New guidance on diagnosis, management of acute hepatic porphyrias

These genetic errors of heme metabolism, although rare, appear to be more common than previously thought, and recent treatment advances have improved the outlook for patients with the diagnoses, according to the American Gastroenterological Association.

The American Gastroenterological Association (AGA) recently issued guidance on diagnosis and management of acute hepatic porphyrias (AHP), which are rare, inborn errors of heme metabolism.

The most common AHP is acute intermittent porphyria (AIP); others include hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase. The rate of symptomatic AHP is thought to be about 1 in 100,000, but genetic studies have shown that as many as 1 in 1,300 people may have a pathogenic variant for AIP.

AHP is associated with chronic symptoms and risk of systemic arterial hypertension, renal and liver disease, and hepatocellular carcinoma, but recent advances in treatment have improved outcomes, the AGA said. The organization offered 12 best practice advice statements:

  • Clinicians should consider screening for AHP in women ages 15 to 50 years with unexplained, recurrent severe abdominal pain without a clear etiology after an initial workup.
  • Initial diagnosis of AHP should be made by biochemical testing, measuring δ aminolevulinic acid, porphobilinogen, and creatinine on a random urine sample.
  • Genetic testing should confirm the diagnosis of AHP in patients with positive biochemical testing.
  • Clinicians should treat acute attacks of AHP that are severe enough to require hospital admission using IV hemin, given daily, preferably into a high-flow central vein.
  • In addition to IV hemin, management of acute attacks of AHP should include pain control, antiemetics, management of systemic arterial hypertension, tachycardia, and hyponatremia, and hypomagnesemia, if present.
  • Clinicians should counsel patients to avoid identifiable triggers that may precipitate acute attacks, such as alcohol and porphyrinogenic medications.
  • In patients with recurrent attacks (four or more per year), clinicians should consider prophylactic heme therapy or givosiran, administered in an outpatient setting.
  • Liver transplantation for AHP should be limited to patients with intractable symptoms and significantly decreased quality of life who are refractory to pharmacotherapy.
  • Patients with AHP should receive annual monitoring for liver disease.
  • Patients with AHP, regardless of the severity of symptoms, should undergo surveillance for hepatocellular carcinoma, beginning at age 50 years, with liver ultrasound every six months.
  • Patients with AHP on treatment should undergo surveillance for chronic kidney disease annually with serum creatinine and estimated glomerular filtration rate.
  • Clinicians should counsel patients on the chronic and long-term complications of AHP, including neuropathy, chronic kidney disease, hypertension, and hepatocellular carcinoma, and the need for long-term monitoring.

The clinical practice update was published Jan. 13 by Gastroenterology.