Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives

Abstract

Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.

Figure 1

Evolution of serum bilirubin before and after LCT in two CN patients performed in our center. A: After fluctuating over a period of 5 yr, serum bilirubin of patient 1 decreased significantly to the lesser value of 11.4 mg/dL in 6 mo. Subsequently, increasing values were observed and the patient was listed for OLT. B: For patient 2, after cell infusions, the serum bilirubin dramatically decreased to the value of 6 mg/dL in 4 mo. At this time, concomitantly to an EBV infection, higher values were observed and the patient underwent OLT. Arrows indicate the timing of cell infusions. TRP: Transplantation.