Clinical Characteristics, Treatment Effects and Risk Factors of Liver Cirrhosis in Patients with Wilson's Disease Hepatic Type

Abstract

Background and aims: Wilson's disease (WD) is a rare autosomal recessive genetic disorder that can be treated with medications. The lack of a single, specific diagnostic indicator leads to diagnostic difficulties, which may result in disease progression to cirrhosis and even liver cancer. Thus, this study aimed to analyze the clinical data, imaging, histopathological manifestations, genetic testing results, and treatment effects of patients with WD hepatic type, and to explore the factors related to WD cirrhosis.

Methods: A single-center retrospective study was performed. 48 WD patients with a Leipzig score ≥ 4 were divided into a cirrhosis group and a non-cirrhosis group based on the presence of cirrhosis. Logistic regression analysis and odds ratios were used to describe the strength of association between risk factors and cirrhosis. The predictive value of the model for cirrhosis occurrence was evaluated by calculating the area under the receiver operating characteristic curve and the cutoff value.

Results: All 48 patients diagnosed with WD had liver damage, with males accounting for 54.17%. The median age at diagnosis was 28 years (range: 10.25-40.5 years), and 39.58% of patients had cirrhosis. The most prevalent mutation was c.2333G>T (p.Arg778Leu), found in 41.30% (19/46) of cases. Imaging revealed fatty liver in 31.25% (15/48) of patients and "honeycomb-like" cirrhosis nodules in 73.68% (14/19). Compared with the non-cirrhosis group, the cirrhosis group had a higher positive rate for the Kayser-Fleischer (K-F) ring, older age at diagnosis, and higher levels of immunoglobulin G, but lower levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, white blood cells, and platelets (p < 0.05). Age at diagnosis (odds ratio = 1.072, 95% confidence interval = 1.007-1.142, p = 0.03) and the K-F ring (odds ratio = 18.657, 95% confidence interval = 1.451-239.924, p = 0.025) were independent risk factors for WD-related cirrhosis. The best values of area under the receiver operating characteristic curve for age at diagnosis combined with the K-F ring in predicting WD cirrhosis were 0.909. The average follow-up time for 33 patients was 48.6 months (range: 12-72 months). The biochemical recovery rate was over 60% after 12-72 months of treatment with zinc gluconate and/or penicillamine.

Conclusions: Age at diagnosis, combined with the K-F ring, is a simple and effective risk factor for WD-related cirrhosis. Zinc gluconate and penicillamine are safe and effective treatments.

Keywords: Age at diagnosis; K-F ring; Liver cirrhosis; Penicillamine; Wilson’s disease; Zinc gluconate.

Fig. 1. Study design flowchart.

WD, wilson’s disease.

Fig. 2. Liver histological manifestations of WD patients.

(A) and (B) show patient 1, a 42-year-old female. Liver tissue pathology (HE staining, 100×) showed “pseudolobules” with severe turbidity in the hepatocytes within the pseudolobules and macrovesicular fatty degeneration in some hepatocytes (F1-F2). There was mild to moderate lamina propria inflammation and “rosettes”. The lesions showed active nodular cirrhosis (G2-3 S3-4). WD, wilson’s disease; HE staining, hematoxylin-eosin staining.

Fig. 3. ROC curve of relevant influencing factors.

The prediction of WD cirrhosis was analyzed using an ROC curve with age at diagnosis, K-F ring, and the combination of age at diagnosis and K-F ring. The AUC values were 0.802, 0.72, and 0.909, respectively. ROC, receiver operating characteristic; AUC, area under the receiver operating characteristic curve; K-F ring, Kayser-Fleischer ring.

Fig. 4. Imaging findings of the patient before and after treatment.

Magnetic resonance imaging of the upper abdomen of a 13-year-old girl. (A) T2 low-signal nodules with unclear boundaries, considered cirrhotic nodules; splenomegaly and ascites; (B) After one year of treatment with zinc gluconate (seven tablets/day) combined with penicillamine (four tablets/day), the T2 low-signal nodules were significantly reduced, and no ascites were seen.