Benzodiazepine-associated hepatic encephalopathy significantly increased healthcare utilization and medical costs of Chinese cirrhotic patients: 7-year experience.
OBJECTIVE
In cirrhosis, hypersensitivity to benzodiazepines (BZD) and precipitating hepatic encephalopathy (HE) have been reported. The aim of this study was to evaluate the safety, economic impact and modifiable factors that are associated with the excess risk of BZD-associated HE in cirrhotic patients.


METHODS
Between July 2005 and March 2012, 1,612 Chinese cirrhotic patients with and without using long-t 1/2-BZD or short-t 1/2-BZD were enrolled and followed up for 6 months.


RESULTS
Among BZD users, the per-person HE-related healthcare utilization and medical costs were found to have progressively increased from 2005 to 2012. Cirrhotic BZD users had a higher percentage of smoking, alcohol drinking, simultaneous consumption of non-BZD drugs, and had a higher incidence of non-cirrhotic chronic illness than non-BZD users. Multivariate analysis indicated that hypoalbuminemia (<3 g/dL), long-acting (t 1/2 > 12-h), high-dosage (>1.5 defined daily dose equivalents) and long-duration (>2-months) BZD use, carrier of variant genotypes (AG + GG) of GABRA 1 (rs2290732) and having the wild genotype (TT) of GABRG 2 (rs211037) were significant predictors of the development of BZD-associated HE in cirrhotic patients. Additionally, synergistic effects of the above significant predictors on BZD-associated HE risk could be identified.


CONCLUSIONS
Our study confirms the clinical and economic impact of BZD-associated HE in cirrhotic BZD-users. Accordingly, extra caution is needed when treating cirrhotic BZD users with the above risk factors in order to avoid the BZD-associated HE in cirrhotic patients.
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Pei-Chang
PC
Lee
Ying-Ying
YY
Yang
Ming-Wei
MW
Lin
Ming-Chih
MC
Hou
Chien-Sheng
CS
Huang
Kuei-Chuan
KC
Lee
Ying-Wen
YW
Wang
Yun-Cheng
YC
Hsieh
Yi-Hsiang
YH
Huang
Chi-Jen
CJ
Chu
Han-Chieh
HC
Lin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D002681:China; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D017048:Health Care Costs / Q000706:statistics & numerical data* / Q000639:trends; D006296:Health Services / Q000191:economics / Q000706:statistics & numerical data*; D006501:Hepatic Encephalopathy / Q000139:chemically induced* / Q000191:economics / Q000235:genetics / Q000628:therapy; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D008103:Liver Cirrhosis / Q000150:complications* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D055815:Young Adult
D006993:Hypnotics and Sedatives; D001569:Benzodiazepines