PTU-116 Inter-relationships between Parameters of Iron Overload and Their Association with Liver Fibrosis Severity in Haemochromatosis

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Abstract

Introduction

In the current era of routine HFE genotyping for suspected haemochromatosis, venesection is performed in C282Y homozygous patients with milder iron overload than was previously the case. It is thus useful to re-evaluate inter relationships between parameters of iron overload and their association with severity of liver fibrosis. We aimed to evaluate these relationships in C282Y homozygous patients undergoing venesection for iron overload.

Methods

Retrospective analysis of departmental haemochromatosis database. We included 114 C282Y homozygous patients (76 men, age [median (range) 54(24–78)) years, who had elevated serum ferritin and had undergone venesection therapy. Data analyses included Pearson regression, Mann-Whitney testing and Cox multiple regression analysis.

Results

At presentation, serum ferritin was 1018 (111–8179 mg/L and serum% iron saturation was 79% (29 – 99%). 73 patients had available liver histology, which showed Pearl grade 4 (0–4) siderosis (the 1 patient with grade 0 siderosis had serum ferritin of 6035 and required removal of 34 units of blood). Ishak fibrosis score was 1(0–6). 15 patients had cirrhosis. Patients underwent venesection of 14 (3–100) units of blood at 1–2 week intervals until serum ferritin fell to the lower end of the normal range. The number of units of blood removed to achieve this correlated significantly with baseline serum ferritin (Pearson r = 0.62 p < 0.001), serum iron saturation (r = 0.36 p < 0.001), liver siderosis grade (r = 0.39 p < 0.001) and (in 16 cases where measured) liver iron concentration (r = 0.91 p < 0.03). These iron storage parameters showed no correlation with age of presentation but were all higher (except siderosis grade) in men than in women (p < 0.01–0.001). Ishak fibrosis score correlated positively with number of units venesected (r = 0.64; p < 0.001), liver iron content (r = 0.75 p < 0.01), baseline serum ferritin (r = 0.68 p < 0.001) and iron saturation (r = 0.34 p < 0.01) but was not significantly associated with age, gender, known alcohol excess (n = 25) or steatosis on liver biopsy (n = 24). Patients with cirrhosis had higher baseline serum ferritin (2523 (680–6908) vs 1018 (111–8179) mg/L p < 0.001) and had more units venesected (42 (18–100) vs (14 (3–69) p < 0.001) than those without. In Cox multiple regression analysis, liver fibrosis stage was independently associated with baseline serum ferritin and number of units venesected (both p < 0.001) but was not associated with age, gender, known alcohol excess or steatosis.

Conclusion

In C282Y homozygous patients, severity of overload, assessed by baseline serum ferritin and number of units venesected, is the main determinant of liver fibrosis severity, which is not associated with age, gender, presence of liver steatosis or known alcohol excess.

Disclosure of Interest

None Declared.

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