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Wilson disease(WND)

MedGen UID:
42426
Concept ID:
C0019202
Disease or Syndrome
Synonyms: Hepatolenticular degeneration; Wilson's disease; WND
SNOMED CT: Wilson's disease (88518009); Hepatolenticular degeneration syndrome (88518009); Copper storage disease (88518009); Wilson disease (88518009); Westphal-Strumpell syndrome (190823004); Westphal-Strumpell cerebral pseudosclerosis (190823004); Pseudosclerotic type of Wilson's disease (190823004); Westphal-Strumpell form of Wilson's disease (190823004); Hepatocerebral degeneration (88518009); Hepatolenticular degeneration (88518009); Kinnier-Wilson disease (88518009); Neurohepatic degeneration (88518009); Progressive lenticular degeneration (88518009); WD - Wilson's disease (88518009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ATP7B (13q14.3)
 
Monarch Initiative: MONDO:0010200
OMIM®: 277900
Orphanet: ORPHA905

Disease characteristics

Excerpted from the GeneReview: Wilson Disease
Wilson disease is a disorder of copper metabolism that, when untreated, can present with hepatic, neurologic, or psychiatric disturbances – or a combination of these – in individuals ages three years to older than 70 years. Manifestations in untreated individuals vary among and within families. Liver disease can include recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations can include dysarthria, movement disorders (tremors, involuntary movements, chorea, choreoathetosis), dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement), dysautonomia, seizures, sleep disorders, or insomnia. Psychiatric disturbances can include depression, bipolar disorder / bipolar spectrum disorder, neurotic behaviors, personality changes, or psychosis. Other multisystem involvement can include the eye (Kayser-Fleischer rings), hemolytic anemia, the kidneys, the endocrine glands, and the heart. [from GeneReviews]
Authors:
Karl Heinz Weiss  |  Michael Schilsky   view full author information

Additional descriptions

From OMIM
Wilson disease is an autosomal recessive disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurologic abnormalities. De Bie et al. (2007) provided a detailed review of the molecular pathogenesis of Wilson disease.  http://www.omim.org/entry/277900
From MedlinePlus Genetics
Wilson disease is an inherited disorder in which excessive amounts of copper accumulate in the body, particularly in the liver, brain, and eyes. The signs and symptoms of Wilson disease usually first appear between the ages of 6 and 45, but they most often begin during the teenage years. The features of this condition include a combination of liver disease and neurological and psychiatric problems.

Liver disease is typically the initial feature of Wilson disease in affected children and young adults; individuals diagnosed at an older age usually do not have symptoms of liver problems, although they may have very mild liver disease. The signs and symptoms of liver disease include yellowing of the skin or whites of the eyes (jaundice), fatigue, loss of appetite, and abdominal swelling.

Nervous system or psychiatric problems are often the initial features in individuals diagnosed in adulthood and commonly occur in young adults with Wilson disease. Signs and symptoms of these problems can include clumsiness, tremors, difficulty walking, speech problems, impaired thinking ability, depression, anxiety, and mood swings.

In many individuals with Wilson disease, copper deposits in the front surface of the eye (the cornea) form a green-to-brownish ring, called the Kayser-Fleischer ring, that surrounds the colored part of the eye. Abnormalities in eye movements, such as a restricted ability to gaze upwards, may also occur.  https://medlineplus.gov/genetics/condition/wilson-disease

Clinical features

From HPO
Malaise
MedGen UID:
65412
Concept ID:
C0231218
Sign or Symptom
A feeling of general discomfort, weakness, or lack of health.
Glycosuria
MedGen UID:
42267
Concept ID:
C0017979
Finding
An increased concentration of glucose in the urine.
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Renal tubular dysfunction
MedGen UID:
57484
Concept ID:
C0151747
Disease or Syndrome
Abnormal function of the renal tubule. The basic functional unit of the kidney, the nephron, consists of a renal corpuscle attached to a renal tubule, with roughly 0.8 to 1.5 nephrons per adult kidney. The functions of the renal tubule include reabsorption of water, electrolytes, glucose, and amino acids and secretion of substances such as uric acid.
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Hyperphosphaturia
MedGen UID:
78638
Concept ID:
C0268079
Disease or Syndrome
An increased excretion of phosphates in the urine.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Increased urinary copper concentration
MedGen UID:
869263
Concept ID:
C4023688
Finding
An increased concentration of copper in the urine.
Pedal edema
MedGen UID:
116085
Concept ID:
C0239340
Pathologic Function
An abnormal accumulation of excess fluid in the lower extremity resulting in swelling of the feet and extending upward to the lower leg.
Limb muscle weakness
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Esophageal varix
MedGen UID:
5027
Concept ID:
C0014867
Disease or Syndrome
Extreme dilation of the submucusoal veins in the lower portion of the esophagus.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Acute liver failure
MedGen UID:
58125
Concept ID:
C0162557
Disease or Syndrome
Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as acute if there is onset of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver.
Atypical or prolonged hepatitis
MedGen UID:
338473
Concept ID:
C1848456
Disease or Syndrome
Hepatocellular carcinoma
MedGen UID:
389187
Concept ID:
C2239176
Neoplastic Process
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1 to 2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Portal fibrosis
MedGen UID:
893107
Concept ID:
C3805083
Disease or Syndrome
Fibroblast proliferation and fiber expansion from the portal areas to the lobule.
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Hypoesthesia
MedGen UID:
6974
Concept ID:
C0020580
Finding
Decreased ability to perceive touch.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Polyneuropathy
MedGen UID:
57502
Concept ID:
C0152025
Disease or Syndrome
A generalized disorder of peripheral nerves.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Hand tremor
MedGen UID:
68689
Concept ID:
C0239842
Finding
An unintentional, oscillating to-and-fro muscle movement affecting the hand.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Limb dystonia
MedGen UID:
152944
Concept ID:
C0751093
Sign or Symptom
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs.
Insomnia
MedGen UID:
214589
Concept ID:
C0917801
Sign or Symptom
Persistent difficulty initiating or maintaining sleep.
Parkinsonism with favorable response to dopaminergic medication
MedGen UID:
375989
Concept ID:
C1846868
Disease or Syndrome
Parkinsonism is a clinical syndrome that is a feature of a number of different diseases, including Parkinson disease itself, other neurodegenerative diseases such as progressive supranuclear palsy, and as a side-effect of some neuroleptic medications. Some but not all individuals with Parkinsonism show responsiveness to dopaminergic medication defined as a substantial reduction of amelioration of the component signs of Parkinsonism (including mainly tremor, bradykinesia, rigidity, and postural instability) upon administration of dopaminergic medication.
Poor motor coordination
MedGen UID:
338471
Concept ID:
C1848453
Finding
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Hyposmia
MedGen UID:
473584
Concept ID:
C2364082
Finding
A decreased sensitivity to odorants (that is, a decreased ability to perceive odors).
Mixed demyelinating and axonal polyneuropathy
MedGen UID:
870461
Concept ID:
C4024907
Disease or Syndrome
Face of the giant panda sign
MedGen UID:
1814396
Concept ID:
C5676832
Sign or Symptom
The face of the giant panda sign on T2-weighted MRI is characterized by preservation of normal signal intensity in the red nuclei and lateral portion of the pars reticulata of the substantia nigra, high signal in the tegmentum, and hypointensity of the superior colliculus. The findings are said to resemble the face of a giant panda.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Osteoarthritis
MedGen UID:
45244
Concept ID:
C0029408
Disease or Syndrome
Osteoarthritis (OA) is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis (Meulenbelt et al., 2006). Clinical problems include pain and joint stiffness often leading to significant disability and joint replacement. Osteoarthritis exhibits a clear predilection for specific joints; it appears most commonly in the hip and knee joints and lumbar and cervical spine, as well as in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints of the hand; however, patients with osteoarthritis may have 1, a few, or all of these sites affected (Stefansson et al., 2003). According to a conservative estimate, greater than 70% of the population of the United States at age 65 years is affected by the disease, reflecting its age dependence. Genetic Heterogeneity of Susceptibility to Osteoarthritis Susceptibility to osteoarthritis has been associated with variation in other genes: OS2 (140600) with variation in the MATN3 gene (602109) on chromosome 2p24; OS3 (607850) with variation in the ASPN gene (608135) on chromosome 9q22; and OS5 (612400) with variation in the GDF5 gene (601146) on chromosome 20q11. Other susceptibility loci for osteoarthritis have been mapped to chromosomes 2q33 (OS4; 610839) and 3p24 (OS6; 612401).
Osteomalacia
MedGen UID:
14533
Concept ID:
C0029442
Disease or Syndrome
Osteomalacia is a general term for bone weakness owing to a defect in mineralization of the protein framework known as osteoid. This defective mineralization is mainly caused by lack in vitamin D. Osteomalacia in children is known as rickets.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Chondrocalcinosis
MedGen UID:
154303
Concept ID:
C0553730
Disease or Syndrome
Radiographic evidence of articular calcification that represent calcium pyrophosphate depositions in soft tissue surrounding joints and at the insertions of tendons near joints (Entheses/Sharpey fibers) .
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
An abnormally high concentration in the circulation of aspartate aminotransferase (AST).
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Hypouricemia
MedGen UID:
113163
Concept ID:
C0221333
Finding
An abnormally low level of uric acid in the blood.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.
Decreased circulating ceruloplasmin concentration
MedGen UID:
472980
Concept ID:
C0240997
Finding
Decreased concentration of ceruloplasmin in the blood.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
High nonceruloplasmin-bound serum copper
MedGen UID:
341229
Concept ID:
C1848459
Finding
An increased concentration of non ceruloplasmin bound copper in the blood.
Increased circulating copper concentration
MedGen UID:
1621432
Concept ID:
C4522127
Finding
An abnormally elevated concentration of copper in the blood circulation. This term refers to the total copper concentration.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Hypoparathyroidism
MedGen UID:
6985
Concept ID:
C0020626
Disease or Syndrome
A condition caused by a deficiency of parathyroid hormone characterized by hypocalcemia and hyperphosphatemia.
Kayser-Fleischer ring
MedGen UID:
57539
Concept ID:
C0152457
Disease or Syndrome
Grey-green or brownish-pigmented ring in the deep epithelial layers at the outer border of the cornea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Wilson disease in Orphanet.

Professional guidelines

PubMed

Mulligan C, Bronstein JM
Neurol Clin 2020 May;38(2):417-432. Epub 2020 Feb 28 doi: 10.1016/j.ncl.2020.01.005. PMID: 32279718
Aggarwal A, Bhatt M
Tremor Other Hyperkinet Mov (N Y) 2018;8:525. Epub 2018 Feb 28 doi: 10.7916/D841881D. PMID: 29520330Free PMC Article
Schilsky ML
Clin Liver Dis 2017 Nov;21(4):755-767. Epub 2017 Aug 10 doi: 10.1016/j.cld.2017.06.011. PMID: 28987261

Recent clinical studies

Etiology

Xue Q, Kang R, Klionsky DJ, Tang D, Liu J, Chen X
Autophagy 2023 Aug;19(8):2175-2195. Epub 2023 Apr 16 doi: 10.1080/15548627.2023.2200554. PMID: 37055935Free PMC Article
Dusek P, Hofer T, Alexander J, Roos PM, Aaseth JO
Biomolecules 2022 May 17;12(5) doi: 10.3390/biom12050714. PMID: 35625641Free PMC Article
Aggarwal A, Bhatt M
Curr Opin Neurol 2020 Aug;33(4):534-542. doi: 10.1097/WCO.0000000000000837. PMID: 32657896
Tako E
Nutrients 2019 Nov 19;11(11) doi: 10.3390/nu11112823. PMID: 31752257Free PMC Article
Saper RB, Rash R
Am Fam Physician 2009 May 1;79(9):768-72. PMID: 20141096Free PMC Article

Diagnosis

Kerkar N, Rana A
Clin Liver Dis 2022 Aug;26(3):473-488. Epub 2022 Jun 25 doi: 10.1016/j.cld.2022.03.008. PMID: 35868686
Mulligan C, Bronstein JM
Neurol Clin 2020 May;38(2):417-432. Epub 2020 Feb 28 doi: 10.1016/j.ncl.2020.01.005. PMID: 32279718
Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML
Nat Rev Dis Primers 2018 Sep 6;4(1):21. doi: 10.1038/s41572-018-0018-3. PMID: 30190489Free PMC Article
Aggarwal A, Bhatt M
Tremor Other Hyperkinet Mov (N Y) 2018;8:525. Epub 2018 Feb 28 doi: 10.7916/D841881D. PMID: 29520330Free PMC Article
Schilsky ML
Clin Liver Dis 2017 Nov;21(4):755-767. Epub 2017 Aug 10 doi: 10.1016/j.cld.2017.06.011. PMID: 28987261

Therapy

Kerkar N, Rana A
Clin Liver Dis 2022 Aug;26(3):473-488. Epub 2022 Jun 25 doi: 10.1016/j.cld.2022.03.008. PMID: 35868686
Tako E
Nutrients 2019 Nov 19;11(11) doi: 10.3390/nu11112823. PMID: 31752257Free PMC Article
Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML
Nat Rev Dis Primers 2018 Sep 6;4(1):21. doi: 10.1038/s41572-018-0018-3. PMID: 30190489Free PMC Article
Schilsky ML
Clin Liver Dis 2017 Nov;21(4):755-767. Epub 2017 Aug 10 doi: 10.1016/j.cld.2017.06.011. PMID: 28987261
Saper RB, Rash R
Am Fam Physician 2009 May 1;79(9):768-72. PMID: 20141096Free PMC Article

Prognosis

Collins CJ, Yi F, Dayuha R, Duong P, Horslen S, Camarata M, Coskun AK, Houwen RHJ, Pop TL, Zoller H, Yoo HW, Jung SW, Weiss KH, Schilsky ML, Ferenci P, Hahn SH
Gastroenterology 2021 Jun;160(7):2367-2382.e1. Epub 2021 Feb 25 doi: 10.1053/j.gastro.2021.02.052. PMID: 33640437Free PMC Article
Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML
Nat Rev Dis Primers 2018 Sep 6;4(1):21. doi: 10.1038/s41572-018-0018-3. PMID: 30190489Free PMC Article
Boga S, Ala A, Schilsky ML
Handb Clin Neurol 2017;142:91-99. doi: 10.1016/B978-0-444-63625-6.00009-4. PMID: 28433114
Medici V, Weiss KH
Handb Clin Neurol 2017;142:35-41. doi: 10.1016/B978-0-444-63625-6.00004-5. PMID: 28433108
Huster D, Kühne A, Bhattacharjee A, Raines L, Jantsch V, Noe J, Schirrmeister W, Sommerer I, Sabri O, Berr F, Mössner J, Stieger B, Caca K, Lutsenko S
Gastroenterology 2012 Apr;142(4):947-956.e5. Epub 2012 Jan 10 doi: 10.1053/j.gastro.2011.12.048. PMID: 22240481Free PMC Article

Clinical prediction guides

Dusek P, Hofer T, Alexander J, Roos PM, Aaseth JO
Biomolecules 2022 May 17;12(5) doi: 10.3390/biom12050714. PMID: 35625641Free PMC Article
Li M, Ma J, Wang W, Yang X, Luo K
BMC Gastroenterol 2021 Sep 1;21(1):339. doi: 10.1186/s12876-021-01911-5. PMID: 34470610Free PMC Article
Oh RC, Hustead TR, Ali SM, Pantsari MW
Am Fam Physician 2017 Dec 1;96(11):709-715. PMID: 29431403
Schilsky ML
Clin Liver Dis 2017 Nov;21(4):755-767. Epub 2017 Aug 10 doi: 10.1016/j.cld.2017.06.011. PMID: 28987261
Huster D, Kühne A, Bhattacharjee A, Raines L, Jantsch V, Noe J, Schirrmeister W, Sommerer I, Sabri O, Berr F, Mössner J, Stieger B, Caca K, Lutsenko S
Gastroenterology 2012 Apr;142(4):947-956.e5. Epub 2012 Jan 10 doi: 10.1053/j.gastro.2011.12.048. PMID: 22240481Free PMC Article

Recent systematic reviews

Xue Z, Chen H, Yu L, Jiang P
Pediatr Neurol 2023 Aug;145:135-147. Epub 2023 May 8 doi: 10.1016/j.pediatrneurol.2023.04.026. PMID: 37354629
Xu J, Deng Q, Qin Q, Vgontzas AN, Basta M, Xie C, Li Y
J Clin Sleep Med 2020 Feb 15;16(2):219-230. Epub 2020 Jan 13 doi: 10.5664/jcsm.8170. PMID: 31992405Free PMC Article
Appenzeller-Herzog C, Mathes T, Heeres MLS, Weiss KH, Houwen RHJ, Ewald H
Liver Int 2019 Nov;39(11):2136-2152. Epub 2019 Jul 10 doi: 10.1111/liv.14179. PMID: 31206982
Ben-Pazi H, Jaworowski S, Shalev RS
Dev Med Child Neurol 2011 Dec;53(12):1077-84. Epub 2011 Sep 27 doi: 10.1111/j.1469-8749.2011.04134.x. PMID: 21950517
Wiggelinkhuizen M, Tilanus ME, Bollen CW, Houwen RH
Aliment Pharmacol Ther 2009 May 1;29(9):947-58. doi: 10.1111/j.1365-2036.2009.03959.x. PMID: 19210288

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