Iron load in NAFLD is linked to a higher risk of liver cancer


Patients with non-alcoholic fatty liver disease (NAFLD) had a significantly higher risk of developing hepatocellular carcinoma (HCC) due to high levels of serum iron biomarkers or transferrin saturation, one researcher reported.

In an analysis of over 18,000 NAFLD patients, elevated serum iron levels greater than 175 μg / dL were associated with a more than twice the risk of developing HCC (HR 2.44, 95% CI 1 , 06-5.62), while lower iron levels (less than 75 g / dL) were associated with a 33% reduction in the risk of HCC (HR 0.67, 95% CI 0.48 -0.93, P

Transferrin saturation levels greater than 35% were also associated with a two-fold increased risk for these patients of developing HCC (HR 2.18, 95% CI 1.27-3.74) compared to those having normal transferrin saturation levels (range 25% to 35%). he said during a presentation at the American Association for the Study of Liver Disease (AASLD) virtual meeting.

During the 4.35 years of follow-up, 192 patients with NAFLD developed HCC, and the majority were white males, older, smokers or previous smokers, and had hypertension, hyperlipidemia or diabetes mellitus. type 2 (T2DM) compared to patients with NAFLD who did not develop HCC (P

Douglas T. Dieterich, MD, of Icahn’s Mount Sinai School of Medicine in New York City, called the results interesting, stating that “we know iron is a pro-inflammatory compound, so that part makes sense. . The real question to ask is: Are these high iron patients heterozygous for hemochromatosis? “

No significant association with the risk of HCC was observed for other iron biomarkers, serum ferritin or total iron binding capacity.

“The fact that ferritin is not associated would argue against this hemochromatosis, another good marker to look for as a prognostic predictor of NASH [nonalcoholic steatohepatitis]”, added Dieterich, who was not involved in this study.

“Non-alcoholic fatty liver disease has become a major contributor to the increased incidence of hepatocellular carcinoma here in the United States,” said Yu. “Iron, an essential metal, is mainly stored in hepatocytes and this metal played a role in the development of HCC-related NAFLD, “describing the limited epidemiological data available for NAFLD patients without hemochromatosis or other major underlying causes of chronic liver disease.

The iron overload was caused by hereditary hemochromatosis, a metabolic risk factor associated with the development of HCC, the researchers noted. Excessive iron deposits have also been associated with microvascular complications of poorly controlled T2DM.

Yu and his colleagues evaluated electronic health record data on 47,970 patients (aged 40 to 89) with NAFLD who did not have hemochromatosis. They were enrolled in a large healthcare system from January 2004 to December 2018. For the current analysis, 18,569 patients were included after being tested for at least one of the four biomarkers of iron – serum ferritin, serum iron. , transferrin saturation or total iron binding. capacity. The NAFLD cohort had compensated cirrhosis, decompensated cirrhosis, and NASH.

The primary outcome measure evaluated the association of serum iron biomarkers with the incidence of HCC in patients with NAFLD. Proportional regression analysis for calculating the incidence of HCC associated with an elevation of an iron biomarker adjusted for demographics, BMI, smoking, and T2DM.

The patients were predominantly Caucasian (93%) and female (51%) with a mean age of 66 years and a mean BMI of 32.5.

“We conclude that this clinical monitoring of serum iron levels, particularly serum iron in transferrin saturation tests, may be a potential strategy to identify patients with NAFLD who are at higher risk for hepatocellular carcinoma,” Yu said.

Limitations of the study included a lack of diversity among participants, limiting the generalizability of the results.

“More research is needed to investigate the association of iron indices on the risk of developing HCC in NAFLD,” the researchers wrote.

  • Zaina Hamza is a writer for MedPage Today, covering gastroenterology and infectious diseases. She is based in Chicago.


The study was funded by the NIH and the University of Pittsburgh Medical Center Hillman Cancer Center.

Yu and his co-authors have disclosed no connection with the industry.


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