This study was to evaluate the antiviral efficacy and safety in nucleoside naive Chinese patients with chronic hepatitis B (CHB) treated with entecavir (ETV) or lamivadine (LVD).
The trial was a randomized, double-blind, double-dummy and control design. 519 nucleoside naive CHB patients were treated with daily dose of ETV 0.5 mg (258 patients) or LVD 100 mg (261 patients) for at least 52 weeks. The primary endpoint was a composite endpoint of HBV DNA < 0.7 MEq/ml by bDNA assay and ALT < 1.25 x ULN at week 48. HBV DNA levels were also measured by the Roche Cobas Amplicor(TM) PCR assay at weeks 12, 24, 36 and 48. Clinical and laboratory adverse events were recorded every 4 weeks.
Baseline characteristics were well balanced between treatment groups. The primary end point were achieved in 90% of ETV treated patients versus 69% of LVD treated patients (P < 0.0001). The mean HBV DNA level decreased 5.9 lg copies/ml (by PCR assay) from baseline in ETV group versus 4.3 lg copies/ml in LVD group (P < 0.0001). The serum HBV DNA become undetectable (< 300 copies/ml by PCR) in 76% of ETV group versus 43% of LVD group (P < 0.0001). The normalization of ALT were 90% in ETV group versus 78% in LVD group (P = 0.0003). The difference of HBeAg seroconversion rates between this 2 groups (15% vs 18%) at week 48 was no statistically significant. The overall incidence of adverse events (AEs) was comparable: 60% of ETV patients and 56% of LVD patients reported AEs; and 3% of ETV patients and 5% of LVD patients reported serious AEs.
ETV achieves better virologic and biochemical improvements in nucleoside-naive patients with CHB while the safety profile is comparable to LVD.
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log(10) versus 5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. CONCLUSION: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.
[Show abstract][Hide abstract] ABSTRACT: Forty years ago in 1967, Professor Blumberg discovered the Australian Antigen, later known as the hepatitis B surface antigen, and was awarded the Nobel Prize. This discovery enables the diagnosis of hepatitis B virus (HBV) infection and defines its epidemiology. Viral hepatitis B infection affects global health situation, and chronic hepatitis B (CHB) is particularly serious in the Asia-Pacific region. HBV vaccines created the first breakthrough in HBV prevention. Through universal HBV vaccination program for the newborns, promoted since the mid-1980s, the main route that perpetuates chronic infection from mother to child is curbed. Most children and young adults now have immunity against HBV infection. The next breakthrough comes with therapy for CHB. This prevents progression to cirrhosis and hepatocellular carcinoma. Standard interferon therapy with modest efficacy has been largely replaced by therapy with nuclos(t)ide analogues or pegylated interferons alfa-2a and -2b. Lamivudine was approved by the FDA USA in 1998, followed by adefovir dipivoxil in 2002, entecavir in 2005, and telbivudine in 2006. Clevudine, tenofovir, and many promising candidates are in different stages of development and clinical trial. This paper critically reviews recent data published or presented since the APASL Consensus and Guideline Update of 2005. Clinical efficacy mostly in patients with raised serum alanine aminotransferase will be analyzed.
Hepatology International 07/2008; 2(2):163-78. DOI:10.1007/s12072-008-9061-6 · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis B infection can lead to liver failure, hepatocellular carcinoma, and death.
To evaluate the effectiveness of antiviral therapy for adults with chronic hepatitis B infection.
Randomized, controlled trials (RCTs) of interferon (alpha2b and pegylated alpha2a), lamivudine, adefovir, entecavir, and telbivudine published from 1990 to 2008.
Randomized, controlled clinical trials of adults with chronic hepatitis B published in English after 1989 that reported death; incidence of hepatocellular carcinoma or liver failure; prevalence and incidence of cirrhosis; presence or seroconversion of hepatitis B e antigen (HBeAg) or surface antigen (HBsAg), viral load of hepatitis B virus DNA; aspartate aminotransferase and alanine aminotransferase (ALT) levels; or fibrosis scores after therapy with interferon-alpha2b, pegylated interferon-alpha2a, lamivudine, adefovir, entecavir, and telbivudine.
Data extracted with standard protocols to calculate risk difference for clinical outcomes, viral load, HBeAg and HBsAg, ALT, histologic scores, and adverse events.
In 16 RCTs (4431 patients), drug treatment did not improve clinical outcomes of chronic hepatitis B infection, but the trials were underpowered. In 60 RCTs that examined intermediate outcomes, no single treatment improved all intermediate outcomes. Low-quality evidence suggested HBsAg clearance after interferon-alpha2b (2 RCTs; 211 patients). Moderate-quality evidence suggested ALT normalization at follow-up after treatment with adefovir (2 RCTs; 600 patients) and HBeAg loss with lamivudine (2 RCTs; 318 patients). With interferon-alpha2b, moderate-quality evidence suggested HBeAg loss (3 RCTs; 351 patients), seroconversion (2 RCTs; 304 patients), and ALT normalization (2 RCTs; 131 patients). Pegylated interferon-alpha2a versus lamivudine improved HBeAg seroconversion (1 RCT; 814 patients) and ALT normalization (2 RCTs; 905 patients) off treatment. Pegylated interferon-alpha2a combined with lamivudine versus lamivudine improved HBeAg loss (1 RCT; 543 patients) and ALT normalization (2 RCTs; 905 patients). Adverse events during antiretroviral therapy occurred in more than 50% of patients but were not associated with increased treatment discontinuation. However, most studies excluded patients with hepatic or renal insufficiency or other serious comorbid conditions. Limitation: Marked heterogeneity in study samples, interventions, and measured outcomes preclude definitive conclusions.
Evidence was insufficient to assess treatment effect on clinical outcomes or determine whether inconsistent improvements in selected intermediate measures are reliable surrogates. Future research is needed to provide evidence-based recommendations about optimal antiviral therapy in adults with chronic hepatitis B infection.
Annals of internal medicine 02/2009; 150(2):111-24. · 17.81 Impact Factor
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