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

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.

Mortality in Pedigrees with Acute Intermittent Porphyria

“…However, in a Norwegian cohort study, the risk of premature death was not increased in a cohort with symptomatic patients with any of the acute hepatic porphyrias (i.e., AIP, hereditary coproporphyria, or variegate porphyria) between 1992 and 2017 [20]. Secondly, the results from a Finnish retrospective longitudinal study among female patients living between 1955 and 2015 are consistent with our observations.…”

“…Another limitation of our study is that we cannot add information on disease and longterm complication-specific mortality and morbidity (e.g., hypertension, chronic kidney disease, hepatocellular carcinoma). For example, it is known that patients with acute hepatic porphyrias are at increased risk of primary liver cancer (~5% prevalence) compared to the general population (~5 per 100,000 persons) [22], and this is associated with an increased risk of mortality [20]. Because data on causes of mortality could not reliably be collected for most individuals in the dataset, we only analyzed all-cause mortality.…”

Risk for incident comorbidities, nonhepatic cancer and mortality in acute hepatic porphyria: A matched cohort study in 1244 individuals

“…With generally improved management of acute attacks; the introduction of exogenous heme treatment in the 1980s, 40 liver transplantation for patients with recurrent attacks 33 and recently givosiran, an mRNA silencing treatment, 41,42 the risk of dying from acute attacks has decreased over the past decades. 11,26,27 Our knowledge about how long-term conditions impact mortality is, however, limited. Many studies report an increased risk of PLC-related deaths, but results are not consistent regarding overall mortality risk.…”

Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy

“…Early diagnosis and accurate treatment have decreased the morbidity and mortality of acute attacks [ 11 , 12 , 18 , 19 ]. Treatment with hematin quickly down regulates the expression of ALAS1 and is currently the only approved therapy for an attack [ 16 , 20 ].…”