Non-Wilson's Disease-Associated Hypoceruloplasminemia

Abstract

Introduction and aim: Low serum ceruloplasmin levels can occur in patients without Wilson's disease (WD) liver disorders. When present, extensive, costly, and potentially harmful additional investigations for WD may be undertaken. The purpose of this study was to document the prevalence of low serum ceruloplasmin levels in adult patients without WD and describe the features commonly associated with this finding.

Materials and methods: Serum ceruloplasmin levels were measured by an enzymatic assay in 3040 adult patients attending an urban, liver diseases outpatient clinic.

Results: A total of 122 (4.0%) patients without WD had serum ceruloplasmin levels less than the lower limit of normal documented at their initial visit. Their mean age was 44 ± 14 years, and 80 (66%) were men. The Model for End-stage Liver Disease (MELD) score was 9.0 ± 4.0. Approximately, one half (65/122, 53%) had underlying viral hepatitis (52% hepatitis B and 48% hepatitis C). When compared with 64 MELD-matched control patients with normal or elevated serum ceruloplasmin levels, there were no significant differences in liver enzyme/function tests, ferritin, creatinine values, or survival. However, the low serum ceruloplasmin cohort patients were younger (43 ± 14 versus 52 ± 13 years, p = 0.0002), less often men (66% vs. 88%, p = 0.001), and viral hepatitis was significantly more common (53% versus 27%, p = 0.0005).

Conclusion: Low serum ceruloplasmin levels were documented in 4.0% of adult patients without WD attending this urban liver diseases outpatient clinic. These patients tend to be younger, less often men, and more often have viral hepatitis as the underlying cause of their liver disease.

Keywords: ALP, alkaline phosphatase; ALT, alanine aminotransferase; ASH, alcoholic steatohepatitis; AST, aspartate aminotransferase; Dx, diagnosis; GGT, gamma-glutamyl transferase; HBV, hepatitis B virus; HCV, hepatitis C virus; INR, international ratio of prothrombin times; MELD, Model for End-stage Liver Disease; NASH, nonalcoholic steatohepatitis; T.Bili, total bilirubin; WD, Wilson Disease; ceruloplasmin; hepatitis; liver; viral hepatitis; wilson's disease.

Figure 1

Underlying liver disease in 122 patients with low serum ceruloplasmin levels (upper panel) and 64 MELD-matched controls (lower panel). Viral hepatitis was significantly more common in patients with low ceruloplasmin compared with controls (53% versus 27%, p = 0.0005). Numbers in figures refer to actual patient numbers. MELD = Model of End-stage Liver Disease

Figure 2

Kaplan–Meier survival analysis at 200-month follow-up in 122 patients with low serum ceruloplasmin levels and 64 MELD-matched controls with normal or elevated serum ceruloplasmin levels. There was no significant difference in survival. Log-rank test: Chi-square-0.55 DF-1, P = 0.46. MELD = Model of End-stage Liver Disease