拉米夫定联合胸腺肽α1治疗慢性乙型肝炎疗效分析

目的比较拉米夫定联合胸腺肽α1与单独应用拉米夫定治疗慢性乙型肝炎(CHB)患者的临床疗效。方法选择52例CHB患者,采用完全随机、对照的方法分成两组。联合治疗组26例,应用拉米夫定100 mg/d,口服,观察疗程18月,胸腺肽α1 1.6 mg/次,皮下注射,2次/周,连续6月;对照组仅给拉米夫定100 mg/d,口服,观察疗程疗18月。结果治疗后12月、18月时,联合治疗组HBV-DNA转阴率、HBeAg、抗-HBe转换率及ALT复常率与拉米夫定组有明显差异性(P<0.05)。结论拉米夫定联合胸腺肽α1治疗CHB患者的疗效优于单用拉米夫定。

阿德福韦酯联合拉米夫定治疗肝硬化失代偿期的近期疗效观察

目的:观察阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期患者的近期疗效。方法:将20例HBV-DNA阳性肝硬化失代偿期患者随机分为二组:拉米夫定治疗组,阿德福韦酯、拉米夫定联合治疗组。治疗前后分别进行生化指标及HBV-DNA定量检测。结果:阿德福韦酯联合拉米夫定治疗组在肝脏生化指标改善及存活率方面均优于对照组,差异有显著性(P<0.05)。结论:阿德福韦酯、拉米夫定联用可发挥优势互补作用,对乙肝肝硬化失代偿期患者的近期疗效更满意。

奈韦拉平齐多夫定拉米夫定复方混悬剂的研究

利用高效液相色谱法对一种奈韦拉平齐多夫定拉米夫定复方抗艾滋病药物口服混悬液进行原辅料相容性、处方筛选、稳定性考察,实验结果表明,该制剂稳定性好,易吸收,主药含量符合要求,加速实验和稳定性实验结果良好。

替诺福韦＋依曲西他滨＋依非韦伦与齐多夫定＋拉米夫定＋依非韦伦两种治疗HIV方案的疗效比较

Johns Hopkins大学医学院的Gallant带领934人组成的研究小组对517例自愿随机接受两种不同方案治疗的HIV感染者的疗效给予了评估。所有患者以前均从未接受抗逆转录病毒治疗，随机分为两组，Ⅰ组接受替诺福韦（tenofovir disoproxil fumarate）、依曲西他滨（emtricitabine）、依非韦伦（efavirenz）每日一次的治疗，Ⅱ组每日2次服用固定剂量的齐多夫定（zidovudine）和拉米夫定（lamivudine），外加每日一次依非韦伦。

肝移植术后替米夫定联合乙肝免疫球蛋白预防乙肝复发的研究

目的:评价在肝移植后替米夫定联合乙肝免疫球蛋白(HBIG)预防乙肝复发的临床疗效和安全性。方法:68例肝移植患者分为2组:32例患者应用拉米夫定联合HBIG预防预防乙肝的复发;36例患者应用替米夫定联合HBIG预防。观察两组患者用药干预后体内乙肝病毒DNA拷贝数(HBV DNA)、乙肝表面抗原(HBsAg)、乙肝E抗原(HBeAg)的变化以及用药过程中的不良反应。结果:拉米夫定联合HBIG组有4例患者在随访期间复发乙肝,复发率为12.5%,而替米夫定联合HBIG组未见患者复发乙肝。两组患者在治疗过程中均未见到明显的药物引起的不良反应。结论:替米夫定联合HBIG在肝移植术后预防乙肝复发中的临床疗效显著、安全性好,具有推广价值。

拉米夫定联合苦参素治疗慢性乙型肝炎临床观察

目的:观察拉米夫定联合苦参素治疗慢性乙型肝炎的疗效。方法:将慢性乙型肝炎分为2组:治疗组服用拉米夫定联合苦参素,对照组单独服用拉米夫定,并观察肝功能情况和肝纤维化指标情况。结果:通过治疗,治疗组肝功能好转情况,HBeAg/抗HBe阴转率,肝纤维化好转情况均优于对照组。结论:苦参素与拉米夫定联合治疗可以促进肝功能恢复正常,明显提高抗病毒疗效,降低肝纤维化指标值。

不同一线ART治疗方案治疗艾滋病的抗病毒效果分析

目的探讨不同一线艾滋病抗病毒治疗(ART)治疗方案对艾滋病的抗病毒作用。方法抽取我院2005年2月—2018年2月经治的80例艾滋病感染者为研究对象,根据治疗方式分为两组。对照组采用替诺福韦+拉米夫定+奈韦拉平,给予观察组齐多夫定+拉米夫定+依非韦伦治疗方案,比较两组治疗效果。结果两组治疗3个月、6个月和9个月时CD4+淋巴细胞计数差异无统计学意义(P> 0.05),同组不同时间段对应指标对比,差异具有统计学意义(P <0.05);对照组治疗3个月、6个月和9个月后的转阴率对比,差异无统计学意义(P> 0.05)。结论不同一线ART治疗方案治疗艾滋病效果明显。

HEPATOLOGY WATCH最新报道（2004年12月）——第55届美国肝病年会汇编

HBV感染恩替卡韦与拉米夫定已报道的两项Ⅲ期研究结果显示，恩替卡韦优于拉米夫定。第一项研究是由DanielShotrva等在648名HBeAg(一)的慢性乙肝患者中进行的一项多中心的双盲试验，这些患者随机接受恩替卡韦0．5r11g／日或拉米夫定100mg／日，持续48周。

A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus

AIM： To determine the therapeutic effect of lamivu- dine in late pregnancy for the interruption of motherto-child transmission （MTCT） of hepatitis B virus （HBV）. METHODS： Studies were identified by searching available databases up to January 2011. Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials （RCTs） with lamivudine treatment in late pregnancy, and newborns or infants whose serum hepatitis B surface antigen （HBsAg）, hepatitis B e antigen （HBeAg） or HBV DNA had been documented. The relative risks （RRs） for inerruption of MTCT as indicated by HBsAg, HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval （CI） to estimate the efficacy of lamivudine treatment. RESULTS： Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis. The overall RR was 0.43 （95% CI, 0.25-0.76; 8 RCTs; Phet- erogeneity= 0.04） and 0.33 （95% CI, 0.23-0.47; 6 RCTs; Pheterogeneity = 0.93） indicated by newborn HBsAg or HBV DNA. The RR was 0.33 （95% CI, 0.21-0.50; 6 RCTs; Pheterogeneity = 0.46） and 0.32 （95% CI, 0.20-0.50; 4 RCTs; Pheterogeneity = 0.33） indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth. The RR （lamivudine vs hepatitis B immunoglobulin） was 0.27 （95% CI, 0.16-0.46; 5 RCTs; Pheterogeneity = 0.94） and 0.24 （95% CI, 0.07-0.79; 3 RCTs; Pheterogeneity = 0.60） indicated by newborn HBsAg or HBV DNA, respectively. In the mothers with viral load 〈 106 copies/mL after lamivudine treatment, the efficacy （RR, 95% CI） was 0.33, 0.21-0.53 （5 RCTs; Pheterogeneity = 0.82） for the interruption of MTCT, however, this value was not significant if maternal viral load was 〉 106 copies/mL after lamivudine treatment （P = 0.45, 2 RCTs）, as indicated by newborn serum HBsAg. The RR （lamivudine initiated from 28 wk of gestation vs control） was 0.34 （95% CI, 0.22-0.52; 7 RCTs; Pheterogeneity = 0.92） and 0.33 （95% CI, 0.22-0.50; 5 RCTs; Pheterogeneity = 0.86） indicated by newborn HBsAg or HBV DNA. The incidence of adverse effects of lamivudine was not higher in the mothers than in controls （P = 0.97）. Only one study reported side effects of lamivudine in newborns. CONCLUSION： Lamivudine treatment in HBV carrier- mothers from 28 wk of gestation may interrupt MTCT of HBV efficiently. Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT. HBV MTCT might be interrupted efficiently if maternal viral load is reduced to 〈 106 copies/mL by lamivudine treatment.

Long-term alpha interferon and lamivudine combination therapy in non-responder patients with anti-HBe-positive chronic hepatitis B:Results of an open,controlled trial

AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.

TT virus infection in patients with chronic hepatitis B and response of TTV to lamivudine

AIM: To investigate the responses of TT virus (TTV) and hepatitis B virus (HBV) to a long-term lamivudine therapy.METHODS: Sixteen patients infected with both TTV and HBV were treated with lamivudine 100 mg daily for 30 months. Blood samples were drawn at the beginning of the therapy and subsequently at month 3, 6, 9, 12 and 30.Serum TTV was quantified by real time PCR and serum HBV was detected by hybridization assay and nested polymerase chain reaction.RESULTS: TTV infection was detected in 100 % of HBV-infected patients. Loss of serum TTV DNA after one year of treatment occurred in 1/16 (6 %) patients. At the end of therapy, TTV DNA was positive in 94 % of them. The decline of HBV viremia was evident at 3 months after therapy and the response rate was 31%, 44 %, 63 %, 50 % and 50 %at month 3, 6, 9, 12 and 30, respectively.CONCLUSION: TTV replication is not sensitive to lamivudine and is highly prevalent in HBV-infected patients.

Safety of lamivudine treatment for chronic hepatitis B in early pregnancy

AIM:To evaluate the safety of lamivudine(LAM) treatment for chronic hepatitis B in early pregnancy.METHODS:A total of 92 pregnant women who received LAM treatment either before pregnancy or in early pregnancy were enrolled in this study.All of the pregnant women volunteered to take lamivudine during pregnancy and were not co-infected with hepatitis C virus,human immunodeficiency virus,cytomegalovirus,or other viruses.All infants received passiveactive immunoprophylaxis with 200 IU hepatitis B immunoglobulin and three doses of 10 μg hepatitis B vaccines(0-1-6 mo) according to the guidelines for the prevention and treatment of chronic hepatitis B.Adverse events were observed throughout the entire pregnancy and perinatal period,and the effectiveness of lamivudine treatment for blocking mother-to-infant transmission of hepatitis B virus(HBV) was evaluated.All adverse events in mothers and infants during pregnancy and the perinatal period and the HBV motherto-infant transmission blocking rate were compared with the literature.RESULTS:Among the 92 pregnant women,spontaneous abortions occurred in 11 cases,while 3 mothers had a second pregnancy after the initial abortion;72 mothers delivered 73 live infants,of whom 68 infants were followed up for no less than 6 mo,and 12 mothers were still pregnant.During pregnancy,the main maternal adverse events were vaginitis(12/72,16.7%),spontaneous abortion(11/95,11.6%),and gestational diabetes(6/72,8.3%);only one case had 1-2 degree elevation of the creatine kinase level(195 U/L).During the perinatal period,the main maternal adverse events were premature rupture of the membranes(8/72,11.1%),preterm delivery(5/72,6.9%),and meconium staining of the amniotic fluid(4/72,5.6%).In addition,2 infants were found to have congenital abnormalities;1 had a scalp hemangioma that did not change in size until 7 mo,and the other had early cerebral palsy,but with rehabilitation training,the infant's motor functions became totally normal at 2 years of age.The incidence of adverse events among the mothers or abnormalities in the infants was not higher than that of normal mothers or HBV-infected mothers who did not receive lamivudine treatment.In only 2 cases,mother-to-infant transmission blocking failed;the blocking rate was 97.1%(66/68),which was higher than has been previously reported.CONCLUSION:Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 wk or throughout the entire pregnancy.

Combination of small interfering RNA and lamivudine on inhibition of human B virus replication in HepG2.2.15 cells

AIM: To observe the inhibition of hepatitis B virus (HBV) replication and expression by combination of siRNA and lamivudine in HepG2.2.15 cells. METHODS: Recombinant plasmid psil-HBV was constructed and transfected into HepG2.2.15 cells. The transfected cells were cultured in lamivudine-containing medium (0.05 μmol/L) and harvested at 48, 72 and 96 h. The concentration of HBeAg and HBsAg was determined using ELISA. HBV DNA replication was examined by real- time PCR and the level of HBV mRNA was measured by RT-PCR. RESULTS: In HepG2.2.15 cells treated with combination of siRNA and lamivudine, the secretion of HBeAg and HBsAg into the supernatant was found to be inhibited by 91.80% and 82.40% (2.89 ± 0.48 vs 11.73 ± 0.38, P < 0.05; 4.59 ± 0.57 vs 16.25 ± 0.48, P < 0.05) at 96 h, respectively; the number of HBV DNA copies within culture medium was also significantly decreased at 96 h (1.04 ± 0.26 vs 8.35 ± 0.33, P < 0.05). Moreover, mRNA concentration in HepG2.2.15 cells treated with combination of siRNA and lamivudine was obviously lower compared to those treated either with siRNA or lamivudine (19.44 ± 0.17 vs 33.27 ± 0.21 or 79.9 ± 0.13, P < 0.05). CONCLUSION: Combination of siRNA and lamivudine is more effective in inhibiting HBV replication as compared to the single use of siRNA or lamivudine in HepG2.2.15 cells.

Treatment strategies using adefovir dipivoxil for individuals with lamivudine-resistant chronic hepatitis B

AIM:To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil(adefovir) in patients with lamivudine-resistant chronic hepatitis B.METHODS:We included 154 consecutive patients in two treatment groups:the "add-on" group(n = 79),in which adefovir was added to ongoing lamivudine treatment due to lamivudine resistance,and the "switch/combination" group(n = 75),in which lamivudine was first switched to adefovir and then re-added later as needed.The "switch/combination" group was then divided into two subgroups depending on whether participants followed(group A,n = 30) or violated(group B,n = 45) a proposed treatment strategy that determined whether to add lamivudine based on the serum hepatitis B virus(HBV) DNA levels(< 60 IU/mL or not) after 6 mo of treatment(roadmap concept).RESULTS:The cumulative probability of virologic response(HBV DNA < 60 IU/mL) was higher in group A than in the "add-on" group and in group B(P < 0.001).In contrast,the cumulative probability of virologic breakthrough was lower in the "add-on" group than in group B(P = 0.002).Furthermore,the risk of virologic breakthrough in the multivariate analysis was significantly lower in the "add-on" group than in group A(hazard ratio = 0.096;95%CI,0.015-0.629;P = 0.015).CONCLUSION:The selective combination of adefovir with lamivudine based upon early treatment responses increased the odds of virologic breakthrough relative to the use of uniform combination therapy from the beginning of treatment.

Lamivudine treatment enabling right hepatectomy for hepatocellular carcinoma in decompensated cirrhosis

A 69-year-old man was admitted to our hospital in October 2003,for further examination of two liver tumors.He was diagnosed with hepatocellular carcinoma(HCC) arising from decompensated hepatitis B virus(HBV)-related cirrhosis.Long-term lamivudine administration improved liver function dramatically despite repeated treatment for HCC.His Child-Pugh score was 9 points at start of lamivudine treatment,improving to 5 points after 1 year.His indocyanine green at 15 min after injection test score was 48%before lamivudine treat-ment,improving to 22%after 2 years and to 5%after 4 years.Radiofrequency ablation controlled the HCC foci and maintained his liver function.In April 2009,abdominal computed tomography revealed a tumor thrombus in the right portal vein.Since his indocyanine green test results had improved to less than 10%,we performed a right hepatectomy,which was successful.To our knowledge,there have been no documented reports of patients undergoing successful right hepatectomy for HCC arising from decompensated cirrhosis.The findings observed in our patient indicate the importance of nucleoside analogs for treating HBV-related HCC.

Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

AM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs2, P= NS; groups 1 vs 3, P= 0.002; groups 1 vs4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P - NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02; groups 1 vs 3, P= NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

Relationship between serum b2-microglobulin levels and virological breakthrough in HBeAg-negative chronic hepatitis B patients,under long-term treatment schedules including lamivudine

AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB.RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3±2.6 vs 3.8±3.4 mo,P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03).CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment,compared to baseline ones, might be a predictor of risk for VB.

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus:A case report

We present a case of fetal liver failure caused by the activation of larnivudine-resistant hepatitis B virus （HBV） nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decornpensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase （ALT） decreased transiently. However, after the start of m-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtLSOI/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtLSOI/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D

AIM: To determine the distribution of viral genotypes for primary or acquired lamivudine resistance. METHODS: A total of 283 patients with chronic hepatitis B virus (HBV) infection (245 patients with chronic hepatitis B and 38 inactive hepatitis B surface antigen carriers) were included in the study. The HBV geno-type was determined by using quantitative real-time polymerase chain reaction and sequence analysis, and tyrosine-methionine-aspartate-aspartate (YMDD) motif mutations were determined using the reverse transcriptase hybridization method. RESULTS: Lamivudine resistance was determined in a total of 25 (10.7%) chronic hepatitis B patients. Eight subjects (4%) had primary resistance to lamivudine, and 17 (53.1%) had secondary resistance to lamivudine. Genotype D, which was isolated from 267 of the patients with chronic HBV infection, was the dominant genotype in Turkey. CONCLUSION: Identification of YMDD motif mutations should have a positive impact on the selection of proper antiviral medication for patients, even for those who are nucleoside nave.