Bile acids may help predict AIP severity, explain liver cancer risk
In AIP, bile acid production is dysregulated and may serve as biomarker: Study
The production of bile acids, which are molecules made by the liver to help with digestion, is dysregulated in people with acute intermittent porphyria (AIP), according to a recent study.
Findings suggest the levels of certain bile acids may serve as an objective biological marker of AIP severity, and researchers think that changes in these liver molecules may help to explain why people with AIP are at an increased risk of developing liver cancer.
The study, “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,” was published in the Journal of Inherited Metabolic Disease.
Porphyrias are a group of genetic disorders marked by defects in the production of heme, a molecule that’s crucial for red blood cells to transport oxygen through the body. Problems with heme production leads to the buildup of intermediary molecules called porphyrins, which ultimately act as the drivers of porphyria symptoms.
AIP caused by mutations in HMBS gene
AIP is specifically caused by mutations in the HMBS gene, which provides instructions to make an enzyme that’s required for heme production.
In people with overt AIP, the disease is marked by attacks where symptoms suddenly appear or worsen. However, one of the mysteries of AIP is that not everyone who carries a mutation in the HMBS gene will experience attacks. This implies that other processes in the body must also be at play in determining whether these mutations actually cause disease.
To gain greater insight into these processes, scientists in France measured the levels of more than 230 different molecules in urine samples collected from 114 people with a HMBS mutation: 84 with overt AIP who had experienced attack symptoms, and 30 who had never experienced an attack. The researchers specifically looked for molecules that were present in significantly different levels between the groups.
Unsurprisingly, many of the molecules identified by this analysis are known to be involved in the biological pathway the body uses to make heme, highlighting the crucial role of these pathways in AIP disease development.
However, the researchers unexpectedly found patients with overt disease also showed differences in the levels of bile acids, which are molecules that are made in the liver and then shipped to the intestines where they help the body break down and digest fats. Bile acids have never been reported to be dysregulated in AIP, though the researchers noted that both bile acids and heme are made in the liver, with some precursor molecules being involved in the production of both heme and bile acids.
“For the first time, our study showed bile acid metabolism alterations in AIP patients,” the researchers wrote, noting that differences in bile acids were “the most significant and striking results of the entire analysis.”
In further analyses, the researchers showed the ratio between two particular types of bile acids (specifically cholic acid and chenodeoxycholic acid) was associated with AIP severity, implying that assessing the levels of bile acids could be a way to objectively track the severity of the disorder. The scientists also speculated that abnormal bile acid levels could contribute to the development of liver cancer, a known risk in AIP.
They noted, however, that it’s not clear whether bile acid dysregulation leads to more severe AIP, or if severe AIP causes bile acids to become dysregulated, so they stressed that more studies are necessary.
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