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Liver transplantation recommended for patients with specific porphyrias
Porphyrias are a group of eight metabolic disorders that result from mutations that affect the heme biosynthetic pathway. They can be classified as hepatic or erythropoietic.
In a new review, Ashwani K. Singal, MD, MS, of the division of gastroenterology and hepatology, University of Alabama, and colleagues discuss ways clinicians can manage patients with porphyria and recommend those with erythropoietic protoporphyria (EPP) or acute intermittent porphyria (AIP) to undergo liver transplantation.
Ashwani K. Singal
Diagnosis of porphyrias is often delayed, but the first screening test for any acute porphyria is a spot urine testing for porphobilinogen (PBG), according to the review. A normal urinary level of PBG (0 mg/L-4 mg/L) is sought to conclude that acute porphyria is not present. Common porphyrias are EPP, porphyria cutanea tarda (PCT) and AIP.
Liver transplantation may be needed for end-stage liver disease secondary to porphyria such as in EPP or for refractory neurovisceral symptoms as in AIP. While the liver transplantation reverses the enzyme defect in AIP, this is not the case in EPP as the dominant site of enzyme defect is in the erythroid cells. According to previous research, since 1980, there have been 62 transplants in 50 EPP cases performed throughout the United States, Europe and Asia. Approximately half required specific pre-transplant measures due to EPP crises or acute liver failure. Previous studies revealed that of those 62 transplants, re-transplantation was needed among seven patients. Post-transplantation survival rates ranged from 47% to 66% at a 10-year follow-up.
Liver transplantation may be needed in patients with AIP due to deficiency of the PBG deaminase gene. The transplantation can correct genetic defects in the liver and restore normal levels of PBG and delta-aminolevulinic acid. Patients with AIP, mostly female, may experience recurring neurovisceral attacks. According to previous research, the first liver transplant for AIP was performed on a 19-year-old woman and cured AIP. However, the neurological state of a patient with acute attacks is unpredictable, therefore researchers recommend a neurological evaluation be performed by a specialist before transplantation. Previous research indicated multiple reports of symptoms of hemorrhaging, renal dysfunction and hepatic artery thrombosis in 14 liver transplantation for AIP cases post-transplantation.
Researchers concluded that liver biopsy should be performed at the first instinct of abnormal liver chemistry, other risk factors for liver disease, a sudden increase in protoporphyria levels or photosensitivity. The most experience in liver transplantation for porphyria patients has been among those with EPP and in AIP.
“Porphyria patients potentially needing liver transplantation should be referred to centers with expertise in the management of porphyria,” Singal told Healio.com/Hepatology.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Although erythropoietic and hepatic porphyrias are rare genetic disorders, they can be associated with significant morbidity and have a major impact on quality of life. Awareness of these disorders among physicians is a key factor in identifying cases, as many patients may undergo an extensive negative evaluation while experiencing progressive neurovisceral or cutaneous symptoms prior to an eventual diagnosis. Liver transplantation can be curative in some cases; however, management of patients prior to undergoing liver transplantation, intraoperatively, and in the post-transplant setting is complex and requires highly specialized care.
Patients with acute intermittent porphyria who are refractory to IV hemin therapy can experience full resolution of symptoms following liver transplantation, as this corrects the genetic defect; however, they may be at risk of long-term neurological sequelae or thrombotic disease and require careful evaluation before and after transplantation. Although liver transplantation may also be considered in patients with erythropoietic protoporphyria who develop advanced liver disease, a risk of recurrence exists since the genetic defect involves erythroid cells and is present within the bone marrow. In this setting, a bone marrow transplant is required to achieve a long-term cure. Timing of bone marrow transplantation following liver transplantation is not well established and carries significant risk, particularly related to infectious complications.