Estudio primario

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Año 2004
Revista Gastroenterology
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Background & Aims: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). Methods: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level ≥1.2 times the upper limit of normal, and serum HBV DNA level ≥6 log10 copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. Results: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG16 was -0.07 in the lamivudine group compared with -2.45 and -2.46 log10 copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log10 copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. Conclusions: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

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Resumen estructurado de revisiones sistemáticas

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Año 2014
Autores Zhang K , Li Z , Chen H
Revista Database of Abstracts of Reviews of Effects (DARE)
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Estudio primario

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Año 2012
Autores Wei, W , Huang, ZM
Revista Zhong Hua Yi Yuan Gan Ran Bing Xue Za Zhi
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Estudio primario

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Año 2008
Revista Journal of hepatology
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BACKGROUND/AIMS:

We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB).

METHODS:

One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily (combination therapy) for 104 weeks in a randomized double-blind study.

RESULTS:

Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups (p=0.936). At week 104, median serum HBV DNA change from baseline (log(10)copies/mL) for monotherapy and combination therapy was -3.41 versus -5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated.

CONCLUSIONS:

Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.

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Estudio primario

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Año 2009
Autores Shim JH , Suh DJ , Kim KM , Lim YS , Lee HC , Chung YH - Más
Revista Hepatology (Baltimore, Md.)

Este artículo no está incluido en ninguna revisión sistemática

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Entecavir (ETV) is currently recommended as a rescue therapy purely for adefovir (ADV)-resistant chronic hepatitis B virus (HBV) infections. We evaluated the efficacy of ETV in patients who were resistant to lamivudine (LAM)/ADV sequential therapy and in those resistant to LAM monotherapy. Fifty LAM/ADV-resistant and 38 LAM-resistant patients who received ETV 1 mg/day for at least 48 weeks were enrolled. Mean baseline serum HBV DNA and alanine aminotransferase (ALT) levels were significantly lower in the LAM/ADV-resistant group, compared with the LAM-resistant group (6.90 versus 7.62 log(10) copies/mL and 102.6 versus 160.2 IU/L; both P < 0.05); hepatitis B e antigen (HBeAg) status and LAM-resistant mutation patterns were similar in the two groups. At week 48, mean reductions in HBV DNA and ALT levels were significantly less in the LAM/ADV-resistant group (-2.96 versus -4.86 log(10) copies/mL and -68.3 versus -128.9 IU/L; both P < 0.05). Achievement of undetectable HBV DNA was also less common in the LAM/ADV-resistant group (10.0% versus 34.2%; P = 0.006), although the rates of HBeAg loss and ALT normalization did not differ between the two groups. Resistance to both LAM and ADV was an independent risk factor for failure of HBV DNA negativity at week 48 (odds ratio, 0.138; P = 0.019). In both LAM/ADV-resistant and LAM-resistant groups, primary responders (> or =1 log decline in HBV DNA at week 12) achieved a significantly greater decrease in HBV DNA levels over the 48-week period, compared with primary nonresponders (-4.18 versus -0.97 and -5.37 versus -2.15 log(10) copies/mL, respectively; both P < 0.05).

CONCLUSION:

The 48-week ETV treatment was less effective in LAM/ADV-resistant than in LAM-resistant patients. Continuing ETV monotherapy could be determined based on the virological response at 12 weeks in LAM/ADV-resistant patients.

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Estudio primario

No clasificado

Año 2012
Autores Li X , Zhong C , Yang S , Fan R , Peng J , Guo Y - Más
Revista Nan fang yi ke da xue xue bao = Journal of Southern Medical University
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OBJECTIVE:

To evaluate the changes in the renal function of patients with chronic hepatitis B (CHB) receiving adefovir dipivoxil (ADV) or telbivudine (L-DT) monotherapy.

METHODS:

This retrospective analysis involved 101 patients with CHB and liver cirrhosis receiving either ADV or L-DT monotherapy for 52 weeks. Serum creatinine, estimates of glomerular filtration rate (eGFR), and the percentage of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) at week 52 were compared with the baseline data between the two groups.

RESULTS:

The mean changes of CR at week 52 from baseline were +0.05 mg/dl in ADV group and -0.12 mg/dl in L-DT group, showing a significant difference between the two groups (P=0.000). No patient was found to have an elevation of creatinine over 0.50 mg/dl. The median change of eGFR at week 52 from baseline differed significantly between ADV and L-DT groups (-4.09 vs+18.32 ml·min(-1)·1.73 m(-2), P=0.000). Ninety-two percent (12/13) of the patients with baseline eGFR<90 ml·min(-1)·1.73 m(-2) shifted to eGFR ≥90 ml·min(-1)·1.73 m(-2) after 52 weeks of L-DT treatment, as compared to 38% (3/8) in ADV group. The proportion of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) in L-DT group increased from 76.36% (42/55) at baseline to 94.55% (52/55) at week 52, while that in ADV group decreased from 82.61% (38/46) at baseline to 78.26% (36/46). The constituent ratios of eGFR at different levels were similar at baseline (P=0.443) but significantly different at week 52 between the two groups (P=0.015).

CONCLUSION:

L-DT treatment is associated with a renoprotective effect in patients with CHB, but the mechanism remains unclear.

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Revisión sistemática

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Año 2013
Autores Huang R , Hao Y , Zhang J , Wu C
Revista Hepatology research : the official journal of the Japan Society of Hepatology
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Aim: The therapeutic effect of interferon (IFN)-α plus adefovir (ADV) combination therapy versus IFN-α monotherapy in chronic hepatitis B (CHB) treatment remains under debate. The objective of the present study was to compare the efficacy between these two regimens in CHB treatment. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, National Knowledge Infrastructure, WANFANG and VIP databases were searched until 15 April 2012. All randomized controlled trials (RCT) comparing IFN-α plus ADV combination therapy versus IFN-α monotherapy for treating CHB patients were included. Review Manager ver.5.1.0 was used for meta-analysis. Results: Our results showed that the rate of undetectable serum hepatitis B virus (HBV) DNA was significantly higher in the IFN-α plus ADV combination group than in the IFN-α monotherapy group, both at 24 weeks (relative risk [RR]=1.74, 95% confidence interval [CI]=1.47-2.05, P<0.00001) and 48 weeks (RR=1.56, 95% CI=1.35-1.80, P<0.00001) of treatment and after treatment (RR=1.35, 95% CI=1.10-1.66, P=0.004). The serum hepatitis B e-antigen (HBeAg) negativation and HBeAg seroconversion rates were also higher in the combination group. However, a greater hepatitis B surface antigen loss rate was not found in the combination group. Forty-eight weeks of combination therapy improved the alanine aminotransferase normalization rate, but did not improve the rate of undetectable HBV DNA or that of HBeAg seroconversion as compared with 24 weeks of combination therapy. Conclusion: Based on the current studies, the efficacy of IFN-α plus ADV combination therapy is superior to IFN-α monotherapy. © 2013 The Japan Society of Hepatology.

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Estudio primario

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Año 2007
Revista Alimentary pharmacology & therapeutics
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BACKGROUND:

Two-thirds of the 350 million people infected with chronic hepatitis B virus live in the Asia-Pacific region. AIM To compare the effects of adefovir dipivoxil therapy between Asian and Caucasian patients with chronic hepatitis B.

METHODS:

The safety and efficacy of 10 mg of adefovir dipivoxil was compared to placebo in 501 Asian (n = 259) or Caucasian (n = 242) HBeAg+ and HBeAg- chronic hepatitis B virus patients treated for 48 weeks in two randomized, double-blind, placebo-controlled studies.

RESULTS:

At week 48, histological improvement was observed in 60% and 56% of Caucasian and Asian patients, respectively. Change in serum hepatitis B virus DNA from baseline to week 48 for the adefovir dipivoxil-treated patients was -3.89 and -3.70 log(10) copies/mL in Caucasian and Asian patients, respectively, while 34 per cent of Caucasian patients and 39 per cent of Asian patients had undetectable serum hepatitis B virus DNA (<400 copies/mL) at week 48. The percentage of patients achieving alanine aminotransferase (ALT) normalization at week 48 was similar in both groups (Caucasian 64 per cent, Asian 63 per cent). No patients developed resistance through week 48. No differences in adverse events or grade 3 or 4 laboratory abnormalities were observed between groups.

CONCLUSIONS:

There were no significant differences in treatment response between Asians and Caucasians. Adefovir dipivoxil was well tolerated and no resistance developed up to week 48 in both racial groups.

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Estudio primario

No clasificado

Año 2011
Autores Yu JH , Shi JP , Wu J , Li XO , Guo JC , Xun YH - Más
Revista Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
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To compare the efficacy and safety of Lamivudine (LAM) plus Adefovir dipivoxil (ADV) combination therapy and Entecavir (ETV) monotherapy for chronic hepatitis B patients. 120 patients with chronic hepatitis B managed in a single-centre clinical practice (median 96 weeks) were split into 2 cohorts, one was treated with de-novo combination Lamivudine (100 mg/day) plus Adefovir (10 mg/day) (LAM+ADV), the other with Entecavir (0.5 mg/day) monotherapy. Serum levels of ALT, creatinine, HBsAg, HBeAg and HBV viral load, together with genotypic resistence were analyzed at 0, 12, 24, 48, 96 weeks, respectively. HBV DNA was determined by real-time PCR. HBsAg and HBeAg were assessed by chemiluminescence. Serum levels of ALT and creatinine were detected by automatic biochemical analyzer. HBV genotypic resistence was tested by direct sequencing. (1) At the time point of 96 weeks, a total of 99 patients (51 cases in combination therapy cohort and 48 case in monotherapy cohort) were compared. The baseline characteristics as for HBV viral load, median age, serum levels of ALT and creatinine were compatible between combination therapy cohort and monotherapy cohort. (2) The rates of HBV DNA values is less than 300 copies/ml and HBV DNA values is less than 1000 copies/ml had no significant difference between LAM + ADV and ETV cohorts by the 12 and 24 weeks (P more than 0.05). (3) At the time point of 48 weeks, the rates of HBV DNA is less than 1000 copies/ml, HBeAg seroconversion, and ALT normalization were similar in both cohorts, though the rate of HBV DNA values is less than 300 copies/ml was obviously higher in combination therapy cohort than that of monotherapy cohort (90.7% vs 76%, P values is less than 0.05). (4) At the time point of 96 weeks, the rates of HBV DNA values is less than 300 copies/ml (96.1% vs 79.2%), HBV DNA values is less than 1000 copies/ml (98% vs 87.5%) and the HBeAg seroconversion (41.7% vs 16.7%) were markedly higher in combination therapy cohort than those of monotherapy cohort statistically (P values is less than 0.05 for all). The mean values of decreases for HBV viral loads and HBsAg levels were smilar in both cohorts at 48 and 96 weeks. (5) Elevated serum creatinine not be found in both cohorts at the end of treatment. (6) No virological breakthrough occurred in combination therapy cohort at the end of treatment. Four patients in monotherapy cohort were found with virological breakthrough at 96 weeks and three cases among were confirmed to be of variants associated with ETV resistance (rtL180M + T184L + M204V). Present study suggests that Lamivudine plus Adefovir dipivoxil de-novo combination therapy was more efficacious than Entecavir monotherapy for CHB patients and the tolerance is compatible.

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Resumen estructurado de revisiones sistemáticas

No clasificado

Año 2011
Autores Chen EQ , Wang LC , Lei J , Xu L
Revista Database of Abstracts of Reviews of Effects (DARE)
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CRD SUMMARY:

This well-conducted review evaluated the effectiveness of rescue combination therapy with adefovir dipivoxil plus lamivudine compared with adefovir dipivoxil monotherapy in lamivudine-resistant chronic hepatitis B patients; it found the combination of adefovir dipivoxil plus lamivudine to be superior in inhibiting hepatitis B virus replication and preventing drug resistance. This conclusion is likely to be reliable.

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