Indian Journal of Medical Sciences Medknow Publications on behalf of Indian Journal of Medical Sciences Trust ISSN: 0019-5359 EISSN: 1998-3654 Vol. 58, Num. 5, 2004, pp. 211-212

Indian Journal of Medical Science Vol. 58 No. 5, May, 2004, pp. 211-212

Letter to Editor

Drug induced serious hepatic adverse reactions in a tertiary care centre: A five-year retrospective analysis

D. Padmini Devi, M. Sushma, S. Guido

Department of Pharmacology, St. John's Medical College, Bangalore - 560034, India. E-mail: p_nidhin@hotmail.com

Code Number: ms04038

Sir,

A serious adverse drug reaction (ADR) is defined as one that requires hospitalization, is permanently disabling, or results in death.¹ This study was performed to determine the characteristics of serious hepatic ADRs in the Department of Gastroenterology in a tertiary care center and to establish a causal relation between drug and disorder based on World Health Organization (WHO) causality definitions.²

A retrospective review of case records of hospitalized patients with the diagnosis of hepatic ADRs (January 1998 to December 2002) in the Department of Gastroenterology, St. John's medical college, Bangalore was done after obtaining Institutional ethical review board clearance. The hepatic disorders were considered as drug induced when:

1. No alternative explanations for the disorder were available.
2. There was a temporal relation with the drug ingestion and liver disease (5-90 days).
3. Improvement in the condition of the patient after dechallenge.

Liver injury was designated hepatocellular, when alanine aminotransferase (ALT) was greater than two times the upper limit of normal (ULN), or the ALT/ alkaline phosphatase (AP) was³ 5; cholestatic when the AP is greater than two times ULN or the ALT/ AP ratio was £ 2: and mixed when the ALT/ AP ratio was two to five and the individual values were greater than two times ULN.³ The relevant data were collected which included age, sex, clinical presentation, viral markers (HAV-IgM, HBs Ag, HBC-IgM, anti HCV), Liver Function Tests (LFTs), complete diagnosis, the details of the drugs used, reaction time (time taken for the ADR to occur after the last exposure to the drug (RT)) and the outcome. The data was subjected to descriptive analysis.

Out of 6302 case records screened, 25 cases were included in the study and categorized as certain (two), probable (20) and possible (three). Certain and probable cases were analyzed (22). The median for age was 51 years (interquartile range 45-57). Male to female ratio was 1.7. The major drug class implicated was anti-tuberculous drugs (ATD) (17), followed by cisplatin, metformin, low molecular weight heparin, chlorpromazine and leflunomide (one case each). The median for RT 29.5 days (interquartile range 14-40) and that for resolution was 18.5 days (interquartile range 14.3-24.3). Serum viral markers were negative and base line LFTs were normal for the patients considered for analysis. Pattern of acute hepatitis was hepatocellular in 11, cholestatic in seven and mixed in four patients each. The outcomee was recovery in 20 patients and mortality in two patients.

The maximum number of patients were³ 50 years old and had acute hepatitis with majority under hepatocellular category as reported in the study by Sargo et al⁴ However, all the drugs implicated in the present study were different from that identified by Sargo et al.⁴ The major drug class implicated in the present study was ATD (77%) similar to a previous Indian study.⁵ Hepatotoxicity induced by metformin, cisplatin, LMWH and leflunomide induced death noticed in this study have been rarely documented in literature. Mortality of 0.4% in the Department of Gastroenterology during the study period was due to serious hepatic ADRs.

D. Padmini Devi, M. Sushma, S. Guido

Department of Pharmacology, St. John's Medical College, Bangalore - 560034, India. E-mail: p_nidhin@hotmail.com

REFERENCES

1. Jobanputra P, Maggs F, Homer D, Bevan J. Monitoring and assessing the safety of disease modifying antirheumatic drugs. Drug Safety 2002;25:1099-105.
2. Edwards RJ, Arnoson KJ. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000;356:1255-9.
3. Kaplowitz N. Causality assessment versus guilt - by - association in drug hepatotoxicity. Hepatology 2001;33:308-9.
4. Sargo C, Clinard F, Ouzair K. Incidence of druginduced hepatic injuries: A French population based study. Hepatology 2002;36:451-5.
5. Kshirsagar NA, Karnade S, Potkar CN. A prospective survey of drug-induced hepatotoxicity in a large hospital. Indian J of Gastroenterol 1992;11:13-5.

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