Session Title: Parallel Session:
HEPATITIS B: THERAPEUTIC ADVANCES
Presentation Date: Apr 15, 2010
TREATMENT OF DECOMPENSATED HBV-CIRRHOSIS: RESULTS FROM 2-YEARS RANDOMIZED TRIAL WITH TELBIVUDINE OR LAMIVUDINE
E.J. Gane1, H.L. Chan2, G. Choudhuri3, D.J. Suh4, A. Chutaputti5, R. Safadi6, T. Tanwandee5, S. Thongsawat7, N. Assy8, S.K. Sarin9, W. Bao10, A. Trylesinski11, C. Avila11
1Middlemore Hospital, Auckland, New Zealand, 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China, 3Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, 4Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 5Phramongkutklao Hospital, Bangkok, Thailand, 6Holy Family Hospital, Nazareth, & Hadassah Medical Center, Jerusalem, Israel, 7Siriraj Hospital, Bangkok, 8Chiang Mai University, Faculty of Medicine, Chiang Mai, Thailand, 9Sieff Government Hospital, Safed, Israel, 10Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India, 11Novartis Pharma Corporation, East Hanover, NJ, USA, 12Novartis Pharma AG, Basel, Switzerland. *email@example.com
Background: Decompensated cirrhotic patients have high morbidity/mortality rate and treatment options are limited. There is urgent need for well tolerated antiviral treatment inducing rapid viral suppression and improving clinical outcomes. Most decompensated cirrhotic patients have some degree of underlying renal insufficiency. Increase of creatinine with tenofovir and lactic acidosis with entecavir has been reported. In decompensated HBV-cirrhosis, LAM is well tolerated and can stabilize/improve liver function Our objective was to evaluate outcomes under telbivudine (LDT) or lamivudine (LAM) in decompensated CHB patients.
Methods: Double blind, randomized trial comparing telbivudine vs lamivudine in 195 (98 LDT,97 LAM) decompensated (CTP>7 and cirrhosis or portal hypertension) CHB patients. MELD scores were evaluated. Renal function was assessed by Cockroft Gault (CG) and MDRD. Values are LSmean±SD. Safety was monitored by an independent DSMB.
Results: At baseline, median age was 52 years, 70% Asian, 73% males, 57% HBeAg negative. In the ITT population, CTP and MELD scores were: 7.9±0.3 and 14.3±0.6 (LDT) and 8.3±0.2 and 15.5±0.6 (LAM), p=ns. 20% of patients had GFR < 80 mL/min. Median overall drug exposure was 104W (LDT) and 100W (LAM) (overall min 1.3-max 121W). At end of treatment, both arms stabilized CTP and MELD scores, median change from baseline: -0.4±0.3 and -0.2±0.7 (LDT); -0.6±0.3 and -1±0.7 (LAM), p=ns. 22% patients had GFR< 80mL/min and change from baseline for CG and MDRD was 0.3±3.6 and 3.3±3.3 (LDT) vs -4.1± 3.4, p=ns and -4.3±3.1,p=0.02 (LAM) respectively. ALT normalization: 58% LDT and 50% LAM. Undetectable HBV DNA (< 300 copies/ml) was achieved in 47% of LDT and 36% of LAM patients, viral breakthrough was 29% in LDT and 39% in LAM. Early (W24) and long term (W104) survival rates were: 96% and 83% for LDT, 91% and 75% for LAM, p=ns. Death occurred in 16 (16%) LDT and 22 (22%) LAM patients. SAEs were consistent with advanced liver disease: 55% for LDT and 61% for LAM. No cases of rhabdomyolysis or lactic acidosis were reported.
Conclusion: In a large number of patients with long term follow-up telbivudine was well tolerated with stabilization of liver function and comparable tolerability to lamivudine.