AGA 急性肝卟啉症诊断和治疗临床实践更新:专家评审,Gastroenterology

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DescriptionThe acute hepatic porphyrias (AHP) are rare, inborn errors of heme-metabolism and include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase. Acute intermittent porphyria is the most common type of AHP, with an estimated prevalence of patients with symptoms of approximately 1 in 100,000. The major clinical presentation involves attacks of severe pain, usually abdominal and generalized, without peritoneal signs or abnormalities on cross-sectional imaging. Acute attacks occur mainly in women in their childbearing years. AHP should be considered in the evaluation of all patients, and especially women aged 15–50 years with recurrent severe abdominal pain not ascribable to common causes. The screening tests of choice include random urine porphobilinogen and δ-aminolevulinic acid corrected to creatinine. All patients with elevations in urinary porphobilinogen and/or δ-aminolevulinic acid should initially be presumed to have AHP. The cornerstones of management include discontinuation of porphyrinogenic drugs and chemicals, administration of oral or intravenous dextrose and intravenous hemin, and use of analgesics and antiemetics. Diagnosis of AHP type can be confirmed after initial treatment by genetic testing for pathogenic variants in HMBS, CPOX, PPOX, and ALAD genes. AHP is also associated with chronic symptoms and long-term risk of systemic arterial hypertension, chronic renal and liver disease, and hepatocellular carcinoma. Patients who have recurrent acute attacks (4 or more per year) should be considered for prophylactic therapy with intravenous hemin or subcutaneous givosiran. Liver transplantation is curative and reserved for patients with intractable symptoms who have failed other treatment options.

MethodsThis expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations.

Best Practice Advice Statements

Best Practice Advice 1Women aged 15–50 years with unexplained, recurrent severe abdominal pain without a clear etiology after an initial workup should be considered for screening for an AHP.

Best Practice Advice 2Initial diagnosis of AHP should be made by biochemical testing measuring δ-aminolevulinic acid, porphobilinogen, and creatinine on a random urine sample.

Best Practice Advice 3Genetic testing should be used to confirm the diagnosis of AHP in patients with positive biochemical testing.

Best Practice Advice 4Acute attacks of AHP that are severe enough to require hospital admission should be treated with intravenous hemin, given daily, preferably into a high-flow central vein.

Best Practice Advice 5In addition to intravenous hemin, management of acute attacks of AHP should include pain control, antiemetics, management of systemic arterial hypertension, tachycardia, and hyponatremia, and hypomagnesemia, if present.

Best Practice Advice 6Patients should be counseled to avoid identifiable triggers that may precipitate acute attacks, such as alcohol and porphyrinogenic medications.

Best Practice Advice 7Prophylactic heme therapy or givosiran, administered in an outpatient setting, should be considered in patients with recurrent attacks (4 or more per year).

Best Practice Advice 8Liver transplantation for AHP should be limited to patients with intractable symptoms and significantly decreased quality of life who are refractory to pharmacotherapy.

Best Practice Advice 9Patients with AHP should be monitored annually for liver disease.

Best Practice Advice 10Patients with AHP, regardless of the severity of symptoms, should undergo surveillance for hepatocellular carcinoma, beginning at age 50 years, with liver ultrasound every 6 months.

Best Practice Advice 11Patients with AHP on treatment should undergo surveillance for chronic kidney disease annually with serum creatinine and estimated glomerular filtration rate.

Best Practice Advice 12Patients should be counseled on the chronic and long-term complications of AHP, including neuropathy, chronic kidney disease, hypertension, and hepatocellular carcinoma, and need for long-term monitoring.