A low level of ceruloplasmin is associated with an atherogenic profile and the presence of MASLD at a younger age

GASON Rémi [UCL] André-Dumont, Stéphanie [UCL] Ausloos, Floriane Wain, Etienne Lanthier, Nicolas [UCL] et al.

Introduction Ceruloplasmin (Cp) is a copper metabolism protein produced by the liver. It is known for its role as a copper transporter in the body, and is notably used as a marker for the diagnosis of Wilson disease. It also has an antioxidant effect, involved in iron metabolism. Several studies have established a link between low ceruloplasminemia and the presence of metabolic dysfunction-associated steatotic liver disease (MASLD), but its significance within this hepatopathy is poorly understood. Aim To record Cp values in a population of MASLD patients < 50 years of age and to study patient characteristics according to this level (anthropometric data, severity of liver disease, diabetic status, insulin resistance, dyslipidemia). Methods Prospective bi-centric study in patients < 50 years of age with MASLD defined by the presence of steatosis and at least one cardiometabolic criterion, in whom a Cp value was requested as part of the liver disease work-up. Patients with Wilson disease proven by abnormal cupruria and alcohol-related liver disease (ALD) were excluded. Results Fifty-five patients were recruited (63% women). Median age was 40 years (20-50 years) and mean BMI 33 kg/m² (± 5.5 kg/m2), with a mean abdominal circumference of 111 cm (± 11 cm). 43% of patients had a known diagnosis of treated dyslipidemia, 44% had treated hypertension and 34% had treated type 2 diabetes. In non-diabetics, the mean HOMA-IR score was 4.4 (± 3.0). Mean blood Cp level was 0.25 g/L (± 0.05 g/L). Mean ferritin was 201 µg/L (± 61 µg/L). The lipid profile showed mean total cholesterol at 191 mg/dL (± 42 mg/dL) with median HDL-c at 42 mg/dL (14-111 mg/dL). Patients showed moderate transaminase disturbances (mean ASAT 46 IU/L ± 25 and mean ALAT 68 IU/L ± 34) with median elasticity at 6.3 kPa (2.2 - 25.1 kPa) for a mean controlled attenuation parameter (CAP) at 312 dB/m (± 58 dB/m) (Fibroscan®). No correlation was found between ceruloplasmin levels and elasticity, CAP, transaminases or other biological values such as ferritin or HOMA-IR. However, by distinguishing two groups of patients on the basis of ceruloplasmin blood assay, with Cp ≤ 0.2 g/L (n=8) and with ceruloplasmin > 0.2 g/L (n=47), we highlighted that patients with Cp ≤ 0.2 g/L are significantly younger than patients with normal Cp: 28 years vs. 42 years, p < 0.0001. On the other hand, their metabolic profile was similar, including BMI (31.6 kg/m² vs. 33.3 kg/m², p = 0.41), abdominal perimeter (110 cm vs. 111 cm, p = 0.8), HOMA-IR (4.9 vs. 4.3, p = 0.69) and ferritin level (262 µg/L vs. 191 µg/L, p = 0.26), with the exception of HLD-c, which was significantly lower in the population with lowered Cp compared with patients with normal levels (34 mg/dL vs. 43 mg/dL, p = 0.03). Despite the younger age, elasticity (6.6 kPa vs. 6.1 kPa, p = 0.5) and CAP (293 dB/m vs. 314 dB/m, p = 0.40) data were similar in both groups. Conclusions In a MASLD population, a lower Cp level is significantly associated with younger age and a riskier atherogenic profile (lower HDL-c), and may be explained by the protein's antioxidant properties. This justifies not using Cp levels solely to exclude Wilson disease, since its low level probably confers an increased cardiovascular and liver risk in these patients. This needs to be assessed in prospective followup studies.