Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis

Abstract

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the U.K. Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation.

Figure 1

Survival after LT for AIP. Two of the 10 patients who underwent LT for AIP died (1 patient at 98 days and 1 patient at 26 months). The median follow-up time was 23.4 months.

Figure 2

AIP activity after LT. (A) Urine PBG/creatinine ratios for 9 of the 10 AIP patients before and after LT. All 9 patients experienced a complete biochemical resolution of their disease (reference level < 1.5 μmol/mmol). The 10th patient had an elevated pretransplant ratio of 74.3 μmol/mmol, but no posttransplant level was available. However, this patient was asymptomatic after transplantation, and the posttransplant level was, therefore, expected to be normal. (B) Short-term urinary PBG/creatinine and ALA/creatinine ratios for a single AIP patient before and after LT. The urinary PBG level returned to normal within 24 hours and remained normal thereafter. The urinary ALA excretion level returned to normal within approximately 72 hours.

Figure 3

Pretransplant and posttransplant performance scores for 9 patients who underwent LT for AIP and had significant postoperative survival. The following scale is used to describe their quality of life: (1) the patient is able to carry out normal activities without restriction, (2) the patient is restricted only from physically strenuous activity, (3) the patient can move freely and is capable of self-care but is incapable of any form of work, (4) the patient is capable of only limited self-care and is mostly confined to a bed or a chair, and (5) the patient is completely reliant on nursing/medical care. All these patients were prevented from performing any type of work before LT; 6 patients were mostly confined to a bed or a chair or were completely reliant on medical/nursing care. LT led to significant improvements in the quality of life for most of the patients; their posttransplant limitations either depended on chronic neurological deficits sustained before transplantation or resulted from those deficits (eg, contractures).