Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome.
BACKGROUND
The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs) as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS.


METHODS
Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients' age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis.


RESULTS
Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23 patients with pyrrolizidine alkaloid-associated HSOS, ten recovered, four developed chronic disease, eight died, and one underwent liver transplantation within 6 months after onset. Blood PPAs were detectable in 24 of 40 patients with concentrations from 0.05 to 74.4 nM. Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively. The positive predictive value was 95.8% and the negative predictive value was 100%, whereas the positive likelihood ratio was 23.81. The level of blood PPAs in the severe group (died or received liver transplantation) was significantly higher than that in the recovery/chronicity group (P=0.004).


CONCLUSIONS
Blood PPAs measured by ultra-performance liquid chromatography-tandem mass spectrometry are highly sensitive and specific for pyrrolizidine alkaloid-associated HSOS. The blood PPA concentration is related to the severity and clinical outcome of pyrrolizidine alkaloid-associated HSOS.
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Hong
H
Gao
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
Jianqing Q
JQ
Ruan
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Jie
J
Chen
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
Na
N
Li
Shanghai Institute of Materia Medica, Shanghai, People's Republic of China.
Changqiang Q
CQ
Ke
Shanghai Institute of Materia Medica, Shanghai, People's Republic of China ; Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines, Shanghai Institute of Materia Medica, Hong Kong, People's Republic of China ; Chinese University of Hong Kong, Hong Kong, People's Republic of China.
Yang
Y
Ye
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong ; Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines, Shanghai Institute of Materia Medica, Hong Kong, People's Republic of China ; Chinese University of Hong Kong, Hong Kong, People's Republic of China.
Ge
G
Lin
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China ; Center of Evidence-Based Medicine Fudan University, Shanghai, People's Republic of China.
Jiyao Y
JY
Wang
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011758:Pyrroles / Q000097:blood*; D011763:Pyrrolizidine Alkaloids / Q000009:adverse effects* / Q000097:blood; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D001798:Blood Proteins; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids
blood protein adducts; drug-induced liver injury; herb; prognostic marker