Hepatotoxicity due to a formulation of Ganoderma lucidum (lingzhi)

Abstract

Ganoderma lucidum, a dry preparation of fungus, is a commonly used Chinese medicine. It has cytoprotective, hepatoprotective, anti-tumor and anti-oxidant effects [ 1 Shiao M.S. Natural products of the medicinal fungus Ganoderam lucidum: occurrence, biological activities, and pharmacological functions. Chem Rec. 2003; 3: 172-180 Crossref PubMed Scopus (228) Google Scholar , 2 Zhang G.L. Wang Y.H. Ni W. Teng H.L. Lin Z.B. Hepatoprotective role of Ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice. World J Gastroenterol. 2002; 8: 728-733 PubMed Google Scholar , 3 Gao Y. Zhou S. Jiang W. Huang M. Dai X. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. 2003; 32: 201-215 Crossref PubMed Scopus (231) Google Scholar ]. It has been commonly used as self-medication for the prevention and treatment of various medical diseases including cancer, liver diseases, hypertension, hyperlipidemia and coronary disease. However, it is known that Chinese herbal medicines can cause hepatotoxicity [ 4 Stedman C. Herbal hepatotoxicity. Semin Liver Dis. 2002; 22: 195-206 Crossref PubMed Scopus (205) Google Scholar , 5 Kaplowitz N. DeLeve L.D. Drug-induced Liver Disease. 1st ed. Marcel Dekker, New York2002 Crossref Google Scholar ]. We report a patient in whom an intake of a formulation of Ganoderma lucidum causes a significant hepatotoxicity in which the liver biochemistry mimics that of acute cholangitis. A 78-year-old Chinese lady presented in July 2003 complaining of malaise, anorexia, generalized pruritus and tea-colour urine for 2 weeks. She had no history of significant alcohol intake. She was taking felodipine for hypertension for 2 years. The baseline liver biochemistry in routine follow-ups for the hypertension was normal. She took regular self-medications including oral calcium and multivitamin tablets daily. She also had regular intake of Ganoderma lucidum (‘lingzhi’) as a health supplement for at least 1 year. However, she started to take a new formulation in powder form of Ganoderma lucidum 4 weeks before the onset of symptoms. Physical examination only revealed marked jaundice. The liver biochemistry on presentation was as follows: albumin 37 g/l (normal 42–50), bilirubin 270 μmol/l (normal 7–19) (direct bilirubin 210 μmol/l), alkaline phosphatase (ALP) 388 U/l (normal 49–138), gamma glutamyltranspeptidase 907 U/l (normal 11–53), alanine aminotransferase 306 U/l (normal 5–31) and aspartate aminotransferase 237 U/l (14–36). The complete blood counts including eosinophil count were normal. The prothrombin time was 10.2 s. In order to exclude acute cholangitis, ultrasonography and computerized tomography of the liver were performed. Both investigations did not show any feature of biliary obstruction or gallstone. Other investigations including anti-mitochrondrial, anti-smooth muscle, anti-nuclear antibodies were all negative. Immunoglobulin titers were within normal range. Hepatitis virus markers including antibody to hepatitis A (IgM), hepatitis B surface antigen (HBsAg), antibody to hepatitis C and antibody to hepatitis E (IgM) were all negative. Histology of the liver biopsy showed both portal and lobular changes as demonstrated in Fig. 1. The histological features were compatible with drug-induced liver damage. The presence of esoinophil infiltrations in the portal tracts suggests that the mechanism of the hepatotoxicity is mediated through an immunoallergic reaction, though the peripheral eosinophil count on presentation was normal. (It was possible that the eosinophil count had normalized by the time of presentation.) She was asked to stop taking this powder formulation of Ganoderma lucidum after hospital admission. The bilirubin level peaked at 400 μmol/l and ALP level at 358 U/l. All the liver biochemical parameters gradually improved to nearly normal levels 5 months later.