Table 156Summary of study quality

StudyNIndex test(s)Selection criteriaReporting biasVerification bias(a)Time between tests(b)Index test threshold selectionBlinding of assessorsExperienced assessorAdequate biopsy sample
Liver function tests
Ho 1986 (prospective)18LFT: ALTConsecutive sample, all receiving MTX (Singapore)YesYes – only included those with high
ALT or high total
MTX dose		UnclearUnclearYesUnclearUnclear
Lenler-Peterson 1982 (retrospective)45 (151 concurrent tests)LFT: galactose tolerance testConsecutive sample, all receiving MTX and having developed fibrosisYesYes – only included those known to have developed fibrosisUnclear(c)Pre-definedUnclearUnclearUnclear
Newman 1989 (retrospective)168 (364 biopsies paired with LFTs, 85 before treatment)LFTs: ALT, AST, bili, AP, PT, albConsecutive sample, before and during MTXUnclear if all analysedNo3 daysUnclearYesUnclear (but IRR of 3 assessors checked)Unclear
O’Connor 1989 (retrospective)78 (147 biopsies paired with LFTs; 52 before and 95 after treatment)LFTs: AST, bili, APUnclear sampling, all had used MTX (normal pre-Tx biopsy)NoNoMaximum 1 weekPre-defined normal rangesYesUnclearUnclear
Paramsothy 1988 (prospective)15LFTs: AST, bili, AP, alb, GGTUnclear sampling, all had used MTXYesNoUnclearPre-defined normal rangesYesUnclearUnclear
Liver scintigraphy and ultrasound scans
Geronemus 1982 (retrospective)24Liver scintigraphy: Tc 99m sulphur colloid scanUnclear sampling, all had long-term MTX useYesNoMaximum 2 monthsPre-specifiedUnclearUnclearUnclear
McHenry 1992 (retrospective)63 (87 paired results)Liver scintigraphy: Tc 99m sulphur colloid scanConsecutive sample, before and during MTXNoNoMaximum 4 weeksPre-specifiedUnclearUnclearUnclear
Mitchell 1987 (prospective)49Liver scintigraphy: Tc 99m sulphur colloid scan UltrasoundUnclear sampling, all had long-term MTX useNoNo1 dayPre-specifiedUnclearYesUnclear
Coulson 1987 (prospective)28 (54 paired tests)UltrasoundUnclear sampling, before and during MTXNoNoMaximum 1 monthPre-specifiedYesYes for ultrasound; unclear for biopsy5 μm sections
PIIINP
Boffa 1996 (prospective)87 (147 paired tests)PIIINPUnclear sampling, all had long-term MTX use
Note: unclear proportion with PsA		NoNo<1 dayPre-specified (d)YesUnclearUnclear
Maurice 2005 (retrospective)34 (46 biopsies with 2–6 assays per biopsy)PIIINPConsecutive sample, all receiving MTX
Note: 22% had inflamm. arthritis		NoNoMaximum 6 monthsPre-specified (d)YesUnclear18 gauge needle
Zachariae 1989 & Risteli 1987 (prospective)73PIIINPConsecutive sample, all receiving MTX (≥6 months)
Note: 45.8% of pilot group had PsA		YesNoUnclearPre-specified (d)YesUnclearUnclear
Zachariae 2001 (retrospective)70 (189 biopsies and 329 assays)PIIINPUnclear sampling, all had MTX use and normal initial biopsy and PIIINP
Note: 38.6% had PsA		YesNo69/70 had ≥3 analyses within a year around the time of biopsyPre-specified (d)UnclearUnclearUnclear
Fibrotest and Fibroscan
Berends 2007 (retrospective)24Fibrotest

Fibroscan - used median value of successful readings on the same day		Unclear samplingYesNo≤18 monthsPre-specifiedYesYesVariable (only one had <10 portal tracts)

Alb: albumin; ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartate aminotransferase; bili: bilirubin; GGT: gamma-glutamyl transferase; IRR: inter-rater reliability; LFT: liver function tests; MTX: methotrexate; PIIINP: aminoterminal peptide of type III procollagen; PsA: psoriatic arthritis; PT: prothrombin time; Tc 99m: Technetium-99m isotope; Tx: treatment

a

Verification bias = did all patients in the studies received the same comparison tests, regardless of initial results

b

Clearly, if the time between the index test and the reference standard is too long it is possible that any discrepancy in findings is not accounted for by inaccuracy in the index test but rather y the clinical status of the participant having changed in the intervening period. However, the time for progression to fibrosis is unclear and any cut-off for a maximum time between tests would be arbitrary; therefore, all studies were included regardless of time between tests, although this will be considered as a risk of bias

c

Study methods state that participants were admitted at 1-year intervals for biopsy and galactose test, which implies they were performed on the same day

d

The threshold for an abnormal PIIINP assay was >4.2 μg/l (based on the reference range in Finnish blood donors); however, the manufacturer’s information leaflet states that the reference range is 2.3–6.4 μg/l based on PIIINP values of apparently healthy adults (19–65 years) although variations in population demographics may mean that slightly different reference limits apply across populations.

From: 12, Methotrexate and monitoring for hepatotoxicity

Cover of Psoriasis
Psoriasis: Assessment and Management of Psoriasis.
NICE Clinical Guidelines, No. 153.
National Clinical Guideline Centre (UK).
Copyright © National Clinical Guideline Centre - October 2012.

Apart from any fair dealing for the purposes of research or private study, criticism or review, as permitted under the Copyright, Designs and Patents Act, 1988, no part of this publication may be reproduced, stored or transmitted in any form or by any means, without the prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publisher at the UK address printed on this page.

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore for general use.

The rights of National Clinical Guideline Centre to be identified as Author of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.