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. 2020 Feb 21;15(1):56.
doi: 10.1186/s13023-019-1273-4.

Sick leave, disability, and mortality in acute hepatic porphyria: a nationwide cohort study

Carl Michael Baravelli  1   2 , Aasne Karine Aarsand  3   4 , Sverre Sandberg  3   5   4 , Mette Christophersen Tollånes  4
Affiliations

Sick leave, disability, and mortality in acute hepatic porphyria: a nationwide cohort study

Carl Michael Baravelli et al. Orphanet J Rare Dis. .

Abstract

Background: Acute hepatic porphyria (AHP) consists of three rare metabolic disorders. We investigated the risk of long-term sick leave, disability pension, and premature death in individuals with AHP compared to the general population.

Methods: In a nationwide cohort study from 1992 to 2017, records of 333 persons (total person-years = 6728) with a confirmed AHP diagnosis were linked to several national compulsory registries (reference population = 5,819,937). We conducted survival analyses to assess additional risk.

Results: Persons with AHP had higher risks of accessing long-term sick leave (adjusted hazard ratio (aHR): 1.5, 95% confidence interval (CI): 1.3, 1.7) and disability pension (aHR: 1.9, CI: 1.5, 2.4). The risk was highest in persons who had been hospitalised for acute attacks, while no additional risk was observed in asymptomatic AHP gene mutation carriers. The median age when accessing disability pension was 45 years, 21 years younger than the general population. AHP was associated with increased risk of mortality due to hepatocellular carcinoma (adjusted mortality rate ratio (aMRR): 84.4, CI: 37.8, 188.2), but no overall increased risk of premature death was observed.

Conclusions: Persons with symptomatic AHP were at increased risk of accessing long-term sick leave and disability pension but not of premature death.

Keywords: Acute hepatic porphyria; Acute intermittent porphyria; Disability pension; Hereditary coproporphyria; Long-term sick leave; Morbidity; Mortality; Premature death; Variegate porphyria.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of eligibility criteria and study sample
Fig. 2
Fig. 2
Risk of long-term sick leave (17 days or more) at least once over a lifetime and disability pension in persons with acute hepatic porphyria and the reference population aged 18 to 67 years. Note: IQR: interquartile range (25th, 75th percentiles); AHP: acute hepatic porphyria; CI: Confidence intervals. The X-scale is logarithmic. Adjusted analysis: Adjusted for age in years (timescale), sex and educational attainment and stratified by birth cohorts.
Fig. 3
Fig. 3
Kaplan-Meier curve for cumulative failure probability estimates of first long-term sick leave event and disability pension from 18 to 67 years of age between persons with acute hepatic porphyria (red line, panel a) and sub groups (red line=hospitalised, green line=non-hospitalised, yellow line=asymptomatic, purple line=unclassified, panel b) and the reference population (blue lines, panel a and b). Note: AHP: acute hepatic porphyria; CI: confidence intervals; 95% confidence intervals displayed on panel A only; 95% confidence intervals in panel A of the reference are too small to detect
Fig. 4
Fig. 4
Diagnostic reasons for a long-term sick leave episode between persons with AHP acute hepatic porphyria and sub-groups and the reference population (aged 18 to 67 years). Note: IRR = Incident rate ratios; CI=Confidence intervals; dis = disorder. The X-scale is logarithmic. Adjusted analysis: Adjusted for age in years, sex and educational attainment and stratified by birth cohorts.
Fig. 5
Fig. 5
Kaplan-Meier curve for cumulative mortality estimates from 18 to 67 years of age between persons with AHP (red line, panel a) and sub groups (red line=hospitalised, green line=non-hospitalised, yellow line=asymptomatic, panel b) and the reference population (blue lines). Note: AHP: acute hepatic porphyria; CI: confidence intervals; 95% CIs displayed on panel A only; 95% CIs in panel A of the reference are too small to detect. Excludes persons with unclassified AHP
See this image and copyright information in PMC

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