Liver transplantation in the management of porphyria.

UNLABELLED: Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Liver transplantation (LT) may be needed for recurrent and/or life-threatening acute attack in acute intermittent porphyria or acute liver failure or end-stage chronic liver disease in erythropoietic protoporphyria. LT in acute intermittent porphyria is curative. Erythropoietic protoporphyria patients needing LT should be considered for bone marrow transplantation to achieve cure. CONCLUSION: This article provides an overview of porphyria with diagnostic approaches and management strategies for specific porphyrias and recommendations for LT with indications, pretransplant evaluation, and posttransplant management.

Single-incision laparoscopic partial cecectomy for appendiceal mucocele in a patient with porphyria photosensitivity.

Erythropoietic protoporphyria (EPP) is a rare hereditary subtype of cutaneous porphyria characterized by photosensitivity. Increased exposure to light irradiation may precipitate acute liver failure, and surgical light-induced intestinal burns and perforations are known to occur. We report a case of EPP in a patient who underwent laparoscopic partial cecectomy for appendiceal mucocele. A 55-year-old man with EPP was presented for treatment of appendiceal mucocele. A light test using two types of laparoscopes (Companies O and S) was performed preoperatively. Light from the laparoscope manufactured by Company O caused photosensitivity; this effect was not observed with light from the laparoscope manufactured by Company S. Therefore, we performed laparoscopic partial cecectomy through a single umbilical incision using the laparoscope from Company S. Except for the incision site, the patient's skin was completely covered using surgical drapes. No intra- or postoperative complications were observed. Histopathological examination of the resected specimen revealed a low-grade appendiceal mucinous neoplasm.

Liver transplantation for inherited metabolic disorders of the liver.

PURPOSE OF REVIEW: Liver transplantation is curative, life saving or both for a range of inherited diseases affecting the liver. Indications, timing and outcome of transplantation for these diseases are the focus of this review. RECENT FINDINGS: Liver transplant represents a mode of gene replacement therapy for several disorders, including Wilson disease, hemochromatosis, tyrosinemia, urea cycle defects and hypercholesterolemia in which the primary defect residing in the liver results in hepatic complications or severe extrahepatic disease. Liver transplant is also an important therapeutic modality in multisystemic genetic disorders with major hepatic disease such as glycogen storage disease types I, III and IV and porphyria. For familial amyloidosis and primary hyperoxaluria, liver replacement eliminates the source of the injurious products that results in extrahepatic disease. Innovations in medical and surgical management of these patients have led to improved outcomes providing an important benchmark for future gene therapy of these disorders. SUMMARY: Recent developments have refined the indications for liver transplant in the treatment of inherited metabolic diseases. The full potential of liver transplant in these disorders can be harnessed by careful patient selection, optimizing timing and perioperative metabolic management of these patients.

[Acute intermittent porphyria: a clinical case]. / La porfiria acuta intermittente: caso clinico.

The acute intermittent porphyria is a rare but very interesting disease from the surgical and anaesthesiological point of view. On the basis of recently observed case the Authors review clinical and pathophysiological data of this entity simulating a variety of acute abdominal conditions and involving important problems from the anaesthesiological and pharmacological point of view. As a matter of fact, the administration of some drugs can provoke a crisis that often involves serious complications (coma), sometimes lethal (respiratory paralysis). However, when a patient needs a surgical treatment for different reasons, the awareness of this condition enables to plan an anaesthesiological management free of risks.

Liver transplantation in a patient with protoporphyria.

A 38-yr-old woman with liver disease due to protoporphyria underwent orthotopic liver transplantation. The resected liver was cirrhotic and contained a massive amount of protoporphyrin, with numerous birefringent pigment deposits. Transplantation was accomplished without difficulty following blood volume exchange to reduce the blood protoporphyrin level. Sequential biopsy specimens obtained through the 13th month after transplantation showed no accumulation of protoporphyrin pigment deposits in the new liver. Portal inflammation observed in the liver biopsy specimen at 6 mo after transplantation resolved spontaneously. Erythrocyte and serum protoporphyrin levels returned to values similar to those in the pretransplantation period when the patient had normal hepatic function; the fecal level was lower. Thus orthotopic liver transplantation can be successfully done in patients with protoporphyria who have severe liver disease. Prolonged follow-up is needed to determine the ultimate outcome, however, as the new liver remains susceptible to protoporphyrin-induced damage.

[Erythrohepatic protoporphyria. A rare differential diagnosis of parenchymatous jaundice]. / Erythrohepatische Protoporphyrie. Eine seltene Differentialdiagnose des parenchymatösen Ikterus.

Parenchymatous jaundice persisted in a 59-year-old woman[correction of man] after cholecystectomy for gallbladder stones. She had a history of skin sensitivity to light. Laboratory tests demonstrated an excessive increase of free protoporphyrin in red blood cells and plasma, as well as abnormal coproporphyrinuria, indicating the diagnosis of far advanced erythropoietic protoporphyria with an hepatobiliary component. Conservative treatment with ursodeoxycholic acid brought no relief and liver transplantation was therefore performed. Bilirubin concentration and all other liver parameters became normal within 2 months postoperatively. No complications have occurred in a follow-up period of one year. The combination of light-sensitive skin with gall-stones and, at a later stage, parenchymatous jaundice should always make one consider protoporphyria. As recognition of the initial liver phase in erythropoietic protoporphyria is decisive for the success of treatment, regular examination of liver parameters and of the porphyrins in blood, urine and stool is recommended.

Erythropoietic protoporphyria: unusual skin and neurological problems after liver transplantation.

The case of a woman with protoporphyria who developed liver failure and underwent liver transplantation is described. During the pretransplant episode of liver failure she developed quadriparesis that rapidly progressed after transplantation to a severe polyneuropathy. Following transplantation she also developed a second-degree burn of the light-exposed abdominal wall. The neuropathy resembled that observed in other forms of porphyria, and it is proposed that the extreme disturbance of protoporphyrin levels associated with protoporphyrin-induced liver failure caused this neuropathy. Such a neuropathy has not previously been described in protoporphyria. Erythrocyte protoporphyrin levels remain high and fecal levels normal, although results of liver tests are normal. She remains photosensitive, which emphasizes that although liver transplantation may be lifesaving in this disorder, it is not curative, and care must be taken to prevent photosensitive damage to skin and light-exposed internal organs.

Anaesthesia for porphyria.

Porphyrias arise due to enzyme defects in the haem synthetic pathway. They are of concern to the anaesthetist as acute crises may be precipitated by anaesthetic drugs. Anaesthesia must be carefully managed in patients with porphyria in order to achieve a successful outcome.

Bone-marrow transplantation for congenital erythropoietic porphyria.

Congenital erythropoietic porphyria, a disorder of haem synthesis, is caused by uroporphyrinogen III synthase deficiency in bone-marrow normoblasts. Uroporphyrins and coproporphyrins accumulate and cause oxidative damage to cells exposed to sunlight. Uroporphyrin overproduction was greatly reduced and skin changes reversed in a girl who received a bone-marrow graft from an HLA-identical sibling at 10 years of age. The patient died 11 months after transplantation because of severe progressive pneumonitis and encephalopathy associated with cytomegalovirus infection, but the encouraging response up to 8 months after engraftment indicates a possible benefit of bone-marrow transplantation in the treatment of this rare but usually fatal inherited disease.

Liver transplantation for protoporphyria. Evidence for the predominant role of the erythropoietic tissue in protoporphyrin overproduction.

Protoporphyria is an inherited disorder of heme biosynthesis characterized by an overproduction of protoporphyrin in the erythropoietic and hepatic tissues, the relative contribution of which in the metabolic disorder has not been directly quantitated. Excess protoporphyrin is eliminated solely by the liver into the bile and feces. We describe the case of a patient with protoporphyria complicated by severe cirrhosis in whom liver transplantation was performed and resulted in almost complete disappearance of skin photosensitivity manifestations and reduction in the level of protoporphyrin in erythrocytes. However, the level of protoporphyrin in feces was not markedly different before and after liver transplantation, which suggests that overproduction of protoporphyrin was unchanged. These findings are consistent with the view that the diseased liver and ensuing low hepatic clearance of protoporphyrin contributed to accumulation of protoporphyrin in the body and that, at least in this patient, the role of the hepatic tissue in the overproduction of protoporphyrin was small in comparison with that of the erythropoietic tissue.