title: Response-guided treatment of cirrhotic chronic hepatitis B patients: multicenter prospective study.
abstract: OBJECTIVE
  To observe the effect of response-guided add-on therapy with adefovir (ADV) and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients.
  
  
  METHODS
  A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete response, HBV DNA ≤ 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000 IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.
  
  
  RESULTS
  Comparison of the three arms demonstrated that early complete virologic response at week 24 was associated with maintained viral suppression (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/mL. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.
  
  
  CONCLUSIONS
  Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Er-Li
authors.initials: EL
authors.lastname: Gu
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Yu
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ji
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiu-Yun
authors.initials: XY
authors.lastname: Ma
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Pan
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Shan-Min
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Xu
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yue-Er
authors.initials: YE
authors.lastname: Wang
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Guang-Bi
authors.initials: GB
authors.lastname: Yao
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing'an District Central Hospital, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Zhang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002681:China; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine
keywords: Adefovir dipivoxil; Cirrhosis; Hepatitis B; Lamivudine; Response-guided therapy