Avoid Split Liver Transplant for EPP Patients, Case Study Recommends

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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After the death of a 20-year-old man with erythropoietic protoporphyria (EPP), clinicians in Japan reported that a split liver transplant — a procedure in which an organ donor’s liver is divided and transplanted into two different people — may not be an effective treatment for EPP patients with liver failure.

“Living donor [liver transplant] as an elective procedure at an earlier stage of EPP might be more suitable, given the unpredictable disease progression after [liver transplant] in patients with EPP,” the authors wrote in a case report.

“Split liver transplantation should preferably be avoided,” the team wrote, nonetheless acknowledging that such a transplant “is an indispensable tool to reduce the waitlist mortality among patients with liver failure.”

If a split liver transplant is needed, they said, “preparations should be made early.”

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The report, “Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication,” was published in the journal Pediatric Transplantation.

EPP is a rare inherited condition caused by the lack of an enzyme called ferrochelatase (FECH), which is necessary for the production of heme, a molecule in red blood cells that helps transport oxygen throughout the body.

The disorder leads to the harmful accumulation of protoporphyrins, which are precursors to vital compounds like heme. This buildup in liver cells — called hepatocytes — and in the tubes that collect bile causes cholestasis, a condition that occurs when the flow of bile from the liver is impaired. Bile is a digestive fluid that dissolves fats and helps remove metabolic waste products and toxins through the intestine.

Cholestasis combined with oxidative stress — a form of cellular damage caused by an imbalance in the production of oxidant molecules and the body’s ability to neutralize them — is called protoporphyric hepatopathy.

A liver transplant is often recommended to EPP patients with severe liver damage. However, this procedure does not cure the disease, which stems from cells in the bone marrow.

According to researchers, there has only been one report of a successful liver and bone marrow transplant to date. The lack of success highlights how difficult it is to treat protoporphyric hepatopathy. A partial or split liver transplant is another option for people with protoporphyric hepatopathy, but complications can occur.

Japanese researchers now reported the case of an EPP patient who underwent a split liver transplant and died when his symptoms returned, followed by cholestasis and bile leakage.

The man was diagnosed with EPP during childhood, and 15 years later developed protoporphyric hepatopathy and liver damage. As a result, he was referred for a liver transplant.

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Doctors performed an erythrocyte porphyrin test, which measures the amount of porphyrins in red blood cells, or erythrocytes. His noncomplexed, or free, protoporphyrin level was 8,852 micrograms per deciliter (mcg/dL; normal range: 0–35 mcg/dL). Genetic tests showed he had a mutation in the FECH gene.

Due to health problems, neither his father, an EPP carrier, nor his mother, were suitable liver donors. Therefore, he was placed on a deceased donor liver transplant waiting list.

“Our plan was to proceed with sequential [bone marrow transplant with the patient’s brother as a potential donor] … when the patient fully recovered following [liver transplant],” the authors wrote.

The man ultimately underwent a split liver transplant with a portion of a liver from a 53-year-old donor.

However, nearly a month later, doctors found that his erythrocyte protoporphyrin level had increased from 4,404 mcg/dL, as measured about two weeks after surgery, to 7,909 mcg/dL. He also had mild cholestasis and a liver biopsy showed the presence of crystal deposits in a Maltese cross pattern. Altogether, the findings indicated he experienced a recurrence of EPP.

Efforts to control his bile leakage failed, and later a difficult-to-treat bacterial infection caused by methicillin-resistant Staphylococcus aureus (MRSA) triggered severe liver graft failure.

The man eventually became bedridden and developed motor neuropathy, a complication of EPP. He died after going into septic shock, a life-threatening condition in which blood pressure drops to a low level after an infection.

“We managed a patient with EPP-induced liver failure who underwent [split liver transplant] but died from multiple postoperative complications that most likely stemmed from a deadly combination of disease recurrence and biliary complication,” the authors wrote.

The team recommended that such transplants be avoided and added that, if the procedure is deemed necessary, it “should be discussed in detail by a multidisciplinary team.”

“Appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft,” they concluded.