【Abstract】ObjectiveTo investigate the prophylactic effect of lamivudine monotherapy on the recurrence of hepatitis B after liver transplantation. MethodsThirtyone patients with hepatitis B related benign decompensated cirrhosis who underwent liver transplantation between February 1999 to June 2002 and survived more than 3 months were analyzed retrospectively. Lamivudine was administered to each patient after operation and some patients before operation for the prophylaxis of HBV recurrence. The HBV markers and HBV DNA in serum and bioptic liver tissues in all patients were evaluated before and after operation. ResultsTotal HBV recurrence rate was 19.4％（6/31） during average 38.2 months (3.2-70.2 months) follow up. HBV recurrence rate was 7.1％(2/28), 16.0％(4/25), 26.1％(6/23) and survival rate was 87.1％(27/31), 80.6％(25/31), 66.1％(20.5/31) after 1-, 3-and 5-year, respectively. One hundred milligram lamivudine administration peroral daily for 2 weeks prior to transplantation enable HBeAg 54.5％(6/11) and HBV DNA 50.0％(5/10) positive patients convert to negative respectively. ConclusionPreoperative administration of lamivudine monotherapy can effectively prevent allograft from HBV re-infection after liver transplantation. Lamivudine should be used to convert HBV DNA and HBeAg to negative.
Objective To assess the efficacy of lamivudine in patients with HBeAg positive chronic hepatitis B.Methods MEDLINE, SCI, Current Content Connect, The Cochrane Library, and Chinese Biomedical Database were searched from the beginning to September 2005, and the references of eligible studies were manually screened. R.andomized controlled trials comparing lamivudine with non-antiviral interventions （ placebo, no treatment and standard care ） in patients with chronic hepatitis B were eligible for inclusion. Two investigators independently assessed the quality and extracted the data. Heterogeneity was examined by Chi-square test. Fixed and random effect meta-analysis were used to pool the data. Subgroup analyses were used in treatment course. Results Eleven R.CTs were included （ n = 1 237 ）. All reported the effect of lamivudine （100 mg/d） , and one of them included lamivudine （25 mg/d）. The treatment duration of 52 weeks and less than 26 weeks were reported in eight and three RCTs, respectively. Six RCTs adequately applied randomization, while other five RCTs were not reported in detail. Four RCTs adequately enforced allocation concealment, five RCTs enforced blinding bitterly. The others were not reported in detail. It was found by meta-analysis that, compared with the control, lamivudine （100 mg/d, 52 W） could significantly clear HBeAg [42.6% vs. 13% , RR 3.20, 95% CI （2.33, 4. 38）] and clearHBVDNA [71.78% vs. 20, 36%, RR3.42, 95%CI （2.80,4.19）], normalize ALT [65% vs. 34.9%, RR1.91, 95%CI （1.64,2.21）], achieve HBeAgseroconversion [16.1% vs. 7.29% , RR2.12, 95%CI （1.24,3.80） ] and histology response [57. 9% vs. 26.2%, RR 2. 17, 95% CI （ 1.67,2.81 ） ] ; Lanfivudine （100 mg/ d, 12 W） could effectively clear HBV DNA [ 50.7% vs 3.92% , RR 8.68, 95% CI （1.72,43.74 ） ] , but was not effective in loss of HBeAg, HBeAg seroconversion and normalization of ALT, Lamivudine （25 mg/d） could effectively clear HBV DNA [97.7% vs. 22.2% , RR 4.41, 95% CI （2.86,6.79） ] and improve histology response [59.3% vs. 30% , RR1.98, 95% CI （1.31,2.99 ） ], but was not effective in HBeAg seroconversion. Conclusions Lamivudine （100 mg/ d） is effective in clearing HBV DNA and HBeAg, normalizing ALT and achieving HBeAg seroconversion.
ObjectiveTo systematically review the efficacy of lamivudine (LAM) plus adefovir (ADV) versus entecavir (ETV) monotherapy for LAM-resistant chronic hepatitis B patients. MethodsWe electronically searched databases including PubMed, The Cochrane Library (Issue 12, 2013), CBM, CNKI, VIP, WanFang Data from their inception to December 2013, to collect randomized controlled trials (RCTs) or cohort studies of LAM+ADV versus ETV for LAM-resistant chronic hepatitis B. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 software. ResultsA total of 13 RCTs and 5 cohort studies involving 1 336 patients were included. The results of meta-analyses of RCTs showed that:there were no significant differences between the LAM+ADV group and the ETV group in the negative rates of serum HBV-DNA (RR=1.00, 95%CI 0.91 to 1.10, P=0.94), HBeAg (RR=0.90, 95%CI 0.70 to 1.17, P=0.43), serum ALT recovery rate (RR=0.97, 95%CI 0.90 to 1.05, P=0.45) and serum HBeAg conversion rate (RR=0.71, 95%CI 0.40 to 1.24, P=0.22) at the 48th week. The results of meta-analyses of cohort studies showed that:there were no significant differences between the two groups in the negative rates of serum HBV-DNA (RR=1.37, 95% CI 0.91 to 2.06, P=0.13) and serum ALT recovery rate (RR=0.99, 95%CI 0.87 to 1.12, P=0.87), but the ETV group had higher serum HBeAg conversion rate (RR=0.24, 95% CI 0.07 to 0.79, P=0.02). ConclusionCurrent evidence shows that the efficacy of LAM+ADV is similar to ETV at the 48th week for LAM-resistant chronic hepatitis B patients. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To investigate the prevention of HBV reinfection in the perioperative period of liver transplantation on HBV-related diseases． Methods Published papers were collected and reviewed． Results HBV-related diseases were the main indications of liver transplantation．The prevention for HBV reinfection affects the survivals remarkably. Nowadays, a lot of medication have been used in the prevention of HBV reinfection， and the therapeutic regimens were different from each other. Conclusion Liver transplantation is an effective treatment for HBV-related disease． Appropriate prevention of HBV reinfection in the perioperative period of liver transplantation is important for the survivals of patients．
Objective To evaluate the effectiveness of combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG) versus LAM monotherapy in prevention of hepatitis B virus recurrence after liver transplantation. Methods Databases including MEDLINE (Ovid), PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CBM, VIP, and CNKI were searched up to Dec. 2008. Clinical trials including randomized controlled, non-randomized concurrent-control and case-control studies about combination therapy with HBIG and LAM versus LAM monotherapy in prevention of hepatitis B virus recurrence after liver transplantation were screened. Trial selection and data extraction were conducted by two reviewers independently. Meta-analysis was performed using RevMan 5.0.18 software. Results Eleven non-randomized concurrent-control studies involving 1 421 patients (1 035 patients in combination therapy group, and 386 patients in LAM monotherapy group) were included. The results of meta-analyses showed: Compared with LAM monotherapy group, the risks of hepatitis B virus recurrence, YMDD mutation, and death associated with HBV recurrence were significantly reduced by 73% (RR=0.27, 95%CI 0.20 to 0.37, Plt;0.000 01), 72% (RR=0.28, 95%CI 0.15 to 0.53, P=0.000 01), and 79% (RR=0.21, 95%CI 0.09 to 0.49, P=0.000 3) respectively in combination therapy group after liver transplantation; overall survival rates of both recipients and grafts in combination therapy group were similar to LAM monotherapy group (RR=1.03, 95%CI 0.95 to 1.11, P=0.51; RR=1.04, 95%CI 0.97 to 1.12, P=0.26). Conclusion Current evidence indicates that compared with LAM monotherapy, combination therapy with LAM and HBIG could reduce the risks of hepatitis B virus recurrence, YMDD mutation, and death associated with HBV recurrence after liver transplantation.
ObjectiveTo systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients. MethodsWe electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05). ConclusionCurrent evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To evaluate the efficacy and safety of antiviral drugs for hepatitis B with YMDD motif variant. Methods We electronically searched MEDLINE (1989-April, 2004), EMBASE (1989-April, 2004), CBMdisc (expand) (1989-April, 2004), and handsearched unpublished Chinese conference proceedings. Randomized and quasi-randomized trials in patients with chronic hepatitis B with YMDD motif variant correlative to lamivudine were collected. Two reviewers extracted the data and assessed the quality of literature independently. The data were then analyzed by RevMan 4.2 software. Results Five studies involving 6 trials and 284 patients were included. According to the results of meta-analysis, antiviral therapy with adefovir plus lamivudine showed significantly better effects on the clearance of serum HBV-DNA and HBeAg and normalization of ALT than that of lamivudine alone (RR 16.61, 95%CI 2.29 to 120.71; RR 6.66, 95%CI 1.23 to 35.88 and RR 6.26, 95%CI 2.29 to 17.12 respectively); also, oxymatrine plus thymothin showed obviously better effects on the clearance of serum HBV-DNA and HBeAg (RR 2.96, 95%CI 1.26 to 6.93 and RR 2.51, 95%CI 1.05 to 5.98 respectively).But adefovir alone showed no better effects on clearance of serum HBV-DNA and HBeAg than that of lamivudine alone (RR 11.00, 95%CI 0.65 to 186.02 and RR 7.00, 95%CI 0.39 to 126.92 respectively); interferon plus lamivudine showed no better effects on the clearance of serum HBV-DNA, HBeAg and the normalization of ALT (RR 3.50, 95%CI 0.90 to 13.58; RR 4.90, 95%CI 0.70 to 35.10 and RR 2.80, 95%CI 0.91 to 8.12 respectively). Chinese herbs plus lamivudine showed no better effects on the clearance of serum HBV-DNA (RR 1.16, 95%CI 0.89 to 1.51). There were no significant side effects in the groups, except flu like symptom in the interferon group, slight kidney impairment in the adefovir group, and aggravation of rare cases in lamivudine group. Conclusions Antiviral therapy with adefovir plus lamivudine, or oxymatrine plus thymothin, shows better effects than with lamivudine alone in terms of antiviral therapy and clinical outcome improvement. However, the evidence is too weak to draw a definite conclusion in this systematic review. Larger sample size and rigorously designed randomized, double blind, placebo control trials are required for future study.
Objective To assess the effectiveness and safety of combination therapy of zidovudine and lamivudine (ZDV+3TC) for preventing mother-to-child transmission (MTCT) of HIV. Methods A systematic review of randomized controlled trials (RCTs) was conducted using the methodology of The Cochrane Collaboration. PUBMED, EMBASE, CINAHL, AIDSearch, AIDSLINE, AIDSTRIALS, The Cochrane Library (Issue 2, 2007), AIDSDRUGS, AIDSinfo, CRD (Center of Review and Dissemination) databases and three Chinese Databases (CBM, CNKI, VIP) were searched from their establishment to 31 May 2007. We also searched documents of governmental and non-governmental organizations (NGOs), and the proceedings of relevant conferences, including the International AIDS Conferences, and the annual Conference on Retroviruses and Opportunistic Infections. RCTs assessing the effects of ZDV+3TC for preventing MTCT were included. Trial selection, quality assessment and data extraction were done by two reviewers independently. Different opinions were resolved by discussion with a third party. Meta-analyses were conducted using The Cochrane Collaboration’s RevMan 4.2.9 software. Results Three studies in breastfeeding populations were included. One trial (PETRA, 1797 participants) found that ZDV+3TC decreased the risk of transmission by 35%-65% within 15 months compared with placebo. However, there was no evidence that ultra-short course ZDV+3TC (during labor) decreased the risk of transmission, compared with placebo. The safety of different courses of ZDV+3TC and placebo were similar (Pgt;0.05). Another trial (SAINT, 1317 participants) found that short course ZDV+3TC (from 36weeks gestation to labor) did not significantly reduce HIV infection among children at 8 weeks after delivery, when compared with single dose nevirapine given to the mother and the infant (Pgt;0.05). No significant difference was found in the maternal and infants mortality and side effects of two groups. One small trial (Moodley1998, 20 participants) found no infant infection in both ZDV+3TC and 3TC alone within 2 weeks after birth. Conclusions Long course (from 36 weeks gestation to 1 week after delivery) and short course (from 36 weeks gestation to labor) ZDV+3TC were more effective than placebo in preventing MTCT of HIV in breastfeeding women with a similar safety profile. Short course ZDV + 3TC had similar effects to single dose nevirapine, and long course ZDV + 3TC had similar effects to lamivudine alone.
Objective To systematically review the effectiveness and safety interferon-α (IFN-α) combined with lamivudine vs. IFN-α alone in treating children with Hepatitis B. Methods Such databases as The Cochrane Library, PubMed, EMbase, Web of Science, CBM, CNKI, VIP and WanFang Data were electronically searched for randomized controlled trials (RCTs) on IFN-α combined with lamivudine in treating children with hepatitis B. Two reviewers screened literature, extracted data, and assessed the methodological quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results 8 RCTs were included, with comparable baseline. The results of meta-analysis showed that, compared to the IFN-α alone group, the combined therapy group had higher negative rates of serum HBV-DNA and HBeAg. There was no significant difference in the positive rate of anti-Hbe and the incidence of adverse reaction between the two groups. Conclusion Current evidence shows that IFN-α combined with lamivudine was more effective than IFN-α alone in treating children’s hepatitis B.
ObjectiveTo investigate the efficacy of lamivudine combined with low-dose hepatitis B immune globulin to prevent HBV reinfection after liver transplantation. MethodsThe clinical data of 76 cases of HBV-related liver disease after liver transplantation using lamivudine combined with low-dose hepatitis B immune globulin to prevent HBV re-infection were retrospectively analyzed, and the HBV re-infection risk factors were analyzed. ResultsSeventy-six patients' HBsAg became negative after liver transplantation, HBV re-infect in 9 cases.The re-infection rate was 9.2% (7/76) and 11.8% (9/76), respectively, in 1-year and 2-year after liver transplantation. ConclusionsLamivudine combined with low-dose hepatitis B immune globulin after liver transplantation can be effective preventing re-infection with HBV.HBeAg positive and HBV-DNA positive before liver transplantation is risk factors of HBV re-infection.