title: Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS): a prospective cohort study.
abstract: OBJECTIVE
  To evaluate mildly abnormal liver function test (LFT) results in general practice among patients who do not have known liver disease.
  
  
  METHODS
  Prospective cohort study of people with abnormal LFT results identified in primary care. Participants were intensively investigated using a common protocol and followed up for 2 years. Substudies investigated the psychological sequelae of abnormal test results, clinicians' reasons for testing, decision options when LFT results were abnormal and early detection of liver fibrosis.
  
  
  METHODS
  Eleven primary-care practices: eight in Birmingham and three in Lambeth.
  
  
  METHODS
  Adults with abnormal LFT results who did not have pre-existing or obvious liver disease. Eight analytes were included in the panel of LFTs.
  
  
  METHODS
  Statistical tests were used to identify the interactions between clinical features, the initial pattern of abnormal LFT results and (1) specific viral, genetic and autoimmune diseases, such as viral hepatitis, haemochromatosis and primary biliary cirrhosis; (2) a range of other serious diseases, such as metastatic cancer and hypothyroidism; (3) 'fatty liver' not associated with the above; and (4) the absence of detectable disease.
  
  
  RESULTS
  Fewer than 5% of people with abnormal LFT results had a specific disease of the liver, and many of these were unlikely to need treatment. The diagnostic potential of the LFT panel is largely subsumed into just two analytes: alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Gamma-glutamyltransferase (GGT) offers a small increase in sensitivity at the margin at the cost of a large loss of specificity. Eighty-four per cent of abnormal LFT results remain abnormal on retesting 1 month later. In many cases, carrying out a definitive or specific test will be more efficient than repeating LFTs, with a view to specific testing only if the test remains abnormal. An ultrasound diagnosis of 'fatty liver' was present in nearly 40% of patients with abnormal LFTs and a small amount of weight loss over 2 years was associated with a reduced incidence of liver fat. There was a J-shaped relationship between alcohol intake and fatty liver in men. An abnormal LFT result causes temporary anxiety, which does not appear to promote sustained behaviour change.
  
  
  CONCLUSIONS
  Liver disease is rare among people with abnormal LFT results in primary care. Only two analytes (ALT and ALP) are helpful in identifying the majority of liver disease. GGT adds little information in return for a high false-positive rate but it is sensitive to alcohol intake. LFT results seldom revert from abnormal to normal over a 1-month period, and modelling shows that repeating an abnormal LFT panel, as recommended in the current guidelines, is inefficient. LFTs are often undertaken to meet perceived patient need for a blood test, but as they are neither specific nor indicative of any particular disease they are among the least suitable tests for this purpose. Obesity and raised ALT provide strong evidence for a presumptive diagnosis of 'fatty' liver. Abnormal LFTs and 'fatty' liver provoke only short-term anxiety and neither is associated with sustained weight loss. Even a small amount of weight loss reduces liver fat.
  
  
  CONCLUSIONS
  (1) the cases of 'fatty liver' and controls should be followed up in the long term to identify features that predict development of hepatosteatosis and then cirrhosis; (2) the acceptability of replacing the traditional six- to eight-analyte LFT panel with a drop down menu including the ALT/ALP combination should be evaluated.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: School of Health and Population Sciences, University of Birmingham, Edgbaston, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Lilford
authors.forename: L
authors.initials: L
authors.lastname: Bentham
authors.forename: A
authors.initials: A
authors.lastname: Girling
authors.forename: I
authors.initials: I
authors.lastname: Litchfield
authors.forename: R
authors.initials: R
authors.lastname: Lancashire
authors.forename: D
authors.initials: D
authors.lastname: Armstrong
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: T
authors.initials: T
authors.lastname: Marteau
authors.forename: J
authors.initials: J
authors.lastname: Neuberger
authors.forename: P
authors.initials: P
authors.lastname: Gill
authors.forename: R
authors.initials: R
authors.lastname: Cramb
authors.forename: S
authors.initials: S
authors.lastname: Olliff
authors.forename: D
authors.initials: D
authors.lastname: Arnold
authors.forename: K
authors.initials: K
authors.lastname: Khan
authors.forename: M J
authors.initials: MJ
authors.lastname: Armstrong
authors.forename: D D
authors.initials: DD
authors.lastname: Houlihan
authors.forename: P N
authors.initials: PN
authors.lastname: Newsome
authors.forename: P J
authors.initials: PJ
authors.lastname: Chilton
authors.forename: K
authors.initials: K
authors.lastname: Moons
authors.forename: D
authors.initials: D
authors.lastname: Altman
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D058070:Asymptomatic Diseases; D005234:Fatty Liver / Q000175:diagnosis; D005260:Female; D006525:Hepatitis, Viral, Human / Q000175:diagnosis; D006801:Humans; D008107:Liver Diseases / Q000175:diagnosis*; D008111:Liver Function Tests / Q000592:standards / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase