BACKGROUND Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF) though with the limitations of surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbeads transplanted intraperitoneally has been shown in animal models. We report our experience of the use of this therapy in children with ALF on named patient basis under a MHRA Specials Manufacture License. METHODS Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads (EMBs) were tested in immunocompetent healthy rats. Subsequently, eight children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessed the host immune response and residual function of the retrieved HMBs either after spontaneous native liver regeneration or at the time of LT. RESULTS Intraperitoneal transplantation of HMBs in healthy rats was safe with preserved synthetic and detoxification functions without the use of immunosuppression. Subsequently, eight children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion), median age of 14.5 days, range 1 day - 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. CONCLUSION The results demonstrate the feasibility and safety of a HMB infusion in children with ALF.

中文翻译：

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海藻酸盐微囊化人肝细胞治疗儿童急性肝功能衰竭

背景 肝移植 (LT) 是急性肝衰竭 (ALF) 患者最有效的治疗方法，尽管存在手术风险的限制和终生免疫抑制的需要。在海藻酸盐中移植微囊化人肝细胞是比全肝置换更有吸引力的选择。腹腔内移植肝细胞微珠的安全性和有效性已在动物模型中得到证实。我们报告了我们根据 MHRA 特殊制造许可证在指定患者基础上对 ALF 儿童使用这种疗法的经验。方法 在免疫活性健康大鼠中测试临床级人肝细胞微珠 (HMB) 和空微珠 (EMB)。随后，八名正在等待合适的 LT 同种异体移植物的 ALF 儿童接受了 HMB 的腹膜内移植。我们监测了手术的并发症，评估了自发性天然肝再生后或 LT 时回收的 HMB 的宿主免疫反应和残余功能。结果 健康大鼠腹膜内移植 HMB 是安全的，保留了合成和解毒功能，无需使用免疫抑制。随后，8 名 ALF 儿童接受了 HMB（4 名新生儿血色病、2 名病毒感染和 2 名在输注时原因不明的儿童），平均年龄 14.5 天，范围 1 天 - 6 岁。该手术耐受性良好，没有并发症。在 8 名儿童中，4 名避免了 LT，而 3 名在干预后成功过渡到 LT。输注后（在 LT 时）回收的 HMB 在结构上完好无损，没有宿主细胞粘附，并含有具有保留功能的活肝细胞。结论 结果证明了 HMB 输注在 ALF 儿童中的可行性和安全性。