Detection of iron deficiency anaemia in cirrhosis: Diagnostic utility of ferritin and MCV in a large UK primary care cohort

Abstract

Abstract Background: Iron deficiency anaemia (IDA) is common yet often under-evaluated in cirrhosis, where chronic inflammation complicates biomarker interpretation. We investigated the diagnostic utility of ferritin and mean cell volume (MCV), testing patterns, and response to oral iron therapy in patients with cirrhosis using UK primary care data. Methods: We conducted a retrospective cohort study using Clinical Practice Research Datalink (CPRD) Aurum (2015–2021), including 43,083 adults with cirrhosis and ≥1 haemoglobin (Hb) result. Anaemia was defined by World Health Organisation (WHO) age- and sex-specific thresholds. Determinants of ferritin testing were analysed using time-dependent Cox models. IDA was defined by ferritin <30, <50, <70, or <100 µg/L within 90 days of anaemia. Sensitivity of MCV thresholds for IDA was evaluated. Hb response to oral iron was assessed in a matched cohort using multivariable logistic regression, stratified by baseline ferritin and MCV. Results: Ferritin was measured in 55.7% of patients; however, only 56.7% of anaemic individuals were tested within 90 days of a low Hb. Among those, 21.2% had a ferritin <30 µg/L. Concurrent testing for C-reactive protein (CRP) and transferrin saturation (TSat) occurred in only 31.7% and 9.1% of cases, respectively. Notably, 37.2% (n = 6,277) of anaemic patients with a nadir MCV of 80–100 fL had no recorded ferritin. Ferritin testing was less likely in younger males (HR 0.75, 95% CI 0.68–0.84); ethnicity and deprivation index had no significant effect. Testing likelihood was higher with MCV <80 fL (HR 1.40, 95% CI 1.30–1.50), but not with MCV 80–95 fL. MCV <95 fL had 91% sensitivity for IDA (ferritin <30 µg/L), lower than the 97.6% specificity reported in guidelines for the general population. Sensitivity declined further at higher ferritin thresholds. Oral iron was associated with greater odds of Hb response (aOR 2.92, 95% CI 2.08–4.12), particularly among those with low baseline ferritin or MCV. However, even at the highest thresholds studied, neither biomarker reliably excluded treatment benefit. Conclusions: Ferritin and MCV remain useful for identifying IDA in cirrhosis, but current thresholds may miss opportunities for diagnosis and treatment. Standardised, haematologist-informed approaches to diagnosing iron deficiency in inflammatory states are needed. Our methods can be applied to other chronic inflammatory conditions to evaluate testing practices, predict response to therapy, and inform decisions on oral versus intravenous (IV) iron treatment.