Sinusoidal obstruction syndrome associated with the ingestion of gynura root

To the Editor:

Gynura root (Gynura segefum) (Lour.) Merr, is a traditional Chinese herbal medicine used for the treatment of bleeding injuries in the rural areas of China. But the root is one of more than 6000 kinds of plants around the globe that contains pyrrolizidine alkaloids (PAs),¹ which can cause hemorrhagic necrosis of liver cells, hepatic giant cell disease, and veno-occlusive disease. When PAs reach the liver, they undergo a catalytic reaction of cytochrome P450, due to which dehydrogenation of PAs and dehydrogenation split base called metabolic pyrroles are formed. When glutathione (GSH) is decreased, the metabolic pyrroles may combine with nucleophilic enzymes, proteins, DNA, and RNA, causing a variety of damages. Because the concentration of GSH in sinusoidal endothelial cells is less than that in the hepatocytes, in zone 3 of the liver acinus, sinusoidal endothelial cells are more sensitive to damage than hepatocytes.^2,, ³ If this condition progresses, it will affect the hepatic vein, and the small vein wall will gradually be hardened. When occlusion occurs, the surrounding liver cells will undergo necrosis, leading to sinusoidal obstruction syndrome (SOS) which is also referred to as hepatic veno-occlusive disease (HVOD).

We report here a case of a patient who was afflicted with hepatomegaly, ascites, jaundice and weight gain after ingesting gynura root. A 37-year-old Asian woman (standard weight was 55 kg) ingested gynura root to correct irregular menstruation, consuming 100 g per day for 1 week. A month later, she started to experience upper abdominal pain, accompanied by fatigue and poor appetite. Since then, the symptoms described above gradually aggravated with abdominal distention. Three months later, the patient was hospitalized. Physical examination showed that jaundiced scleras, hepatomegaly, and shifting dullness were positive. Laboratory tests showed hypoproteinemia (ALB 28 g/L; normal: 35–55 g/L), serum total bilirubin was 41.1 μmol/L (normal: 3.4–17.1 μmol/L), and AST was 54 U/L (normal: 0–40 U/L). She gained 5 kg during the course of her illness. Her abdominal CT scan showed, in non-contrast scan phase, hepatomegaly, uneven density, patchy and low-density changes, and abdominal fluid; in the arterial enhancement scan phase, hepatomegaly was seen and the liver had heterogeneous enhancement in portal venous scan phase and lag phase, there were characteristics of map-like strengthening areas and low-perfusion areas, the two areas were mixed, hepatic veins were not clearly visible, hepatic segments of inferior vena cava were flat, and there was no lateral expansion and collateral circulation of the remote inferior vena cava. A laparoscopic abdominal exploration and liver biopsy operation result showed a congestive liver without nodules. Postoperative pathology showed that the central venous hepatic lobule and hepatic sinusoid were significantly congestive and extensive. The majority of the liver cells at the central areas of hepatic lobule had an obvious atrophy and necrosis, and the individual vein wall had a thickening and hyaline degeneration. The surrounding liver cells of the portal area had a fatty degeneration. Her liver pathology demonstrated that she had a SOS. The patient was treated with ursodeoxycholic acid capsules (750 mg/day), low-molecular weight dextran (500 ml/day), and prostaglandin E1 (10 μg/day). After therapy, her clinical symptoms finally improved and her ascites have subsided. After discharge from the hospital, the patient continued to take ursodeoxycholic acid capsules. Eight months later, her liver function test showed normal results (ALB 39 g/L, serum total bilirubin 15.2 μmol/L, AST 25 U/L), and abdominal B-mode examination showed normal liver size without ascites.

SOS is characterized by a post-sinusoidal portal hypertension; it is a rare disease and its early symptoms are atypical. The diagnosis of SOS depends on its histopathology. The disease is mainly caused by the hematopoietic stem cell transplantation and the usage of high-dose chemotherapy drugs during the liver transplantation phase, as well as the consumption of certain herbs.⁴ Defibrotide, tissue plasminogen activator, antithrombin III, prostaglandin E1, low-dose heparin, low-molecular weight heparins and ursodeoxycholic acid are administered to treat SOS. The treatment of liver cirrhosis involves liver transplantation and transjugular intrahepatic porto-systemic shunts (TIPS) on patients who show portal hypertension signs.⁵ At present, there are a few reports on the occurrence of SOS after the intake of gynura root^6,, ⁷ and almost all SOS patients presented with poor prognosis.⁸ The differences between the patient in this case and those in previous cases are: (1) SOS diagnosis is difficult. We used a laparoscopic abdominal exploration and liver biopsy, combined abdominal CT with pathologic examination, and finally obtained a clear diagnosis; (2) A study using an in vitro technique indicated the dose of PAs-related toxicity, with necrosis at high concentrations and apoptosis and abnormalities of the cytoskeleton at lower concentrations.⁹ WHO has indicated that the lowest intake causing disease may be 1 mg total PAs per day for a 70 kg adult.¹⁰ The patient took a large dose of gynura root, suggesting that although the dose of intake of gynura root with PAs, and duration of medication is to some degree correlated with SOS severity and patient prognosis. Individual factors also played an important role; (3) Illness was obviously relieved through active treatment, and re-examination showed excellent conditions. In most areas of China, people can be easily confused by panax notoginseng and gynura root because the Chinese names of panax notoginseng (san qi in Chinese) and gynura root (tu san qi in Chinese) are very similar. Owing to this, people select gynura root for disease treatment over panax notoginseng because it is cheaper. Panax notoginseng is a precious Chinese herbal and thus commands a higher price. Such incidences, as the case presented in this study, are common occurrences. The patient in this case took gynura root because of these reasons. Thus, in China, the hepatic toxicity of the gynura root should be given enough attention. The Chinese traditional herbal medicine should meet specific and appropriate standards of safety and quality, and the government should provide risk management actions and public education to the consumers of gynura root.