Incidence of liver cancer in AHPs linked to AIP diagnosis: Analysis
Cancer incidence also highest among older, female, symptomatic patients
The incidence of liver cancer is highest among adults with acute hepatic porphyrias (AHPs) who are older, female, symptomatic, and diagnosed with acute intermittent porphyria (AIP), one of the most common AHP subtypes.
Those are the results of a pooled analysis of published studies conducted by a team of U.S. researchers who aimed to “determine incidence of [liver cancer] in AHP and specific subtypes of AHP,” and thus identify patients in high-risk groups. Incidence is a measure of how frequently a disease occurs in a certain population over a specific time period.
The analysis also found that common risk factors for liver disease — such as liver cirrhosis, alcohol use, and viral hepatitis — were associated with an elevated incidence of liver cancer among AHP patients.
“The findings from this study would hopefully provide an insight into the high-risk groups for [liver cancer] screening in clinical practice during the clinical care of patients with AHP,” the researchers wrote.
Their study, “Hepatocellular Carcinoma in Acute Hepatic Porphyria: A Meta-Analysis of Observational Studies,” was published in the journal Digestive Diseases and Sciences.
Researchers investigated data from 12 studies involving 2,735 patients
Porphyria is a group of genetic disorders marked by a disruption in the production of heme, a molecule that facilitates oxygen transport in red blood cells. As a result, heme building blocks, called porphyrins, and their precursors, build up to toxic levels and cause damage.
In hepatic porphyrias, these molecules accumulate in the liver and interfere with liver function — which can lead to scarring, also known as fibrosis, or cirrhosis, and raise the risk of liver cancer. The most common types of AHP are AIP, hereditary coproporphyria, or HCP, and variegate porphyria, called VP.
Hepatocellular carcinoma, or HCC, is the most common primary malignant cancer of the liver, with liver cirrhosis being the leading risk factor for its development. A previous review study indicated that the risk of developing HCC in people with porphyrias was 5% higher than in the general population. Because of the connection to liver cancer, it’s been recommended that AHP patients undergo liver cancer screening starting at the age of 50.
In this study, a team of researchers pooled data from several published studies that reported on HCC in AHP patients. Their goal was to determine the incidence of HCC in AHP and its subtypes, as well as to identify risk factors for the development of HCC.
Following a database search, the team selected 12 studies involving 2,735 AHP patients for inclusion in the analyses. More than half of the patients were female (62%) and most had AIP (80%). This was followed by VP, found for 14%, and HCP, seen in 6%.
Female patients found to have higher incidence of liver cancer than males
A total of 115 cases of HCC were reported. The pooled overall incidence, or occurrence of new HCC cases across all AHP patients, was 0.3 per 100 person-years. Person-years is a composite measure that considers the number of people assessed and the time they were followed; 100 person-years refers to data gathered from 100 people followed over the course of one year.
Regarding sex, females with AHP had a higher HCC incidence than males (0.4 vs. 0.3 per 100 person-years). Also, HCC incidence was nearly twice as high in patients who were symptomatic versus those who were asymptomatic (0.9 vs. 0.5 per 100 person-years).
Among the various AHP subtypes, AIP patients had the highest annual incidence of HCC at 0.4 per 100 person-years, followed by VP at 0.3 per 100 person-years, and HCP at 0.2 per 100 person-years.
Compared with AHP patients without HCC, those with liver cancer were older and had a higher prevalence of cirrhosis, alcohol use, and chronic viral hepatitis. HCC also was associated with higher levels of the porphyrins porphobilinogen (PBG) and aminolevulinic acid (ALA) in the urine.
The pooled annual incidence of [hepatocellular carcinoma, or liver cancer] in AHP patients is 0.3%, with higher risk in certain [groups] of patients depending on AHP type, patient demographics, other liver disease risk factors, and symptomatic status of the disease.
To explain the elevated risk of HCC in AHPs, the researchers suggested that high levels of PBG and ALA in liver cells may lead to oxidative stress, a type of cell damage resulting from an imbalance between oxidative and antioxidant molecules, and DNA damage, thus triggering cancer.
“The pooled annual incidence of HCC in AHP patients is 0.3%, with higher risk in certain [groups] of patients depending on AHP type, patient demographics, other liver disease risk factors, and symptomatic status of the disease,” the researchers wrote.
The team also noted that future studies will be needed to “develop a risk score for HCC as a basis for following a cost-effective approach for screening and surveillance of HCC in patients with AHP.”
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