<scp>EXPLORE</scp> B: A prospective, long‐term natural history study of patients with acute hepatic porphyria with chronic symptoms

Cassiman, David; Kauppinen, Raili; Monroy, Susana; Lee, Ming‐Jen; Bonkovsky, Herbert L.; Thapar, Manish; Guillén‐Navarro, Encarna; Minder, Anna‐Elisabeth; Hale, Cecilia; Sweetser, Marianne T.; Ivanova, Aneta

doi:10.1002/jimd.12551

Cited by 10 publications

(2 citation statements)

References 46 publications

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“…Currently, a significant and unresolved debate exists in the literature regarding the natural progression of patients with Acute Hepatic Porphyria. There is ongoing uncertainty surrounding the origin and mechanisms underlying the chronic symptoms observed in patients, leading to a dichotomy in the classification of patients into “sporadic attacks” and “recurrent attacks.” This classification dilemma has contributed to several uncertainties regarding the optimal medical management and treatment strategies for these individuals ( 6 , 8 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Neurofilament light chain as a biomarker for acute hepatic porphyrias

Sgobbi,

Serrano,

Badia

et al. 2024

Front. Neurol.

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BackgroundAcute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP.MethodsWe conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times (“high excretors”); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN).ResultsDuring acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy.ConclusionThis study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.

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Section: Discussionmentioning

confidence: 99%

Neurofilament light chain as a biomarker for acute hepatic porphyrias

Sgobbi,

Serrano,

Badia

et al. 2024

Front. Neurol.

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“…• Intense pain, mainly in the abdomen, requiring hospital admission attacks. 33 In a different observational study, chronic symptoms were reported in 85% of AIP patients with sporadic attacks (< four attacks/year) and 46% of patients with latent AIP (no attacks). 34 Chronic pain is usually the most commonly reported symptom, followed by tiredness, anxiety, nausea and sleeping disorders.…”

Section: Laboratory Findingsmentioning

confidence: 96%

Portuguese Consensus on Acute Porphyrias: Diagnosis, Treatment, Monitoring and Patient Referral

Brito Avô,

Pereira,

Oliveira

et al. 2023

Acta Med Port

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Acute porphyrias are a group of rare genetic metabolic disorders, caused by a defect in one of the enzymes involved in the heme biosynthesis, which results in an abnormally high accumulation of toxic intermediates. Acute porphyrias are characterized by potentially life-threatening attacks and, for some patients, by chronic manifestations that negatively impact daily functioning and quality of life. Clinical manifestations include a nonspecific set of gastrointestinal, neuropsychiatric, and/or cutaneous symptoms. Effective diagnostic methods are widely available, but due to their clinical heterogeneity and non-specificity, many years often elapse from symptom onset to diagnosis of acute porphyrias, delaying the treatment and increasing morbidity. Therefore, increased awareness of acute porphyrias among healthcare professionals is paramount to reducing disease burden. Treatment of acute porphyrias is centered on eliminating the potential precipitants, symptomatic treatment, and suppressing the hepatic heme pathway, through the administration of hemin or givosiran. Moreover, properly monitoring patients with acute porphyrias and their relatives is fundamental to preventing acute attacks, hospitalization, and long-term complications. Considering this, a multidisciplinary panel elaborated a consensus paper, aiming to provide guidance for an efficient and timely diagnosis of acute porphyrias, and evidence-based recommendations for treating and monitoring patients and their families in Portugal. To this end, all authors exhaustively reviewed and discussed the current scientific evidence on acute porphyrias available in the literature, between November 2022 and May 2023.

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EXPLORE B: A prospective, long‐term natural history study of patients with acute hepatic porphyria with chronic symptoms

Cassiman

Kauppinen²,

Monroy

et al. 2022

J of Inher Metab Disea

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One-year data from EXPLORE Part A showed high disease burden and impaired quality of life (QOL) in patients with acute hepatic porphyria (AHP) with recurrent attacks. We report baseline data of patients who enrolled in EXPLORE Part B for up to an additional 3 years of follow-up. EXPLORE B is a long-term, prospective study evaluating disease activity, pain intensity, and QOL in patients with AHP with ≥1 attack in the 12 months before enrollment or receiving hemin or gonadotropin-releasing hormone prophylaxis. Data were evaluated in patients with more (≥3 attacks or on prophylaxis treatment) or fewer (<3 attacks and no prophylaxis treatment) attacks. Patients in the total population (N = 136), and more (n = 110) and fewer (n = 26) attack subgroups, reported a median (range) of 3 (0-52), 4 (0-52), and 1 (0-2) acute attacks, respectively, in the 12 months prior to the baseline visit. Pain, mood/sleep, digestive/bladder, and nervous system symptoms were each experienced by ≥80% of patients; most received hemin during attacks. Almost

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EXPLORE B: A prospective, long‐term natural history study of patients with acute hepatic porphyria with chronic symptoms

Cited by 10 publications

References 46 publications

Neurofilament light chain as a biomarker for acute hepatic porphyrias

Neurofilament light chain as a biomarker for acute hepatic porphyrias

Portuguese Consensus on Acute Porphyrias: Diagnosis, Treatment, Monitoring and Patient Referral

EXPLORE B: A prospective, long‐term natural history study of patients with acute hepatic porphyria with chronic symptoms

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