Experience from the Combined GLOBE (NV-02B-007/CLDT600A2302) and 015 (NV-02B-015) Study Clinical Safety Database. C. Avila 1 , R. Laeufle 2 , W.B. Bao 3 1 Novartis Pharma AG, Fabrikstrasse 6, Basel, Switzerland, 2 Novartis Pharma AG, Basel, Switzerland, 3 Novartis Pharma, East Hanover, US Background: Creatine phosphokinase (CK) is a commonly used marker of muscle damage and is elevated by many factors (e.g. exercise, injury, drugs). Normal CK levels are affected by muscle mass and elevated levels are described during the natural course of CHB. 22% of patients in the GLOBE study had pretreatment Grade 1-4 CK elevations. Methods: We reviewed data from this combined study clinical safety database, and describe the experience of CK elevation and its relationship to adverse event reports of muscle related symptoms. Results: The frequency of new onset of Grade 3-4 CK elevations in telbivudine-treated patients (combined database ITT population) was 1.8% (15/847), 6.3% (53/838), 3.2% (27/826) and 5.1% (40/786) from weeks 0-24, 24-52, 52-76 and 76-104 respectively. The frequency of Grade 3-4 CK elevations for all patients from week 0-104 was 12.6% (107/847). The majority of Grade 3-4 CK elevations were asymptomatic, rarely resulted in discontinuation or interruption, spontaneously declined within 1 or 2 visits and were not associated with more frequent muscle-related adverse events. Cumulative data from this combined database showed no relationship of the degree of increased CK to acute or persistent muscle disease. Conclusion: CK elevations are associated with HBV disease and were also common during the GLOBE and 015 trials and were not predictive of the development of muscle related symptoms. Onset of muscle-related symptoms should prompt clinical and treatment review, including concomitant medications. Backgrounds: Leptin plays a crucial role in the regulation of energy balance and body weight control by activating the long form of the leptin receptor (Ob-RL). Epidemiologic studies showed that obesity is one of the factors associated with HBV related hepatocellular carcinoma. Methods: Huh7 cells were transiently transfected with 1.3 copies of HBV-replicon plasmid. After 48h, cells were harvested and total RNA of the cells were extracted and reverse-transcribed into cDNA. Long form and short form leptin receptor (Ob-RL, Ob-RS) mRNA transcription levels were assayed by Real-time PCR respectively. And mRNA transcription levels and protein expression of Ob-RL and Ob-RS in HepG2.2.15 cells were also detected. Results: After transfected by 1.3 copies HBV-replicon plasmid, the mRNA transcription level of Ob-RL was inhibited significantly (**P<0.01), but the mRNA transcription level of Ob-RS did not change, and the Ob-RL protein expression was reduced. In HepG2.2.15 cells, the mRNA transcription level of Ob-RL was also significantly lower than the mRNA transcription level of Ob-RL in HepG2 cells, while the mRNA transcription of Ob-RS in HepG2.2.15 and HepG2 cells didn't show significant difference. Besides, the protein expression level of Ob-RL in HepG2.2.15 was also lower than it in HepG2 cells. Conclusion: HBV replication down-regulated the expression of long form leptin receptor in cell cultures, which could in part explain the clinical observation of obesity in association with development of serious sequelae in HBV infections.