Living-Donor Liver Transplantation for Erythropoietic Protoporphyria: A Case Report and Literature Review.

Erythropoietic protoporphyria (EPP) is a very rare disease with an estimated prevalence of 1 in 200,000 individuals. Decreased ferrochelatase activity causes the accumulation of protoporphyrin in the body, and light exposure results in the generation of active oxygen, causing photosensitivity. Liver damage has the greatest influence on the prognosis, and liver transplantation is the only treatment option for patients with decompensated liver cirrhosis. We report a case of living-donor liver transplantation for decompensated liver cirrhosis associated with EPP. The patient was a 52-year-old male who led a normal life except for mild photosensitivity. When the patient was 37-year-old, hepatic dysfunction was noticed. At 48-year-old, high erythrocyte protoporphyrin levels, skin biopsy, and genetic tests resulted in a diagnosis of EPP. The patient underwent living- donor liver transplantation because of decompensated liver cirrhosis. In the operating room and intensive care unit, a special light-shielding film was applied to all light sources to block light with harmful wavelengths during treatment. Due to the need for special measures, a lecture on patients with EPP was given before surgery to deepen understanding among all medical professionals involved in the treatment. As a result, no adverse events occurred during the perioperative period, and the patient was discharged on the 46th post-operative day. Currently, the transplanted liver is functioning extremely well, and the patient is alive 3 years post-transplant. Herein, we describe a case of living donor liver transplantation for EPP with a brief literature review.

Recovery From Severe Systemic Peripheral Neuropathy Secondary to Erythropoietic Protoporphyria by Liver Transplant: A Case Report.

Erythropoietic protoporphyria is a rare inherited metabolic disorder involving the heme biosynthesis pathway and leads to the accumulation of protoporphyrin in the erythrocytes or liver. Although peripheral neuropathy is known to develop occasionally in other types of porphyria, it rarely occurs in patients with erythropoietic protoporphyria. A 16-year-old boy was transferred to our hospital due to end-stage liver disease secondary to erythropoietic protoporphyria. Severe systemic peripheral neuropathy, similar to that presented in Guillain-Barré syndrome, developed; it was promptly managed with mechanical ventilation. Electrophysiological assessment of the presented neuropathy showed no responsiveness, indicating severe axonopathy. Six weeks after the transfer, liver transplant was performed.Postoperatively, hepatorenal syndromes improved immediately, and his erythrocyte protoporphyrin level decreased from 6291 to 174 µg/dL red blood cells.The patient started to move his limbs gradually and was weaned from mechanical ventilation 2 months after liver transplant. Eventually, he was discharged from hospital and was able to ambulate with assistance 10 months after liver transplant. To our knowledge, this is the first report detailing the clinical course in a patient with erythropoietic protoporphyria who recovered from severe systemic peripheral neuropathy after liver transplant.

Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. CASE PRESENTATION: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. CONCLUSION: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

Successful Liver Transplantation for Liver Failure With Erythropoietic Protoporphyria by Covering the Operating Theater Lights With Polyimide Film: A Case Report.

BACKGROUND: Erythropoietic protoporphyria is a rare disease of heme biosynthesis resulting in excessive accumulation of protoporphyrin in various organs. The most typical symptom is photosensitivity caused by activated protoporphyrins (wavelength ~400 nm). Accumulated protoporphyrin in the liver also causes liver failure, and liver transplantation is the only life-saving treatment. Phototoxic injury to abdominal organs has been reported during liver transplantation. Thus, to avoid phototoxic injury during liver transplantation, it has previously been conducted with only shadowless lights and ceiling lights off in the operating theater. Here, we report a case of a safe and successful liver transplantation in a patient with erythropoietic protoporphyria where the operating theater lights were covered with polyimide film. CASE PRESENTATION: A 50-year-old man presented with hepatic failure owing to erythropoietic protoporphyria. Before liver transplantation, the shadowless lights and ceiling lights in the operating theater were covered entirely with polyimide film. This filter completely blocked the harmful wavelength of light (400-470 nm). Orthotopic liver transplantation was safely and successfully performed with adequate illumination and patient monitoring. The patient followed a normal postoperative course without phototoxic injuries or protoporphyrin re-accumulation. CONCLUSION: Covering not only shadowless lights but also all ceiling lights in the operating theater with the polyimide film allowed safe surgery, safe anesthesia, and safe monitoring of the patient who underwent liver transplantation for severe liver failure owing to erythropoietic protoporphyria.

Perioperative Anesthetic Management of Patients Having Liver Transplantation for Uncommon Conditions.

This review focuses on the perioperative anesthetic management of patients having liver transplantation (LT) performed for several uncommon indications or in combination with rare pathology. Conditions discussed in the article include Alagille syndrome, hypertrophic cardiomyopathy, Gilbert's syndrome, porphyria, Wilson's disease, and Budd-Chiari syndrome. In comparison to other indications, LT in these settings is infrequent because of the low incidence of these pathologies. Most of these conditions (with the exception of Gilbert syndrome) are associated with a high probability of significant perioperative complications and increased mortality and morbidity. Experience in management of these unusual conditions is only gained over time. Developing clinical pathways for patients with these conditions should result in outcomes similar to LT performed for more common indications.

[Cutaneous changes in long-standing erythropoietic protoporphyria]. / Hautveränderungen bei lange bestehender erythropoetischer Protoporphyrie.

Erythropoietic protoporphyria results in highly increased photosensitivity of the skin. Solar irradiation causes sunburn-like symptoms with erythema, edema and wheals. We report the case of a 60-year-old man suffering from erythropoietic protoporphyria since his childhood who additionally developed chronic cutaneous lichenoid papules in sun-exposed skin areas. Vaporization with both electrocautery and carbon dioxide laser proved to be a successful treatment option.

Total hip arthroplasty in very young bone marrow transplant patients.

Concerns remain about total hip arthroplasty (THA) performed in very young patients, especially those with complex medical history such as allogeneic bone marrow transplantation (ABMT). This study retrospectively reviews the perioperative courses and functional outcomes of ABMT patients <21 years old undergoing primary uncemented THA. Nine THAs were performed in five ABMT patients at an average age of 19.7 years. The interval between ABMT and THA was 73.0 months with clinical follow-up of 25.8 months. Harris Hip Scores (HHS) increased dramatically from preoperatively 44.5 (range, 31.1-53.4) to postoperatively 85.2 (range, 72.0-96.0) and all patients subjectively reported a good (four hips) to excellent (five hips) overall outcome. There was one reoperation for periprosthetic fracture fixation but there were no infections or revisions performed. Despite the history of severe hematopoietic conditions requiring ABMT, these very young patients do appear to have improved pain and function following primary THA with short-term follow-up.

Delayed immune recovery following sequential orthotopic liver transplantation and haploidentical stem cell transplantation in erythropoietic protoporphyria.

A nine-yr-old boy with EPP suffered from severe skin burns and liver failure caused by progressive cholestasis and fibrosis. OLT was performed without major complications. Four months following liver transplantation he underwent parental haploidentical HSCT. The myeloablative conditioning regimen was relatively well tolerated and hematological engraftment was rapid (on day 10). Protoporphyrin concentrations returned to normal following HSCT. However, immune recovery was significantly delayed. Varicella zoster virus reactivation resulted in impaired vision, prolonged hospitalization and eventually in multiorgan failure and death. Sequential liver and haploidentical HSCT proved feasible though a high risk procedure in this EPP patient. The management of post-IST after these combined transplantations remains a challenge and needs to be further established.

Bone marrow-derived cells promote liver regeneration in mice with erythropoietic protoporphyria.

BACKGROUND: Bone marrow transplantation can reverse hepatic protoporphyrin accumulation and prevent the hepatobiliary complications characteristic of erythropoietic protoporphyria. The aim of this study was to assess the recruitment capacity of bone marrow cells in the damaged liver and their possible contribution to the improved or recovered hepatic function in a murine model of erythropoietic protoporphyria (EPP). METHODS: Lethally irradiated female EPP mice were transplanted with bone marrow cells from healthy male mice and were monitored during 12 or 36 weeks. Two groups of animals killed 12 weeks after transplant were also treated with granulocyte colony-stimulating factor. RESULTS: Cell transplantation decreased porphyrin contents in erythrocytes and liver. Improved hepatic structure and function and reduced hepatic fibrosis were observed, especially 36 weeks after transplant. Bone marrow-derived cells (22%-35%) were identified in the liver of recipient mice by means of fluorescence in situ hybridization (chrY-FISH) or green fluorescent protein staining and were characterized by immunofluorescence staining. The livers of recipients contained 20% to 30% myofibroblasts (alpha-smooth muscle actin-positive cells), 40% CK19-positive cells, and 10% to 28% hepatocytes (albumin-positive cells) derived from the donor bone marrow. CONCLUSIONS: Bone marrow-derived cells play a significant role in restoring and regenerating hepatic tissue in EPP mice. Hepatic repair was associated with fibrogenesis, enhanced by granulocyte colony-stimulating factor treatment, and almost normal liver structure and function was observed in the long term (36 weeks posttransplant).

Protection from phototoxic injury during surgery and endoscopy in erythropoietic protoporphyria.

Erythropoietic protoporphyria is an inherited condition characterized by pronounced solar photosensitivity and in a minority of patients severe liver disease that necessitates liver transplantation for survival. Phototoxic injury to abdominal organs and skin has been reported in several cases of liver transplantation surgery, including a few transplants in which protective light filters were used. This study discusses the optimal characteristics of light filters used during liver transplantation surgery. An experimental model is used to evaluate the relative protection of different filters, and the results are compared with theoretical calculations regarding the risk for phototoxic injury from light sources in health-care procedures. Whether protective measures are warranted in other illuminated procedures besides liver transplantation has been discussed often but never studied. This study elucidates the risk for phototoxic injury in endoscopy, laparoscopy, and non-liver transplant surgery. A theoretical model and epidemiological data are considered. Our findings indicate that endoscopy, laparoscopy, and surgical procedures other than liver transplantation are safe in the noncholestatic protoporphyria patient and that general recommendations for using filters in these situations are not warranted. Among the tested filters, a flexible yellow filter omitting wavelengths below 470 nm is recommended for liver transplant surgery. This filter has been readily accepted by surgeons and offers a good balance between protection and altered visual color perception. The experimental model, using hemolysis of protoporphyrin-loaded erythrocytes as a measure of phototoxicity, has substantiated theoretical findings on relative filter protection.

Liver transplantation for erythropoietic protoporphyria with hepatic failure: a case report.

Erythropoietic protoporphyria (EPP) is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excessive production and biliary excretion of protoporphyrin. The main clinical features--photosensitivity and hepatobiliary disease that may progress to liver failure--are caused by the toxicity of protoporphyrin. Orthotopic liver transplantation is an effective treatment of liver failure caused by EPP. In this report we have described an EPP Chinese man with end-stage liver disease. He was successfully transplanted. A 3-year follow-up study of protoporphyrin levels, liver tests, and liver biopsies showed no EPP recurrence after liver transplantation.

Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis.

We report the case of a middle-age patient presenting with severe progressive protoporphyric cholestasis. To halt further progression of liver disease, medical treatment was given aimed at different mechanisms possibly causing cholestasis in erythropoietic protoporphyria. Within eighty days, liver biochemistry completely normalized and liver histology markedly improved. Bone marrow transplantation was performed to prevent relapse of cholestatic liver disease by correcting the main site of protoporphyrin overproduction. Thirty-three months after cholestatic presentation and ten months after bone marrow transplantation, liver and porphyrin biochemistry remains normal. The patient is in excellent condition and photosensitivity is absent. The theoretical role of each treatment used to successfully reverse cholestasis and the role of bone marrow transplantation in erythropoietic protoporphyria are discussed. Medical treatment can resolve hepatic abnormalities in protoporphyric cholestasis. Bone marrow transplantation achieves phenotypic reversal and may offer protection from future protoporphyric liver disease.

Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria.

Erythropoietic protoporphyria is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excess production and biliary excretion of protoporphyrin. The main clinical features, photosensitivity and hepatobiliary disease that may progress to liver failure, are caused by the toxicity of protoporphyrin. Liver transplantation has been used to treat liver failure in erythropoietic protoporphyria, but excess production of protoporphyrin by the bone marrow continues causing recurrence of liver disease in the majority of patients. This is the first report of successful sequential liver and bone marrow transplantation in a patient with liver failure as a result of erythropoietic protoporphyria. This combination corrected the severe phenotype, resolving the severe photosensitivity and halting erythropoietic protoporphyria associated liver graft injury. Splenectomy seemed to facilitate the successful bone marrow transplant.

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.