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Cetirizine-induced hepatotoxicity: case series and review of the literature

Cetirizine-induced hepatotoxicity: case series and review of the literature Drug-induced liver damage is a frequently encountered clinical table caused by many drugs. Cetirizine is a widely preferred and prescribed antihistaminic agent for allergic disorders due to its non-sedative properties. In view of the literature, we present four cases of hepatotoxicity due to cetirizine use. We conclude that in patients with high levels of liver enzymes of unknown origin, cetirizine as well as other hepatotoxic drugs should be reconsidered. Key words: cetirizine, hepatotoxicity revealed that he had been diagnosed with contact dermatitis Introduction and that 10 mg/day cetirizine had been started by a dermatology Cetirizine is a cholinergic, nonsedating, second-generation specialist three days previously. He had no history of alcohol histamine-1 receptor-blocking agent widely used in allergic dis- use nor any other drug use or chronic disease. His physical ex- orders. Its elimination has been reported to be slow in the el- amination was normal. Biochemical tests revealed total choles- derly and in people with liver disease [1]. Severe liver failure terol 228 mg/dL (normal range 140–220 mg/dL) and triglycerides and cholestatic and hypersensitivity hepatitis induced by anti- 163 mg/dL (normal range 40–160 mg/dL); total bilirubin, total histamines such as cyproheptadine, loratadine and terfenadin protein, albumin, globulin, lactate dehydrogenase (LDH), amy- have been reported previously [2,3]. Increases of alanine amino- lase and fasting blood glucose levels were within normal limits. transferase (ALT) [2], hepatitis [4–8], and cholestasis [9–11] due Leucocyte, erythrocyte and thrombocyte counts were normal. to cetirizine use have been also reported. Here we report four HBsAg, anti-HCV, anti-HAV IgM, Anti-HEV, CMV IgM, and EBV- hepatotoxicity cases resulting from cetirizine use and review VCA were negative; his anti-HB level was positive. IgG, IgM and the literature. IgA levels were within normal ranges, while IgE was high (303 IU; normal range 0–100 IU). Antinuclear antibody (ANA), antimitochondrial antibody (AMA) and anti-smooth muscle an- Case presentation tibody (ASMA) were negative. Abdominal ultrasound examina- tion of the liver was normal. In the peripheral blood smear, 66% Case 1: A 46-year-old male patient was admitted with com- neutrophils, 28% lymphocytes, 4% eosinophils and 2% plaints of fatigue over the past seven days. His medical history Submitted: 14 May 2016; Revised: 10 June 2016; Accepted: 17 June 2016 V C The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/gastro/article-abstract/6/3/228/2909369 by Ed 'DeepDyve' Gillespie user on 22 August 2018 Cetirizine-induced hepatotoxicity | 229 monocytes were detected. Serum iron level, iron-binding capac- Case 3: A 66-year-old female patient was admitted with fa- ity, ferritin, ceruloplasmin and thyroid function tests (TFTs) tigue and jaundice. She had been started on cetirizine for the were within normal limits. Liver biopsy was planned but was complaint of itching a week ago. She had no alcohol or any not approved by the patient. Cetirizine was discontinued imme- other drug use. Her physical examination revealed jaundice of diately. He was advised not to take any medicine and to avoid the skin and sclera and palpable liver under her ribcage at the any intake harmful to the liver. In the follow-up two weeks midclavicular line. Total, direct and indirect bilirubins were later, ALT was 45 U/L (normal range 13–40 U/L), and gamma- 9.36, 6.39 and 2.97 mg/dL, respectively, and eosinophils were in- glutamyl transferase (GGT) was 264 U/L (normal range 9–50 U/L). creased in the peripheral smear. Iron parameters, TFT and other In the second follow-up, GGT was 95 U/L (normal range 9–50 U/ biochemical values were normal. ANA, AMA and ASMA were L), and ALT, aspartate aminotransferase (AST) and other tests negative. HBsAg, anti-HBc, anti-HCV, anti-HBs, anti-HAV IgM, were within normal ranges two months later. CMV IgM, EBV-VCA and Salmonella and Brucella agglutination Case 2: A 21 year-old female patient was admitted with com- tests were negative. Abdominal ultrasonography revealed hepa- plaints of generalized jaundice and fatigue. She had been tomegaly, and magnetic resonance cholangiopancreatography started on cetirizine five days previously for complaints of (MRCP) was normal. Liver biopsy revealed enlarged cells with itching. No other drug or alcohol use was involved. Her physical macrosteatosis, cholestasis and mixed inflammatory infiltration examination was normal except for jaundice. Total bilirubin with increased eosinophils in portal areas and parenchyma was 6.3 mg/dL, and direct bilirubin was 2.4 mg/dL, while total (Figure 1). Cetirizine was immediately discontinued. In the cholesterol, triglycerides, total protein, albumin and whole follow-up, GGT was 90 U/L, while AST, ALT and other biochemi- blood counts were within normal range. Iron parameters and cal tests were all normal three weeks later. TFT were normal. HBsAg, anti-HBc IgM, anti-HCV, anti-HBs, Case 4: A 40-year-old female patient, who had been pre- anti-HAV IgM, CMV IgM, EBV-VCA and Salmonella and Brucella scribed cetirizine, 10 mg/day, four days previously by a derma- agglutination levels were negative. ANA, AMA and ASMA were tologist because of generalized itching complaint, was admitted negative. Abdominal ultrasonography revealed mild hepato- to our department with the complaint of fatigue. She did not megaly and hepatosteatosis grade I. Liver biopsy was planned have a history of any other drug or alcohol use. Her physical but the patient did not approve. Cetirizine-induced toxic hepati- examination, iron parameters, TFT and other laboratory test re- tis was considered, and the drug was stopped. In the follow-up, sults were normal except for AST, ALT, ALP and GGT. HBsAg, ALT was 139 U/L, AST 53 U/L, alkaline phosphatase (ALP) 71 U/L anti-HBs, anti-HBc IgM, anti-HAV IgM, anti-HCV, CMV IgM, EBV- (normal range 40–140 U/L) and GGT 20 U/L, while bilirubins re- VCA and Salmonella and Brucella agglutination tests were neg- turned to normal two weeks later. All biochemical tests re- ative. Abdominal ultrasonography was normal. Cetirizine was turned to their normal ranges a month later. discontinued. Liver biopsy was not performed due to lack of the patient’s approval. In follow up as month later, her biochemical values had returned to normal. Demographic features and laboratory test results of these four cases at their admission are presented in Table 1. Discussion Drug-induced liver damage is a frequently encountered clinical table and is encountered as side effects of many drugs. Asymptomatic patients may be admitted with elevated liver function tests results as well as with hepatitis findings. There are three types of hepatotoxic drug reaction based on biochemi- cal parameters: hepatocellular damage, cholestatis and mixed Figure 1. Liver biopsy of Case 3 shows macrosteatosis places (A, hematoxylin- type. Classification is based on the following formula using ALP eosin staining, x100) and mixed inflammatory infiltration including eosinophils; (B, hematoxylin-eosin, x200) in portal areas and parenchyma. and ALT levels: R ratio¼ (ALT/ upper limit of normal range) / Table 1. Patient characteristics and laboratory test results Case 1 Case 2 Case 3 Case 4 Age (years) 46 21 66 40 Sex Male Female Female Female Duration of cetirizine use (days) 3 5 7 4 IgE level (IU) 303 30 17 36 Eosinophil count 420 100 1000 100 AST (NR: 10–40 U/L) 419 188 685 47 ALT (NR: 13–40 U/L) 461 443 667 59 ALP (NR: 40–140 U/L) 153 404 111 843 GGT (NR: 9–50 U/L) 545 44 144 411 R ratio 10,57 3,84 21,1 0,24 Hepatic damage type Hepatocellular Mixed Hepatocellular Cholestatic RUCAM score 10 10 11 9 ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase; NR: normal range; R ratio¼ (ALT/ upper limit of normal range) / (ALP/ upper limit of normal range); RUCAM: Roussel Uclaf Causality Assessment Method Downloaded from https://academic.oup.com/gastro/article-abstract/6/3/228/2909369 by Ed 'DeepDyve' Gillespie user on 22 August 2018 230 | A. Coskun et al. (ALP/ upper limit of normal range). (1) If the R ratio is 5 or ALT Conflict of interest statement: none declared. exceeds twice the upper limit, the reaction is classified as hepa- tocellular toxicity; (2) if the R ratio is 2 and ALT is over the nor- References mal limit, the reaction is designated as cholestatic toxicity; and 1. Campoli-Richards D, Buckley M and Fitton A. Cetirizine. A a (3) if the R ratio is between 2 and 5, the reaction is mixed type review of its pharmacological properties and clinical poten- [12]. Based on this classification, Case 1 and Case 3 were evalu- tial in allergic rhinitis, pollen-induced asthma, and chronic ated as hepatocellular, Case 2 was mixed, and Case 4 was the urticaria. Drugs 1990;40:762–81. cholestatic type. 2. Arendt C and Bernheim J. Double-blind comparison of main- Hepatotoxicity can also be categorized as immune and non- tenance treatment of chronic idiopathic urticaria by cetiri- immune. Hepatotoxicity involving the immune system is also zine and terfenadine. Curr Ther Res 1989;46:724–34. referred to as allergic reaction or hypersensitivity [13]. The pres- 3. Larrey D, Palazzo L and Benhamou JP. Terfenadine and hepa- ence of eosinophils in a peripheral blood smear, increased eo- titis. Ann Intern Med 1985;103:634. sinophil count and elevated blood IgE level in Case 1 suggested 4. Bera F, Sipruhis JP, Jonville-Bera AP, et al. Cytolytic hepatic in- hypersensitivity. volvement after administration of cetirizine (Zyrtec (in Since our patients had no history of alcohol use, blood trans- French). Gastroenterol Clin Biol 1993;17:770–1. fusion, tooth extraction, any surgical operation, close contact 5. Pompili M, Basso M, Grieco A, et al.Recurrent acute hepatitis with hepatitis patients, history of a systemic disease or any associated with use of cetirizine. Ann Pharmacother other drug use, cetirizine was considered to the likely cause for 2004;38:1844–7. the increased values of the liver tests (AST, ALT, ALP, GGT and 6. Sanchez-Lombrana JL, Alvarez RP, Saez LR, et al. Acute hepati- total bilirubin). Any other sources causes that may cause hepa- tis associated with cetirizine intake. J Clin Gastroenterol totoxicity such as viral causes, autoimmune causes, gallstones, 2002;34:493–5. hemochromatosis and endocrinological causes (hypothyroidism 7. Watanabe M, Kohge N and Kaji T. Severe hepatitis in a patient and hyperthyroidism) hepatitis were ruled out through viral se- taking cetirizine. Ann Intern Med 2001;135:142–3. rology, ultrasonography, ANA, AMA, ASMA, ferritin, iron, serum 8. Jurawan R and Smith A. Severe hepatitis in a primary scleros- iron-binding capacity, free T3, free T4 and TSH examinations. If ing cholangitis patient receiving recent cetirizine therapy. N available, measurement of serum cetirizine level, or challenge Z Med J 2010;123:106–7. test could have supported the strenght of our diagnosis. In diag- 9. D ıaz-San  chez A, Mar ın-Jime ´ nez I and Aldeguer M. Benign re- nosing drug–induced hepatotoxicity, measurement the levels of current intrahepatic cholestasis simulating cetirizine- liver-kidney microsomal antibody (anti-LKM2), and the antibody induced toxic hepatitis (in Spanish). Gastroenterol Hepatol against cytochrome P450 may be useful [5]. In our cases, re-use 2010;33:68–9. of the drug did not encountered. Tests to measure the serum 10. Rodr ıguez-Gomez  SJ, Zamora-Mart ınez T, Bailador-Andre ´s C, levels of liver-kidney microsomal antibody (anti-LKM2), and the et al. Severe intrahepatic cholestasis associated with cetiri- antibody against cytochrome P450 were not available. Liver zine (in Spanish). Gastroenterol Hepatol 2009;32:383–4. biopsy was approved and performed in only one patient. 11. Fong DG, Angulo P, Burgart LJ, et al. Cetirizine-induce chole- A markedly high GGT level immediately suggested a toxic stasis. J Clin Gastroenterol 2000;31:250–3. cause [2,4]. Drug-induced hepatitis has been reported in many 12. Danan G and Benichou C. Causality assessment of adverse re- studies [14]. High levels of liver enzymes and possible hepatitis actions to drugs-I. A novel method based on the conclusions development have been shown in various studies [2,3]. of international consensus meetings: application to drug- Although it has been suggested that elevated liver enzyme lev- induced liver injuries. J Clin Epidemiol 1993;46:1323–30. els could sometimes result from cetirizine use [1,2], hepatitis 13. Leise MD, Poterucha JJ and Talwalkar JA. Drug-induced liver has been reported in only five case reports in the literature [4– injury. Mayo Clin Proc 2014;89:95–106 8]. In two of the four cases, cetirizine was used for allergic der- 14. Chitturi S, Teoh NC and Farrell GC. Hepatic drug metabolism matitis, but it was discontinued due to elevated levels of liver and liver disease caused by drugs. In: Feldman M, Friedman enzymes. When the drug was later accidentally re-administered LS, Brandt LJ (eds). Gastrointestinal and Liver Disease, volum 2, to the same patient , liver enzymes were again reported to be in- 10th ed. Philadelphia: Saunders, 2016, 1442–77. creased [4,5]. It is interesting that in our four cases, all enzyme 15. Sahai A and Villeneuve JP. Terfanadine–induced cholestatic levels except for GGT were within normal limits at the follow-up hepatitis. Lancet 1996;348:552–3. two months after cetirizine had been stopped. The literature re- 16. Freneaux E, D Larrey, Berson A, et al. Hepatitis caused by cy- veals liver function tests returning to normal limits within three proheptadine (Periactine). A case and review of the literature months in terfenadin and cyproheptadine-induced hepatitis (in French). Gastroenterol Clin Biol 1988;12:573–5. cases [15,16]. We conclude that, in patients with high levels of liver enzymes and hepatitis of unknown cause, cetirizine as well as other hepatotoxic drugs should be suspected. 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Cetirizine-induced hepatotoxicity: case series and review of the literature

Gastroenterology Report , Volume 6 (3) – Aug 1, 2018

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Oxford University Press
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© The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University
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2052-0034
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10.1093/gastro/gow025
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Abstract

Drug-induced liver damage is a frequently encountered clinical table caused by many drugs. Cetirizine is a widely preferred and prescribed antihistaminic agent for allergic disorders due to its non-sedative properties. In view of the literature, we present four cases of hepatotoxicity due to cetirizine use. We conclude that in patients with high levels of liver enzymes of unknown origin, cetirizine as well as other hepatotoxic drugs should be reconsidered. Key words: cetirizine, hepatotoxicity revealed that he had been diagnosed with contact dermatitis Introduction and that 10 mg/day cetirizine had been started by a dermatology Cetirizine is a cholinergic, nonsedating, second-generation specialist three days previously. He had no history of alcohol histamine-1 receptor-blocking agent widely used in allergic dis- use nor any other drug use or chronic disease. His physical ex- orders. Its elimination has been reported to be slow in the el- amination was normal. Biochemical tests revealed total choles- derly and in people with liver disease [1]. Severe liver failure terol 228 mg/dL (normal range 140–220 mg/dL) and triglycerides and cholestatic and hypersensitivity hepatitis induced by anti- 163 mg/dL (normal range 40–160 mg/dL); total bilirubin, total histamines such as cyproheptadine, loratadine and terfenadin protein, albumin, globulin, lactate dehydrogenase (LDH), amy- have been reported previously [2,3]. Increases of alanine amino- lase and fasting blood glucose levels were within normal limits. transferase (ALT) [2], hepatitis [4–8], and cholestasis [9–11] due Leucocyte, erythrocyte and thrombocyte counts were normal. to cetirizine use have been also reported. Here we report four HBsAg, anti-HCV, anti-HAV IgM, Anti-HEV, CMV IgM, and EBV- hepatotoxicity cases resulting from cetirizine use and review VCA were negative; his anti-HB level was positive. IgG, IgM and the literature. IgA levels were within normal ranges, while IgE was high (303 IU; normal range 0–100 IU). Antinuclear antibody (ANA), antimitochondrial antibody (AMA) and anti-smooth muscle an- Case presentation tibody (ASMA) were negative. Abdominal ultrasound examina- tion of the liver was normal. In the peripheral blood smear, 66% Case 1: A 46-year-old male patient was admitted with com- neutrophils, 28% lymphocytes, 4% eosinophils and 2% plaints of fatigue over the past seven days. His medical history Submitted: 14 May 2016; Revised: 10 June 2016; Accepted: 17 June 2016 V C The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/gastro/article-abstract/6/3/228/2909369 by Ed 'DeepDyve' Gillespie user on 22 August 2018 Cetirizine-induced hepatotoxicity | 229 monocytes were detected. Serum iron level, iron-binding capac- Case 3: A 66-year-old female patient was admitted with fa- ity, ferritin, ceruloplasmin and thyroid function tests (TFTs) tigue and jaundice. She had been started on cetirizine for the were within normal limits. Liver biopsy was planned but was complaint of itching a week ago. She had no alcohol or any not approved by the patient. Cetirizine was discontinued imme- other drug use. Her physical examination revealed jaundice of diately. He was advised not to take any medicine and to avoid the skin and sclera and palpable liver under her ribcage at the any intake harmful to the liver. In the follow-up two weeks midclavicular line. Total, direct and indirect bilirubins were later, ALT was 45 U/L (normal range 13–40 U/L), and gamma- 9.36, 6.39 and 2.97 mg/dL, respectively, and eosinophils were in- glutamyl transferase (GGT) was 264 U/L (normal range 9–50 U/L). creased in the peripheral smear. Iron parameters, TFT and other In the second follow-up, GGT was 95 U/L (normal range 9–50 U/ biochemical values were normal. ANA, AMA and ASMA were L), and ALT, aspartate aminotransferase (AST) and other tests negative. HBsAg, anti-HBc, anti-HCV, anti-HBs, anti-HAV IgM, were within normal ranges two months later. CMV IgM, EBV-VCA and Salmonella and Brucella agglutination Case 2: A 21 year-old female patient was admitted with com- tests were negative. Abdominal ultrasonography revealed hepa- plaints of generalized jaundice and fatigue. She had been tomegaly, and magnetic resonance cholangiopancreatography started on cetirizine five days previously for complaints of (MRCP) was normal. Liver biopsy revealed enlarged cells with itching. No other drug or alcohol use was involved. Her physical macrosteatosis, cholestasis and mixed inflammatory infiltration examination was normal except for jaundice. Total bilirubin with increased eosinophils in portal areas and parenchyma was 6.3 mg/dL, and direct bilirubin was 2.4 mg/dL, while total (Figure 1). Cetirizine was immediately discontinued. In the cholesterol, triglycerides, total protein, albumin and whole follow-up, GGT was 90 U/L, while AST, ALT and other biochemi- blood counts were within normal range. Iron parameters and cal tests were all normal three weeks later. TFT were normal. HBsAg, anti-HBc IgM, anti-HCV, anti-HBs, Case 4: A 40-year-old female patient, who had been pre- anti-HAV IgM, CMV IgM, EBV-VCA and Salmonella and Brucella scribed cetirizine, 10 mg/day, four days previously by a derma- agglutination levels were negative. ANA, AMA and ASMA were tologist because of generalized itching complaint, was admitted negative. Abdominal ultrasonography revealed mild hepato- to our department with the complaint of fatigue. She did not megaly and hepatosteatosis grade I. Liver biopsy was planned have a history of any other drug or alcohol use. Her physical but the patient did not approve. Cetirizine-induced toxic hepati- examination, iron parameters, TFT and other laboratory test re- tis was considered, and the drug was stopped. In the follow-up, sults were normal except for AST, ALT, ALP and GGT. HBsAg, ALT was 139 U/L, AST 53 U/L, alkaline phosphatase (ALP) 71 U/L anti-HBs, anti-HBc IgM, anti-HAV IgM, anti-HCV, CMV IgM, EBV- (normal range 40–140 U/L) and GGT 20 U/L, while bilirubins re- VCA and Salmonella and Brucella agglutination tests were neg- turned to normal two weeks later. All biochemical tests re- ative. Abdominal ultrasonography was normal. Cetirizine was turned to their normal ranges a month later. discontinued. Liver biopsy was not performed due to lack of the patient’s approval. In follow up as month later, her biochemical values had returned to normal. Demographic features and laboratory test results of these four cases at their admission are presented in Table 1. Discussion Drug-induced liver damage is a frequently encountered clinical table and is encountered as side effects of many drugs. Asymptomatic patients may be admitted with elevated liver function tests results as well as with hepatitis findings. There are three types of hepatotoxic drug reaction based on biochemi- cal parameters: hepatocellular damage, cholestatis and mixed Figure 1. Liver biopsy of Case 3 shows macrosteatosis places (A, hematoxylin- type. Classification is based on the following formula using ALP eosin staining, x100) and mixed inflammatory infiltration including eosinophils; (B, hematoxylin-eosin, x200) in portal areas and parenchyma. and ALT levels: R ratio¼ (ALT/ upper limit of normal range) / Table 1. Patient characteristics and laboratory test results Case 1 Case 2 Case 3 Case 4 Age (years) 46 21 66 40 Sex Male Female Female Female Duration of cetirizine use (days) 3 5 7 4 IgE level (IU) 303 30 17 36 Eosinophil count 420 100 1000 100 AST (NR: 10–40 U/L) 419 188 685 47 ALT (NR: 13–40 U/L) 461 443 667 59 ALP (NR: 40–140 U/L) 153 404 111 843 GGT (NR: 9–50 U/L) 545 44 144 411 R ratio 10,57 3,84 21,1 0,24 Hepatic damage type Hepatocellular Mixed Hepatocellular Cholestatic RUCAM score 10 10 11 9 ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase; NR: normal range; R ratio¼ (ALT/ upper limit of normal range) / (ALP/ upper limit of normal range); RUCAM: Roussel Uclaf Causality Assessment Method Downloaded from https://academic.oup.com/gastro/article-abstract/6/3/228/2909369 by Ed 'DeepDyve' Gillespie user on 22 August 2018 230 | A. Coskun et al. (ALP/ upper limit of normal range). (1) If the R ratio is 5 or ALT Conflict of interest statement: none declared. exceeds twice the upper limit, the reaction is classified as hepa- tocellular toxicity; (2) if the R ratio is 2 and ALT is over the nor- References mal limit, the reaction is designated as cholestatic toxicity; and 1. Campoli-Richards D, Buckley M and Fitton A. Cetirizine. A a (3) if the R ratio is between 2 and 5, the reaction is mixed type review of its pharmacological properties and clinical poten- [12]. Based on this classification, Case 1 and Case 3 were evalu- tial in allergic rhinitis, pollen-induced asthma, and chronic ated as hepatocellular, Case 2 was mixed, and Case 4 was the urticaria. Drugs 1990;40:762–81. cholestatic type. 2. Arendt C and Bernheim J. Double-blind comparison of main- Hepatotoxicity can also be categorized as immune and non- tenance treatment of chronic idiopathic urticaria by cetiri- immune. Hepatotoxicity involving the immune system is also zine and terfenadine. Curr Ther Res 1989;46:724–34. referred to as allergic reaction or hypersensitivity [13]. The pres- 3. Larrey D, Palazzo L and Benhamou JP. Terfenadine and hepa- ence of eosinophils in a peripheral blood smear, increased eo- titis. Ann Intern Med 1985;103:634. sinophil count and elevated blood IgE level in Case 1 suggested 4. Bera F, Sipruhis JP, Jonville-Bera AP, et al. Cytolytic hepatic in- hypersensitivity. volvement after administration of cetirizine (Zyrtec (in Since our patients had no history of alcohol use, blood trans- French). Gastroenterol Clin Biol 1993;17:770–1. fusion, tooth extraction, any surgical operation, close contact 5. Pompili M, Basso M, Grieco A, et al.Recurrent acute hepatitis with hepatitis patients, history of a systemic disease or any associated with use of cetirizine. Ann Pharmacother other drug use, cetirizine was considered to the likely cause for 2004;38:1844–7. the increased values of the liver tests (AST, ALT, ALP, GGT and 6. Sanchez-Lombrana JL, Alvarez RP, Saez LR, et al. Acute hepati- total bilirubin). Any other sources causes that may cause hepa- tis associated with cetirizine intake. J Clin Gastroenterol totoxicity such as viral causes, autoimmune causes, gallstones, 2002;34:493–5. hemochromatosis and endocrinological causes (hypothyroidism 7. Watanabe M, Kohge N and Kaji T. Severe hepatitis in a patient and hyperthyroidism) hepatitis were ruled out through viral se- taking cetirizine. Ann Intern Med 2001;135:142–3. rology, ultrasonography, ANA, AMA, ASMA, ferritin, iron, serum 8. Jurawan R and Smith A. Severe hepatitis in a primary scleros- iron-binding capacity, free T3, free T4 and TSH examinations. If ing cholangitis patient receiving recent cetirizine therapy. N available, measurement of serum cetirizine level, or challenge Z Med J 2010;123:106–7. test could have supported the strenght of our diagnosis. In diag- 9. D ıaz-San  chez A, Mar ın-Jime ´ nez I and Aldeguer M. Benign re- nosing drug–induced hepatotoxicity, measurement the levels of current intrahepatic cholestasis simulating cetirizine- liver-kidney microsomal antibody (anti-LKM2), and the antibody induced toxic hepatitis (in Spanish). Gastroenterol Hepatol against cytochrome P450 may be useful [5]. In our cases, re-use 2010;33:68–9. of the drug did not encountered. Tests to measure the serum 10. Rodr ıguez-Gomez  SJ, Zamora-Mart ınez T, Bailador-Andre ´s C, levels of liver-kidney microsomal antibody (anti-LKM2), and the et al. Severe intrahepatic cholestasis associated with cetiri- antibody against cytochrome P450 were not available. Liver zine (in Spanish). Gastroenterol Hepatol 2009;32:383–4. biopsy was approved and performed in only one patient. 11. Fong DG, Angulo P, Burgart LJ, et al. Cetirizine-induce chole- A markedly high GGT level immediately suggested a toxic stasis. J Clin Gastroenterol 2000;31:250–3. cause [2,4]. Drug-induced hepatitis has been reported in many 12. Danan G and Benichou C. Causality assessment of adverse re- studies [14]. High levels of liver enzymes and possible hepatitis actions to drugs-I. A novel method based on the conclusions development have been shown in various studies [2,3]. of international consensus meetings: application to drug- Although it has been suggested that elevated liver enzyme lev- induced liver injuries. J Clin Epidemiol 1993;46:1323–30. els could sometimes result from cetirizine use [1,2], hepatitis 13. Leise MD, Poterucha JJ and Talwalkar JA. Drug-induced liver has been reported in only five case reports in the literature [4– injury. Mayo Clin Proc 2014;89:95–106 8]. In two of the four cases, cetirizine was used for allergic der- 14. Chitturi S, Teoh NC and Farrell GC. Hepatic drug metabolism matitis, but it was discontinued due to elevated levels of liver and liver disease caused by drugs. In: Feldman M, Friedman enzymes. When the drug was later accidentally re-administered LS, Brandt LJ (eds). Gastrointestinal and Liver Disease, volum 2, to the same patient , liver enzymes were again reported to be in- 10th ed. Philadelphia: Saunders, 2016, 1442–77. creased [4,5]. It is interesting that in our four cases, all enzyme 15. Sahai A and Villeneuve JP. Terfanadine–induced cholestatic levels except for GGT were within normal limits at the follow-up hepatitis. Lancet 1996;348:552–3. two months after cetirizine had been stopped. The literature re- 16. Freneaux E, D Larrey, Berson A, et al. Hepatitis caused by cy- veals liver function tests returning to normal limits within three proheptadine (Periactine). A case and review of the literature months in terfenadin and cyproheptadine-induced hepatitis (in French). Gastroenterol Clin Biol 1988;12:573–5. cases [15,16]. We conclude that, in patients with high levels of liver enzymes and hepatitis of unknown cause, cetirizine as well as other hepatotoxic drugs should be suspected. Downloaded from https://academic.oup.com/gastro/article-abstract/6/3/228/2909369 by Ed 'DeepDyve' Gillespie user on 22 August 2018

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Gastroenterology ReportOxford University Press

Published: Aug 1, 2018

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