Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids

Abstract

OBJECTIVE: Hepatic sinusoidal obstruction syndrome (HSOS) induced by a Chinese medicinal herb Tusanqi is increasingly being reported in recent years. The aim of the study was to investigate the possibility of using blood pyrrole‐protein adducts test as a confirmatory diagnostic method. METHODS: Patients with HSOS according to international diagnostic criteria associated with Tusanqi from January 2006 to August 2010 in Zhongshan Hospital Fudan University were included and clinical features were collected. Pyrrole‐protein adducts in blood sample were determined with ultra performance liquid chromatography‐mass spectrometry (UPLC‐MS) while pyrrolizidine alkaloids (PAs) in available herbal preparations were analyzed by high performance liquid chromatography‐ultraviolet (HPLC‐UV). RESULTS: Five patients (age 41–72 years, median age 54 years, all women) were included. Ascites (5/5), jaundice (5/5) and hepatomegaly (4/5) were common manifestations. The imaging features were diffused, patchy hepatic enhancement, periportal edema and ascites. Pathology ascertained that blood flow was obstructive at the site of sinusoid. PAs (Seneionine and seneciphylline) were identified in all the three available herbal preparations ingested by the HSOS patients. Pyrrole‐protein adducts were unequivocally found in all the five blood samples. Two patients recovered, two developed chronic illness and one died due to liver failure and hepatic encephalopathy. CONCLUSIONS: The detection of blood pyrrole‐protein adducts using a UPLC‐MS approach is a specific, reliable, unambiguous and confirmatory test for HSOS induced by PA, and should be used together with the conventional HSOS clinical diagnostic criteria for the definitive diagnosis of PA‐induced HSOS.

Blood Pyrrole-Protein Adducts—A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans

“…Using this method, we unequivocally identified pyrrole-protein adducts in the blood of 5 HSOS patients, who consumed PA-containing herbs (15,35). We also identified toxic PAs in the consumed herbs and thus confirmed PA-ILI in these patients.…”

“…PAs are probably the most common phytotoxins that induce liver injury in humans and livestock (20)(21)(22)(35)(36). However, the definitive diagnosis of liver injury associated with PAs is highly challenging and not accessible.…”

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

“…Recently, development of an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) assay for identification of pyrroleprotein adducts in peripheral blood may prove to be a useful supplement to conventional diagnostic methods. 111 With either mild or moderate cases of SOS, removal of the offending agent may offer good prospects for clinical recovery. In the most severe cases of herbal toxin-induced SOS in adults, hepatic failure may ensue.…”

Diagnostic performance of Contrast-enhanced CT in Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstructive Syndrome

“…Sometimes, HSOS occurs after the ingestion of pyrrolizidine alkaloids (PAs) which are contained in about 3% of the world’s flowering plants3. One of the most wide-use herbals containing PAs is gynura segetum4567. Clinical presentations of HSOS include jaundice, right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain.…”

“…However, it is difficult to detect PAs in dietary supplements or herbals because PAs are found in quiet a lot of herbals and the component of herbals is complex. Recently, an ultra-performance liquid chromatography-mass spectrometry assay was used to determine pyrrole-protein adducts in peripheral blood568, which provided a useful approach to establish the diagnosis of PAs-induced HSOS. However, the assay does not apply to clinical practice due to high expense and unavailability in most hospital.…”