The Drug-induced Liver Injury Diagnostic Scale can be used to determine the likelihood of liver injury being caused by a drug exposure. This was found to have a high level of validity, inter-rater reliability, and discriminatory capacity in assessing patients for possible drug-induced liver injury.
Component Scores:
(1) temporal relationship between drug intake and onset of clinical picture
(2) exclusion of alternative causes
(3) extrahepatic manifestations
(4) intentional or accidental reexposure to the drug
(5) previous report in the literature of liver injury associated with the drug
Temporal Relationship Between
Drug Intake and Onset of Clinical Picture
|
Temporal Relation |
Finding |
Points |
|
time from drug intake until onset of first clinical or laboratory manifestation |
< 4 days, first exposure |
1 |
|
|
<= 4 days, re-exposure |
3 |
|
|
4 days to 8 weeks, first exposure |
3 |
|
|
> 4 days, re-exposure |
1 |
|
|
> 8 weeks, first exposure |
1 |
|
time from withdrawal of the drug until the onset of manifestations |
0 - 7 days |
3 |
|
|
8 - 15 days |
0 |
|
|
> 15 days, drug not persistent after withdrawal |
-3 |
|
|
> 15 days, drug persistent after withdrawal |
0 |
|
time from withdrawal of drug until normalization of laboratory values |
<= 2 months, hepatocellular pattern |
3 |
|
|
<= 6 months, cholestatic or mixed pattern |
3 |
|
|
> 2 months, hepatocellular pattern |
0 |
|
|
> 6 months, cholestatic or mixed pattern |
0 |
where:
• normalization of liver function tests indicates a decrease in values to below two times the upper limit of the normal reference range
• for cholestatic or mixed patterns of liver injury, alkaline phosphatase is the primary liver function test monitored
• for hepatocellular or mixed patterns, alanine aminotransferase (ALT) is the primary liver function test monitored
Exclusion of Alternative Cause
Alternative causes:
(1) viral hepatitis (HAV, HBV, HCV, CMV, EBV)
(2) alcoholic liver disease
(3) biliary tree obstruction
(4) pre-existing liver disease
(5) pregnancy
(6) acute hypotension
Exclusion of alternative causes:
(1) viral hepatitis: negative serology
(2) alcoholic liver disease: negative history of alcohol intake and AST/ALT index < 2
(3) biliary tree obstruction: negative ultrasound studies and/or ERCP
(4) pre-existing liver disease: no clinical or laboratory evidence of liver disease in past; histologic findings on liver biopsy
(5) pregnancy: male or negative pregnancy test
(6) acute hypotension: no history of significant hypotension
|
Finding |
Points |
|
alternative cause completely excluded |
3 |
|
alternative cause partially excluded |
0 |
|
possible alternative cause detected |
-1 |
|
probable alternative cause detected |
-3 |
Extrahepatic Manifestations
Number of the following present (0 to 5)
(1) rash
(2) fever
(3) arthralgias
(4) eosinophilia (> 6%)
(5) cytopenia (anemia, thrombocytopenia, agranulocytosis)
|
Number of Extrahepatic Manifestations |
Points |
|
4 or 5 |
3 |
|
2 or 3 |
2 |
|
1 |
1 |
|
none |
0 |
Intentional or Accidental Reexposure to Drug
|
Reexposure |
Points |
|
positive rechallenge test |
3 |
|
not rechallenged |
0 |
|
negative rechallenge test |
0 |
where
• positive rechallenge = increase of liver function tests of at least 2 times the upper limit of the normal reference range
• negative rechallenge = all other situations
Previous Report in Literature of
Drug Induced Liver Injury Associated with Drug
|
Previous Report |
Points |
|
yes |
2 |
|
no and drug marketed for <= 5 years |
0 |
|
no and drug marketed for > 5 years |
-3 |
liver injury diagnostic scale =
= (points for temporal relationship) + (points for exclusion of other causes) + (points for extrahepatic manifestations) + (points for reexposure) + (points for previous reports of injury)
Interpretation:
• minimum score: -8 (reference says -6)
• maximum score: 20
• If more than one drug is under suspicion, scores are computed for each drug and the drug with the maximum score is considered the most likely involved in the liver injury.
|
Diagnostic Scale |
Diagnosis |
|
> 17 |
definite |
|
14 - 17 |
probable |
|
10 - 13 |
possible |
|
6 - 9 |
unlikely |
|
< 6 |
excluded |
Purpose: To use the Drug-Induced Liver Injury Diagnostic Scale to determine the likelihood of liver injury being caused by drug exposure.
Specialty: Gastroenterology, Pharmacology, clinical
Objective: risk factors, criteria for diagnosis, severity, prognosis, stage
ICD-10: K71,
