Finland Study Shows Declines in Deaths, Hospitalizations in Women

Lindsey Shapiro PhD avatar

by Lindsey Shapiro PhD |

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The number of deaths or acute attacks in women with acute hepatic porphyria (AHP) that required hospitalization decreased significantly since 1980, although more than half of them still reported some acute symptoms, according to a natural history study in Finland.

The life expectancy for women with AHP is now the same as in the general population and recent advances in diagnosis and treatment likely account for these improvements, although liver cancer remains a concern among older AHP patients, according to the researchers.

The study, “Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy,” was published in Molecular Genetics and Metabolism Reports.

AHP is a genetic disorder caused by disruptions to the production of heme, a molecule essential for red blood cells to transport oxygen throughout the body. This results in a toxic buildup of porphyrins and their precursors, which help build heme, in the liver and other organs.

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Symptoms include sudden, severe attacks consisting of pain, urinary and gastrointestinal problems, and neurological changes that can last for days to weeks. AHP is most commonly diagnosed in women between the ages of 20 to 40.

Advances in early diagnosis and treatment have decreased the acute attacks’ severity and mortality in recent years, but AHP remains associated with long-term consequences that include chronic kidney disease and liver cancer.

“The object of this study was to obtain further insight on the natural course of AHP at present among female patients,” the researchers wrote.

They evaluated long-term data from 107 women with AHP from the Helsinki University Hospital porphyria patient registry who were diagnosed between 1955–2015 at a median age of 24.

Sixty-five were diagnosed with acute intermittent porphyria (AIP), 40 with variegate porphyria (VP), and two with hereditary coproporphyria (HCP). All are forms of AHP.

Fifty-nine women, or 55% of the group, had acute symptoms that did not require hospitalization, and nearly half (46%) experienced symptoms more than 20 times during the follow-up period.

A total of 105 attacks requiring hospitalization occurred in 43 women during 1954–2015. Among them, 14 women (33%) experienced classic AHP symptoms, including pain, gastrointestinal dysfunction, transient mental symptoms, and red urine.

Prolonged attacks, which are marked by nerve damage, low blood sodium, or more significant neurological issues, were observed in 15 women (35%).

Twelve women (28%) had severe attacks — including symptoms such as cardiac problems, respiratory failure, and limb paralysis — which were associated with poor prognosis. Severe attacks were often associated with misdiagnosis or mistreatment, which had led to disease exacerbations.

Overall, patients considered their symptoms to significantly affect their well-being, with 58% of women perceiving their attacks as extremely severe.

Six women had chronic symptoms, all of whom had a history of multiple disease attacks.

“This emphasizes the importance of active investigation and management of symptoms at the early phase to avoid disease exacerbation,” the researchers wrote.

Weight loss and the luteal phase of the menstrual cycle, which occurs between ovulation and menstruation, were the most common triggering factors associated with an attack across the entire study period. Infections and medications were considered triggering factors in the early years of the study, but this effect diminished significantly in recent years, according to researchers.

“Symptoms are currently triggered by hormonal changes and weight loss emphasizing the importance of early recognition and active management to avoid disease exacerbation,” the researchers wrote.

The percentage of women with AHP symptoms has gradually decreased since the 1960s, with cases requiring hospitalization dropping significantly over time in those diagnosed with AIP. Furthermore, the incidence of AIP decreased substantially since 1980.

Thirty-two deaths were reported — 10 were caused by acute attacks, seven were due to liver cancer, and one was caused by kidney failure. The remaining 14 deaths were unrelated to AHP.

Almost one-third of all deaths (31%) occurred as a result of an acute attack between 1957-1979. The incidence and severity of acute attacks decreased substantially after that. This decline is likely due to advances in diagnosis and care, the researchers noted.

In particular, liver transplants, which can cure AHP by normalizing porphyrin metabolism, were introduced in 2002 for patients with recurrent attacks.

Furthermore, the use of Givlaari (givosiran), a therapy developed by Alnylam Pharmaceuticals, has also significantly reduced the frequency and severity of attacks in the last few years, the researchers noted.

“Death due to acute porphyria has become rare, and in our survey the life expectancy increased substantially during the follow-up and does not differ from that of the normal female population at present,” the researchers emphasized. “Despite 22% of the female patients had died of primary liver cancer, the life expectancy increased more than 10 years during the follow-up.”

Given that liver cancer still contributes significantly to AHP-associated mortality, it should be screened for in patients over age 50, in line with other studies, the researchers said.