ORIGINAL ARTICLE Gastroenterology & Hepatology http://dx.doi.org/10.3346/jkms.2012.27.3.268 • J Korean Med Sci 2012; 27: 268-273 Spontaneously Reported Hepatic Adverse Drug Events in Korea: Multicenter Study Hee Kwon1,*, Suk-Hyang Lee2,*, Seong-Eun Kim1, Jae-Hyun Lee1,3, Yung-Koo Jee4, Hye-Ryun Kang5, Byung-Joo Park6, Jung-Won Park1,3, and Chein-Soo Hong1,3 1Severance Regional Pharmacovigilance Center, Seoul; 2College of Pharmacy, Ajou University, Suwon; 3Department of Internal Medicine, Yonsei University College of Medicine, Seoul; 4Department of Internal Medicine, Dankook University College of Medicine, Cheonan; Departments of 5Internal Medicine, and 6Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea *Hee Kwon and Suk-Hyang Lee contributed equally to this work. Received: 23 July 2011 Accepted: 26 December 2011 Address for Correspondence: Jung-Won Park, MD Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel: +82.2-2228-1961, Fax: +82.2-393-6884 Email: parkjw@yuhs.ac This study was supported by a grant from Korean Food and Drug Administration (09182KFDA842) in 2010. Hepatic adverse drug reactions (ADRs) to certain drugs may differ within each country, reflecting different patterns of prescription, socioeconomic status, and culture. The purpose of this study was to assess the suspected cause of hepatic ADRs using the spontaneously reported pharmacovigilance data from Korea. A total of 9,360 spontaneously reported adverse drug events (ADEs) from nine Pharmacovigilance Centers were analyzed. Risk of hepatic ADEs was assessed by calculating the reporting odds ratio (ROR). Of the 9,360 cases, 567 hepatic ADEs were reported. The most frequently prescribed drug classes inducing hepatic ADEs were anti-tuberculotics, cephalosporins, valproic acids, penicillins, quinolones, non-steroidal anti-inflammatory drugs (NSAIDs), anti-viral agents, and statins. ROR values were especially high in anti-tuberculosis drugs, systemic antifungal drugs for systemic use, anti-epileptics, propylthiouracil, and herbal medicines. Underlying diseases such as tuberculosis (6.9% vs 0.9%), pneumonia (4.9% vs 1.7%), intracranial injury including skull fracture (4.5% vs 0.9%), HIV (3.4% vs 0.4%), subarachnoid hemorrhage (2.8% vs 0.5%), and osteoporosis (2.4% vs 1.4%) were significantly more common in hepatic ADE group. In conclusion, anti-infective drugs, anti-epileptics, NSAIDs and statins are the most common suspects of the spontaneously reported hepatic ADEs, in Korea. Careful monitoring for such reactions is needed for the prescription of these drugs. Key Words: Drug-Induced Hepatitis; Etiology; Spontaneous Pharmacovigilance INTRODUCTION Drug-induced liver diseases are important adverse drug reac- tions (ADRs) and impart significant medical burdens to pa- tients, doctors, and pharmaceutical companies. Drugs are im- portant causes of` acute hepatitis, an extreme ADR, and are re- sponsible for approximately 15.6% of liver transplantation for acute liver failure (1). The true incidence of hepatic ADRs is dif- ficult to determine, but is reported to be between 1 in 10,000 and 1 in 100,000 patients (2). Drug-induced ADRs to the liver is the single most important reason for drug withdrawal from the market and can halt drug development (3, 4). Post-market sur- veillance using a reporting system is therefore especially impor- tant for hepatic ADRs. Clinical studies have shown marked differences in such caus- ative drugs. In Korea (5-7) and East Asian countries (8), herbal medicines, antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported as major causative agents of hepatic ADRs. In Western countries and the United States, antibiotics, acetaminophen, NSAIDs, anti-tuberculosis agents, and central nervous system agents were recognized as major culprits (1, 9, 10). These studies were primarily performed by experienced hepatologists with hospitalized patients suffering from severe drug-induced liver disease. These studies may have limitations due to selection biases, including more serious he- patic ADRs, and focused on the general features of drug-induced liver diseases. Since 2006, spontaneous reporting in pharmacovigilance systems has been established successfully in Korea (11), and the collected data were analyzed. Spontaneous ADR reporting systems have weak points such as inaccuracy of ADR diagnosis, underreporting, and an inability to obtain ADR incidences (12, 13), but is useful for signal detections of hepatic ADRs, and the reporting odds ratio has been recognized as a useful tool for de- tection of disproportionally reported drugs for a ADEs (14, 15). However, data from spontaneous reporting pharmacovigilance programs may allow evaluation of the general aspects of hepat- ic ADRs. In this study, we evaluated the drugs suspected as the causative drugs of hepatic ADRs and measured the reporting odds ratio (ROR) values using the spontaneous reporting phar- © 2012 The Korean Academy of Medical Sciences. 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