Pyrrolizidine alkaloids hepatic veno-occlusive disease

ZUCKERMAN, M STEENKAMP, V., STEWART, M.J., Hepatic veno-occlusive disease as a result of a traditional remedy confirmation of toxic pyrrolizidine alkaloids as the cause, using an in vitro technique., J. Clin. Pathol., 2002, 55, 676-679. 

In a South African study 20 children were identified as suffering from hepatic veno-occlusive disease thought to be caused by the administration of traditional remedies (3). The predominant clinical presentation was ascites and hepatomegaly. Nine children died. The surviving patients progressed to cirrhosis and portal hypertension. In four cases early urine specimens were available, and in all of these the presence of pyrrolizidine alkaloids was confirmed. 

Comfrey Symphytum officinale Anti-inflammatory gastritis diarrhea Hepatic veno-occlusive disease possible teratogen/carcinogen. (Note many other plants also contain hepatotoxic pyrrolizidine alkaloids-see Table 11-46). 

Pyrrolizidine alkaloids Gastroenteritis, hepatic veno-occlusive disease. 

Hepatic veno-occlusive disease leading to death was reported in a 23-year-old man who ingested 4 to 5 cooked comfrey leaves daily for 1 to 2 weeks (Yeong et al. 1990). Two cases of veno-occlusive disease were reported in women who took comfrey-pepsin tablets for 6 months. The daily doses included 280 mg/kg total pyrrolizidine alkaloids in one patient and 988 mg/kg total pyrrolizidine alkaloids in the other patient (Huxtable 1987). 

Chen, Z., and R.-H. Huo. 2010. Hepatic veno-occlusive disease associated with toxicity of pyrrolizidine alkaloids in herbal preparations. Neth. J. Med. 68 (6) 252-260. 

Ridker PM, Ohkuma S, McDermott WV, Trey C, Huxtable RJ (1985) Hepatic veno-occlusive disease associated with consumption of pyrrolizidine alkaloid-containing dietary supplements. Gastroenterology 88 1050-1054... 

Veno-occlusive disease (VOD) describes the occlusion of small hepatic veins and is defined as a radicular form of the Budd-Chiari syndrome. A variety of endotheliotoxic noxae, particularly phytotoxins, are responsible for this clinical picture. In 1951 reports were simultaneously published for the first time both in South Africa (G. Selzer et al.) and Jamaica (K. R. Hill) dealing with this disease of the small venous branches, which results from chronic intoxication with pyrrolizidine alkaloids, (s. pp 548, 571) Similar morphological and clinical effects can also be caused by cytostatic agents (6-mercaptopurine, dacarbazine, thioguanine), azathioprine, contraceptives and exposure to X-rays. Since 1957, the term Stuart-Bras syndrome has also been used to describe the occlusion of the small hepatic veins, (s. p. 832)... 

Pyrrolizidine alkaloids cause obstruction of the hepatic venous system and can lead to hepatic necrosis. Clinical manifestations include abdominal pain, ascites, hepatomegaly, and raised serum transaminases. The prognosis is often poor, death rates of 20-30% being reported. In an outbreak of veno-occlusive disease in the Sarguja district of India, probably caused by consumption of cereals mixed with Crotalaria seeds, 28 of 67 patients died (19). 

A 49-year-old woman was diagnosed with veno-occlusive disease, a form of Budd-Chiari syndrome. The patient had portal hypertension associated with obliteration of the smaller hepatic venules. A liver biopsy specimen showed centrilobular necrosis and congestion. The woman had been regularly taking two products that contained comfrey, one for 6 months and the other for 4 months. Analyses of products taken indicated an estimated intake of pyrrolizidine alkaloids of 0.49 to 1.45 ng/kg daily. Other supplements being taken by the woman included a number of vitamins, minerals, and sterotrophic adrenal bovine extract (Ridker et al. 1985). 

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