Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India

Abstract

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Keywords: AASLD, American Association for the Study of Liver Diseases; ACLF, Acute on Chronic Liver Failure; ALF, Acute Liver Failure; ALT, Alanine Transaminase; AST, Aspartate Transaminase; Cu, Copper; DP, D-Penicillamine; EASL, European Association for the Study of the Liver; GAS for WD, Global Assessment Scale for Wilson's Disease; HCC, Hepatocellular Carcinoma; INR, International Normalized Ratio; KF, Kayser-Fleischer; LT, Liver Transplantation; MARS, Molecular Absorption Recirculating System; MELD, Model for End-Stage Liver Disease; MRI, Magnetic Resonance Imaging; NGS, Next-Generation Sequencing; NWI, New Wilson's Index; PELD, Pediatric end stage liver disease; TPE, Total Plasma Exchange; TTM, Tetrathiomolybdate; WD, Wilson's Disease; Wilson's disease scoring; genetic disorder; modified Leipzig scoring; rare disease.

Figure 1

Circulation of copper in the body.

Figure 2

Golden-brown Kayser-Fleischer (KF) ring.

Figure 3

Vacuous smile in Wilson's disease.

Figure 4

MRI changes in Wilson's disease. (A) Flair axial brain MRI showing hyperintensities in bilateral putamen and thalami with hypointensity of globus pallidi in a patient with neurological manifestations; (B) T1W axial brain MRI showing hyperintensity of bilateral globus pallidi in a patient with hepatic form of WD; (C) Flair axial brain MRI showing hyperintensities in dorsal midbrain and subcortical white matter signal changes in temporal region in a patient with neurological form of WD; (D) T2W axial MRI brain depicting “face of giant panda”; (E, F) Central pontine myelinolysis–like pontine signals changes in WD in flair axial brain MRI. MRI, Magnetic Resonance Imaging; WD, Wilson's Disease.

Figure 5

Elastosis perforans serpiginosa secondary to long-term D-penicillamine use. Multiple annular plaques seen over bilateral forearms with hyperpigmented papules arranged at the periphery, and few papules showing central small keratotic plugging.