Table 2.
The patients' updated RUCAM for the cholestatic or mixed liver injury of DILI4
| Items for cholestatic or mixed liver injury | Score | Result |
|---|---|---|
| 1. Time to onset from the beginning of the drug/herb | ||
| 5-90 days (rechallenge: 1-90 days) | +2 | +2 |
| <5 or >90 days (rechallenge: >90 days) | +1 | |
| Alternative: Time to onset from cessation of the drug/herb (except for slowly metabolized chemicals: <30 days) | +1 | |
| 2. Course of ALP after cessation of the drug/herb | ||
| Percentage difference between ALP peak and normal | ||
| Decrease ≥50% within 180 days | +2 | +2 |
| Decrease < 50% within 180 days | +1 | |
| No information, persistence, increase, or continued drug/herb use | 0 | |
| 3. Risk factors | 0 | |
| Alcohol use current drinks/d: >2 for women, >3 for men) | +1 | |
| Alcohol use (current drinks/d: ≤2 for women, <3 for men) | 0 | |
| Pregnancy | +1 | |
| Age > 55 years | +1 | |
| Age < 55 years | 0 | |
| 4. Concomitant use of drug(s)/herb(s) | 0 | |
| None or no information | 0 | |
| Concomitant drug/herb with incompatible time to onset | 0 | |
| Concomitant drug/herb with compatible or suggestive time to onset | -1 | |
| Concomitant drug/herb known as hepatotoxin and with compatible or suggestive time to onset | -2 | |
| Concomitant drug/herb with evidence for its role in this case (positive rechallenge or validated test) | -3 | |
| 5. Search for alternative causes | Tick if | Tick if not |
| Group I (7 causes) | neg. | done |
| HAV: Anti-HAV-IgM | - | |
| HBV: HBsAg, anti-HBc-IgM, HBV-DNA | - | |
| HCV: Anti-HCV, HCV-RNA | - | |
| HEV: Anti-HEV-IgM, anti-HEV-IgG, HEV-RNA | - | |
| Hepatobiliary sonography/colour Doppler sonography of liver vessels/endosonography/CT/MR | - | |
| Alcoholism (AST/ ALT ≥ 2) | ||
| Acute recent hypotension history (particularly if underlying heart disease) | - | |
| Group II (5 causes) | - | |
| Complications of underlying disease(s) such as sepsis, metastatic malignancy, autoimmune hepatitis, | ||
| chronic hepatitis B or C, primary biliary cholangitis or sclerosing cholangitis, genetic liver diseases | ||
| Infection suggested by PCR and titer change for | - | |
| CMV (anti-CMV-IgM, anti-CMV-IgG) | ||
| EBV (anti-EBV-IgM, anti-EBV-IgG) | ||
| HSV (anti-HSV-IgM, anti-HSV-IgG) | ||
| VZV (anti-VZV-IgM, anti-VZV-IgG) | - | |
| Evaluation of group I and II | - | |
| All causes—groups I and II—reasonably ruled out | - | |
| The 7 causes of group I ruled out | - | |
| 6 or 5 causes of group I ruled out | ||
| Less than 5 causes of group I ruled out | +2 | |
| Alternative cause highly probable | +1 | |
| 0 | +2 | |
| -2 | ||
| -3 | ||
| 6. Previous hepatotoxicity of the drug/herb | ||
| Reaction labeled in the product characteristics | +2 | |
| Reaction published but unlabelled | +1 | |
| Reaction unknown | 0 | 0 |
| 7. Response to unintentional reexposure | ||
| Doubling of ALP with the drug/herb alone, provided ALP below 2N before reexposure | +3 | +3 |
| Doubling of ALP with the drugs(s)/herbs(s) already given at the time of the first reaction | ||
| The increase of ALP but less than N in the same conditions as for the first administration Other situations |
+1 -2 0 |
|
| Total score for the case | 9 |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis D virus; HEV, hepatitis E virus; CMV, cytomegalovirus; EBV, Ebstein Barr virus; HSV, Herpes simplex virus; VZV, Varicella Zoster virus; CT, computerised tomography; MR, magnetic resonance imaging; IgM, Immunoglobulin M; IgG, Immunoglobulin G; PCR, polymerase chain reaction; DNA, deoxyribonucleic acid; RNA, ribonucleic acid; N: normal