Liver Transplantation for Acute Intermittent Porphyria

Abstract

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early.

Acute Hepatic Porphyria: Pathophysiological Basis of Neuromuscular Manifestations

“…First, during acute neurovisceral attacks, it is recommended to screen the patient for potentially identifiable and treatable trigger factors (i.e., withdrawal of porphyrinogenic drugs and infectious diseases), classify the severity and possible outcomes of the presentation ( Souza et al, 2021 ), and provide specific therapies for the treatment, such as glucose overload therapy (high doses of glucose infusion) in mild episodes (or as a transient therapy in cases without ready availability of other specific therapies) and hemin-based therapies for moderate and severe presentation (i.e., hematin and heme arginate) ( Anderson and Collins, 2006 ; Anderson, 2019 ; Souza et al, 2021 ). In cases with severe presentation and no specific therapies available, hemodialysis may also be used as an exceptional life-saving measure, and liver transplantation has been previously reported in small case series as a possible successful treatment for patients with recurrent attacks ( Anderson and Collins, 2006 ; Anderson, 2019 ; Lissing et al, 2021 ; Souza et al, 2021 ).…”

“…There is no recognizable difference in the general rates of complications, retransplantation, or survival after transplantation in patients with AIP compared with other inherited metabolic disorders. The worst outcomes and the highest rates of complications are observed in patients with previously established severe neurological compromise and in some individuals with chronic kidney disease ( Lissing et al, 2021 ). Combined kidney and liver transplantation has been rarely performed in AHP, mainly in patients with severe metabolic decompensation and chronic kidney disease as a serious complication in late-stage disease course ( Lissing et al, 2021 ).…”

“…The worst outcomes and the highest rates of complications are observed in patients with previously established severe neurological compromise and in some individuals with chronic kidney disease ( Lissing et al, 2021 ). Combined kidney and liver transplantation has been rarely performed in AHP, mainly in patients with severe metabolic decompensation and chronic kidney disease as a serious complication in late-stage disease course ( Lissing et al, 2021 ). There is still low evidence to propose allogeneic hepatocyte transplantation rather than traditional liver transplantation for AIP, despite some studies with the Hmbs -deficient mouse model showing important reduction in ALA and PBG plasma levels ( Lissing et al, 2021 ).…”

Porphyrias in the Age of Targeted Therapies

“…The only curative treatment approach for AHP is orthotopic liver transplantation (OLT), which has been shown to lead to rapid normalization of ALA and PBG levels and effectively prevent further acute porphyria attacks [38,39]. However, due to high morbidity and mortality, OLT is usually only considered as a last resort in individuals with very frequent recurring acute attacks who cannot be sufficiently well controlled using other treatment approaches.…”

Pediatric metabolic liver diseases: Evolving role of liver transplantation

“…The porphyrin levels need to be maintained by plasmapheresis or by heme infusion. The outcome following LT is excellent but with a differential favorable prognosis in those with mild-to-moderate neurological symptoms than those with severe symptoms prior to LT[ 61 ]. Liver shows black discoloration macroscopically in erythropoietic protoporphyria[ 10 ].…”