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How to Diagnose and Exclude Drug-Induced Liver Injury.
Dig Dis. 2015; 33(4):472-6.DD

Abstract

The diagnosis of drug-induced liver injury (DILI) is largely a diagnosis of exclusion because, with the possible exception of protein:drug adducts in paracetamol overdose, there are no laboratory, biopsy or imaging tests that alone are capable of establishing an unequivocal diagnosis of DILI. However, it is increasingly appreciated that drugs that cause DILI typically have characteristic clinical presentations or 'signatures' that can be very useful in the diagnosis of DILI. Indeed, knowing a drug's DILI signature (or sometimes signatures) and the incidence rate of DILI during treatment with that drug are perhaps the most useful pieces of historical information in arriving at the diagnosis of DILI. Components of the signature include the typical latency from the onset of treatment, whether there are extrahepatic manifestations, whether the injury is hepatocellular, cholestatic or mixed, and sometimes characteristic features on biopsy or serological testing (e.g. liver autoantibodies). A major advance has been the establishment of the LiverTox website (http://livertox.nih.gov/) which provides open access to standardized entries for over 600 different drugs, including the characteristic clinical presentations of DILI when known. LiverTox will also calculate the causality score for individual cases using the RUCAM instrument and case-specific data entered by the site user. However, the problem with standard diagnostic instruments such as the RUCAM is that DILI signatures are not incorporated into the scoring system. The person entering data must therefore subjectively weigh the RUCAM score with the characteristic DILI signature(s) of the drug to arrive at a diagnosis. In the future, it should be possible to construct improved diagnostic instruments that objectively incorporate DILI signatures, data-based estimates of the incidence rates of DILI from each implicated drug, and perhaps genetic variants associated with the risk of DILI.

Authors+Show Affiliations

Hamner-University of North Carolina Institute for Drug Safety Sciences, University of North Carolina, Chapel Hill, N.C., USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26159261

Citation

Watkins, Paul B.. "How to Diagnose and Exclude Drug-Induced Liver Injury." Digestive Diseases (Basel, Switzerland), vol. 33, no. 4, 2015, pp. 472-6.
Watkins PB. How to Diagnose and Exclude Drug-Induced Liver Injury. Dig Dis. 2015;33(4):472-6.
Watkins, P. B. (2015). How to Diagnose and Exclude Drug-Induced Liver Injury. Digestive Diseases (Basel, Switzerland), 33(4), 472-6. https://doi.org/10.1159/000374091
Watkins PB. How to Diagnose and Exclude Drug-Induced Liver Injury. Dig Dis. 2015;33(4):472-6. PubMed PMID: 26159261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - How to Diagnose and Exclude Drug-Induced Liver Injury. A1 - Watkins,Paul B, Y1 - 2015/07/06/ PY - 2015/7/11/entrez PY - 2015/7/15/pubmed PY - 2016/4/5/medline SP - 472 EP - 6 JF - Digestive diseases (Basel, Switzerland) JO - Dig Dis VL - 33 IS - 4 N2 - The diagnosis of drug-induced liver injury (DILI) is largely a diagnosis of exclusion because, with the possible exception of protein:drug adducts in paracetamol overdose, there are no laboratory, biopsy or imaging tests that alone are capable of establishing an unequivocal diagnosis of DILI. However, it is increasingly appreciated that drugs that cause DILI typically have characteristic clinical presentations or 'signatures' that can be very useful in the diagnosis of DILI. Indeed, knowing a drug's DILI signature (or sometimes signatures) and the incidence rate of DILI during treatment with that drug are perhaps the most useful pieces of historical information in arriving at the diagnosis of DILI. Components of the signature include the typical latency from the onset of treatment, whether there are extrahepatic manifestations, whether the injury is hepatocellular, cholestatic or mixed, and sometimes characteristic features on biopsy or serological testing (e.g. liver autoantibodies). A major advance has been the establishment of the LiverTox website (http://livertox.nih.gov/) which provides open access to standardized entries for over 600 different drugs, including the characteristic clinical presentations of DILI when known. LiverTox will also calculate the causality score for individual cases using the RUCAM instrument and case-specific data entered by the site user. However, the problem with standard diagnostic instruments such as the RUCAM is that DILI signatures are not incorporated into the scoring system. The person entering data must therefore subjectively weigh the RUCAM score with the characteristic DILI signature(s) of the drug to arrive at a diagnosis. In the future, it should be possible to construct improved diagnostic instruments that objectively incorporate DILI signatures, data-based estimates of the incidence rates of DILI from each implicated drug, and perhaps genetic variants associated with the risk of DILI. SN - 1421-9875 UR - https://www.unboundmedicine.com/medline/citation/26159261/How_to_Diagnose_and_Exclude_Drug_Induced_Liver_Injury_ L2 - https://www.karger.com?DOI=10.1159/000374091 DB - PRIME DP - Unbound Medicine ER -