title: High dose lamivudine in HBV-related cirrhotic patients with unsatisfactory response after adefovir add-on.
abstract: BACKGROUND
  Before tenofovir approval for chronic hepatitis B therapy, the clinical management of patients with suboptimal response or virological breakthrough during combination treatment with lamivudine and adefovir dipivoxil was a difficult clinical challenge.
  
  
  OBJECTIVE
  In order to improve virologic response and reduce the risk of decompensation, we evaluate the efficacy of a high dose of lamivudine on chronic HBV patients who have previously presented an unsatisfactory response during treatment with lamivudine 100mg/day and adefovir 10mg/day.
  
  
  METHODS
  Six patients with HBV-related liver cirrhosis were prospectively enrolled. All were HBeAg-negative and presented a suboptimal response or virological breakthrough after "adefovir add-on" because of development of clinical breakthrough during Lamivudine treatment. Lamivudine dose was increased to 200 or 300 mg, depending on viral load. After 12 months of follow-up, virological and biochemical response were evaluated.
  
  
  RESULTS
  After 12 months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant decrease of serum HBV DNA (mean reduction 2,62 ± 1,15 Log10 UI/ml, P = 0.03) and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable within 6 months. No patient developed liver decompensation and no significant changes occurred in serum creatinine, serum and urinary electrolytes. No adverse events were registered.
  
  
  CONCLUSIONS
  In our experience, rescue strategy with high-dose lamivudine inhibited viral replication leading to undetectability of serum HBVDNA. This rescue treatment presented a good safety profile, without adverse events during the study period. Customized increase of nucleos(t)ide analogues dose in difficult-to-treat patients may be a proficient approach in challenging clinical setting.
authors: Department of Clinical Medicine, Gastroenterology Unit, St. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
authors: Marco
authors: M
authors: Montagnani
authors: Marina
authors: M
authors: Giandinoto
authors: Andrea
authors: A
authors: Lisotti
authors: Silvia
authors: S
authors: Galli
authors: Francesco
authors: F
authors: Azzaroli
authors: Federica
authors: F
authors: Buonfiglioli
authors: Laura
authors: L
authors: Turco
authors: Rita
authors: R
authors: Aldini
authors: Giuseppe
authors: G
authors: Mazzella
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil