Clinical diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic adverse drug reactions

doi:10.1016/S0168-8278(00)80127-0

Journal of Hepatology

Volume 33, Issue 6, December 2000, Pages 949-952

https://doi.org/10.1016/S0168-8278(00)80127-0 Get rights and content

Abstract

Background/Aim: Due to an absence of specific markers, the diagnosis of drug-induced hepatotoxicity is necessarily based on circumstantial evidence and is often inaccurate. We have evaluated the use of the clinical diagnostic scale (CDS) in the causality assessment of hepatotoxic adverse drug reaction (ADR) reports.

Methods: 135 hepatic adverse ADRs reported to the Committee on Safety of Medicines in North East England 1992–6 were evaluated. Initially, “International Consensus Criteria” were used to classify reactions as “drug-related”, “drug-unrelated” and “indeterminate”. Using the CDS, each ADR was then categorised as either definite drug hepatotoxicity (score > 17), probable (14–17), possible (10–13), unlikely 6., 7., 8., 9., or drug hepatotoxicity excluded (6).

Results: 49 ADRs were considered drug-related, 65 unrelated and 21 indeterminate. Reports classified as drug-related by consensus criteria scored higher on the CDS, with a median score of 12, range: 8–15, than either the indeterminate (8; [3–12]) or drug-unrelated reports (5; [2–11]) (p<0.0001). A CDS score of > 9, identified 88% of the cases classified as drug-related hepatotoxicity by consensus criteria and excluded 98% of those unrelated to the drugs.

Conclusions: CDS scoring correlates well with the international consensus classification and may be a useful tool in the routine evaluation of suspected hepatotoxic drug reactions.

Section snippets

Materials and Methods

The study received prior approval from the Newcastle upon Tyne Joint Ethics Committee. The Committee on Safety of Medicines obtained consent from the physicians and pharmacists within the Northern Region who had reported suspected hepatic ADRs, between 1992–1996, to divulge patients' names and clinical details. The reporting doctors were requested to obtain prior consent from patients. During 1997–1998, the case records for each patient were obtained and were systematically reviewed for the

Results

Out of 188 hepatotoxic reactions received between 1992–1996, 181 reports were traced. Excluding two duplicate reports and 24 GP reports, where consent from the reporting doctor could not be obtained, 155 reports were reviewed. Of these reports, 138 patients had case records available for review. Follow-up liver function tests were available 0–2555 days (median 118 days) post-reaction. After a review of their case notes, three further patients who acquired chronic hepatitis C following the

Discussion

The clinical diagnostic scale (CDS) was developed and validated in a single centre using a random sample of 50 cases of suspected, drug-induced liver injury, with the classification of these 50 cases by three clinicians used as the “gold standard” (3). In our study, the CDS has been compared with a more objective and widely accepted standard - the international consensus criteria - using a larger group of suspected hepatic ADRs. These criteria have been used previously by us to define and

Acknowledgements

This work was supported in part by the EUROHEPATOX Biomed Programme of the European Union (contract: BMH4-CT96-0658). We are grateful to Vivian Snaith for secretarial support.

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In studies consisting of both DILI and HILI cases, patients underwent liver biopsy in 13%.16 In other case series studies, results of liver biopsy were not available,17–19 or histological results were extracted from the medical charts without any further reported quantitative or qualitative details or evaluations.20 It appears that at present liver biopsy is a facultative rather than an obligatory measure for DILI and HILI case assessment.
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Clinical diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic adverse drug reactions

Abstract

Section snippets

Materials and Methods

Results

Discussion

Acknowledgements

J Hepatol

Hepatology

Criteria of drug-induced liver disorders: report of an international consensus meeting

J Hepatol

Adverse reactions to drugs

Br Med J