A22 A HIDDEN CAUSE OF DRUG-INDUCED LIVER FAILURE
Bibliographic record
Abstract
Nimesulide is a non-steroidal anti-inflammatory drug with relative selectivity for cyclooxygenase-2 enzyme marketed in 1985. Nimesulide was never approved for use in Canada, United States, United Kingdom, Australia, or New Zealand due to safety concerns. Multiple reports in the literature have linked nimesulide to severe liver injuries ranging from marked aminotransferase elevation to acute liver failure (ALF), need for liver transplantation, and death. Such reports have led to nimesulide’s withdrawal from the market in Finland and Spain in 2002, and in Ireland in 2007; however, it remains widely available in more than 50 countries worldwide. The mechanism for its hepatotoxicity remains unknown. We report a fatal case of ALF sustained by consumption of a “herbal” product purchased in Canada. Chart review. A 52-year-old female developed jaundice and malaise with rapid progression to ALF. Her past medical history was significant for type 2 diabetes, hypothyroidism, sickle cell trait, and breast adenocarcinoma in remission. Her medications included metformin, levothyroxine, tamoxifen, and “herbal” medications (Arjun heart tonic, R. Pyine and Hari tablets). She had no risks factors for chronic liver disease and family history was non-contributory. After initial presentation to a community hospital, she was transferred to a liver transplant center where she developed encephalopathy associated with worsening liver function. Serologies were negative for viral, auto-immune, and metabolic etiologies. Acetaminophen and ethanol levels were undetectable. Imaging showed patent hepatic vasculature, normal biliary ducts and hepatic parenchyma. Her clinical status deteriorated further and she underwent an orthotropic liver transplant three weeks after presentation. The liver explant appeared pale and shrunken. Histopathologic examination showed subacute massive paracinar and periportal necrosis compatible with drug-induced liver injury. Since the patient’s labeled “herbal” medications did not include hepatotoxic drugs, the “herbal” products were analyzed by our medicinal chemistry lab and revealed presence of high concentrations of nimesulide and chlordiazepoxide within two of the three herbal products. Four days postoperatively, she passed away due to sepsis and multiorgan failure. In Canada, 73% of the population regularly consumes herbal products. The majority (59%) of herbal medicines sold in North America contain ingredients that are not listed on the label. Here, we report a fatal case of ALF sustained by consumption of a commercially available herbal product that contained a known pharmaceutical product that is neither approved nor marketed in Canada. This case highlights the urgent need for governmental regulation and consumer safety policies regarding the manufacture, importation and dispensing of herbal/natural products to prevent serious adverse events. None
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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; a candidate call from one teacher head, not a consensus.
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".