Associations of reticulocyte hemoglobin equivalent with erythrocyte indices and serum ferritin in anemic patients with hepatocellular carcinoma: A retrospective study

Cancer‑related anemia is common in patients with hepatocellular carcinoma (HCC), and its pathogenesis is complex due to the coexistence of chronic liver disease, portal hypertension, hypersplenism, inflammation, nutritional disorders and tumor‑related factors. The present retrospective study characterized anemia morphology in 96 anemic patients with HCC before initiation of their first antitumor therapy, and examined the associations of reticulocyte hemoglobin equivalent (RET‑He) with erythrocyte indices and serum ferritin (SF), with a focus on whether RET‑He and SF displayed distinct patterns of association with hematological parameters. The data collected included sex, age, Barcelona Clinic Liver Cancer stage, Child‑Pugh grade, splenomegaly/hypersplenism, hemoglobin (Hb) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), absolute reticulocyte count (RET#), RET‑He and SF. Patients were compared by anemia severity, morphological type and RET‑He level, and Spearman'a correlation was used to assess relationships between RET‑He and other parameters. Mild, moderate and severe anemia occurred in 41 (42.71%), 52 (54.17%) and 3 (3.13%) patients, respectively. Macrocytic, normocytic, simple microcytic and microcytic hypochromic anemia were found in 29 (30.21%), 40 (41.67%), 5 (5.21%) and 22 (22.92%) patients, respectively. A total of 26 patients (27.08%) had RET‑He ≤29 pg, and the median SF was 248.5 ng/ml (interquartile range, 146.8‑346.0 ng/ml). Compared with mild anemia, moderate‑to‑severe anemia was associated with lower MCV, MCH, MCHC and RET‑He, and higher proportions of RET‑He ≤29 pg and microcytic hypochromic anemia (all P<0.05). RET‑He was lowest in the microcytic group (P<0.001). Patients with RET‑He ≤29 pg had lower Hb concentration, MCV, MCH, MCHC and RET# (all P<0.05). Spearman's analysis indicated that RET‑He was positively correlated with Hb concentration, MCV, MCH, MCHC and RET# (all P<0.05), but not with SF (P=0.408). In conclusion, anemia in patients with HCC demonstrated heterogeneous morphological patterns, and microcytic anemia was associated with lower RET‑He levels. RET‑He was associated with erythrocyte indices related to hemoglobinization, whereas no such association was observed with SF. The dissociation between RET‑He and SF suggests that these markers may reflect different aspects of iron metabolism and erythropoiesis in HCC. RET‑He may offer complementary information on erythroid hemoglobinization not directly captured by SF, but its clinical utility requires further validation. SF should be interpreted cautiously in the context of chronic liver disease, inflammation and tumor‑related factors.