Hepatocyte Transplantation in Acute Liver Failure

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Hepatocyte Transplantation in Acute Liver Failure

Bilir BM, Guinette D, Karrer F, et al

Liver Transpl. 2000;6:32-40

The majority of patients with acute liver failure (ALF) die waiting for

orthotopic liver transplantation (OLT). No other treatment modality is shown

to improve survival. This study was conducted to assess the safety and

feasibility of hepatocyte transplantation (HT) and subsequent engraftment

and function of donor cells. Functional and structural integrity of

cryopreserved and thawed human hepatocytes were assessed by their

morphological characteristics, induction of P-4501A1 transcription, and

survival in vivo by xenotransplantation into rats. Five patients with severe

ALF underwent intrasplenic (4 patients) and/or intrahepatic (2 patients) HT

through angiography under cyclosporine immunosuppression. All patients had

grade III to IV encephalopathy and factor V levels less than 0.5 U/mL, were

ventilator and dialysis dependent, and were not OLT candidates. Three of the

5 patients who survived 48 hours after HT had substantial improvement in

encephalopathy scores, arterial ammonia levels, and prothrombin times.

Clinical improvement was paralleled by an increase in aminopyrine and

caffeine clearances. All 3 patients lived substantially longer than expected

based on clinical experience after HT (12, 28, and 52 days) but eventually

died. Postmortem examination showed the presence of transplanted hepatocytes

in liver and spleen by light microscopy and fluorescent in situ

hybridization (FISH). Cryopreserved and thawed human hepatocytes can be

transplanted into recipients with ALF with some acceptable but definite

complications. Engraftment of donor hepatocytes was proven by histological

examination and FISH by both transjugular biopsy and at autopsy. Improvement

in brain edema, encephalopathy grade, and clearance of antipyrine and

caffeine suggested function, albeit with a 24- to 72-hour delay

posttransplantation.

[Guest guest]

Hepatocyte Transplantation in Acute Liver Failure

Bilir BM, Guinette D, Karrer F, et al

Liver Transpl. 2000;6:32-40

The majority of patients with acute liver failure (ALF) die waiting for

orthotopic liver transplantation (OLT). No other treatment modality is shown

to improve survival. This study was conducted to assess the safety and

feasibility of hepatocyte transplantation (HT) and subsequent engraftment

and function of donor cells. Functional and structural integrity of

cryopreserved and thawed human hepatocytes were assessed by their

morphological characteristics, induction of P-4501A1 transcription, and

survival in vivo by xenotransplantation into rats. Five patients with severe

ALF underwent intrasplenic (4 patients) and/or intrahepatic (2 patients) HT

through angiography under cyclosporine immunosuppression. All patients had

grade III to IV encephalopathy and factor V levels less than 0.5 U/mL, were

ventilator and dialysis dependent, and were not OLT candidates. Three of the

5 patients who survived 48 hours after HT had substantial improvement in

encephalopathy scores, arterial ammonia levels, and prothrombin times.

Clinical improvement was paralleled by an increase in aminopyrine and

caffeine clearances. All 3 patients lived substantially longer than expected

based on clinical experience after HT (12, 28, and 52 days) but eventually

died. Postmortem examination showed the presence of transplanted hepatocytes

in liver and spleen by light microscopy and fluorescent in situ

hybridization (FISH). Cryopreserved and thawed human hepatocytes can be

transplanted into recipients with ALF with some acceptable but definite

complications. Engraftment of donor hepatocytes was proven by histological

examination and FISH by both transjugular biopsy and at autopsy. Improvement

in brain edema, encephalopathy grade, and clearance of antipyrine and

caffeine suggested function, albeit with a 24- to 72-hour delay

posttransplantation.