Homeopathy-medicine induced severe alcoholic hepatitis A Case Report

Despite the thorough documentation and comprehensive analysis presented in this case report, the journal article's impact is limited by several critical factors.
The primary drawback is the reliance on a single case study, which severely restricts the generalizability of the findings. Without corroborative data from additional cases or larger studies, the conclusions drawn remain speculative and may not reflect broader clinical realities.
Furthermore, the absence of a control group undermines the strength of the causal relationship between the homoeopathic medicine and the development of alcoholic hepatitis.
This gap in the methodology leaves room for alternative explanations and reduces the reliability of the findings. Potential biases, particularly in patient self-reporting and recall, further detract from the robustness of the conclusions.

1. Homeopathy-medicine induced severe alcoholic hepatitis A Case Report Dr. Arjun S MD Part 1 Dept of Medicine JIMS Homoeopathic Medical College & Hospital

2. Table of contents 01 04 02 05 03 06 Liver Diseases Article Critical Appraisal Merits & Demerits Conclusion References

3. Gilbert Syndrome Decreased hepatic bilirubin uptake is believed to contribute to unconjugated hyperbilirubinemia of Gilbert’s syndrome (GS) Serum bilirubin concentrations are most often <3 mg/dl Males are more affected compared to females It’s a benign condition In gilbert syndrome, UGT1A1 mechanism is slightly deficient so it results in the slow conversion Only 30% have the symptoms

4. Alcoholic Hepatitis Alcoholic liver disease consist of three major lesions ie ; fatty live Alcoholic hepatitis , liver cirrhosis 10 – 30% of heavy drinkers are affected Alcoholic hepatitis is generally thought to occur with excessive drinking that takes place over a period of at least 20 years (2) Clinical symptoms : jaundice , inflammation , fever , fatigue & painfully enlarged liver

5. Risk Factors of Alcoholic Liver Disease

6. Non-Alcoholic Fatty Liver Disease (NAFLD) NAFLD is strongly associated with obesity/overweight, and insulin resistance Associated with metabolic syndrome (hypertension, obesity and diabetes) AST will be >400 usually Enhanced liver fibrosis (ELF), NAFLD fibrosis score (NFS), fib 4 score are the latest method to assess the fibrosis The progression of NAFLD - 1 stage of progression every 14 years for NAFL and 1 stage of progression every 7 years for patients with NASH.

7. Homeopathy-medicine induced severe alcoholic hepatitis A Case Report Title

8. Authors Rajaguru Paramaguru The Liver Unit, Ernakulam Medical Centre, Kochi, Kerala, India Gastroenterology, Ernakulam Medical Centre, Kochi, Kerala, India Pathology, PVS Memorial Hospital Ltd, Kochi, Kerala, India Cyriac Abby Philips Philip Augustine Gastroenterology, Ernakulam Medical Centre, Kochi, Kerala, India Rizwan Ahamed

9. About Journal Publisher: BMJ Case Reports CP Date of Publication: May 28, 2019 Volume: 12 Issue: 5 DOI: https://doi.org/10.1136/bcr-2019-229627

10. We present a teetotaler with compensated non-alcoholic fatty-liver-disease related cirrhosis who presented with acute worsening of his chronic liver disease. The acute event was not discernible even after extensive work up and finally a trans jugular liver biopsy revealed features suggestive of severe alcoholic hepatitis. Summary

11. The patient and the family denied occult alcohol use when questioned over multiple times and finally, the culprit ’alcohol’ was found to be the homoeopathy medicines that the patient was consuming over a month for treatment of Gilbert’s syndrome. We retrieved and tested the homoeopathy drug for alcohol content and found an alarming 18% ethanol in the same, confirming our diagnosis. Summary

12. Alcoholic hepatitis (AH) is a devastating disease that clinically presents with acute onset of jaundice and coagulation failure with ascites or hepatic encephalopathy. The syndrome can present as acute on chronic liver failure which is associated with high mortality in the presence of infections and multiple organ failure. Background

13. Chronic alcohol abuse appears to be associated with the development of AH, but the key trigger for its development is still unclear, since it has been noted to occur in patients with recent alcohol use and also in binge drinkers, such that environmental and genetic factors may also be central to the event. The amount and duration of alcohol abuse for development of AH depends on the individual patient. Alcohol consumption usually within a 2-month period prior to onset of jaundice is usually noted in patients with AH. Background

14. Complementary medicine use has been on the rise among the general population and patients with chronic disease with regard to presumed ‘safety and efficacy’, without required clinical trials on the same, but through advertisements and promotional activities. Alcohol intoxication linked to Ayurvedic medicine consumption has also been documented in literature. And intoxications and poisonings due to homoeopathic drugs are well known. Background

15. In this report, we present the interesting but devastating case of a man with compensated cirrhosis and Gilbert’s syndrome (the latter a benign congenital unconjugated hyperbilirubinaemia state) who took homoeopathic medicines for 1 month leading to severe AH that was diagnosed on liver biopsy. Furthermore, we also provide strong evidence, through advanced drug testing , linking the homoeopathy drugs that caused severe drug induced liver injury mimicking AH in the patient. Background

16. A 38-year-old obese man (body mass index 35.4). Diagnosed with compensated Non Alcoholic Fatty Liver Disease related Cirrhosis and associated Gilbert’s syndrome. Was prescribed Homoeopathic- medication for 1 month for treatment of unconjugated hyperbilirubinemia. Paternal family history of heart disease and fatty liver disease was significant. Case Presentation

17. The baseline serum total bilirubin prior to starting the homoeopathic drugs was 4.2 mg/dL (normal up to 1.2) with direct bilirubin 0.6 mg/dL (normal 0.1–0.4). After consuming the medicines for a period of 2 weeks, due to feeling of drowsiness, slurring of speech and lethargy, akin to ‘intoxication’, the medication frequency was modified by the treating homoeopath after which liquid formulation was decreased and quantity of tablets increased to five per hour. Case Presentation

18. Two weeks later, the patient noticed yellowish darkening of urine and of eyes, that was associated with bilateral leg swelling. After a visit to the homeopath thereafter, the patient underwent repeat liver test that revealed total bilirubin 12.8 mg/dL with direct bilirubin 9.6 mg/dL , aspartate transaminase 202 IU/L (normal <38), alanine transaminase 82 IU/L (normal <40) and was referred to a higher medical center for further management. Case Presentation

19. At admission to our liver unit, repeat liver tests showed total bilirubin 29.8 mg/dL with direct bilirubin 15.6 mg/dL , aspartate transaminase (AST) 138 IU/L , alanine transaminase (ALT) 42 IU/L , gamma-glutamyl-transpeptidase 292 IU/L (normal up to 140) with AST:ALT ratio >2 and international normalized ratio 3.8. Blood tests for acute viral hepatitis A, E and for hepatitis B and C were negative. Case Presentation

20. In the absence of identifiable causes for the acute event, the patient underwent trans jugular liver biopsy after informed consent from the wife. Histopathology of the liver revealed ballooned hepatocytes (figure 1B, arrow), mononuclear-cell-predominant mixed-portal inflammation (figure 1B, dashed arrow), hepatocellular, canalicular and cholangiolar cholestasis (figure 1B, arrow heads), foamy Kupffer cells (figure 1C, arrow), hepatocellular eosinophilic degeneration and extensive pericellular fibrosis in the background of cirrhosis suggestive of acute AH . Case Presentation

21. Based on the biopsy findings, further confrontation with the patient and family including sessions with psychologist and a psychiatrist, regarding occult alcohol use was non-contributory. Case Presentation

22. Homoeopathy drugs ingested by the patient were retrieved triple-quadruple-gas-chromatography-coupled-mass-spectroscopic evaluation yielded an alarming cumulative ethanol concentration of 18.3% v/v concentration which was equivalent of fortified wine such as sherry or port. Case Presentation

23. The exact total volume of liquid and number of pills consumed by the patient during the time of homoeopathic treatment could not be ascertained by us since these were discarded after consumption by the patient, except for an explanatory evidence of consumption of ‘many, many bottles’ as per the patient’s spouse, which was also timely linked to the drowsiness and intoxication states experienced by the patient. A final diagnosis of homoeopathy drug induced AH was made, with hepatocellular type of liver injury (R ratio >5) and Roussel Uclaf Causality Assessment Method score was suggestive of probable adverse drug reaction. Case Presentation

24. The patient’s Model for End Stage Liver Disease score was 34 at admission . The patient and family were strongly counselled regarding the need for liver transplantation to increase survival. Nutritional management, antimicrobials and intravenous N-acetyl cysteine were started in the patient after which initial improvement in liver tests were noted, but without further improvement in liver disease severity score. In view of severe AH features on the liver biopsy, the patient was started on oral prednisolone, 40 mg/day in two divided doses. Outcome & Follow Up

25. Model for End-Stage Liver Disease score: This score is a valuable tool for assessing the severity of liver disease and guiding the management of patients with end-stage liver disease. It is widely used in clinical practice to prioritize patients for liver transplantation and to predict mortality risk, helping to ensure that the sickest patients receive timely and appropriate care. Components of the MELD Score: Serum Bilirubin Serum Creatinine International Normalized Ratio (INR): A measure of blood clotting, reflecting the liver's ability to produce clotting factors. Interpreting the MELD Score: < 9: Low risk of mortality 10-19: Moderate risk of mortality 20-29: High risk of mortality 30-39: Very high risk of mortality ≥ 40: Extremely high risk of mortality

26. On the eighth day, a Lille Model score was calculated to look for corticosteroid treatment response. The Lille Model score was 0.98 suggestive of non-response to steroid treatment. In view of high liver disease severity scores and chances of clinical worsening, the patient was referred for further management to a liver transplant center. Outcome & Follow Up

27. In the absence of matching living donors in the family, the patient was listed in the deceased liver donation programme . However, clinical deterioration was rapid with the onset of infections and ultimately the patient developed multiple organ failure and succumbed to his illness 1 month and 12 days after his initial presentation to our unit. Outcome & Follow Up

28. Lille Model Score The Lille score is a prognostic tool used to assess the response and predict the prognosis of patients with severe alcoholic hepatitis who are undergoing treatment with corticosteroids . Components of Lille Score : Age of the patient (in years) Albumin level (in g/L) at day 0 of corticosteroid therapy Bilirubin level (in µmol/L) at day 0 of corticosteroid therapy Bilirubin level (in µmol/L) at day 7 of corticosteroid therapy Prothrombin time (PT) or international normalized ratio (INR) at day 0 Change in bilirubin level between day 0 and day 7 Interpreting the Lille Score: Lille Score ≤ 0.45 : This indicates a good response to corticosteroid therapy, and continuation of treatment is recommended. Lille Score > 0.45 : This indicates a poor response to corticosteroid therapy, and discontinuation of treatment is usually recommended, as these patients are unlikely to benefit from continued corticosteroid therapy.

29. We present the rare event of ‘drug induced’ AH in a patient with compensated cirrhosis and provide strong linkage of the acute insult to homoeopathy-drug by state-of-the-art toxicology analysis of the retrieved medicines. Dantas and Rampes demonstrated that the mean incidence of adverse effects of homoeopathic medicines was greater than placebo in controlled clinical trials and a larger incidence of pathogenetic effects in healthy volunteers taking homoeopathic medicines were noted, even though the minor in nature. Discussion

30. Posadzki et al , in their study, demonstrated mild-to-severe adverse events, including four fatalities with homoeopathy medicines. The most common adverse events noted in their cohort of patients were allergic reactions followed by intoxications. Discussion

31. Boatto and colleagues showed that 9 out of 30 subjects gave positive alcohol breath test results (0.11– 0.82 g/L) when tests were taken within 1 min after drinking homoeopathic mother tincture . The WHO has published directives and concerns on the quality control issues for homoeopathic medicines and multiple reports on high alcohol content in homoeopathy medicines have been rife on social and news media. Discussion

32. At risk patients and the general population need to be educated regarding the fact that complementary and alternative medications are not without side-effects. Governmental regulatory policies and public health awareness on complementary medicine use is an unmet need in developing countries entrenched in use of non-evidence-based complementary medicine practices. Discussion

33. Unreliable Video as Reference https://news4sanantonio.com/news/local/homeopathic-treatment-contains-as-much-alcohol-as-whiskey

34. Were patient’s demographic characteristics clearly described? Was the patient’s history clearly described and presented as a timeline? Was the current clinical condition of the patient on presentation clearly described? Were diagnostic tests or assessment methods and the results clearly described? Was the intervention(s) or treatment procedure(s) clearly described? Was the post-intervention clinical condition clearly described? Were adverse events (harms) or unanticipated events identified and described? Does the case report provide takeaway lessons? Critical Appraisal: yes No Yes Yes UC Yes Yes Yes

35. Merits of the Journal Use of Advanced Diagnostic Tools Learning about Unhomoeopathic Practices Rare Case Documentation

36. Demerits of the Journal Alcoholic liver damage is caused by long-term alcohol use, and as this instance only involved two weeks of homoeopathic medication use, it cannot be concluded. A single case report is insufficient to establish the validity of a medication system. Reputable homoeopathic medicinal products adhere to the WHO's recommended safety requirements in this case the pharmaceutical corporation and its caliber are not specified.

37. Conclusions Despite the thorough documentation and comprehensive analysis presented in this case report, the journal article's impact is limited by several critical factors. The primary drawback is the reliance on a single case study , which severely restricts the generalizability of the findings . Without corroborative data from additional cases or larger studies, the conclusions drawn remain speculative and may not reflect broader clinical realities.

38. Conclusions Furthermore, the absence of a control group undermines the strength of the causal relationship between the homoeopathic medicine and the development of alcoholic hepatitis. This gap in the methodology leaves room for alternative explanations and reduces the reliability of the findings. Potential biases, particularly in patient self-reporting and recall , further detract from the robustness of the conclusions.

39. Thank You Any Questions?