levocetirizine ( lcz ) , an active enantiomer of cetirizine , is a second - generation antihistamine that was approved by the us food and drug administration in 2008 for the relief of symptoms associated with allergic diseases in adults and children [ 1 - 3 ] .
although it has some side effects  such as sleepiness , headache , dry mouth , vision problems , palpitation , and fatigue  it is considered to be effective and safe treating allergic disease .
we present the first report of lcz - induced liver injury with histologic confirmation in a 48-year - old man without a history of hepatobiliary disease .
a 48-year - old man without significant medical history was referred from the dermatology department due to jaundice and generalized pruritus .
the patient did not report any fatigue , anorexia , nausea , abdominal discomfort , fever , rash , myalgia , muscle weakness , swelling , and recent illness .
medication in recent use included lcz 5 mg daily for 2 months , and the patient had been taking bepotastine besilate 10 mg daily until 2 months ago .
he did not report taking any other medications including statins , over - the - counter medications , herbal medications including red ginseng or any extract or nutritional supplements .
specific history of exposure to hepatotoxic chemicals or familial history of liver disease was not identified .
initial blood pressure was 110/70 mmhg , pulse rate 88/min , respiratory rate 18/min , and body temperature 36.7c .
laboratory findings revealed prothrombin time 11.8 s , international normalized ratio 0.88 , aspartate aminotransferase ( ast ) 1,208 iu / l , alanine aminotransferase ( alt ) 2,043
iu / l , total bilirubin 8.68 mg / dl , direct bilirubin 7.23 mg / dl , alkaline phosphatase 184 u / l , lactate dehydrogenase 463
iu / l , protein 5.9 g / dl , albumin 3.9 g / dl , and creatine phosphokinase 21 iu / l .
serologic viral marker evaluations revealed hepatitis b surface antigen negative , antibody to hepatitis b surface antigen positive , antibody to hepatitis b core antigen negative , anti - hepatitis c virus negative and anti - human immunodeficiency virus negative .
serum anti - mitochondrial antibody , anti - smooth muscle antibody , anti - nuclear antibody , anti - dsdna antibody , anti - neutrophil cytoplasm antibody , and anti - liver kidney microsome antibody were negative .
an abdominal sonography revealed no evidence of extrahepatic obstruction , biliary ductal disease , cholelithiasis , or hepatic parenchymal abnormalities .
for histologic evaluation , a percutaneous ultrasonography - guided liver biopsy was performed without complications .
there was an increased amount of connective tissue extending from the portal area and inflammation around apoptotic hepatocytes ( fig .
the patient stopped taking lcz immediately after evaluation and all kinds of liver enzymes were normalized within 3 weeks after discontinuation ( fig .
the patient visited the outpatient department several times after discharge and has maintained normal liver function .
drug - induced liver injury ( dili ) is a rare but potentially life - threatening adverse drug reaction .
a large number of drugs have deleterious effects on the liver , and dili is a major cause of acute liver injury and liver transplantation .
dili is responsible for ~10% of all adverse drug reactions in the united states . in korea ,
the annual extrapolated incidence of dili in hospitalized patients at a university hospital was 12/100,000 persons / year .
the mechanism of dili is unknown , but it is not associated with medication dose , particularly idiosyncratic dili . because of its low incidence , idiosyncratic dili can not be detected in preclinical testing or clinical trials .
the r - enantiomer of cetirizine dihydrochloride , which has favorable pharmacodynamic and pharmacokinetic characteristics  has been demonstrated to be safe and effective for the treatment of allergic diseases , as evidenced by the low number of adverse effects in clinical trials .
a similar number of patients reported treatment - emergent adverse events with lcz and placebo .
the most common treatment - emergent adverse events are headache ( 4.6% ) , fatigue ( 1.8% ) , and dry throat ( 1.4% ) .
one patient in the lcz group showed cellulitis ( 0.4% ) as a serious adverse event .
a previous report of lcz - induced hepatitis showed less severe hepatic inflammation compared with our case ( ast 113 iu / ml and alt 115 iu / ml vs. ast 1,208 iu / ml and alt 2,043 iu / ml , respectively ) .
this difference of severity was originated in which the previous case was detected by routine liver function test after using lcz only for 2 weeks , but our patient exhibited jaundice after taking lcz for 2 months . because hepatotoxicity is not included in the lcz prescribing information and only one case of lcz - induced liver injury has been reported , hepatotoxicity was not monitored in our case .
therefore , any drug could cause dili . patients with dili can present with symptoms similar to those of patients with hepatobiliary disease of other causes , and therefore it is important to maintain a high index of clinical suspicion in determining the diagnosis
. the clinical presentations of dili are acute hepatitis and/or cholestasis , although idiosyncratic reactions frequently occur in a background of higher incidence rates of mild asymptomatic liver injury .
our patient did not have a specific past medical history , nor show serologic or radiologic findings .
based on the timing of lcz administration and the clinical course , we could suspect lcz - induced liver injury . because the patient conducted liver biopsy and recovered after withdrawal of lcz
numerous drugs have been reported to cause liver injury , but only one case of lcz - induced liver injury , which lacked histologic confirmation , has been described . furthermore , unlike the previous case of lcz - induced liver injury , our patient showed > 20-fold elevation of serum ast and alt levels . to our knowledge , this is the first reported case of lcz - induced liver injury confirmed by liver biopsy .
lcz is generally well tolerated and widely used , and it has consistently demonstrated high response rates and a favorable side - effect profile . although its hepatotoxicity is not established , lcz could be associated with acute liver injury . in conclusion
, lcz is an effective and well - tolerated drug for the treatment of allergic diseases ; however , clinicians should be aware of its potential hepatotoxicity .
 levocetirizine is a second - generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease . 
 there was only one case report of levocetirizine - induced liver toxicity , but a liver biopsy was not performed . in this article , we present the first case of levocetirizine - induced liver injury with histologic findings . 
 a 48-year - old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis . 
 laboratory findings revealed acute hepatitis with cholestasis . 
 a liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes . 
 the patient fully recovered 3 weeks after withdrawing levocetirizine . 
 although levocetirizine is safe and effective , physicians should be aware of its potential hepatotoxicity . 
INTRODUCTION
CASE REPORT
DISCUSSION