Aspirin is widely used for treatment or prophylaxis of many diseases. Although aspirin is used chronically for preventing cardiovascular diseases especially, liver function is rarely monitored because of unpredictable and uncommon hepatotoxicity induced by aspirin. We evaluated changes in liver func...
Aspirin is widely used for treatment or prophylaxis of many diseases. Although aspirin is used chronically for preventing cardiovascular diseases especially, liver function is rarely monitored because of unpredictable and uncommon hepatotoxicity induced by aspirin. We evaluated changes in liver function indicators and compared to acetaminophen and NSAIDs. We retrospectively analyzed EMR data (n=28788) of patients who took study drugs and had liver function tests (LFT) during study period from 2009.7.1 to 2010.6.30 at a tertiary hospital and evaluated the above information. Patients not having LFT results at these three standard points of time (baseline, during medication, and after finishing medication) were excluded. During medication, mean changes of Alanine transaminase (ALT), Aspartate transaminase (AST), Total Bilirubin (TB) were increased and that of serum albumin (Alb) was decreased, with the largest effect from aspirin (n=461; 16.8, 14.9, 0.28, -0.24) and the smallest from celecoxib (n=127; 3.4, 5.2, 0.11, -0.16). In addition, aspirin caused more changes of blood liver function indicators in patient group with liver disease (n=128, 27.4, 26.9, 0.53, -0.3) than those in patient group without liver disease (n=357, 12.5, 13.1, 0.23, -0.24). Taking low dose aspirin for prophylaxis purpose with long-term medication may be associated with liver injury. Our study is just a signal regarding the possibility of hepatotoxicity among patients taking low dose aspirin in a hospital setting, and thus it needs to be further investigated.
Aspirin is widely used for treatment or prophylaxis of many diseases. Although aspirin is used chronically for preventing cardiovascular diseases especially, liver function is rarely monitored because of unpredictable and uncommon hepatotoxicity induced by aspirin. We evaluated changes in liver function indicators and compared to acetaminophen and NSAIDs. We retrospectively analyzed EMR data (n=28788) of patients who took study drugs and had liver function tests (LFT) during study period from 2009.7.1 to 2010.6.30 at a tertiary hospital and evaluated the above information. Patients not having LFT results at these three standard points of time (baseline, during medication, and after finishing medication) were excluded. During medication, mean changes of Alanine transaminase (ALT), Aspartate transaminase (AST), Total Bilirubin (TB) were increased and that of serum albumin (Alb) was decreased, with the largest effect from aspirin (n=461; 16.8, 14.9, 0.28, -0.24) and the smallest from celecoxib (n=127; 3.4, 5.2, 0.11, -0.16). In addition, aspirin caused more changes of blood liver function indicators in patient group with liver disease (n=128, 27.4, 26.9, 0.53, -0.3) than those in patient group without liver disease (n=357, 12.5, 13.1, 0.23, -0.24). Taking low dose aspirin for prophylaxis purpose with long-term medication may be associated with liver injury. Our study is just a signal regarding the possibility of hepatotoxicity among patients taking low dose aspirin in a hospital setting, and thus it needs to be further investigated.
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제안 방법
The database used in this study included information on unidentifiable codes representing patient, patient’s age and disease code, 4 LFT results, dates of the laboratory test measurement, and drug prescription(generic/brand name, prescription date and duration).
According to our study design, we analyzed LFT results at three standard times of points (before, during and after medication) (Fig. 1). Baseline result (A) is result just before starting of taking drugs.
EMR database (N=28788) was used for this study to overcome difficulties induced by confounding factors such as age, disease, other organ dysfunction in clinical settings and analyze systemically. NSAIDs evaluated in this study were 8 groups (17 drugs) from the formulary commonly prescribed in this hospital.
This study was retrospective, using only the EMR database and analyzed the transition of liver function indicators by each medication. We did not identify the damage of the hepatocyte through biopsy.
대상 데이터
This study was a retrospective analysis of EMR data collected from the Seoul National University Hospital (SNUH) in Korea from July 1 2009 through June 302010. Institutional Review Board approval was obtained (IRB#H-1012-046-644).
EMR database (N=28788) was used for this study to overcome difficulties induced by confounding factors such as age, disease, other organ dysfunction in clinical settings and analyze systemically. NSAIDs evaluated in this study were 8 groups (17 drugs) from the formulary commonly prescribed in this hospital. We broadly classified 17 drugs to 4 or 5 groups (aspirin, acetaminophen, non-selective NSAID (aceclofenac), selective COX-2 inhibitors (celecoxib) and compared them.
데이터처리
We also compared between underlying liver disease group and non-liver disease group to investigate susceptibility of hepatotoxicity. Average differences were obtained by paired t-test. Null hypotheses of no difference were rejected if p-values were less than .
성능/효과
We analyzed the proportion of patients based on LFT results at the point of worst LFT during medication (B) which was abnormal during the medication according to our criteria of evaluating LFT; normal, abnormal, severe abnormal. Aspirin showed the worst profiles in these abnormal and severe abnormal results (ALT (28.2/7.6%), AST (26.8/5.4%), TB (16.3/ 4.1%), Alb (19.8/1.2%)). APAP, non-selective NSAID including aceclofeanc, celecoxib followed in order.
28,29) Although APAP is well-known as its hepatotoxicity, APAP was not the worst profile in hepatotoxicity in our study. In results of abnormal proportion and average LFT values at the points of worst LFT during medication, APAP was lower than aspirin. In addition, liver damage degree without underlying liver disease group was more severe than one of group with underlying liver disease.
In our study, non-selective NSAIDs included acetic acid derivatives (aceclofenac, diclofenac, etodolac, ketorolac), propionic acid derivatives (dexibuprofen, fenoprofen, ibuprofen, ketoprofen, naproxen, zaltoprofen), oxicams (meloxicam, piroxicam), morniflumate, nabumetone, which were classified by their chemical structure. According to review article comparing incidence of hepatotoxicity between non-analgesics, NSAIDs were various; diclofenac (19.5%), ibuprofen (8.4%), sulindac (7.1%), aspirin (6.9%), naproxen (6.4%), piroxicam (5.4%), nimesulide (3.3%). Other NSAIDs were only 0.
The result was that after starting medication, ALT, AST and TB were mostly increased and Alb were decreased, but increased ALT, AST, TB and Alb overall tend to be recovered within 30 days after finishing medication. During medication, changes of ALT, AST, TB and alb were aspirin (16.
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