. However, the mechanism of its pleiotropic effect remains unclear. This systematic review provides a comprehensive evaluation of all available evidence concerning the function of HIF-1α in transplant-induced hepatic IRI. Data were obtained through a search of Medline (PubMed), Embase, and the Cochrane Library literature review on the effect of HIF-1α in IRI (from inception to 12/2014). RevMan was used to calculate standardized mean difference (SMD) and 95% confidence intervals (CIs). Forty articles met inclusion criteria with 2 clinical and 38 basic studies. Two clinical trials (n = 68) revealed ischemic preconditioning (IPC) aroused protection after hepatic IRI based on the higher level of HIF-1α in IPC group compared with control group. In vitro studies confirmed the salutary effect of IPC disappearance in the inhabitation of stabilized HIF-1α. In vivo animal studies showed different HIF-1α expression and distribution patterns in the ischemia and reperfusion stage due to distinctive partial oxygen pressure gradient intra-liver, and 5 animal studies (n=66) showed that stabilized HIF-1α treatment was associated with lower alanine aminotransferase (ALT) (SMD = -1.58; 95% CI =- 2.65, -0.52) when compared with unstabilized HIF-1α group. Not only decreased liver IR injury, stabilized HIF-1α during the acute phase of IR could also promote graft regeneration capacity leading to better initial function and survival rate. More rigorous studies are needed to gauge the effectiveness due to insufficient sample size and possible publication bias.