Therapeutic approach to acute crises of hepatic porphyrias

Abstract

Acute hepatic porphyria is a genetic disorder affecting enzymes involved in heme biosynthesis. The most common subtype is acute intermittent porphyria, accounting for 80% of cases. Other types include hereditary coproporphyria, variegate porphyria, and delta-aminolevulinic acid dehydratase deficiency.

Attacks in acute hepatic porphyria are triggered by the induction of hepatic ALA synthase 1, leading to the accumulation of neurotoxic heme intermediates, delta-aminolevulinic acid, and porphobilinogen. Women experience attacks more frequently than men.

Acute porphyria attacks are characterized by severe, diffuse abdominal pain, muscle weakness, autonomic neuropathy (including hypertension, tachycardia, nausea, vomiting, and constipation), and changes in mental status. Early recognition of the disease is crucial as it requires urgent medical attention and treatment. Management includes intravenous opioids, glucose, hemin, and the removal of triggering factors.

Preventive treatment options include hormone suppression therapy, off-label prophylactic hemin, Givosiran, and exceptionally liver transplantation.