Background: hepatotoxicity due to herbal remedies is being increasingly recognized. Centella asiatica (Centella asiatica Linn Urban) is commercialized for multiple conditions. Its active principles are pentacyclic triterpenic saponosides (asiaticoside, madecassoside).Clinical case studies: we present three women (61, 52 and 49 years old) who developed jaundice after taking Centella asiatica for 30, 20 and 60 days. Respective laboratory tests: ALT: 1193, 1694 and 324 U/L; ALP: 503, 472 and 484 U/L; bilirubin: 4.23, 19.89 and 3.9 mg/dl. The first patient also had ASMA 1/160 and AMA 1/320.Respective pathological diagnoses: granulomatous hepatitis with marked necrosis and apoptosis; chronic hepatitis with cirrhotic transformation and intense necroinflammatory activity, and granulomatous hepatitis.All patients improved with Centella asiatica discontinuation, and ursodeoxycholic acid 10 mg/kg/day.The first patient took Centella asiatica again, with recurrence of the damage. The second one had taken this herb a year before.Conclusions: many plants synthesize hepatotoxic compounds. Germander, Skullcap and Glycyrrhizin contain di-or triterpenic active principles, which can produce hepatic injury by promoting apoptosis and altering cell membranes. We hypothesize that these mechanisms may have resulted in injuries associated with Centella asiatica. The presence of autoantibodies and granulomas also favors an immune-mediated mechanism. Ursodeoxycholic acid has anti-apoptotic properties, but we cannot rule out that Centella asiatica discontinuation alone may have resulted in patient improvement.

It has been proposed that in the human liver, the estrogen receptor gene may become inappropriately expressed as a consequence of HBV integration, contributing to cell transformation. This study was undertaken to examine estrogen receptor status in patients with hepatitis B virus infection and to analyze the expression of progesterone receptor and of a heat-shock 27,000-D protein (hsp27), both of which are estrogen regulated in estrogen target tissues. Receptor proteins were detected in liver biopsy specimens by immunocytochemistry using antireceptor monoclonal antibodies; a monoclonal antibody was also used to detect hsp27. Estrogen receptor and progesterone receptor were mainly seen in the nuclei of hepatocytes. The presence of hepatitis B virus infection did not always result in elevated estrogen receptor expression, but in general the expression of this receptor protein was higher in hepatitis B virus-positive patients than in patients with the same pathological findings (hepatitis, cirrhosis, hepatocarcinoma) but without hepatitis B virus. This was more clearly seen in the patients with hepatitis. Although estrogen receptor expression was moderate to high in many samples, the expression of the two biochemical markers of estrogen action at postreceptor levels (progesterone receptor and hsp27) was low or absent in most of the liver tissues examined, suggesting that in the liver the interaction of estrogen-estrogen receptor-DNA has characteristics inherent to this tissue.

Primary biliary cirrhosis has a definite female preponderance. Increased estrogen levels have been found in patients with this disease; however no studies indicate the status of sex hormone steroid receptors in primary biliary cirrhosis patients. In this study the occurrence and distribution of estrogen receptors, progesterone receptors and androgen receptors in liver biopsy specimens from patients with primary biliary cirrhosis were examined and compared with these receptors in the normal liver. In addition, three heat-shock proteins associated with steroid receptors (90 kD, 70 kD and 27 kD) were examined. All of the receptor proteins were detected on immunocytochemical study using specific receptor antibodies; monoclonal and polyclonal antibodies were also used to detect the heat-shock proteins. Normal bile duct epithelial cells displayed low-to-moderate amount of estrogen receptors and abundant 90- kD, 70- kD and 27-kD heat-shock protein expression, whereas normal hepatocytes showed moderate estrogen receptor and 90-kD heat-shock protein and high 70-kD heat-shock protein expression. Expression of 70-kD heat-shock protein was due mainly to the constitutive form of this protein (hsc72). In patients with primary biliary cirrhosis, significant increases in estrogen receptor and 90-kD heat-shock protein content were seen in bile duct cells and in hepatocytes. Levels of 27-kD heat-shock protein were also increased in some of the primary biliary cirrhosis biopsy specimens. The expression of progesterone receptor and androgen receptor was very low in normal and primary biliary cirrhosis bile duct cells and hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

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