title: Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis.
abstract: Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. hlychan@cuhk.edu.hk
authors.forename: H L Y
authors.initials: HL
authors.lastname: Chan
authors.forename: Y C
authors.initials: YC
authors.lastname: Chen
authors.forename: E J
authors.initials: EJ
authors.lastname: Gane
authors.forename: S K
authors.initials: SK
authors.lastname: Sarin
authors.forename: D J
authors.initials: DJ
authors.lastname: Suh
authors.forename: T
authors.initials: T
authors.lastname: Piratvisuth
authors.forename: B
authors.initials: B
authors.lastname: Prabhakar
authors.forename: S G
authors.initials: SG
authors.lastname: Hwang
authors.forename: G
authors.initials: G
authors.lastname: Choudhuri
authors.forename: R
authors.initials: R
authors.lastname: Safadi
authors.forename: T
authors.initials: T
authors.lastname: Tanwandee
authors.forename: A
authors.initials: A
authors.lastname: Chutaputti
authors.forename: C
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: W
authors.initials: W
authors.lastname: Bao
authors.forename: C
authors.initials: C
authors.lastname: Avila
authors.forename: A
authors.initials: A
authors.lastname: Trylesinski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000150:complications*; D017093:Liver Failure; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009705:Nucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D019259:Lamivudine; D000410:Alanine Transaminase; D013936:Thymidine