High Iron Levels in Blood Linked to Increased Risk of Liver Cancer in NAFLD

Patients with nonalcoholic fatty liver disease (NAFLD) who have high blood iron levels are at an elevated risk of developing hepatocellular carcinoma (HCC), according to a study presented at The Liver Meeting Digital Experience, which is run by the American Association for the Study of Liver Diseases.

Researchers conducted the study because although prior research has illustrated that elevated levels of iron in the blood from hereditary hemochromatosis can raise the risk of HCC, little is known about the effect of this condition in NAFLD.

HCC, the most common type of liver cancer, is thought to affect about 25% of adults worldwide.

Researchers at the University of Pittsburgh used electronic health records (EHRs) from their medical center to identify patients aged 40 to 89 years diagnosed with NAFLD between 2004 and 2018.

A Cox proportional hazard regression model was used to calculate HRs and the 95% CIs for HCC incidence associated with elevated levels of any 1 of the 4 iron biomarkers, adjusting for age, sex, race, body mass index, history of type 2 diabetes (T2D), and smoking.

Of 47,165 patients identified, 18,569 patients had at least 1 measurement of serum iron, transferrin saturation, total iron binding capacity (TIBC), and serum ferritin eligible for analysis.

After an average 4.35 years of follow-up, 224 patients developed HCC.

Compared with those who did not develop HCC, patients with NALFD who developed cancer were more likely to be older, male, and past or present smokers. They were also more likely to have a history of T2D and hypertension, but lower levels of lipids.

In addition, when it came to associations between HCC risk and iron levels, an elevated level of serum iron (more than 175 mcg/dL) was linked with more than double the HCC risk of normal serum iron levels.

A higher level of transferrin saturation, or more than 35%, was linked with a 2-fold increase in HCC risk, compared with a normal transferrin saturation of 25% to 35%.

Total iron binding capacity did not have a statistically significant link to HCC risk, nor did elevated serum ferritin levels.

“NAFLD may contribute to the rising incidence of HCC in the U.S. However, only a small fraction of NAFLD patients eventually develop HCC. The liver is the primary reservoir of body iron. The iron overload can cause hepatotoxicity and liver damage,” Jian-Min Yuan, MD, PhD, the senior author of the study, the chair of cancer prevention at UPMC Hillman Cancer Center, and a professor of epidemiology at the University of Pittsburgh School of Medicine, said in a statement. “A direct link between serum iron level and HCC risk would support a harmful role of iron elevation on HCC development in NAFLD patients.”

The findings must be confirmed in larger, prospective studies, allowing for patients at higher risk to be followed more closely. But Yuan also said that “since serum iron levels change constantly in response to physiologic needs, more research is needed to understand the clinical implications of persistence and magnitude of serum iron elevation, as well as the lack of association of ferritin levels with HCC risk in NAFLD patients.”

Reference

Yu YC, Behari J, Luu HN, et al. Elevated serum iron levels are associated with increased risk of hepatocellular carcinoma incidence among patients with nonalcoholic fatty liver disease Presented at: The Liver Meeting Digital Experience; November 12-15, 2021. Poster 1048.