This is a useful article in evaluation of elevated ferritin levels in adults. This approach is NOT applicable in young children but may have some use in adolescents. In young children, other considerations include HLH and macrophage activation. In newborns, elevation of ferritin (along with liver dysfunction) may be indicative of GALD (gestational alloimmune liver disease).
W. Palmer et al. AJG 2020; 115: 1353-55. How I Approach Patients With Elevated Serum Ferritin
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PC Parkin et al. J Pediatr 2020; 217:189-91.
In this study, the authors conducted a secondary analysis of data from the Optimizing Early Child Development Study (Toronto) with 745 healthy children. The authors note that the setting is from a high resource area with high maternal education.
Key finding:
Based on this study, the authors recommend obtaining a ferritin level at 12 months of age at same time when a hemoglobin is recommended.
My take: The implication of this study is that iron deficiency, even in the absence of socioeconomic status, can have a detrimental effect on cognitive outcomes.
Related blog post: Nutrition Week (Day 6) Iron Deficiency in Breastfed Infants
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Serum ferritin levels were independently shown to be a risk factor for poor response to treatment in hepatitis C virus (HCV) infection (Hepatology 2012; 55: 1038-47). This article adds additional information to previous work which has shown that increased iron can be a comorbid factor in chronic viral hepatitis and other liver diseases.
This study used the Swiss Hepatitis C Cohort Study (SCCS) (n=3648). In this group, the success of treatment with pegylated interferon alpha and ribavirin were correlated with clinical and histological features.
Ferritin levels ≥ the sex-specific median values was one of the strongest pretreatment predictors of treatment failure (OR 0.45). It had a similar predictive effect as the IL28B genotype. In addition, higher ferritin levels were associated with severe liver fibrosis (OR 2.67) and steatosis (OR 2.29). For women the sex-specific median for ferritin level was 85 μg/L and for men it was 203 μg/L. The authors note that these cutoffs are quite close to the upper limits of normal of the general population (150 and 300 respectively).
Mechanistically, HCV interferes with the host’s iron metabolism leading to iron accumulation in the liver. Part of this is explained by down-regulation of hepcidin (Help with hepcidin). Part is due to ferritin acting as an acute phase reactant to inflammation. Ultimately, excess iron promotes liver inflammation, oxidative stress and mitochondrial dysfunction.
How important ferritin will be with newer therapies is not clear. It is likely that patients that are less responsive to dual therapy (pegylated interferon/ribavirin) will have poorer response as well to triple or quadruple therapies.
Additional references/previous related posts:
In some patients with inflammatory bowel disease (IBD), treatment of anemia associated with IBD sometimes results in more symptomatic benefit than treatment of the IBD. Yet, anemia remains common in IBD, both in children and adults (Inflamm Bowel Dis 2012; 18: 513-19).
Using a cross-sectional observational study design, a tertiary adult and pediatric IBD center reviewed consecutive clinic patients in April 2009. The prevalence of anemia was 70% (41/59) children, 42% (24/54) adolescents, and 40% (49/124) adult. In addition, iron deficiency anemia was more common in the pediatric population: 36/41 children and 20/23 adolescents. In the adults with anemia, only 55% (27/49) were iron deficient. One of the key determinants of anemia was disease activity.
Interestingly, among patients with iron deficiency, younger age was inversely associated with treatment with iron therapy: 13% of children, 30% of adolescents, and 48% of adults.
Other important aspects of anemia in IBD:
Additional references:
gutsandgrowth 