Indian Journal of Gastroenterology

, Volume 37, Issue 1, pp 9–17 | Cite as

Clinical outcomes, histopathological patterns, and chemical analysis of Ayurveda and herbal medicine associated with severe liver injury—A single-center experience from southern India

  • Cyriac Abby Philips
  • Rajaguru Paramaguru
  • Adarsh K. Joy
  • K. L. Antony
  • Philip Augustine
Original Article



Ayurvedic and herbal medicines (AHM) are known to cause varying degrees of drug-induced liver injury (DILI). Clinical, biochemical, histological spectrum and outcomes of AHM linked to severe DILI are not well studied.


Out of 1440 liver disease patients, 94 were found to have a severe liver injury and associated AHM intake. Thirty-three patients were suspected to have AHM-DILI on Roussel Uclaf Causality Assessment Scoring Method. Forty-seven and 30 of retrieved AHM samples were analyzed for heavy metals and hepatotoxic volatile organic compounds (hVOCs), respectively. Eleven patients ingested AHM from unregistered traditional healers (UTH). Clinicopathological outcomes were analyzed in 27 patients (who underwent liver biopsy) and outcomes with respect to chemical analyses were studied in 33 patients.


Males predominated (70.4%) with mean age 46.9±15.8 years. Mean follow up was 119.2±81.4 days. The median duration of drug intake was 28 days (10 – 84). Five patients died (18.5%). Hepatic encephalopathy, hypoalbuminemia, and hepatic necrosis were significantly associated with mortality (p < 0.005). Arsenic and mercury ingestion was significantly associated with death (p < 0.005). hVOCs were detected in more than 70% of samples. AHM intake from UTH was associated with higher mortality.


Adequate regulation and scrutiny regarding AHM use among the general population is an unmet need. Early liver biopsy after clinical identification of at-risk patients can expedite definitive treatment with a liver transplant.


Ayurveda Drug-induced liver injury Fibrosis Heavy metals Hepatotoxicity Herbal medicines Histopathology Liver biopsy Liver injury Liver necrosis Volatile organic compounds 


Compliance with ethical standards

Conflict of interest

CAP, RP, AKJ, KLA, and PA declare that they have no conflict of interests.

Ethics statement

The authors declare that the study was performed in a manner to conform to the Helsinki Declaration of 1975, as revised in 2000 and 2008, concerning human and animal rights. The protocol was approved by the Institutional Ethics Committee and informed consent was obtained from the study subjects. The authors are responsible for the findings and the content of the paper.

Supplementary material

12664_2017_815_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)
12664_2017_815_MOESM2_ESM.docx (13 kb)
ESM 2 (DOCX 13 kb)
12664_2017_815_MOESM3_ESM.docx (20 kb)
ESM 3 (DOCX 20 kb)


  1. 1.
    Kleiner DE. The pathology of drug-induced liver injury. Semin Liver Dis. 2009;29:364–72.CrossRefPubMedGoogle Scholar
  2. 2.
    Bent S, Ko R. Commonly used herbal medicines in the United States: a review. Am J Med. 2004;116:478–85.CrossRefPubMedGoogle Scholar
  3. 3.
    Seeff LB. Herbal hepatotoxicity. Clin Liver Dis. 2007;11:577–96.CrossRefPubMedGoogle Scholar
  4. 4.
    Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34, 1934 e1-4.Google Scholar
  5. 5.
    Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105:2396–404.CrossRefPubMedGoogle Scholar
  6. 6.
    Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37:3–17.CrossRefPubMedGoogle Scholar
  7. 7.
    Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89:806–15.Google Scholar
  8. 8.
    Danan G, Benichou C. Causality assessment of adverse reactions to drugs—I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol. 1993;46:1323–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Agarwal VK, McHutchison JG, Hoofnagle JH, Drug-Induced Liver Injury Network. Important elements for the diagnosis of the drug-induced liver injury. Clin Gastroenterol Hepatol. 2010;8:463–70.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    de Boer YS, Sherker AH. Herbal and dietary supplement-induced liver injury. Clin Liver Dis. 2017;21:135–49.CrossRefPubMedGoogle Scholar
  11. 11.
    Ou P, Chen Y, Li B, et al. Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital. Spring. 2015;4:802.Google Scholar
  12. 12.
    Björnsson E, Talwalkar J, Treeprasertsuk S, et al. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010;51:2040–8.Google Scholar
  13. 13.
    Czaja AJ. Drug-induced autoimmune-like hepatitis. Dig Dis Sci. 2011;56:958–76.CrossRefPubMedGoogle Scholar
  14. 14.
    Sebode M, Schulz L, Lohse AW. “Autoimmune(-Like)” drug and herb induced liver injury: new insights into molecular pathogenesis. Int J Mol Sci. 2017;18:E1954.CrossRefPubMedGoogle Scholar
  15. 15.
    Kleiner DE, Chalasani NP, Lee WM, et al. Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology. 2014;59:661–70.Google Scholar
  16. 16.
    Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148:1340–52.Google Scholar
  17. 17.
    Kleiner DE, Chalasani NP, Conjeevaram HS, Bonkovsky HL, Russo MW, Davern TJ. Relationship of biochemical to histologic findings and the pathological pattern of injury among cases identified in the NIH Drug-Induced Liver Injury Network (DILIN) study. Gastroenterology. 2007;132:A773.Google Scholar
  18. 18.
    Björnsson E, Kalaitzakis E, Olsson R. The impact of eosinophilia and hepatic necrosis on prognosis in patients with drug-induced liver injury. Aliment Pharmacol Ther. 2007;25:1411–21.CrossRefPubMedGoogle Scholar
  19. 19.
    Saper RB, Phillips RS, Sehgal A, et al. Lead, mercury, and arsenic in US- and Indian-manufactured ayurvedic medicines sold via the internet. JAMA. 2008;300:915–23.Google Scholar
  20. 20.
    Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the US drug induced liver injury network. Hepatology. 2014;60:1399–408.Google Scholar
  21. 21.
    Sharma B, Singh S, Siddiqi NJ. Biomedical implications of heavy metals induced imbalances in redox systems. Biomed Res Int. 2014;2014:640754.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Wahlang B, Beier JI, Clair HB, et al. Toxicant-associated steatohepatitis. Toxicol Pathol. 2013;41:343–60.Google Scholar
  23. 23.
    Tolman KG, Sirrine RW. Occupational hepatotoxicity. Clin Liver Dis. 1998;2:563–89.CrossRefGoogle Scholar
  24. 24.
    Cotrim HP, Andrade ZA, Parana R, Portugal M, Lyra LG, Freitas LA. Nonalcoholic steatohepatitis: a toxic liver disease in industrial workers. Liver. 1999;19:299–304.CrossRefPubMedGoogle Scholar
  25. 25.
    Perez CA, Bosia JD, Cantore MS, et al. Liver damage in workers exposed to hydrocarbons. Gastroenterol Hepatol. 2006;29:334–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Neuberger M, Rappe C, Bergek S, et al. Persistent health effects of dioxin contamination in herbicide production. Environ Res. 1999;81:206–14.Google Scholar
  27. 27.
    Malaguarnera G, Cataudella E, Giordano M, Nunnari G, Chisari G, Malaguarnera M. Toxic hepatitis in occupational exposure to solvents. World J Gastroenterol. 2012;18:2756–66.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Indian Society of Gastroenterology 2018

Authors and Affiliations

  • Cyriac Abby Philips
    • 1
  • Rajaguru Paramaguru
    • 2
  • Adarsh K. Joy
    • 3
  • K. L. Antony
    • 4
  • Philip Augustine
    • 5
  1. 1.Department of Hepatology and Liver Transplant MedicinePVS Memorial HospitalKochiIndia
  2. 2.Department of PathologyPVS Memorial HospitalKochiIndia
  3. 3.Sophisticated Test and Instrumentation CentreCochin University of Science and TechnologyKochiIndia
  4. 4.Envirodesigns Eco LabsKochiIndia
  5. 5.Department of GastroenterologyPVS Memorial HospitalKochiIndia

Personalised recommendations