Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes
Yifan Wang, Qiang Zheng, Zhen Sun, Chenhua Wang, Jin Cen, Xinjie Zhang, Yan Jin, Baihua Wu, Tingting Yan, Ziyuan Wang, Qiuxia Gu, Xingyu Lv, Junjie Nan, Zhongyu Wu, Wenbin Sun, Guoyu Pan, Ludi Zhang, Lijian Hui, Xiujun Cai
Abstract
Liver resection is the first-line treatment for primary liver cancers, providing the potential for a cure. However, concerns about post-hepatectomy liver failure (PHLF), a leading cause of death following extended liver resection, have restricted the population of eligible patients. Here, we engineered a clinical-grade bioartificial liver (BAL) device employing human-induced hepatocytes (hiHeps) manufactured under GMP conditions. In a porcine PHLF model, the hiHep-BAL treatment showed a remarkable survival benefit. On top of the supportive function, hiHep-BAL treatment restored functions, specifically ammonia detoxification, of the remnant liver and facilitated liver regeneration. Notably, an investigator-initiated study in seven patients with extended liver resection demonstrated that hiHep-BAL treatment was well tolerated and associated with improved liver function and liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant further testing of hiHep-BAL for PHLF, the success of which would broaden the population of patients eligible for liver resection.