Birraux J, Genin B, Sinigaglia C, Mage R, Morel P, Le Coultre C
Department of Paediatrics, Clinic of Paediatric Surgery, Children's Hospital and Hôpital Cantonal, University Hospitals of Geneva, Switzerland.
Eur J Pediatr Surg. 1998 Aug;8(4):224-9. doi: 10.1055/s-2008-1071159.
Acute hepatic insufficiency (AHF) is one of the major challenges of intensive care medicine. Liver transplantation is the current solution to unsuccessful medical management. Owing to the lack of organ donors, other methods such as hepatocyte transplantation (HcTX) and bioartificial livers need to be explored. The aim of our experimental study is to evaluate the effect of hepatocyte transplantation on the survival in AHF animals intoxicated with D-Galactosamine (D-Gal).
The first step consists of the determination of the dose of D-Gal needed to induce at least 80% mortality between 48 and 72 hours. Two groups of a single strain of male Wistar rats are then compared, one being intoxicated with D-Gal (control group), the other receiving and HcTX in the splenic parenchyma 48 hours after intoxication.
The required dose to achieve AHF is 3 gr/kg body weight (Gr. 0). Survival rates are as follow: Gr. 1: D0: 93%; from D1 to D28: 13%. Gr. 2: D0: 80%; D1 and D2: 33%; D3: 20%; D4: 13%, from D5 to D28: 6%. (D0 = Day of transplantation). Liver enzymes show a peak of deterioration at 24 hours, then return to normal values in both groups. Histological examination of those animals still alive and sacrificed on day 28 demonstrates a restitutio ad integrum of hepatic structure. In Group 2, it is possible to observe remaining living hepatocytes in the splenic parenchyma.
When HcTX is performed 48 hours after D-Gal intoxication, i.e., when the animals begin to develop AHF symptoms, animal survival only significantly improves between days 0 and 3. Unlike other trials, we cannot demonstrate an improvement in long-term survival. Thus, according to this particular experimental model, HcTX is not an alternative for the treatment of AHF.
急性肝衰竭（AHF）是重症医学面临的主要挑战之一。肝移植是当前药物治疗无效时的解决办法。由于器官供体短缺，需要探索其他方法，如肝细胞移植（HcTX）和生物人工肝。我们实验研究的目的是评估肝细胞移植对用D-半乳糖胺（D-Gal）诱导中毒的AHF动物存活率的影响。
第一步是确定在48至72小时内诱导至少80%死亡率所需的D-Gal剂量。然后比较两组单一品系的雄性Wistar大鼠，一组用D-Gal中毒（对照组），另一组在中毒48小时后接受脾实质内的肝细胞移植。
实现急性肝衰竭所需的剂量为3克/千克体重（第0组）。存活率如下：第1组：移植当天（D0）：93%；从第1天到第28天：13%。第2组：D0：80%；第1天和第2天：33%；第3天：20%；第4天：13%，从第5天到第28天：6%。（D0 = 移植日）。两组肝酶在24小时时均出现恶化高峰，然后恢复到正常水平。对那些在第28天仍存活并被处死的动物进行组织学检查，显示肝结构完全恢复。在第2组中，可以观察到脾实质内仍有存活的肝细胞。
在D-Gal中毒48小时后进行肝细胞移植，即当动物开始出现急性肝衰竭症状时，动物存活率仅在第0天至第3天有显著提高。与其他试验不同，我们未能证明长期存活率有所改善。因此，根据这个特定的实验模型，肝细胞移植不是治疗急性肝衰竭的替代方法。
