https://www.journal-of-hepatology.eu/article/S0168-8278(18)32388-2/pdf

Burden of liver diseases in the world

ISOLATED ALTERATIONS OF BIOCHEMICAL MARKERS OF LIVER DAMAGE in a seemingly healthy patient can present a challenge for the clinician. In this review we provide a guide to interpreting alterations to liver enzyme levels. The functional anatomy of the liver and pathophysiology of liver enzyme alteration are briefly reviewed. Using a schematic approach that classifies enzyme alterations as predominantly hepatocellular or predominantly cholestatic, we review abnormal enzymatic activity within the 2 subgroups, the most common causes of enzyme alteration and suggested initial investigations.

/pdf/liver-enzyme-alteration-a-guide-for-clinicians-jxz9dbq4z2.pdf

Liver enzyme alteration: a guide for clinicians

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60439-5.pdf

Wilson's Disease

This book is one of our contemporary medical bibles. It needs no introduction; those who have frequent need of it know it very well, and those who use it less often seek it out on the library shelf when problems arise. The book is truly encyclopedic. Everything relevant discovered during the six-year intervals between publication finds its way into these pages. By today's standards, its 1,778 closely packed small-print pages are a bargain. The mutant gene is both hero and villain in this book. It is reponsible for the biochemical abnormality that results in disease, no matter how rare a given abnormality may be. By the same token, however, it is truly an experiment of nature, shedding light on fundamental metabolic sequences and biologic mechanisms. This volume, more than most, explains the contributions of the laboratory to clinical medicine. Each chapter seems to have been rewritten, so that the exciting

The Metabolic Basis Of Inherited Disease.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22261

Diagnosis and treatment of Wilson disease: an update.

Wilson disease is an inherited autosomal recessive disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs such as the brain and the cornea. Originally Wilson disease was described as a neurodegerative disorder associated with cirrhosis of the liver. Later, Wilson disease was observed in children and adolescents presenting with acute or chronic liver disease without any neurologic symptoms. While diagnosis of neurologic Wilson disease is straightforward, it may be quite difficult in non-neurologic cases. Up to now, no single diagnostic test can exclude or confirm Wilson disease with 100% certainty. In 1993, the gene responsible for Wilson disease was cloned and localized on chromosome 13q14.3 (MIM277900) (1, 2). The Wilson disease gene ATP7B encodes a P-type ATPase. More than 200 disease causing mutations of this gene have been described so far (3). Most of these mutations occur in single families, only a few are more frequent (like H1069Q, 3400delC and 2299insC in Caucasian (4-6) or R778L in Japanese (7), Chinese and Korean patients). Studies of phenotype-genotype relations are hampered by the lack of standard diagnostic criteria and phenotypic classifications. To overcome this problem, a working party discussed these problems in depth at the 8th International Meeting on Wilson disease and Menkes disease in Leipzig/Germany (April 16-18, 2001). After the meeting, a preliminary draft of a consensus report was mailed to all active participants and their comments were incorporated in the final text.

Diagnosis and phenotypic classification of Wilson disease

This Clinical Practice Guideline (CPG) has been developed to assist physicians and other healthcare providers in the diagnosis and management of patients with Wilson's disease. The goal is to describe a number of generally accepted approaches for diagnosis, prevention, and treatment of Wilson's disease. Recommendations are based on a systematic literature review in the Medline (PubMed version), Embase (Dialog version), and the Cochrane Library databases using entries from 1966 to 2011. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system used in other EASL CPGs was used and set against the somewhat different grading system used in the AASLD guidelines (Table 1A and B). Unfortunately, there is not a single randomized controlled trial conducted in Wilson's disease which has an optimal design. Thus, it is impossible to assign a high or even a moderate quality of evidence to any of the questions dealt with in these guidelines. The evaluation is mostly based on large case series which have been reported within the last decades.

EASL Clinical Practice Guidelines: Wilson's disease

https://www.gastrojournal.org/article/S0016-5085(07)00418-0/pdf

Late-onset Wilson's disease.

Wilson disease is an autosomal recessive inherited disorder of copper metabolism resulting in pathological accumulation of copper in many organs and tissues. ATP7B is the gene product of the Wilson disease gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. Mutations of the gene result in impaired trafficking of copper in and through the hepatocytes. More than 200 mutations of Wilson disease gene were found, the most common ones being H1069Q (in Europe) and R778L (in Asia). Wilson disease may present under a variety of clinical conditions, commonly as liver and/or neuropsychiatric disease. The pathogenesis of hepatic and neurologic Wilson disease is a direct consequence of copper accumulation. Presence of copper causes oxidative stress resulting in cell destruction. The diagnosis of Wilson disease requires a combination of a variety of clinical symptoms, biochemical tests, and detection of gene mutations, which are the basis of a score proposed by a group of international experts. Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine). Treatment of presymptomatic patients or maintenance therapy can also be accomplished with zinc.

Pathophysiology and clinical features of Wilson disease.

Clinical presentation of Wilson disease can vary widely; therefore diagnosis is not always straightforward. Wilson disease is not just a disease of children and young adults, but may present at any age. The key features of Wilson disease are liver disease and cirrhosis, neuropsychiatric disturbances, Kayser-Fleischer rings, and acute episodes of hemolysis, often in association with acute liver failure. Diagnosis is particularly difficult in children and in adults presenting with active liver disease. None of the available laboratory tests is perfect and may not be specific for Wilson disease. A detailed neurologic examination is required for all cases. Neuroimaging and electrophysiologic methods are helpful. To overcome the diagnostic challenge, several clinical signs (Kayser-Fleischer rings, neurologic symptoms) and laboratory features (copper in serum, urine, liver; serum ceruloplasmin; genetic testing) are scored 0 (absent) to 2 (present) and the Leipzig score is calculated. If the score is ≥4, the diagnosis of Wilson disease is very likely. For asymptomatic siblings of index patients, mutation analysis is the most reliable approach.

Peter Ferenci

Papers

Diagnosis and phenotypic classification of Wilson disease

EASL Clinical Practice Guidelines: Wilson's disease

Late-onset Wilson's disease.

Pathophysiology and clinical features of Wilson disease.

Diagnosis of Wilson disease