Regular Use of Blood Letting Shows Ability to Ease EPP Liver Disease
Phlebotomy, or regular rounds of blood letting, eased symptoms of liver injury in three people with erythropoietic protoporphyria (EPP), according to a small study.
Besides supporting the utility of phlebotomy in treating this patient population, study findings suggest a potential role for the ABCG2 protein in the mechanisms that underlie liver disease in EPP.
“Phlebotomy has proven to be an effective treatment option in EPP patients with severe liver damage. Further research is needed to elucidate the pathophysiology [disease mechanisms] of EPP in order to suppress porphyrin production and [ease] liver damage,” the researchers wrote.
The study, “Role of phlebotomy in the treatment of liver damage related to erythropoietic porphyria,” was published in the journal Scientific Reports.
Porphyria encompasses a group of genetic disorders characterized by impaired production of heme — a molecule that helps transport oxygen throughout the body. As a result, heme precursors, called porphyrins, build to toxic levels in different tissues and organs, disrupting their function.
EPP is a type of porphyria that is caused by mutations in the FECH gene, leading to the buildup of protoporphyrin in the skin, bone marrow, plasma (the liquid component of blood), and the liver.
While its hallmark symptom is light sensitivity due to the buildup of protoporphyrins in the skin, about 10–20% of patients also show liver injury as a result of its accumulation in liver cells. For some, this can lead to severe liver damage or failure.
Phlebotomy has emerged as a treatment approach for other types of porphyria, such as congenital erythropoietic porphyria (CEP). In the procedure, a portion of the patient’s blood is removed from the body at regular intervals. Over time, excess porphyrin levels fall and symptoms ease.
A team of researchers in Japan examined the clinical characteristics of liver disease in seven EPP patients (six males) with a median age of 31, and determined the therapeutic effects of phlebotomy in three of them.
Genetic testing confirmed the presence of FECH mutations in six patients. All seven people had elevated protoporphyrin blood levels and reported extreme light sensitivity.
Liver injury was also observed in all seven patients. Hepatocytes — the liver’s main functional cells — were injured in one person, while two people showed signs of cholestatic injury, or damage to the system that produces bile, a digestive fluid. Another patient had both types of injury, and three others could not be classified.
Jaundice, a yellowing of the skin indicative of liver disease, was initially observed in two people.
Patients were given three standard treatments — ursodeoxycholic acid, colestyramine, and cimetidine — in various combinations.
Due to a continued severity of liver damage, phlebotomy was added in three cases. Just before its initiation, all three patients had jaundice and significantly elevated protoporphyrin levels.
Two of these patients had started with five rounds plasma exchange therapy — a procedure in which a patient’s blood is passed through a machine that filters out the plasma and replaces it with fresh donor plasma. This treatment did not ease the liver injury.
Four rounds of phlebotomy were then performed for each person, with 400 mL of blood removed the first round and 200 mL each subsequent round. Phlebotomy led to reductions in protoporphyrins and an easing in liver injury in both patients.
The third patient underwent three rounds of phlebotomy without plasma exchange, and similar improvements were seen.
“Although the effectiveness of phlebotomy in EPP patients has been shown this time, it is necessary to investigate the mechanism … in the future,” the researchers wrote.
To understand mechanisms that might underlie liver damage in EPP, liver biopsies were performed on three patients, including two who underwent phlebotomy.
In these two patients, protoporphyrin accumulated in hepatocytes and the bile duct. Levels of the protein ABCG2 were low in areas of excessive protoporphyrin in these people, but not in the third patient who had less severe liver disease. ABCG2 is a protein involved in porphyrin transport, and its activity has been previously implicated in EPP.
These findings further support ABCG2’s potential role in the onset and worsening of liver dysfunction.
“However, we have not directly proved the causal relationship between the decreased expression of ABCG2 and liver damage, and further investigation is required in the future,” the researchers added.