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 UK 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. Liver Transpl 18:195–200, 2012. © 2011 AASLD.

Liver Transplantation for the Management of Acute Intermittent Porphyria: A Case Report

“…A previously published review reported an incidence of HAT of 40% (4 out of 10 patients) with development early at 30 days out to 9 months [7]. Due to the increased incidence of HAT in AIP patients following transplant, we suggest use of anticoagulation postoperatively [2]. Our patient was prescribed prophylaxis with enoxaparin as well as low dose aspirin for the first 9 months post-transplantation.…”

“…A retrospective study performed in the UK described the outcome of LT in 10 patients (median age: 31 years [range 18 years to 50 years]; 9 females) with AIP and recurrent neurovisceral attacks and poor quality of life. Clinical and biochemical remission occurred in all patients, with PBG and ALA levels returning to normal within 24 h to 72 h [2].…”

“…Nebulized pentamidine, rather than sulfamethoxazole-trimethoprim, was used for pneumocystis pneumonia prophylaxis to decrease risk for potential exacerbation. Based on a reported higher rate of hepatic artery thrombosis (HAT) in patients with AIP who have undergone LT, the patient was started on therapeutic enoxaparin for a total of 9 months of treatment [2]. Nine months after transplant, she has no clinical or biochemical signs of porphyria, normal graft function (liver function tests included alanine aminotransferase 9 U/L, aspartate aminotransferase 13 U/L, alkaline phosphatase 26 U/L, total bilirubin 0.2 mg/dl, albumin 4.4 g/dl), and reported improved quality of life.…”

“…Previous experience with "domino" liver transplants have shown that livers from donors with AIP can develop acute attacks associated with accumulation of porphyrin precursors and recipients will potentially go on to develop AIP [2].…”

Indications for liver transplant and AASLD guidelines

“…2,3 We wonder whether RVR (32.8%) had any effect on the result of the association between SVR and hemoglobin decline or upon RBV pharmacokinetics in the study by Holmes et al 1 It is known that plasma RBV levels at week 8, rather than the actual hemoglobin levels or ITPase deficiency in patients with HCV-1 1 and genotype 2/3 infection, 1,4 have been associated with SVR. Since the very important role of the genetic variation in interleukin (IL)28B on predicting response to Peg-IFN-based therapies either without 3,5,6 or with new direct antiviral agents 7 has been recognized, it seems also necessary to take the IL28B genotype into consideration in elucidating the influence of RBV levels on SVR in HCV-1 patients, without otherwise detracting from the results by Holmes et al …”