Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion.

BACKGROUND

A practical method of monitoring engraftment by transplanted hepatocytes for the purpose of bridging human liver failure to native regeneration is described.

METHODS

A previously healthy 37-year-old female with a 2-week history of a febrile illness presented with fulminant liver failure. Findings on admission included the following: illicit drug use, serum hepatitis B surface antigen positive, grade 1 encephalopathy, prothrombin time (pt) >100 sec, F7<1%, NH3 150 micromol/L, alanine aminotransferase 4079 U/L, total bilirubin level 11.4 mg/dl, and glucose 70 mg/dl (on IV D10). With immunosuppression, 8.8x10(8), 96% viable human hepatocytes were intraportally infused. Clinical chemistries, total sHLA class I, and ELISA to measure donor-specific sHLA-A1 and -B8 were recorded. Serial transjugular liver biopsies were performed and pooled for histological examination, DNA extraction, and HLA DNA typing.

RESULTS

The patient fully recovered. At months 3 and 4 with donor biopsy specimen class I HLA DNA no longer detectable, immunosuppression was tapered off. The patient is clinically normal, serum hepatitis B surface antigen negative at 10 months of follow-up.

CONCLUSIONS

Bridging liver failure with donor hepatocytes with HLA class I antigen disparate from recipients is clinically feasible, and allows for a marker, combined with serial graft histology, to safely wean immunosuppression when native liver regeneration succeeds.