Cholestasis induced by Chinese herbal remedy Xia-Ku-Hua-Tan-Pian
Bibliographic record
Abstract
To the Editor: Traditional Chinese herbal remedies are increasingly used in the Western world. They are available without prescription and are generally perceived as a harmless, natural alternative to prescribed medication. However, serious concerns about adverse effects caused by herbal medications have been raised. Indeed, at least 31 cases of hepatotoxicity (including at least two fatalities) have been reported (1). Unfortunately, identification of the specific agent responsible for adverse effects is often difficult as most of these remedies contain several ingredients. As many as 32% of herbal products available in the USA also contain undeclared components or even heavy metals (2). Hepatotoxicity related to herbs classically presents with a marked inflammatory component (3–5). To our knowledge bland cholestasis without a significant hepatitic component has not yet been described with Chinese herbal remedies. We report a case of profound cholestasis induced by a Chinese expectorant formula called Xia-Ku-Hua-Tan-Pian. A 53-year-old female presented with progressive fatigue and jaundice and gradually increasing pruritus. Two months before she started taking a herbal remedy called Xia-Ku-Hua-Tan-Pian. Its ingredients are listed in Table 1. She took no other medication at this time. Even though her family physician stopped the remedy the symptoms remained unchanged over the period of 2 weeks. She was then put on ursodeoxycholic acid (UDCA) in the dose of 15 mg/kg b.w. and referred to our liver clinic. On examination she was jaundiced with multiple scratch marks on her skin. The bloodwork was as follows: aspartate transaminase – 30 U/L (3–30), alanine transaminase – 24 U/L (3–30), alkaline phosphatase (ALP) – 164 U/L (30–120), bilirubin – 180 umol/l (3–17). Albumin, prothrombin time-international normalized ratio, haemoglobin, leucocytes and platelet count were normal. Further investigations excluded viral and autoimmune hepatitis. Abdominal ultrasound and magnetic resonance cholangiopancreatography were both normal. Liver biopsy showed marked cholestasis, canalicular bile plugs, and bile pigment in macrophages and hepatocytes. There was also a patchy and mild portal lymphoid infiltrate with a few eosinophils, mild ductular reaction and no ductopenia. She was also put on cholestyramine 8 g/daily for her pruritus. The symptoms slowly resolved over next weeks. Whether UDCA contributed to this seems likely but remains unproven. Bloodwork performed 2 months later showed normal serum ALP, γ-glutamyl transferase and transaminases. Total bilirubin was 28 umol/l. All her clinical symptoms had resolved completely. The increasing number of reports describing various and often serious reactions to herbal medicines indicates their wide availability and increasing use. The traditional Chinese herb, Aristolochia sp., advocated for weight loss, may induce kidney failure (6) leading to its ban in some countries (7). This emphasizes the necessity of reporting all cases of unexpected side effects related to all medication including herbal remedies. In this way, public awareness of potential risks of these agents, universally perceived as safe and risk-free ‘natural’ medicines, will be enhanced. In this report, we describe the first case of hepatotoxic reaction secondary to Xia-Ku-Hua-Tan-Pian, a herbal formula consisting of 15 ingredients. Some of these ingredients, such as radix astragali membranaceus or semen coicis lachryma-jobi are in fact advertised as being hepatoprotective. However three ingredients, radix salviae miltiorrhizae, radix angelicae sinensis and radix paeoniae lactiflorae have been reported to cause very aggressive hepatotoxicity, in two cases with a fatal outcome (1, 8). Unlike the above-mentioned reports, our patient experienced typical ‘bland’ cholestasis that is occasionally seen in predisposed individuals taking hormonal contraception or anabolic steroids. Our case adds to the spectrum of potential liver manifestations linked to traditional Chinese herbal remedies and again shows that these agents can be harmful and indeed cause significant complications.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.007 |
| Insufficient payload (model declined to judge) | 0.012 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".