Phytotherapy-Induced Hepatocytotoxicity: A Case Report.

Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and an immune response leading to a hypersensitivity reaction to the products. We have recently treated a 39-year-old man with hepatotoxicity resulting from a combination of a green tea-containing powder and a branched-chain amino acid supplement that was commenced 2 months previously. The hepatotoxicity resolved by stopping the consumption of these products and no other cause was detected. We decided to perform a lymphocyte toxicity assay (LTA) to determine if there was laboratory support for this diagnosis. LTA (% toxicity) represents the response of the mitochondria to toxic injury. To determine the role of the proinflammatory and anti-inflammatory cytokines and chemokines in the patient's reaction, we measured the level of cytokines and chemokine in the media of growing cells, exposed to each product or to a combination of products. The increased cytokines and chemokines are presented as the x-fold elevations from the upper limit of normal (ULN) for matrix metalloproteinase (MMP) (pg/mL × 1.5 ULN) and interleukin (IL)-1ß (pg/mL × 1.8 ULN). Higher elevations were found for interferon (IFN)-ß, IFN-γ, IL-8, IL 13, IL-15 (pg/mL × 2 ULN), regulated upon activation, normal T cell expressed and presumably secreted (RANTES) (pg/mL × 2 ULN), and nuclear factor (NFκB) (pg/mL × 3 ULN). The highest increases were for vascular endothelial factor (VEGF) (pg/mL × 10 ULN), tumor necrosis factor (TNF)-α, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL × 13 ULN). An examination of cellular markers showed the difference between programmed cell death (apoptosis) and cell death due to necrosis. In our case, cytokeratin-ccK18 (M-30) U/L was within the normal limits, suggesting that apoptosis was normal, while ccK8(M65) U/L was elevated at 1.5 × ULN. This result implies that upon the treatment of the patient's lymphocytes with the products, the mechanism of toxicity is necrosis. In susceptible individuals, the combination of protein and herbal tea produces mitochondrial toxicity and a strong T-lymphocyte-1 response, leading to HILI. There is a need of international reporting of adverse drug reactions by clinicians, laboratories, and pharmaceutical manufacturers to drug regulatory authorities. This requires internationally accepted standard definitions of reactions, as well as criteria for assessment.

Fibrotest-Actitest: the biochemical marker of liver fibrosis--the Israeli experience.

BACKGROUND: The Fibrotest-Actitest is a six-parameter scoring system that allows quantification of liver fibrosis and inflammation. This test has been validated by several studies in hepatitis B and C viruses and alcoholic liver disease, with a high correlation between the liver biopsy and the results of the FT-AT (AUROC between 0.78 and 0.95). The FT-AT was introduced in Israel (Rambam Laboratory) in March 2005. OBJECTIVES: To assess the results of HCV patients who underwent the test during the period March 2005 to February 2006. METHODS: Serum was taken and brought to the central laboratory performing the tests within 4 hours. Six parameters were evaluated using commercial kits approved by the designer of the test (Biopredictive): total bilirubin, gamma-glutamyltransferase, alpha-2 macroglobulin, haptoglobin, alanine aminotransferase, and apolipoprotein-A1. The results were sent to the website of Biopredictive (France), which provided the FT-AT score online using a patented formula. RESULTS: Of the 325 patients tested, only 4 were not interpretable because of hemolysis. Patients' age ranged from 7 to 72 years (median 42); 54% were female. Liver biopsy was performed in 81 patients and was compared with the results of the Fibrotest. Findings were as follows: 27% of the patients were F0, 19% F1, 20% F2, 17% F3 and 17% F4; 18% were A0, 32% A1, 28% A2 and 22% A3. The AUROC curve comparing the Fibrotest with liver biopsy with a cutoff point at F2 and A2 for significant fibrosis and inflammation was 0.85 and 0.79 respectively. CONCLUSION: Fibrotest is a simple and effective method to assess liver fibrosis and inflammation and can be considered an alternative to liver biopsy in most patients with HCV.

Prevalence and predictive signs for gastrointestinal lesions in premenopausal women with iron deficiency anemia.

INTRODUCTION: The reported rates of gastrointestinal (GI) lesions among pre-menopausal women with iron deficiency anemia (IDA) vary considerably. AIM: To assess the prevalence of significant gastrointestinal lesions among symptomatic and asymptomatic pre-menopausal women with IDA, and to shed light on potential predictors of their presence. METHODS: Clinical, endoscopic, and histological data was collected from 116 pre-menopausal women with IDA. All women underwent upper and lower gastrointestinal tract endoscopies, duodenal biopsies, and small bowel evaluation with small bowel series or computed tomography. RESULTS: The mean age was 33 years (range: 18-45). Clinically, significant lesions were demonstrated in 30%, the majority in the upper gastrointestinal tract. Helicobacter pylori gastritis was the most common finding (16%). Celiac disease was detected in 6%. No malignant lesions were detected. The prevalence of lesions was highest among women with symptoms of heartburn and regurgitation. The presence of upper gastrointestinal symptoms (OR: 3.67, 95%CI: 2.14-5.03; P = 0.002), MCV lower than 70 pg (OR: 1.88, 95%CI: 1.27-3.91; P = 0.04), and hemoglobin levels less than 10 g/dl (OR: 1.71, 95%CI: 1.19-4.07; P = 0.05) were associated with an increased likelihood of significant gastrointestinal lesions; history of heavy menstrual blood loss was associated with negative findings (OR: 0.46, 95%CI: 0.27-0.69; P = 0.002). CONCLUSIONS: Upper GI findings, mainly HP gastritis and celiac disease, were the most common pathologic findings. Initial evaluation of IDA in premenopausal women may include urea breath test and celiac serology. Further endoscopic evaluation can be reserved for those women who are found to be negative in the initial evaluation, as well as in cases of failure of IDA remission after successful HP eradication.