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.

Background: The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus (HBV) suppression. Objective: To compare the antiviral efficacy of telbivudine and adefovir dipivoxil, and the effects of switching from adefovir to telbivudine, in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B. Design: Randomized, controlled, open-label trial. Setting: 16 outpatient clinics. Patients: 135 treatment-naive, HBeAg-positive adults with chronic hepatitis B. Intervention: Patients were randomly assigned in a 1:1:1 ratio to 52 weeks of telbivudine (group A) or adefovir (group B), or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks (group C). One hundred thirty-one patients completed 52 weeks of treatment. Measurements: The primary efficacy comparison was serum HBV DNA reduction at week 24, with a secondary comparison at week 52. Results: At week 24, mean HBV DNA reduction was greater in group A than in pooled groups B and C (-6.30 vs. -4.97 log10 copies/mL; difference, -1.33 log10 copies/mL [95% CI, -1.99 to -0.66 log10 copies/mL]; P < 0.001), and more patients in group A were polymerase chain reaction-negative (39% vs. 12%; odds ratio, 4.46 [CI, 1.86 to 10.72]; P < 0.001). At week 52, the mean residual HBV DNA level was lower in group A and group C than in group B (3.01 log10 copies/mL [group A] and 3.02 log10 copies/mL [group C] vs. 4.00 log10 copies/mL [group B]; difference, -0.99 log10 copies/mL [CI, -1.67 to -0.32 log10 copies/mL] and -0.98 log10 copies/mL [CI, -1.64 to -0.32 log10 copies/mL]; P = 0.004). Adverse events were similar across groups; the most common were upper respiratory symptoms, headache, back pain, and diarrhea. Limitations: The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy. Conclusion: Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment. After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir. © 2007 American College of Physicians.

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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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.

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.

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.

ABSTRACT:

BACKGROUND:

Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV) and adding adefovir (ADV) or tenofovir (TFV). At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB). The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance.

METHODS:

We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs) of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT) levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD) in HBV DNA levels and safety were reviewed.

RESULTS:

Six eligible trials (451 patients in total) were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR) were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated.

CONCLUSIONS:

LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

Whether the combination of lamivudine (LAM) plus adefovir (ADV) de novo is more effective than entecavir (ETV) monotherapy in patients with HBV-associated decompensated cirrhosis is still controversial. We searched seven randomized controlled trials that included 411 patients in this meta-analysis. There are 205 and 206 patients in these two groups separately. The pooled risk ratio (RR) and mean difference (MD) were used to assess the treatment effects. ETV monotherapy significantly improved Child-Turcotte-Pugh (CTP) scores (MD = 0.33, 95%CI [0.21-0.44], P < .00001), and was associated with lower rates of serum creatinine increase compared LAM + ADV combination therapy (RR = 4.76, 95%CI [1.11-20.33], P = .04) at 48 weeks. The reduction of alanine aminotransferase (ALT) levels, HBV DNA levels, the rate of ALT normalization, undetectable HBV DNA, HBV e antigen (HBeAg) loss, HBeAg seroconversion and mortality were similar between the two groups. ETV is more effective than LAM + ADV in improving CTP scores at 48 weeks. Both of the LAM + ADV and ETV had similar efficacy in improving virological and biochemical parameters at 48 weeks of follow-up. Furthermore, use of these agents in decompensated HBV patients was generally safe and well tolerated at 48 weeks. However, the nephrotoxicity of ADV, and the potential adverse effects of ETV should be considered and monitored during prolonged therapy.