title: Nephrotoxicity caused by oral antiviral agents in patients with chronic hepatitis B treated in a hospital for tropical diseases in Thailand.
abstract: BACKGROUND
  There is increasing concern about the potential for nephrotoxicity in patients with chronic hepatitis B (CHB) treated long-term with nucleotide analogs.
  
  
  METHODS
  We examined renal dysfunction and its associated risk factors in patients with CHB treated with antiviral regimens containing either nucleosides or nucleotide analogs. We undertook a retrospective cohort study from 2006 to 2014 at the Hospital for Tropical Diseases, Bangkok, Thailand, and analyzed the data of 102 patients with a median follow-up time of 44.5 months (range 4-101 months).
  
  
  RESULTS
  Seventy-three patients were treated with an antiviral regime containing a nucleoside analog, and 29 with a regime containing a nucleotide analog. Abnormally elevated serum creatinine concentration was observed in 12 patients (11.8 %) after 8 years of treatment. Thirty one percent of patients treated with nucleotide analogs had elevated serum creatinine levels and three of these patients (10.3 %) developed nephrotoxicity. In contrast, serum creatinine concentrations were elevated in three of the 73 patients treated with a nucleoside analog (4.1 %), and none developed nephrotoxicity. The incidence of renal dysfunction by the nucleotide analog regimen was cumulative, with 11.1, 21.0, 26.5 and 47.6 % of patients affected after 2, 4, 6 and 8 years, respectively. Univariate and multivariate analysis indicated that a nucleotide analog-based regimen significantly predicted renal dysfunction (odds ratio 10.5, 95 % confidence intervals 2.6-42.4, P <0.001).
  
  
  CONCLUSIONS
  The long-term use of nucleotide analogs increased the risk of nephrotoxicity in patients with CHB. Thus, the regular assessment of renal function is recommended for all patients with CHB, particularly those treated with a nucleotide analog.
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. agmyintthu.90@gmail.com.
authors.forename: Aung Myint
authors.initials: AM
authors.lastname: Thu
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. kittiyod.poo@mahidol.ac.th.
authors.forename: Kittiyod
authors.initials: K
authors.lastname: Poovorawan
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. chatporn.kit@mahidol.ac.th.
authors.forename: Chatporn
authors.initials: C
authors.lastname: Kittitrakul
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. apichart.non@mahidol.ac.th.
authors.forename: Apichart
authors.initials: A
authors.lastname: Nontprasert
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. natthida.sri@mahidol.ac.th.
authors.forename: Natthida
authors.initials: N
authors.lastname: Sriboonvorakul
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. weerapong.phu@mahidol.ac.th.
authors.forename: Weerapong
authors.initials: W
authors.lastname: Phumratanaprapin
authors.affiliation: Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. pisittkvn@yahoo.com.
authors.forename: Pisit
authors.initials: P
authors.lastname: Tangkijvanich
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. wattana.leo@mahidol.ac.th.
authors.forename: Wattana
authors.initials: W
authors.lastname: Leowattana
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. polrat.wil@mahidol.ac.th.
authors.forename: Polrat
authors.initials: P
authors.lastname: Wilairatana
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006761:Hospitals; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology; D019259:Lamivudine / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009399:Nephrons / Q000187:drug effects* / Q000473:pathology; D063065:Organophosphonates / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D000077712:Telbivudine; D000068698:Tenofovir / Q000009:adverse effects; D013785:Thailand / Q000453:epidemiology; D013936:Thymidine / Q000009:adverse effects / Q000031:analogs & derivatives; D014330:Tropical Medicine
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine; D013936:Thymidine