Liver abnormalities are common in people with porphyrias EPP, XLP
Dysfunction may be tied to risk of worse outcomes for some patients
Liver abnormalities are common among people with erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP), a large U.S. study suggests.
While the abnormalities were mild in most cases, in a small fraction of patients they may be tied to a risk of worse outcomes. In fact, at least half the reported deaths were associated with liver disease.
These findings call attention to the need of “earlier recognition, close monitoring, better understanding, and effective management of liver involvement in patients with protoporphyria,” the researchers wrote. The study, “Liver involvement in a large cohort of patients with erythropoietic protoporphyria or X-linked protoporphyria,” was published in Hepatology Communications.
Porphyria refers to a group of genetic disorders that result from impairments in producing heme, a molecule crucial for oxygen transport in red blood cells. Each form of porphyria is linked to a deficiency or malfunction of a specific enzyme involved in producing heme that causes heme precursors to build up to toxic levels.
EPP and XLP are caused by mutations in the FECH and ALAS2 genes, leading to elevated protoporphyrin levels. Studies have shown that EPP and XLP patients have a higher risk of developing liver abnormalities, but there’s still “limited information on the determinants of risk and progression of liver disease,” in these patients.
Liver problems in EPP, XLP
Here, researchers in the U.S. analyzed data from EPP and XLP patients enrolled in the Longitudinal Study of the Porphyrias (NCT01561157), which was conducted across 12 sites in the National Institutes of Health (NIH)-supported Porphyrias Consortium.
The analysis included data from 322 patients who were a median age of 33.3. Most were diagnosed with EPP (91.3%), while 8.7% had XLP. The patients were followed for a median of 3.9 years. Half (52%) were women and most were white (95.3%).
Liver analyses were available for 235 patients (73%) at or within a year of their enrollment and abnormalities were found in 132 of them (56.2%), most being mild. In 50 patients, abnormal liver test results were sustained for at least six months.
Eleven patients (eight with EPP, three with XLP) had advanced protoporphyric hepatopathy, a severe liver condition marked by liver damage and progressive liver failure that can occur in both conditions as a result of protoporphyrins accumulating in the liver.
Fifty-four patients underwent surgery to remove the gallbladder, called a cholecystectomy. Most (49 patients) had the surgery before they enrolled in the study. Eight patients required a liver transplant, while four had a bone marrow transplant.
The need for a liver transplant was higher among XLP patients than among those with EPP, which suggests “XLP may confer greater risk, perhaps due to higher protoporphyrin levels,” the researchers wrote.
Eight patients died. In four cases, the cause of death was liver failure due to protoporphyric hepatopathy. Two others died as a result of complications of a bone marrow transplant. One patient died from hepatocellular carcinoma, the most common type of liver cancer.
“These findings … highlight the need to identify and evaluate at-risk patients early, monitor for disease progression, and select those who might benefit from disease-modifying treatments as these become available,” the researchers wrote.
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