Prospective Study
Copyright ©The Author(s) 2017.
World J Hepatol. Oct 18, 2017; 9(29): 1141-1157
Published online Oct 18, 2017. doi: 10.4254/wjh.v9.i29.1141
Table 6 Causality assessment for cases 1-26 of the liver injury study cohort, using the updated Roussel Uclaf Causality Assessment Method[25]
RUCAM items with attribution of scores (SC)CASES 1-26
SC1234567891011121314151617181920212223242526
1 Time to onset from the beginning of the herb
5-90 d+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+1+2+2+2+2+2+2+2
< 5 or > 90 d+1
Alternative: Time to onset from cessation of the herb
≤ 15 d+1
2 Course of ALT after cessation of the herb
Decrease ≥ 50% within 8 d+3+3+3+3+1+3
Decrease ≥ 50% within 30 d+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2
No information of continued drug use000
Decrease ≥ 50% after the 30th day00
Decrease < 50% after the 30th day or recurrent increase-2
3 Risk factors
Alcohol use (current drinks/d: > 2 for woman, > 3 for men)+1
Alcohol use (current drinks/d: ≤ 2 for woman, ≤ 3 for men)00000000000000000000/00000000
Age ≥ 55 yr+1+1+1+1+1+1+1+1+1+1+1+1+1+1+1
Age < 55 yr0000000000000
4 Concomitant drug(s)/herb(s)
None or no information000000000/00
Concomitant drug/herb with incompatible time to onset00000
Concomitant drug/herb with compatible or suggestive time to onset-1-1-1-1
Concomitant drug/herb known as hepatotoxin and with compatible or suggestive time to onset-2-2-2-2-2-2-2-2-2
Concomitant drug with evidence for its role in this case (positive rechallenge or validated test)-3
5 Search for alternative causes Group I (7 causes)
HAV: Anti-HAV-IgMØØNNØNØØØØNNØØNNØ/ØØØØØØNØ
HBV: Anti-HBC-IgM, HBV-DNAØØNNØNØØØØNNNNØØNNØ/ØØØNØØNØ
HCV: Anti-HCV, HCV-RNAØØNØØNNØØØNNNNØØNNØ/ØØØNØØØØ
HEV: Anti-HEV-IgM, anti-HEV-IgG, HEV-RNAØØØØØØØØØØØØØØØØØØØ/ØØØØØØØØ
Hepatobiliary sonography/colour Doppler sonography of liver vessels/endo-sonography/CT/MRCØØØØØØØØØØØØØNØØØØØ/ØØØØØØØØ
AlcoholismNNNNNNNNNNNNNNNNNNN/NNNNNNNN
Acute recent hypotension history (particularly if underlying heart disease)NNNNNNNNNNNNNNNNNN/NNNNNNNN
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 titre change forNNNNNNNNNNNNNNNNNNN/NNNNNNNN
CMV (anti-CMV-IgM, anti-CMV-IgG)
EBV (anti-EBV-IgM, anti-EBV-IgG)ØØØØØØØØØØØØØØØØØØØ/ØØØØØ ØØØØ
HSV (anti-HSV-IgM, anti-HSV-IgG)ØØØØØØØØØØØØØØØ+ØØ/ØØØØØØØØ
VZV (anti-VZV-IgM, anti-VZV- IgG)ØØØØØØØØØØØØØØØØØØØ/ØØØØØØØØ
Evaluation of group I and IIØØØØØØØØØØØØØØØØØØØ/ØØØØØØØ
All causes - groups I and II - reasonably ruled out+2
The 7 causes of group I ruled out+1
6 or 5 causes of group I ruled out000000000
Less than 5 causes of group I ruled out-2-2-2-2-2-2-2-2-2-2-2-21-2-2-2-2-2-2
Alternative cause highly probable-3
6 Previous information on hepatotoxicity of the herb
Reaction labelled in the product characteristics+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2+2/ +2+2+2+2+2+2+2+2
Reaction published but unlabelled+1+1
Reaction unknown000
7 Response to unintentional
reexposure
Doubling of ALT with the herb alone, provided ALT below 5 ULN before reexposure+3
Doubling of ALT with the herb already given at the time of first reaction+1+1
Increase of ALT but less than ULN in the same conditions as for the first administration-2
Other situations00000000000000000000000000
Total score for case4376-135343-175745666/74534653
Total score for causality: ≤ 0/excluded; 1-2/unlikely; 3-5/possible; 6-8/probable; ≥ 9/highly probable. Considered were the items for the hepatocellular type of liver injury and the data of 26 patients with normal ALT values at hospital admission, who experienced elevated ALT levels > 5 × ULN after use of herbal TCM. In the above section 4 (part 1 of the tabula) of concomitant drug(s), the following TCM herbs and drugs were considered. In the section 5 (search for alternative causes in part 2 of the tabula), the symbol of (n) denotes that the obtained result was negative, whereas (Ø) indicates that assessment was not performed. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CT: Computed tomography; HAV: Hepatitis A virus; HBc: Hepatitis B core; HBV: Hepatitis B virus; HCV: Hepatitis C virus; CMV: Cytomegalovirus; EBV: Epstein Barr virus; HEV: Hepatitis E virus; HSV: Herpes simplex virus; MRC: Magnetic resonance cholangiography; PCR: Polymerase chain reaction; RUCAM: Roussel Uclaf Causality Assessment Method; ULN: Upper limit normal; VZV: Varicella zoster virus.