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Post-liver transplant infections linked to high iron regulator, low serum iron

Recently published data revealed an association between increases in hepcidin and ferritin and decreases in iron and an increased risk for infection following orthotopic liver transplantation, according to recently published data.

“Acute events, such as infection, trauma, and surgery, lead to rapid drops in serum iron, or ‘stress hypoferremia,’ and increased iron storage,” Jennifer K.L. Chow, MD, from the Tufts Medical Center, Boston, and colleagues wrote. “This decrease in iron availability, or iron-withholding from host serum, may serve as a defense mechanism after infection or other stressful events and is referred to as ‘nutritional immunity.’”

To assess the association between iron-related markers and infection, the researchers prospectively followed 128 patients for 6 months after orthotopic liver transplantation. Serial blood plasma samples were collected 72 hours after liver transplantation, weekly while hospitalized and during outpatient visits, and within 48 hours of suspected infectious events.

Excluding patients with recurrent HCV and those with peri-transplant infections or infections that occurred within the first week posttransplant, 47 patients had either definite (n = 35) or possible infections (n = 12) at 1-week posttransplant. Median time between transplant and infection was 53 days (range, 16-69 days) for definite infections and 55 days (range, 14-94 days) for possible infections. The most common infections included cholangitis, intra-abdominal abscesses, peritonitis and bloodstream infections.

Patients with infections had more red blood cell transfusion days (HR = 1.19; 95% CI, 1.04-1.38) and tube feed days (HR = 1.02; 95% CI, 1.01-1.04), more often underwent two-stage liver transplant (HR = 2.84; 95% CI, 1.58-5.11), had longer hospital stays (HR = 1.1; 95% CI, 1.7-1.12 and re-admissions posttransplant (HR = 3.04; 95% CI, 2.15-4.29), and had more posttransplant surgical complications.

Patients with definite infection posttransplant had significantly higher (P < .001) median hepcidin (200 ng/mL; range, 113-269 ng/mL) compared with those who did not develop infections (102 ng/mL; range, 78-113 ng/mL), significantly higher (P = .003) median ferritin (518 ng/mL; range, 320-824 ng/mL) compared with those who did not develop infection (350 ng/mL; range, 184-495 ng/mL), and significantly lower (P = .05) median iron (43 µg/dL; range, 17-74 µg/dL) compared with those without infection (62 µg/dL; range, 51-70 µg/dL). There were no differences between those who did and did not develop infection for hepcidin or ferritin at baseline or 30 days.

Multivariate analysis confirmed that patients who developed infections had a significant increase posttransplant in hepcidin (HR = 1.43; 95% CI, 1.05-1.93) and ferritin (HR = 1.51; 95% CI, 1.12-2.05), and a significant decrease in iron (HR = 1.76; 95% CI, 1.2-2.57).

“The biology of iron metabolism provides a plausible pathophysiologic basis for a clinically meaningful relationship between iron and infection,” the researchers concluded. “By beginning to explore how iron markers behave in the setting of clinical infection, this sets the stage for future investigations of iron markers measured at standardized time points to determine diagnostic cutoffs, such as positive predictive and negative predictive values.” – by Talitha Bennett

Disclosure: Chow reports no relevant financial disclosures. Please see the full study for the other researchers’ relevant financial disclosures.