Digestive Diseases and Sciences

, Volume 59, Issue 7, pp 1603–1616 | Cite as

Benzodiazepine-Associated Hepatic Encephalopathy Significantly Increased Healthcare Utilization and Medical Costs of Chinese Cirrhotic Patients: 7-Year Experience

  • Pei-Chang Lee
  • Ying-Ying Yang
  • Ming-Wei Lin
  • Ming-Chih Hou
  • Chien-Sheng Huang
  • Kuei-Chuan Lee
  • Ying-Wen Wang
  • Yun-Cheng Hsieh
  • Yi-Hsiang Huang
  • Chi-Jen Chu
  • Han-Chieh Lin
Original Article


Background and Objectives

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.


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.


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.


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.


Benzodiazepines Hepatic encephalopathy Cirrhotic patients GABRA genotype 



This work was funded by research grants NSC100-2314-B-010-059-MY3 and NSC 101-2314-B-075-011-MY3 from the National Science Council, and V102C-014 and V102C-016 by the Taipei Veterans General Hospital. The authors thank members of the Division of Taiwan’s National Health Insurance (NHI) medical costs statistic center, Taipei Veterans General Hospital; Lin Yu-Zhen, Huang Jing-Han, Wei Xiu-Mei and Peng Chi-Yi for their excellent technical assistances.

Conflict of interest


Supplementary material

10620_2013_3021_MOESM1_ESM.docx (44 kb)
Supplementary material 1 (DOCX 44 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Pei-Chang Lee
    • 1
    • 3
  • Ying-Ying Yang
    • 2
    • 3
    • 4
  • Ming-Wei Lin
    • 7
  • Ming-Chih Hou
    • 1
    • 3
    • 5
  • Chien-Sheng Huang
    • 3
    • 6
  • Kuei-Chuan Lee
    • 1
    • 3
  • Ying-Wen Wang
    • 3
  • Yun-Cheng Hsieh
    • 1
    • 3
  • Yi-Hsiang Huang
    • 1
    • 3
    • 4
  • Chi-Jen Chu
    • 1
    • 3
  • Han-Chieh Lin
    • 1
    • 3
  1. 1.Division of Gastroenterology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Division of General Medicine, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Faculty of MedicineNational Yang-Ming University School of MedicineTaipeiTaiwan
  4. 4.Institute of Clinical Medicine, Faculty of MedicineNational Yang-Ming University School of MedicineTaipeiTaiwan
  5. 5.Endoscopic Center for Diagnosis and TreatmentTaipei Veterans General HospitalTaipeiTaiwan
  6. 6.Division of Thoracic Surgery, Department of SurgeryTaipei Veterans General HospitalTaipeiTaiwan
  7. 7.Institute of Preventive Medicine, Faculty of MedicineNational Yang-Ming University School of MedicineTaipeiTaiwan

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