Reversal of post-hepatectomy liver failure using a bioartifical liver supporting system implanted with clinical-grade human induced hepatocytes

Here, we developed a clinical-grade bioartificial liver (BAL) device by implanting with directly reprogrammed human hepatocytes (hiHep) manufactured and cryopreserved under current good manufacturing practice (cGMP) conditions. Notably, in a porcine PHLF model induced by 85% hepatectomy, hiHep-BAL treatment showed a remarkable survival benefit, as well as improvements of liver metabolic gene expression, ammonia detoxification, and liver regeneration. Furthermore, an investigator-initiated study in seven patients with extended liver resection (NCT05035108) demonstrated that hiHep-BAL treatment was well tolerated without complications and associated with ameliorative liver function and remarkable liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant the further efficacy testing of hiHep-BAL for PHLF followed by the future broadening the patients eligible for liver resection in clinics. To determine the therapeutic mechanism of hiHep-BAL on PHLF,we performed a whole-genome RNA-sequencing analysis of PHLF livers from the No-BAL group versus normal liver to determine PHLF-associated genes. Expression profile of hiHep-BAL-treated livers on day 4 and 8 were then compared to identify the reverted PHLF genes, as potential hiHep-BAL-regulated genes. Empty-BAL group was used as a control to exclude the effect of blood.