title: Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients.
abstract: Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required.
  
  
  
  To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)-monoinfected patients.
  
  
  
  PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)).
  
  
  
  In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing 'real-world' clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations.
  
  
  
  Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need.
authors.affiliation: Division of Gastroenterology and Hepatology, "A.M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lampertico
authors.affiliation: Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
authors.forename: H L Y
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Toronto Centre for Liver Diseases, University Health Network, Toronto, ON, Canada.
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
authors.affiliation: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: S I
authors.initials: SI
authors.lastname: Strasser
authors.affiliation: Department of Nephrology and Intensive Care, Campus Virchow, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schindler
authors.affiliation: Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Berg
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D009705:Nucleosides / Q000627:therapeutic use; D009711:Nucleotides / Q000627:therapeutic use; D000068698:Tenofovir / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D009711:Nucleotides; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir