bilities and organization may differ among them. For diagnosis of hepatic ADRs, underlying causes of hepatitis such as viral hepatitis, autoimmune hepatitis, alcoholic liver disease, steato- hepatitis, and other metabolic diseases should be excluded (23). The enrolled cases were from spontaneous reports of both non- hepatologist and hepatologist physicians, pharmacists, and nurses. Clinical data were not detailed in the reports, and we could not evaluate the clinical courses and features of enrolled patients. Hepatic ADRs are usually classified as hepatocellular, mixed, and cholestatic (3). We could not classify hepatic ADRs with this classification scheme, but merely indicated the regis- tered WHO-ART coding, which is the official coding system for the pharmacovigilance program for hepatic ADRs in this study (16). We also used WHO-UMC criteria for causality assessment. The criteria classify ADEs as certain, probable, possible, unlike- ly, conditional and unassessable. In this study, only 6.9% and 22.6% of hepatic ADRs are certain or probable. This means that significant portion of the hepatic ADRs in this study may not be actually the cause of hepatitis. Some antibiotics with very low risk of hepatotoxicities, such as glycopeptides antibiotics and aminoglycosides were reported as the suspects, but their ROR values are 0.7 and 1.2, respectively, and possibility of misdiag- nosis could not be excluded. Many investigators have used the Russel Uclaf Causality As- sessment Model (RUCAM) for assessing hepatic ADRs (24, 25), but there are limitations in clinical use as it has lower reliability (26). WHO-UMC criteria are globally accepted causality assess- ment criteria for ADRs in general. Compared to RUCAM, WHO- UMC criteria may have some weak points in subjectivity and limited reproducibility. Many criteria for causality assessment are currently available, but they share key components for assess- ment, such as chronological relationship between administra- tion of drug and onset of ADRs, exclusion of other possible causes not involving drugs, previous information on similar events at- tributed to the suspected drugs, improvement after discontinu- ation of causative drugs, and aggravation or reappearance of ADR by re-administration of causative drugs. However, our data may have advantages for obtaining the general aspects of drugs that cause hepatic ADRs in Korea compared with previous stud- ies done by hepatologists with patients admitted due to hepatic ADRs. This study included cases of hepatic ADRs with various severities. Anti-infective drugs were the most common cause of hepatic ADRs in this study. However, marked differences in ROR values were found among the anti-infectives. As is known, anti-tuber- culosis and anti-fungal agents have high ROR values. In this study, anti-viral agents were also emerging as the important causes of hepatic ADRs. In Korea, the prevalence of tuberculo- sis is very high and the prevalence of HIV infection is soaring, and our data might reflect the situation. Cephalosporins are also important causes of hepatic ADRs, as they are commonly 272 http://jkms.org Kwon H, et al. • Spontaneously Reported Hepatic Adverse Drug Events prescribed in Korea. However, their ROR values were not ele- vated compared with the incidence of non-hepatic ADRs due to cephalosporins. Marked differences in underlying diseases requiring treat- ment were found in our study. Patients with hepatic ADRs more frequently suffered from tuberculosis, pneumonia, brain injury or subarachnoid hemorrhage, and HIV infection. The differences may reflect the drugs that cause hepatic ADRs. Infection with HIV is generally considered a predisposition to hepatic ADRs. HIV infection is a well-known risk factor for drug allergy; and the relationship between HIV and hepatic ADRs is therefore apparent (27). It is unclear whether HIV infection is related to the development of hepatic ADRs, but it is not surprising that HIV-infected patients are susceptible to hepatic ADRs, as they commonly are treated with drugs well known to cause hepatic ADRs such as isoniazid, rifampicin, trimethoprim-sulfamethox- azole, NSAIDs, and antiviral agents (28). In this study, there were no differences in ages or gender ratios between hepatic and non-hepatic ADR groups. Age and gender have been previously regarded as risk factors for hepatic ADRs. Traditionally, patients at advanced ages and women were as- sumed to be susceptible groups (7, 21), but this assumption be- comes now controversial. There was no difference in age or gen- der between hepatic or non-hepatic ADR groups in this study. Our result was consistent with that of Shapiro and Lewis (29), which reviewed published data and did not find any evidence that patients at advanced ages or women were more suscepti- ble to hepatic ADRs caused by any drug. Our study showed that anti-infectives, anti-epileptics, and NSAIDs are the most commonly prescribed drugs for the spon- taneously reported hepatic ADRs in Korea. Careful monitoring for drug-induced ADRs is needed for tuberculosis, pneumonia, intracranial injuries, and HIV infections. As this study is based on the spontaneous reporting program, it may contribute to the recognition of the general aspects of hepatic ADRs occurred in hospitals of Korea. REFERENCES 1. Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver trans- plantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. 2. Larrey D. Epidemiology and individual susceptibility to adverse drug re- actions affecting the liver. 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