What is the treatment for acute hepatic porphyria?

Treatment of Acute Hepatic Porphyria

Acute attacks severe enough to require hospitalization must be treated immediately with intravenous hemin at 3-4 mg/kg body weight daily for 4 days, preferably through a high-flow central vein, combined with aggressive pain control and supportive care. 1

Acute Attack Management

Primary Treatment: Intravenous Hemin

• Administer hemin 3-4 mg/kg body weight once daily for typically 4 days 1, 2
• Deliver preferably into a high-flow central vein via peripherally inserted central catheter (PICC) or central port to minimize thrombophlebitis risk 1
• Use heme bound to human serum albumin when available for better vein tolerance and heme stabilization 1
• Collect random urine for ALA, PBG, and creatinine before starting hemin treatment 1
• Hemin rapidly down-regulates hepatic ALAS1 expression, stopping overproduction of neurotoxic ALA and PBG 1
• Symptom relief typically requires 48-72 hours, though neurologic recovery varies significantly 1
• Clinical response occurs in 85.5% of treatment courses based on FDA-reviewed studies 2

Essential Supportive Care

• Stop all precipitating factors immediately, particularly medications that induce cytochrome P450 enzymes 1
• Provide aggressive pain management with appropriate analgesics (opioids are safe in AHP) 1, 3
• Administer antiemetics for nausea and vomiting 1, 3
• Give intravenous carbohydrate loading at approximately 300 g/day in adults during early attack stages 1
• Monitor and correct electrolytes, particularly hyponatremia and hypomagnesemia, which occur from hypovolemia and SIADH 1
• Correct hyponatremia slowly if present 1

Seizure Management (Critical Caveat)

• Avoid barbiturates, hydantoins, carbamazepine, and valproic acid - these are contraindicated in AHP 1
• Safe anticonvulsant options include: magnesium sulfate, benzodiazepines, and levetiracetam 1

Prevention of Recurrent Attacks

Trigger Avoidance

• Counsel all patients to avoid: alcohol, porphyrinogenic medications, fasting/caloric deprivation, tobacco, physical/psychological stress, and acute illness 1
• Consult online drug safety databases at https://www.porphyria.org/patient-resources/drug-safety-database-for-ahp/ 1
• Sex hormones, particularly progesterone, are known attack precipitants 1

Prophylactic Therapy for Recurrent Attacks (≥4 attacks/year)

• Consider givosiran (subcutaneous RNAi therapy targeting hepatic ALAS1) or prophylactic hemin infusions 1, 3
• Givosiran represents the most effective prophylactic treatment, providing durable normalization of ALA levels and significantly reducing attack frequency 4
• Prophylactic hemin can be given weekly or once-twice during luteal phase for cyclic attacks, though timing is often difficult 1
• Chronic hemin use carries risks: need for indwelling central catheters, infections, and iron overload requiring screening 1

Management of Menstrual-Associated Attacks

• First-line approach: GnRH analogues initiated during days 1-3 of cycle to prevent ovulation 1
• Add low-dose estradiol skin patch after 3 months if GnRH analogue prevents attacks, to prevent menopausal symptoms and bone loss 1
• Do not continue GnRH treatment beyond 6 months without low-dose estrogen supplementation 1
• Avoid progesterone-only contraceptives (implants, IUDs with progesterone) as these achieve significant systemic levels 1
• Low-dose estrogen-progestin combinations may be tolerated but use with caution 1
• Barrier methods and progesterone-free IUDs are safe 1

Long-Term Monitoring and Complications

Follow-Up Schedule

• Symptomatic patients require at least annual follow-up, more frequently if receiving prophylactic treatment or having continued attacks 1
• Schedule follow-up within one month after hospitalization for acute attack 1

Hepatocellular Carcinoma Surveillance

• Perform liver imaging every 6-12 months after age 50 in patients with recurrent attacks or past symptoms 1
• Measure serum alpha-fetoprotein, though it is not elevated in most AHP patients with HCC 1
• HCC risk is well-documented and develops more commonly in symptomatic patients over age 60 1
• No evidence of increased HCC risk in latent porphyria cases 1

Additional Monitoring

• Screen for chronic kidney disease and hypertension - chronic renal disease occurs in up to 29-59% of symptomatic AIP patients 5, 6
• Assess for chronic neuropathy in patients with history of severe attacks 6
• Screen for iron overload in patients receiving chronic prophylactic hemin 1

Psychiatric and Pain Management

• Refer patients with chronic pain to pain management specialists to optimize treatment and manage opioid dependence risk 1
• Provide psychiatric evaluation and treatment for co-existent anxiety or depression, which significantly impact quality of life 1

Treatment of Last Resort

Liver Transplantation

• Orthotopic liver transplantation is curative but reserved for severe, disabling, intractable attacks refractory to hemin therapy 1
• OLT carries significant morbidity and mortality, making it a last resort option 1
• Patients with advanced neuropathy, quadriplegia, and respiratory paralysis are poor transplant candidates 1
• Combined liver-kidney transplantation benefits some patients with both recurrent attacks and end-stage renal disease 1