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. AIMS: 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.
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. AIMS: 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: F Nevens; J Main; P Honkoop; D L Tyrrell; J Barber; M T Sullivan; J Fevery; R A De Man; H C Thomas Journal: Gastroenterology Date: 1997-10 Impact factor: 22.682
Authors: S Manolakopoulos; S Bethanis; S Koutsounas; J Goulis; J Vlachogiannakos; E Christias; A Saveriadis; C Pavlidis; C Triantos; A Christidou; G Papatheodoridis; D Karamanolis; D Tzourmakliotis Journal: Aliment Pharmacol Ther Date: 2007-11-05 Impact factor: 8.171
Authors: R Idilman; S Kaymakoglu; F Oguz Onder; E Ahishali; M Bektas; K Cinar; B Pinarbasi; S Karayalcin; S Badur; Y Cakaloglu; A Mithat Bozdayi; H Bozkaya; A Okten; C Yurdaydin Journal: J Viral Hepat Date: 2009-02-12 Impact factor: 3.728
Authors: Marion G Peters; H w Hann Hw; Paul Martin; E Jenny Heathcote; P Buggisch; R Rubin; M Bourliere; K Kowdley; C Trepo; D f Gray Df; M Sullivan; K Kleber; R Ebrahimi; S Xiong; Carol L Brosgart Journal: Gastroenterology Date: 2004-01 Impact factor: 22.682
Authors: Andrea Lisotti; Francesco Azzaroli; Federica Buonfiglioli; Marco Montagnani; Flavio Alessandrelli; Giuseppe Mazzella Journal: Int J Med Sci Date: 2008-10-23 Impact factor: 3.738