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Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome.

Gao H, Ruan JQ, Chen J, Li N, Ke CQ, Ye Y, Lin G, Wang JY - Drug Des Devel Ther (2015)

Bottom Line: Patients' age, sex, biochemistry test results, and a detailed drug history were recorded.Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively.The blood PPA concentration is related to the severity and clinical outcome of pyrrolizidine alkaloid-associated HSOS.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

ABSTRACT

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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Suggested procedures for the diagnosis of PA-induced HSOS.Abbreviations: HSOS, hepatic sinusoidal obstruction syndrome; ILI, induced liver injury; DILI, drug-induced liver injury; PA, pyrrolidizine alkaloid.
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f3-dddt-9-4861: Suggested procedures for the diagnosis of PA-induced HSOS.Abbreviations: HSOS, hepatic sinusoidal obstruction syndrome; ILI, induced liver injury; DILI, drug-induced liver injury; PA, pyrrolidizine alkaloid.

Mentions: Although the Seattle criteria were based on patients who underwent bone marrow transplantation, they were shown to be useful for diagnosis in patients with HSOS caused by PA-containing herbs. A detailed history of herb ingestion, modified Seattle criteria, and blood PPA levels are key points for the diagnosis of PA-associated HSOS. We suggest using the diagnostic flow chart for PA-associated HSOS, as illustrated in Figure 3.


Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome.

Gao H, Ruan JQ, Chen J, Li N, Ke CQ, Ye Y, Lin G, Wang JY - Drug Des Devel Ther (2015)

Suggested procedures for the diagnosis of PA-induced HSOS.Abbreviations: HSOS, hepatic sinusoidal obstruction syndrome; ILI, induced liver injury; DILI, drug-induced liver injury; PA, pyrrolidizine alkaloid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554430&req=5

f3-dddt-9-4861: Suggested procedures for the diagnosis of PA-induced HSOS.Abbreviations: HSOS, hepatic sinusoidal obstruction syndrome; ILI, induced liver injury; DILI, drug-induced liver injury; PA, pyrrolidizine alkaloid.
Mentions: Although the Seattle criteria were based on patients who underwent bone marrow transplantation, they were shown to be useful for diagnosis in patients with HSOS caused by PA-containing herbs. A detailed history of herb ingestion, modified Seattle criteria, and blood PPA levels are key points for the diagnosis of PA-associated HSOS. We suggest using the diagnostic flow chart for PA-associated HSOS, as illustrated in Figure 3.

Bottom Line: Patients' age, sex, biochemistry test results, and a detailed drug history were recorded.Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively.The blood PPA concentration is related to the severity and clinical outcome of pyrrolizidine alkaloid-associated HSOS.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

ABSTRACT

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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus