抗乙肝病毒治疗对乙肝相关性肝癌行TACE术后复发转移与免疫功能的影响

分析乙肝相关性肝癌行TACE术后应用抗乙肝病毒治疗对复发转移与免疫功能的影响。方法 将选取于2022年2月-2024年2月接受TACE手术的60例乙肝相关性肝癌患者结合其术后治疗方法分为两组。对照组行常规治疗;观察组行常规+抗乙肝病毒治疗。评估两组疗效与复发概率。结果 术后当天,两组CD4+等指标水平相当,P>0.05;术后4周,观察组各项指标改善明显,CD4+、CD4+/CD8+与自然杀伤细胞较高,CD8+较低,P<0.05。术后4周,观察组天门东氨酸氨基转移酶等均有所下降,低于对照组,P<0.05。观察组术后复发概率较低,疗效显著,P<0.05。结论 乙肝相关性肝癌患者治疗环节,若患者符合TACE手术指征且接受手术疗法,术后,对其行抗乙肝病毒治疗,可有效提升治疗效果,降低患者复发转移风险,优化患者免疫功能指标,提升患者肝功能恢复水平。

预防性抗乙肝病毒治疗对减少结核病合并乙肝患者抗结核药物性肝损伤发生的临床价值分析

目的:探究预防性抗乙型肝炎病毒(hepatitis B virus,HBV)治疗对减少结核病合并乙肝患者抗结核药物性肝损伤(anti-tuberculous drug-induced liver injury,ATB-DILI)发生的临床价值。方法:选取2021年1月—2023年1月浏阳市人民医院158例初治肺结核合并乙肝患者作为研究对象,根据HBV-DNA水平,将其分为阴性组(HBV-DNA<100 IU/mL)、阳性组(HBV-DNA≥100 IU/mL),将阳性组进一步分为低病毒载量组(HBV-DNA为100~<2×106 IU/mL)、高病毒载量组(HBV-DNA≥2×106 IU/mL),将各组患者按随机数字表分为预防性抗HBV治疗组、对照组,分别命名为A1组(阴性对照组)、A2组(阴性治疗组)、B1组(低病毒对照组)、B2组(低病毒治疗组)、B3组(高病毒对照组)和B4组(高病毒治疗组);所有患者均接受规范抗结核和保肝药物治疗,治疗组另接受抗HBV药物治疗,比较各组患者在抗结核治疗过程中肝损伤的发生情况。结果:阳性对照组的肝损伤发生率高于阴性对照组(P<0.05);阴性对照组患者的肝损伤发生率为31.11%高于阴性治疗组为9.09%(P<0.05);阳性对照组患者的肝损伤发生率为68.57%高于阳性治疗组为20.00%(P<0.05);按病毒载量分层的对照组、治疗组肝损伤发生情况为,HBV阴性、低病毒载量、高病毒载量的治疗组患者肝损伤发生率均低于同级别病毒载量对照组患者(P<0.05);对照组患者HBV阳性重度肝损发生率明显高于HBV阴性重度肝损发生率(P<0.05);HBV阴性、经预防性抗HBV治疗的患者中度肝损伤发生率降低(P<0.05);HBV阳性和经预防性抗HBV治疗的患者重度肝损伤发生率降低(P<0.05);治疗组肝损伤的患者最高血清丙氨酸转氨酶、天冬氨酸转氨酶值均明显低于对照组(P<0.05)。结论:结核病合并乙肝患者的HBV载量越高,肝损伤发生率越高,肝损伤严重程度越重;预防性抗HBV治疗可降低肝损伤发生率,预防严重肝损伤的发生;结核病合并乙肝患者在抗结核治疗过程中HBV可反弹出现HBV再激活;预防性抗HBV治疗能有效抑制HBV再激活;结核病合并乙肝患者在抗结核治疗过程中,肝损伤发生时间集中在2个月内,肝损伤恢复时间集中在0.5~1个月。

抗乙肝病毒药不是万能灵药

在临床上总能遇到这样的患者，他们在接受抗乙肝病毒药物治疗后，效果不是很理想，就开始怀疑药物究竟有没有用。目前被国内外专家公认的疗效确切的抗乙肝病毒药只有α干扰索和口服系列核苷类药物（拉米夫定、阿德福韦、替比夫定、恩替卡韦），但即使应用了抗乙肝病毒药物，也确实有治疗失败的患者，主要问题有以下几方面：

γ干扰素血清浓度对肺结核合并HBV感染患者选择性抗病毒治疗的临床意义

目的探讨采用监测γ干扰素(IFN-γ)血清浓度指导肺结核合并乙型肝炎病毒(HBV)感染患者抗病毒治疗的临床意义。方法对156例肺结核合并HBV感染患者治疗前检测的IFN-γ血清浓度与肝脏炎症活动度半定量积分(SSS)进行相关分析,并依据IFN-γ血清浓度水平及是否接受恩替卡韦抗病毒治疗将受试者分为A组(高IFN-γ血清浓度加用恩替卡韦抗病毒治疗)、B组(高IFN-γ血清浓度)及C组(低IFN-γ血清浓度)。所有肺结核合并HBV感染患者均给予优化抗结核方案(2HTE(S)Lfx/4HT)治疗。结果患者IFN-γ血清浓度与SSS评分呈正相关(r=0.6158,P<0.05),HBV-DNA定量与SSS无相关性(r=0.3265,P>0.05)。A组治疗后,HBV-DNA定量及IFN-γ血清浓度较治疗前明显下降;肝功能损害程度、HBV-DNA定量及IFN-γ血清浓度均明显低于B组(均P<0.01);HBV-DNA定量明显低于C组(P<0.01),但肝功能水平及IFN-γ血清浓度水平与C组比较差异无统计学意义(均P>0.05)。B组治疗后,肝功能损害程度、HBV-DNA定量及IFN-γ浓度均明显高于C组(P<0.01);乙肝再激活率较C组明显升高(P<0.01)。结论 IFN-γ浓度能反映肝脏炎症活动程度,对于高IFN-γ血清浓度的肺结核合并HBV感染患者进行抗结核治疗同时给予恩替卡韦抗病毒治疗,能有效降低肝功能损害率及损害程度,而对低IFN-γ血清浓度患者不进行抗病毒治疗仍有较高的安全性,在肝脏穿刺病理检查困难的条件下,IFN-γ血清浓度有望为此类患者抗结核治疗过程中是否选择抗病毒治疗提供临床依据。

自拟清热化湿疏肝汤治疗乙肝肝硬化(湿热内蕴证)的临床疗效观察

目的:探讨分析自拟清热化湿疏肝汤治疗乙肝肝硬化(湿热内蕴证)的疗效。方法:选取2018年10月至2019年3月中国中医科学院广安门医院南区收治的乙肝肝硬化(湿热内蕴证)患者104例作为研究对象,按照随机数字表法随机分为观察组和对照组,每组52例。对照组给予常规西药(拉米夫定+富马酸替诺福韦二吡呋酯片+复方甘草酸苷)治疗,观察组在常规西药治疗的同时给予自拟清热化湿疏肝汤治疗,2组均持续治疗6个月。比较2组患者治疗前后症状评分、肝功能、肝纤维化指标变化、临床疗效和安全性。结果:与治疗前比较,2组治疗后主症、次症和总症状评分,血清ALT、AST和r-GGT水平,血清HA、PC-III、IV-C、LN水平水平均下降(P<0.05),且治疗后观察组上述评分和血清学指标均低于对照组(P<0.05);观察组临床疗效与对照组比较,差异有统计学意义(P<0.05),且观察组总有效率为94.23%,明显高于对照组的78.85%(P<0.05);2组不良反应发生率比较,差异无统计学意义(P>0.05),且均未出现肾损害。结论:对乙肝肝硬化(湿热内蕴证)患者在常规西药治疗的同时给予自拟清热化湿疏肝汤可减轻症状,改善肝功能,控制肝纤维化,且疗效理想,安全可靠。

拉米夫定治疗慢性乙肝儿童的临床观察

目的通过观察慢性乙肝儿童使用拉米夫定治疗18个月来评估其临床效果和安全性,为我国慢性乙肝儿童使用拉米夫定提供参考依据。方法所有患儿均来自2009年7月～2012年7月在我院及本县中医院肝病科。选择80例患儿随机分配成观察组(40例)及对照组(40例),另选择40例成年人为成人对照组;儿童治疗组给予拉米夫定3mg(Kg.d),最大剂量不超过100mg/d;儿童观察组不接受抗病毒治疗,只给予护肝降酶等对症处理;成人对照组给予拉米夫定100mg/d,观察三组对拉米夫定治疗的安全性及疗效等。结果 (1)儿童慢性乙型肝炎使用拉米夫定抗病毒治疗18个月安全有效,治疗组未发现严重不良反应,儿童的生长、发育未受影响。(2)儿童慢性乙型肝炎使用拉米夫定抗病毒治疗效果上与成人相似,治疗18个月后转氨酶复常率、血清学转换率、HBV-DNA转阴率、YMDD变异率统计学上均无差异。(3)在治疗组与对照组的儿童中,转氨酶复常率、血清学转换率、HBV-DNA转阴率、YMDD变异率统计学上均存在差异。(4)儿童慢性乙型肝炎使用拉米夫定抗病毒治疗出现HBSAg消失/血清学转换的发生率可能比成人治疗后多见,有待进一步研究。结论慢性乙肝儿童使用拉米夫定抗病毒治疗18个月是安全有效的,与成人相仿。

苦参素治疗慢性乙型肝炎的临床研究进展

目的:了解近三年苦参素用于慢性乙型肝炎临床治疗的最新研究进展。方法:使用数据库检索2016年1月至2019年1月苦参素用于慢性乙型肝炎治疗及肝硬化抗乙肝病毒治疗的临床研究,并对临床研究结果进行分析汇总。结果:苦参素广泛用于抗乙肝病毒治疗及肝纤维化、肝硬化辅助治疗中。苦参素在慢性乙型肝炎治疗中主要通过与核苷类抗乙肝病毒药物、生物药物、中药、辅助常规治疗药物联合给药的方式进行治疗。通过与苦参素的联合用药后,治疗组的抗乙肝病毒治疗效果均更显著,同时伴随免疫力的提高、肝纤维化程度的缓解。结论:采用苦参素治疗慢性乙肝后,乙肝病毒的抑制效果明显提高,肝纤维化程度得到改善,降低炎症反应,促进肝功能恢复。苦参素是非常有应用前景的慢性乙型肝炎的治疗药物,同时,也具有深入研究、开发的潜质。

恩替卡韦分散片在HBV相关肝癌术后的临床应用及意义

评价恩替卡韦分散片抗病毒治疗在HBV相关肝癌术后的临床应用价值。94例伴高滴度HBV-DNA肝细胞肝癌术后患者随机分为A、B两组。A组43例手术切除;B组51例手术后口服恩替卡韦分散片0.5 mg/d。比较两组术后肝癌复发转移情况和无瘤生存率等。所有病例均获随访,期间肿瘤复发42例(44.68%),死亡29例(30.85%)。治疗组和对照组1、2、3年无瘤存活率分别为90.19%、74.51%、62.74%和76.74%、55.81%、39.53%,两组比较差异有统计学意义(P=0.013)。HBV相关肝癌患者术后应用恩替卡韦抗病毒治疗,可提高无瘤生存率,延缓肿瘤复发。

Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata

AIM： To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier. METHODS： HBV-transgenic mice were divided into 3 groups （control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group） and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay （ELISA） method. Serum HBV DNA was detected by real-time polymerase chain reaction （RT-PCR）. Serum T helper （h） 1 cytokine interleukin （IL）-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment. RESULTS： Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 88.81, P12wk = 0.000 〈 0.01）. Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet （F12wk = 20.71, P12wk = 0.000 〈 0.01）. However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 ± 0.38 and 10.56 ± 0.78 ng/L, respectively （t8wk = -16.51, P8wk = 0.000 〈 0.01）. Compared with the serum levels of IL-2 in the normal diet-treated mice （2.48 ± 0.17 ng/L; t8wk = 13.23, P8wk = 0.000 〈 0.01）. Serum levels before and after Styela plicata treatment of IL-6 were 63.62 ± 6.31 and 54.52 ± 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the normal diet-treated mice （60.84 ± 4.21 ng/L）. Histological analysis of liver from Styela plicata-treated HBV-transgenic mice also showed catabatic status in inflammation and hepatitis B surface antigen. CONCLUSION： Styela plicata may be an effective anviral medicine in treating chronic hepatitis B.

Molecular characteristics and stages of chronic hepatitis B virus infection

Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection may present in one of the four phases of infection: immune tolerance, immune clearance [hepatitis B eantigen (HBeAg)-positive chronic hepatitis B (CHB)], inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.

Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.

Current trends in management of hepatitis B virus reactivation in the biologic therapy era

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

Management of chronic hepatitis B in pregnancy

Pregnancy associated with chronic hepatitis B (CHB) is a common and important problem with unique challenges. Pregnant women infected with CHB are different from the general population, and their special problems need to be considered: such as the effect of hepatitis B virus (HBV) infection on the mother and fetus, the effect of pregnancy on replication of the HBV, whether mothers should take HBV antiviral therapy during pregnancy, the effect of these treatments on the mother and fetus, how to carry out immunization of neonates, whether it can induce hepatitis activity after delivery and other serious issues. At present, there are about 350 million individuals with HBV infection worldwide, of which 50% were infected during the perinatal or neonatal period, especially in HBV-endemic countries. Currently, the rate of HBV infection in thechild-bearing age group is still at a high level, and the infection rate is as high as 8.16%. Effective prevention of mother-to-child transmission is an important means of reducing the global burden of chronic HBV infection. Even after adopting the combined immunization measures, there are still 5%-10% of babies born with HBV infection in hepatitis B e antigen positive pregnant women. As HBV perinatal transmission is the main cause of chronic HBV infection, we must consider how to prevent this transmission to reduce the burden of HBV infection. In this population of chronic HBV infected women of childbearing age, specific detection, intervention and follow-up measures are particularly worthy of attention and discussion.

Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

AIM： To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus （HCV） infection, and its relation to disease severity. METHODS： We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen （HBsAg）, antibody to hepatitis B surface antigen （anti- HBs）, and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study. RESULTS： Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis （CAH）. Of these 169 patients, 85 （50.3%） tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 （6d.5%） and 14 （23.7%） respectively （P 〈 0.001）. Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them （12%; occult HBV infection）. CONCLUSION： Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B

AIM： To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS： Eighty patients who had received lamivudine treatment for various periods and had a lamivudineo resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus （HBV） DNA at 0, 12 and 48 wk and serum alanine aminotransferase （ALT） levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS： We found serum ALT became normalized in 72 （87.5%） of the 80 patients, and HBV DNA decreased by ≥ 2 Ioglo copies/mL in 60 （75%） of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION： These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

Interplay between hepatitis B virus and the innate immune responses:implications for new therapeutic strategies

Hepatitis B virus(HBV) infection is still a worldwide health problem;however,the current antiviral therapies for chronic hepatitis B are limited in efficacy.The outcome of HBV infection is thought to be the result of complex interactions between the HBV and the host immune system.While the role of the adaptive immune responses in the resolution of HBV infection has been well characterized,the contribution of innate immune mechanisms remains elusive until recent evidence implicates that HBV appears to activate the innate immune response and this response is important for controlling HBV infection.Here,we review our current understanding of innate immune responses to HBV infection and the multifaceted evasion by the virus and discuss the potential strategies to combat chronic HBV infection via induction and restoration of host innate antiviral responses.

Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after radical hepatectomy

Objective： To assess the effect of antiviral therapy for hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC） after radical hepatectomy. Methods： A total of 478 HBV-related HCC patients treated by radical hepatectomy were retrospectively collected. Patients in the treatment group （n=141） received postoperative lamivudine treatment （100 rag/d）, whereas patients in the control group （n=337） did not. Recurrence-free survival （RFS） rates, overall survival （OS） rates, treatments for recurrent HCC and cause of death were compared between the two groups. Propensity score matching （PSM） analysis was also conducted to reduce confounding bias between the two groups. Results： The 1-, 3-, and 5-year RFS rates didn＇t significantly differ between the two groups （P=0.778）; however, the 1-, 3-, and 5-year OS rates in the treatment group were significantly higher than those in the control group （P=0.002）. Similar results were observed in the matched data. Subgroup analysis showed that antiviral treatment conferred a significant survival benefit for Barcelona Clinical Liver Cancer stage A/B patients. Following HCC recurrence, more people in the treatment group were able to choose curative treatments than those in the control group （P=0.031）. For cause of death, fewer people in the treatment group died of liver failure than those in the control group （P=0.041）. Conclusion： Postoperative antiviral therapy increases chances of receiving curative treatments for recurrent HCC and prevents death because of liver failure, thereby significantly prolonging OS, especially in early- or intermedian-stage tumors.

Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B

AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d.The biochemical response,as assessed by serum alanine aminotransferase(ALT) activity,virologic response,as assessed by serum hepatitis B virus DNA(HBV DNA) titer,serologic response,as assessed by hepatitis B e antigen(HBeAg) status,and virologic breakthrough with genotypic mutations were assessed.RESULTS:Two-hundred and fifty-four patients [clevudine(n = 118) vs entecavir(n = 136)] were enrolled.In clevudine-treated patients,the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96(80.9% and 91.2% in the entecavir group,respectively),the mean titer changes in serum HBV DNA were-6.03 and-6.55 log 10 copies/mL(-6.35 and-6.86 log 10 copies/mL,respectively,in the entecavir group),and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1%(74.4% and 83.8%,respectively,in the entecavir group).These results were similar to those of entecavir-treated patients.The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine,which was similar to patients treated with entecavir(22.8% and 27.7%,respectively).The virologic breakthrough in the clevudine group occurred in 9(7.6%) patients at weeks 48 and 15(12.7%) patients at week 96,which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M.There was no virologic breakthrough in the entecavir group.CONCLUSION:In antiviral-naive CHB patients,longterm treatment outcomes of clevudine were not inferior to those of entecavir,except for virologic breakthrough.

Retrospective analysis of hepatitis B virus reactivation after rituximab combination chemotherapy in patients with B-cell lymphoma

Objective： The aim of the study was to investigate the reactivations of hepatitis B virus （HBV） after rituximab- containing chemotherapy in patients with B-cell lymphoma with surface antigen of hepatitis B virus （HBsAg）-positive, or hepatitis B core antibody （HBcAb）-positive. Methods： A retrospective study of HBV-related markers was performed before and after dtuximab-containing treatment in 189 consecutive patients with CD20-positive B-cell lymphoma. Results： Among the 189 non-Hodgkin＇s lymphoma （NHL） patients who received rituximab combination chemotherapy, 31 （16.6%） were HBsAg positive and 82 （43.9%） HBsAg negative/HBcAb positive, and 76 were HBsAg and HBcAb negative. Of the 31 HBsAg positive patients, 3 （9.7%） experienced reactivation of HBV. The prevalence of HBV reactivation was 4.0% （1/25） in patients who received prophylactic antiviral treatment and 33.3% （2/6） in those who did not receive prophylactic antiviral treatment （P = 0.032）. Prophylactic antiviral treatment decreased the rate of HBV reactivation. Among the 82 HBsAg negative/HBcAb positive patients, 1 （1.2%） experienced HBV reactivation leading to serious hepatitis. Conclusion： Our experience indicates that rituximab-based therapy may cause serious HBV-related complications and even death in HBsAg-positive patients. Preemp- tive use of antiviral treatment enabled successful management of HBV reactivation. In HBsAg-negative and HBcAb-positive lymphoma patients the prevalence of HBV reactivation is low （1.2%）. Close monitoring HBV until at least 6 months after anticancer therapy is required, prophylactic antiviral therapy needs to be evaluated further.