Porphyrin precursors and risk of primary liver cancer in acute intermittent porphyria: A case–control study of 188 patients

Lissing, Mattias; Wester, Axel; Vassiliou, Daphne; Floderus, Ylva; Harper, Pauline; Sardh, Eliane; Wahlin, Staffan

doi:10.1002/jimd.12676

Cited by 6 publications

(1 citation statement)

References 38 publications

(124 reference statements)

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“…Several studies have found a connection between porphyria and other diseases [ 13 – 15 ]. In fact, a possible association between AIP and liver cancer was identified in a cohort study through investigation on porphyria biomarkers [ 16 ]. In another cohort study comprising patients with AIP, researchers confirmed a high risk of primary liver cancer and identified a strong association with AIP biomarkers [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Causal effect of porphyria biomarkers on alcohol-related hepatocellular carcinoma through Mendelian Randomization

Yang,

Wang,

Sun

et al. 2024

PLoS ONE

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Purpose According to some cohort studies, an association exists between acute intermittent porphyria (AIP) and liver cancer. However, establishing a definitive causal relationship between porphyria and hepatocellular carcinoma (HCC) remains challenging. Prexisting studies regarding porphyria biomarkers and alcohol-related hepatocellular carcinoma (AR-HCC) make possible an entry point. In this study, we aimed to investigate the causal relationships between biomarkers of two types of porphyria, AIP and congenital erythropoietic porphyria (CEP), and AR-HCC. Methods Single-nucleotide polymorphisms (SNPs) associated with porphobilinogen deaminase (PBGD) and uroporphyrinogen-III synthase (UROS), along with outcome data on AR-HCC, were extracted from public genome-wide association studies (GWAS). The GWAS data were then used to explore the potential causal relationships via a two-sample Mendelian randomization (MR) analysis. The effect estimates were calculated using the random-effect inverse-variance-weighted (IVW) method. Additionally, the Cochrane’s Q test, MR-Egger test, and leave-one-out analysis were conducted to detect heterogeneity and pleiotropy in the MR results. Results Using the IVW method as the primary causal effects model in the MR analyses, we found that both PBGD (effect estimate = 1.51; 95% CI, from 1.08 to 2.11, p = 0.016) and UROS (effect estimate = 1.53; 95% CI, from 1.08 to 2.18, p = 0.018) have a significant causal effect on AR-HCC. Conclusion Our findings revealed a causal effect of both PBGD and UROS on AR-HCC, suggesting that both AIP and CEP have a causal association with AR-HCC.

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Section: Introductionmentioning

confidence: 99%

Causal effect of porphyria biomarkers on alcohol-related hepatocellular carcinoma through Mendelian Randomization

Yang,

Wang,

Sun

et al. 2024

PLoS ONE

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Nontargeted urine metabolomic analysis of acute intermittent porphyria reveals novel interactions between bile acids and heme metabolism: New promising biomarkers for the long‐term management of patients

Lefebvre,

Eguether,

Thévenot

et al. 2024

J of Inher Metab Disea

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Acute intermittent porphyria is an inherited error of heme synthesis. The underlying pathophysiology, involving mainly hepatic heme synthesis, is poorly understood despite its occurrence, and the severity of acute porphyria attack is still difficult to control. A better understanding of the interactions between heme synthesis and global metabolism would improve the management of AIP patients. An untargeted metabolomic analysis was performed on the urine of 114 patients with overt AIP and asymptomatic carriers using liquid chromatography coupled to high‐resolution mass spectrometry. The collected data were analyzed by combining univariate and multivariate analyses. A total of 239 metabolites were annotated in urine samples by matching chromatographic and mass spectral characteristics with those from our chemical library. Twenty‐six metabolites, including porphyrin precursors, intermediates of tryptophan or glycine metabolism and, unexpectedly, bile acids, showed significant concentration differences between the phenotypic groups. Dysregulation of bile acid metabolism was confirmed by targeted quantitative analysis, which revealed an imbalance in favor of hydrophobic bile acids associated with changes in conjugation, which was more pronounced in the severe phenotype. Using a random forest model, the cholic acid/chenodeoxycholic acid ratio enables the differential classification of severe patients from other patients with a diagnostic accuracy of 84%. The analysis of urine samples revealed significant modifications in the metabolome of AIP patients. Alteration in bile acids provides new insights into the pathophysiology of chronic complications, such as primary liver cancer, while also providing new biomarker candidates for predicting the most severe phenotypes.

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Preguntas PICO y metodología DELPHI para mejorar el manejo de los pacientes con porfiria hepática aguda

Riera-Mestre,

García Morillo,

Castelbón Fernández

et al. 2024

Revista Clínica Española

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Porphyrin precursors and risk of primary liver cancer in acute intermittent porphyria: A case–control study of 188 patients

Cited by 6 publications

References 38 publications

Causal effect of porphyria biomarkers on alcohol-related hepatocellular carcinoma through Mendelian Randomization

Causal effect of porphyria biomarkers on alcohol-related hepatocellular carcinoma through Mendelian Randomization

Nontargeted urine metabolomic analysis of acute intermittent porphyria reveals novel interactions between bile acids and heme metabolism: New promising biomarkers for the long‐term management of patients

Preguntas PICO y metodología DELPHI para mejorar el manejo de los pacientes con porfiria hepática aguda

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