Test Profiles Time for a Change. Tony Badrick (AACB Harmonisation Committee)

Transcription

1 Test Profiles Time for a Change Tony Badrick (AACB Harmonisation Committee)

2 1. Why Profiles 2. Profiles A. LFT B. Electrolyte C. Renal D. Bone 3. Summary

3 Same clothes!! Harmonisation!

4 Same car!! Harmonisation!

5 Same house!! Harmonisation!

6 Harmonisation! Why?? Because we can afford it! We don t like change! conservative We focus on the small! We want to be different Professional!!

7 Harmonisation! How do we get change! Evolution Some one dies - dinosaur Revolution We are forced to change $

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9 Boundaries Community patients Screening Not only option specific test Investigation Recommended How often Considerations in guidelines LFT ordered (%) Type 2 Diabetes No 7 Yes when on glitazones and prior to Metformin Hypertension Yes 2.9 Lipid Disorders Yes 12.4 Particularly when on medications Weakness/ Tiredness Yes 20.5 Health Checks No 16.2 Overweight/ Obesity Yes 8.6 Beach data

10 Core Tests in a Profile? Is test specific to the organ or system? If not specific why include it? Does an abnormal result add additional diagnostic or prognostic information to the other tests? Does the added information justify the cost? Is there a clinical intervention available?

11 Opportunistic Screening Ast, GGT Alcohol abuse Total Protein paraproteinaemia Glucose Urate

12 Why Not? Less efficient for labs Cost will go up anyway Competitive advantage Who blinks first

13 Usual Components of the LFT

14 BALLETS: Standard Profile: Alt, Ast, GGT, Bili, ALP, Protein, Albumin, Globulin Age/Sex Reference intervals Any abnormality in any test followed up

15 Patient and clinical characteristics, including age, sex, ethnic group, country of birth, reason for blood testing, medication and history of illness, substance abuse, travel, immunisation and transfusion history; Alcohol use, via a standardised questionnaire; Weight, height, waist and hip circumference measurements; Repeat of the eight-analyte LFT panel; Blood for specific (auto-immune, genetic and viral) diseases in the liver work up ;

16 Ultrasound scan (USS) of the upper abdomen. Any tumours of the hepatobiliary system were noted and the liver was classified as normal, echobright (in three levels of intensity) or cirrhotic. A sample of ultrasound films were reviewed by the study radiologist. 2 year followup

17 All Causes of Abnormal LFT Cause Percentage (n) NAFLD 26.4 (295) At-risk alcohol intake Non-Fatty liver Fatty liver 14.0 (156) 11.3 (126) PBC 0.81 (9) HBV 0.72 (8) Haemochromatosis Homozygote [C282Y 0.54 (6) or H63D] Comp. heterozygote 0.36 (4) [C282Y + H63D] Other (inc. cancer, 0.36 (4) drug, abscess) HCV* 0.17 (2) PSC* 0.17 (2) A1AD* 0.17 (2) Unexplained group 45.1 (504)

18 Frequency of Abnormal LFT Tests in NAFLD

19 BALLETS Findings Liver function tests should be used sparingly in primary care. When a chronic disease affecting the liver is suspected, a panel of two analytes (Alt and ALP) should be used, supplemented by bilirubin if an acute disease or poisoning is suspected. When the clinician wishes to exclude a non-liver disease or simply reassure the patient, a selection should be made from a dropdown menu of tests, and tests that provide a clear pointer to the next appropriate step should be favoured.

20 Results <5% of people with an abnormal LFT panel had liver disease 1.7% needed treatment (antiviral/ venesection)

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22 ALFIE Followed up followed up all those who had had an incident batch of LFTs in primary care to subsequent liver disease or mortality over a maximum period of 15 years (approximately 2.3 million tests in 95,000 people). The target population consisted of patients with no obvious signs of liver disease. The health technologies being assessed are primary care and LFTs

23 Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE). Authors: Donnan PT, McLernon D, Dillon JF, Ryder S, Roderick P, Sullivan F, Rosenberg W Journal: Health Technology Assessment Volume: 13 Issue: 25 Publication date: May 2009

24 The most striking observations of this study are that: (1) liver disease is not common in those with ALFTs over a median follow-up time of 3.7 years; (2) GGT shows highest sensitivity for liver disease above other LFTs and is a good predictor of liver disease and liver mortality after adjustment for the bias of selective testing; (3) ALFTs are predictive of death from non-hepatic causes (particularly albumin); and (4) the rise in the number of LFTs requested does not alter the prevalence of abnormal tests.

25 ALFIE Conversely, although highly specific for liver disease, those with ALFTs are still mostly people who did not develop clinically apparent liver disease in the time-frame of this study. All cause mortality is a much more common outcome in this study than liver disease. This suggests that these tests may be better markers of poor health than liver disease, thus possibly justifying the increasing use of LFTs as a screen for general illness.

26 Comment on BALLETS: Evidence for the use of liver enzymes as a screening test A recent large general practice study based in Birmingham, 1118 patients with raised liver enzymes were thoroughly investigated, and a liver related cause could only be identified in 55% of patients. Continued reliance on alanine transaminase (ALT) elevation has contributed to both over-referral; in one study, 33% of secondary care referrals from general practitioners on investigation had simple steatosis only, as well as under-referral; nearly 50% of those who required investigations in primary care were neither referred nor adequately investigated in another study from the same region. Matthew J. Armstrong, Diarmaid D. Houlihan, et al. Journal of Hepatology, Volume 56, Issue 1, Pages , 2012.

27 Liver enzymes don t assess the degree of liver injury nor do they predict clinical outcomes. Lack of correlation of elevated liver enzymes with the degree of liver injury or loss of function None of the validated prognostic models used in clinical decision making such as Child-Pugh score, King s College Criteria, Model for Endstage Liver Disease (MELD) or UK End Stage Liver Disease (UKELD) include liver enzymes as their components.

28 The LFT Aspartate transaminase and alanine transaminase Specificity ALT superior Relationship r= 0.90/0.92

29 Total Protein in LFT Included as a screen for monoclonal gammopathy. Can opportunistic case-finding of paraproteins be clinically justified? Ann Clin Biochem Jul;42(Pt 4): Beetham R, Howie N, Soutar R. 1% of all malignancies. Definition of hyperproteinaemia hypergammaglobulinaemia Cost effective? Intervention? no evidence that detection improved the quality of life for patients Bhoji Watts, Leslie Burnett, and Doug Chesher Measurement of Total Protein Is Not a Useful Inclusion in Liver Function Test Profiles Clinical Chemistry 2000; v. 46, p $1.2 million unnecessary expenditure

30 Reflex Testing Using existing tests to suggest more specific tests in particular situations Cost/efficiency Automated process?? Consultation fee implication

31 De Ritis Ratio Validated as a marker of severity in chronic liver diseases secondary to alcohol, non alcoholic fatty liver disease (NAFLD), and primary sclerosing cholangitis (PSC). Reflects the structural changes (the degree of fibrosis) within the liver which precede any deterioration in liver function. Using a cut-off value of 0.8 for the AST/ ALT ratio, and in combination with established risk factors for chronic liver disease such as presence of diabetes and obesity (the BARD score) a negative predictive value of greater than 95%, to rule out significant liver scarring in NAFLD can be achieved. AST/ALT ratio also correlates with other accepted prognostic scores for liver disease such as the Child-Pugh and Model for End Stage Liver Disease (MELD)

32 Value as a Diagnostic test perhaps we should be adding more? Response to Stuart Smellie Article: David J Harman, Guruprasad Padur Aithal AST/ALT is validated as a marker of severity in chronic liver diseases secondary to alcohol, NAFLD, and primary sclerosing cholangitis. AST/ALT reflects the structural changes (the degree of liver fibrosis) within the liver which precede any deterioration in liver function. Cut-off value of 0.8 for the AST/ ALT ratio, and in combination with established risk factors for chronic liver disease such as presence of diabetes and obesity (the BARD score), a negative predictive value of greater than 95%, to rule out significant liver scarring in NAFLD can be achieved. Routine reporting of AST/ALT ratio would improve the clinical utility of the liver profile without added cost.

33 Reference Intervals What is normal in the population Alt GGT

34 Electrolytes

35 Chloride and Bicarbonate Anion gap not routinely reported Chloride provides no more information than Sodium except in unusual circumstances Bicarbonate not useful in most patients

36 Renal

37 Urate Not useful as a screen for gout Not useful as a renal function test

38 Urea Historical inclusion Not useful except in specific situations Not as sensitive nor specific as egfr

39 Bone

40 Bone and Calcium Phosphate provides no more information than calcium Magnesium

41 E/LFT P e r c e n t a g e Electrolytes Calcium Phosphate Magnesium Corrected Calcium Glucose Urea Urate Creatinine Alk Phos ALT AST GGT Albumin Total Protein Total Bilirubin Conj. Bilirubin Calc Globulins LD Cholesterol Triglycerides The Survey asked if the laboratory offered an E/LFT profile and 78% of public laboratories did not offer such a profile whereas 83% of private laboratories did.

42 Financial Incentives Cost of average profile test - <0.20c Incentive to do 5 Perverse inceptive -?change MBS to 4 + reflex

43 GROUP P2 - CHEMICAL Quantitation in serum, plasma, urine or other body fluid (except amniotic fluid), by any method except reagent tablet or reagent strip (with or without reflectance meter) of: acid phosphatase, alanine aminotransferase, albumin, alkaline phosphatase, ammonia, amylase, aspartate aminotransferase, bicarbonate, bilirubin (total), bilirubin (any fractions), C- reactive protein, calcium (total or corrected for albumin), chloride, creatine kinase, creatinine, gamma glutamyl transferase, globulin, glucose, lactate dehydrogenase, lipase, magnesium, phosphate, potassium, sodium, total protein, total cholesterol, triglycerides, urate or urea - 1 test Fee: $9.70 Benefit: 75% = $ % = $ tests described in item Fee: $11.65 Benefit: 75% = $ % = $ tests described in item Fee: $13.65 Benefit: 75% = $ % = $ tests described in item Fee: $15.65 Benefit: 75% = $ % = $ or more tests described in item Fee: $17.70 Benefit: 75% = $ % = $15.05

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45 ACB Suggestion

46 Harmonisation Time to ask what should we be doing? Reduce cost and confusion Important as we have more electronic requesting and e- records Is test for screening or monitoring Reflex testing? We need to know more about the utility of these basic tests!

47 Patterns of abnormality in the index LFT. The entries are the proportions of patients with abnormality in the row analyte given that the column analyte is abnormal. For example, the proportion of abnormal ALTs among patients whose AST is abnormal is 0.88; the proportion of abnormal ASTs among those with abnormal ALTs is Analyte Analyte % abnorma ALT AST Bilirubin ALP GGT Albumin Globulin Total Protein l ALT AST Bilirubin ALP GGT Albumin 2, Globulin Total Protein

48 The effect of increasing the threshold of abnormality for four analytes. Lilford R J et al. BMJ Open 2013;3:e by British Medical Journal Publishing Group