|
| Items for cholestatic or mixed liver injury | Score | Result |
|
| (1) Time to onset from the beginning of the drug/herb | | |
| (i) 5–90 days (rechallenge: 1–90 days) | +2 | +2 |
| (ii) <5 or >90 days (rechallenge: >90 days) | +1 | □ |
| Alternative: time to onset from cessation of the drug/herb | | |
| (iii) except for slowly metabolized chemicals: ≤30 days | +1 | □ |
| (2) Course of ALP after cessation of the drug/herb | | |
| Percentage difference between ALP peak and N | | |
| (i) Decrease ≥50% within 180 days | +2 | +2 |
| (ii) Decrease <50% within 180 days | +1 | □ |
| (iii) No information, persistence, increase, or continued drug/herb use | 0 | □ |
| (3) Risk factors | | |
| (i) Alcohol use: current drinks/d: >2 for women, >3 for men | +1 | □ |
| (ii) Alcohol use: current drinks/d: ≤2 for women, ≤3 for men | 0 | 0 |
| (iii) Pregnancy | +1 | □ |
| (iv) Age ≥ 55 years | +1 | □ |
| (v) Age < 55 years | 0 | 0 |
| (4) Concomitant use of drug(s)/herb(s) | | |
| (i) None or no information | 0 | □ |
| (ii) Concomitant drug/herb with incompatible time to onset | 0 | □ |
| (iii) Concomitant drug/herb with compatible or suggestive time to onset | −1 | −1 |
| (iv) Concomitant drug/herb known as hepatotoxin and with compatible or suggestive time to onset | −2 | □ |
| (v) Concomitant drug/herb with evidence for its role in this case (positive rechallenge or validated test) | −3 | □ |
| (5) Search for alternative causes | Tick if negative | Tick if not done |
| Group I (7 causes) | | |
| (i) HAV: anti-HAV-IgM | X | □ |
| (ii) HBV: HBsAg, anti-HBc-IgM, and HBV-DNA | X | □ |
| (iii) HCV: anti-HCV and HCV-RNA | X | □ |
| (iv) HEV: anti-HEV-IgM, anti-HEV-IgG, and HEV-RNA | X | □ |
| (v) Hepatobiliary sonography/colour Doppler sonography of the liver vessels/endosonography/CT/MRC | X | □ |
| (vi) Alcoholism (AST/ALT ≥ 2) | X | □ |
| (vii) Acute recent hypotension history (particularly in case of underlying heart disease) | X | □ |
| Group II (5 causes) | | |
| (i) Complications of underlying disease(s) such as sepsis, metastatic malignancy, autoimmune hepatitis, chronic hepatitis B or C, primary biliary cholangitis or sclerosing cholangitis, and genetic liver diseases | X | □ |
| (ii) Infection suggested by PCR and titer change for | | |
| (iii) CMV (anti-CMV-IgM and anti-CMV-IgG) | X | □ |
| (iv) EBV (anti-EBV-IgM and anti-EBV-IgG) | X | □ |
| (v) HSV (anti-HSV-IgM and anti-HSV-IgG) | X | □ |
| (vi) VZV (anti-VZV-IgM and anti-VZV-IgG) | □ | X |
| Evaluation of group I and II | | |
| (i) All causes: groups I and II reasonably ruled out | +2 | □ |
| (ii) The 7 causes of group I ruled out | +1 | +1 |
| (iii) 6 or 5 causes of group I ruled out | 0 | 0 |
| (iv) Less than 5 causes of group I ruled out | −2 | □ |
| (v) Alternative cause highly probable | −3 | □ |
| (6) Previous hepatotoxicity of the drug/herb | | |
| (i) Reaction labelled in the product characteristics | +2 | +2 |
| (ii) Reaction published but unlabelled | +1 | □ |
| (iii) Reaction unknown | 0 | □ |
| (7) Response to unintentional reexposure | | |
| (i) Doubling of ALP with the drug/herb alone, provided ALP below 2N before reexposure | +3 | □ |
| (ii) Doubling of ALP with the drugs(s)/herbs(s) already given at the time of first reaction | +1 | □ |
| (iii) Increase of ALP but less than N in the same conditions as for the first administration | −2 | □ |
| (iv) Other situations | 0 | 0 |
| Total score for the case | 6 |
|
