Application of nucleoside analogues to liver transplant recipients with hepatitis B

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients

BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.

Current prodrug strategies for improving oral absorption of nucleoside analogues

Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.

Effects of two novel nucleoside analogues on different hepatitis B virus promoters

AIM: To explore the effects of the nucleoside analogues β-L-D4A and β-LPA on hepatitis B virus (HBV) promoters. METHODS: Four HBV promoters were amplified by polymerase chain reaction (PCR) and subcloned into the expression vector pEGFP-1. The four recombinants controlled by HBV promoters were confirmed by restriction analysis and sequencing. Human hepatoma HepG2 cells transfected with the recombinant plasmids were treated with various concentrations of β-L-D4A and β-LPA. Then, enhanced green fluorescent protein (EGFP)-positive cells were detected by fluorescence microscopy and using a fluorescence activated cell sorter (FACS). RESULTS: Four HBV promoters were separately obtained and successfully cloned into pEGFP-1. Expression of EGFP under the control of the surface promoter (Sp) and the X promoter (Xp) was inhibited by β-L-D4A in a dose-dependent manner, while expression of EGFP under the control of the core promoter (Cp) and Xp was inhibited by β-LPA in a dose-dependent manner. CONCLUSION: The two novel nucleoside analogues investigated here can inhibit the activities of HBV promoters in a dose-dependent manner. These findings may explain the mechanisms of action by which these two novel compounds inhibit HBV DNA replication.

Effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B

Objective: To study the effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who received antiviral therapy in Infectious Diseases Hospital of Shanghai Huangpu District between April 2014 and October 2016 were selected as the research subjects and divided into 3 groups, group A received entecavir therapy, group B received adefovir dipivoxil therapy and group C received lamivudine therapy. 24 weeks and 48 weeks after treatment, the levels of liver fibrosis indexes in serum as well the levels of DC and the expression of surface markers in peripheral blood of the three groups were measured respectively. Results: After treatment, serum hyaluronic acid (HA), procollagen III (PC-III), laminin (LN) and collagen type IV (C-IV) levels of all groups were significantly lower than those before treatment, and the number of myeloid DC (mDC) and plasmacytoid DC (pDC) in peripheral blood as well as the expression levels of DC surface molecules CD80, CD86, CD1αand HLA-DR in peripheral blood were significantly higher than those before treatment. After treatment, the serum levels of HA, PC-III, LN and C-IV in group A were significantly lower than those in group B and C, and the number of mDC and pDC in peripheral blood as well as the expression of DC surface molecules CD80, CD86, CD1α and HLA-DR in peripheral blood were significantly higher than those in group B and C. Conclusion: Antiviral therapy by nucleoside analogues can effectively inhibit liver fibrosis and improve peripheral blood DC function in patients with chronic hepatitis B, and Entecavir function is better than that of adefovir dipivoxil and lamivudine.

Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B

AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two hepatitis B envelope antigen(HBeAg)positive CHB patients were enrolled and divided equally into two groups.One group received telbivudine(LDT,600 mg/d),and the other group received lamivudine(LAM,100 mg/d).Clinical,virological and immunological parameters were assessed at the baseline and at 4,12,24,36 and 48 wk.RESULTS:Both groups achieved significant hepatitis B virus(HBV)replication inhibition and alanine aminotransferase normalization at 48 wk.At the baseline,compared to healthy controls,CHB patients had a lower circulating CD8 T cell frequency(29.44%±11.55%vs 37.17%±7.30%,p=0.03)and higher frequencies of programmed death 1 positive CD8 T cells(pD-1+CD8 T)(16.48%±10.82%vs 7.02%±3.62%,p=0.0001)and CD4+CD25+Foxp3+T regulatory cells(Tregs)(23.64%±9.38%vs 13.60%±6.06%,p=0.001).On therapy,at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid(HBV DNA)and HBeAg declining,the frequencies of pD-1+CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups.At treatment week 4,patients treated with LDT had a lower frequency of pD-1+CD8 T cells compared to patients treated with LAM(10.08%±6.83%vs 20.51%±20.96%,p=0.02).The frequency of pD-1+CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level(r=0.45,p=0.01)and HBeAg level(r=0.47,p=0.01)at treatment week 24,but the frequency of Treg cells was only significantly correlated with the HBeAg level(r=0.44,p=0.02).Furthermore,the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.CONCLUSION:NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines.This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.

Microwave-assisted Green and Efficient Synthesis of N^6-(2-Hydroxyethyl)adenosine and its Analogues

An efficient protocol for the synthesis of N^6-（2-Hydroxyethyl）adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Using water as solvent makes our method eco-friendly and easy to handle with.

Purine nucleotides and their metabolites in patients with type 1 and 2 diabetes mellitus

We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 and 40 type 2 diabetic patients. The increased dephosphorylation of adenine and guanine nucleotides, indicated by increased Ado, Ino, Guo and Hyp concentrations as the products of purine nucleotide degradation, suggests serious energy metabolism disruptions in diabetes. An increase in AMP, GMP, IMP concentrations, as well as a decrease in AEC and GEC values, points to significant alterations in erythrocyte purine nucleotide concentration.

Cloning and Sequence Analysis of Disease Resistance Gene Analogues from Three Wild Rice Species in Yunnan

Two sets of degenerate oligonucleotide primers were designed according to amino acid conserved regions of reported plant disease resistance genes which encode proteins that contain nucleotide-binding site and leucine-rich repeats(NBS-LRR), and the plant disease resistance genes which encode serine/threonine protein kinase(STK). By polymerase chain reaction(PCR), disease resistance gene analogues have been amplified from three wild rice species in Yunnan Province, China. The DIN A fragments from amplification have been cloned into the pGEM-T vector respectively. Sequencing of the DNA fragments indicated that 7 classes, 2 classes and 6 classes NBS-LRR disease resistance gene analogues from Oryza rufipogon Griff. , Oryza officinalis Wall. , and Oryza meyeriana Baill. were obtained respectively. The two representative fragments of TO12 from Oryza officinalis Wall, and TR19 from Oryza rufipogon Griff, belong to the same class and homology of their sequences are 100%. The result shows that the sequences of the same class disease resistance gene analogues have no difference among different species of wild rice. 5 classes STK disease resistance gene analogues were also obtained among which 4 classes from Oryza rufipogon Griff. , 1 class from Oryza officinalis Wall. By comparison analysis of amino acid sequences. we found that the obtained disease resistance gene analogues have very low identity(low to 25%) with the reported disease resistance gene L6, N, Bs2, Prf, Pto, Lr10 and Xa21 etc. The finding suggests that the obtained disease resistance gene analogues are analogues of putative disease resistance genes that have not been isolated so far.

Quick and Simple Spectrophotometric Method of Identification of the Thermal State of Meat on the Basis of Composition and Content of Free Nucleotides

At present, there is no method for identifying meat frozen in a thermal state acceptable for production control. The role of free nucleotides in the processes of refrigeration and storage of meat, affecting the structural and mechanical properties of muscle tissue, the formation of taste and its biological value is known. In this article we compared methods for identifying the thermal state of meat based on the determination of the composition and content of free nucleotides by high-performance liquid chromatography (HPLC) and spectrophotometry [SF]. High-purity reference substances were used: free nucleotides—ATP, ADP, AMP, IMP and nucleosides-inosine and hypoxanthine. It has been experimentally established that the characteristic peaks of the absorption spectra for extracts of free nucleotides of meat frozen depended from thermal state of meat. The content of ATP is 21.8 times higher in meat frozen in a fresh state, and the amount of IMF is 12.3 times lower than in meat frozen after cooling. The results of studies of meat frozen using the HPLC method and the developed SF method show the adequacy of the data obtained by both methods. SF-method based on the determination of the optical density of the extracts of free nucleotides is recommended to justify the choice of technological process meat defrost modes.

Role of human nucleoside transporters in pancreatic cancer and chemoresistance

The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5%changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade.Investigations into the mechanisms of pancreatic cancer development,progression and acquired chemoresistance have been constant for the past few decades,thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters.This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer,more specifically human equilibrative nucleoside transporter 1/2(hENT1,hENT2),and human concentrative nucleoside transporter 1/3(hCNT1,hCNT3),while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer.The review also discusses the incidence,current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer.Furthermore,we address the importance of chemoresistance in nucleoside analogue drugs,in particular,gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.

基于代谢组学的‘海尔特兹’红树莓果实中核苷、核苷酸和类似物含量的变化规律研究

本研究基于代谢组学,采用液相色谱-质谱联用法,针对‘海尔特兹’红树莓4个不同时期果实中17种核苷、核苷酸和类似物含量及变化规律进行研究。结果表明:在海尔特兹’红树莓果实发育过程中,脱氧胞苷酸、5-甲基脱氧胞苷、玉米素核苷、N-[(5-羟基-2-吡啶基)甲基]腺苷、反式玉米素-O-葡萄糖苷核糖苷、1-甲基腺苷、鸟苷、2-苯基氨基腺苷、1,7-二甲基鸟苷和胞苷2’,3’-环磷酸的含量在青果时期最高;UDP-4-脱氢-6-脱氧-D-葡萄糖和dTDP-D-葡萄糖的含量在黄果时期最高;尿苷二磷酸葡萄糖、8-羟基鸟苷、胞苷的含量在红果时期最高;1-甲基肌苷和脂酰腺苷酸的含量在深红果时期最高。本研究阐明了17种核苷、核苷酸和类似物在‘海尔特兹’红树莓在果实发育中的含量变化规律,为后期相关研究及应用提供了参考。

核苷类似物治疗乙型肝炎肝硬化并发食管静脉曲张临床价值研究

目的:探讨核苷类似物治疗乙型肝炎肝硬化并发食管静脉曲张临床价值。方法:选取乙型肝炎肝硬化并发食管静脉曲张患者88例,根据是否抗病毒治疗分为对照组(33例)和治疗组(55例)。比较两组患者治疗前后肝功能指标[白蛋白(ALB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)]、Child-Pugh评分和凝血功能指标[凝血酶原时间(PT)、凝血酶原活动度(PTA)]以及治疗后乙型肝炎病毒DNA(HBV-DNA)阴转率、食管静脉曲张程度和消化道出血情况。结果:抗病毒治疗后,治疗组患者TBIL、ALT、AST较治疗前降低,ALB较治疗前升高(均P<0.05)。抗病毒治疗后,治疗组患者PT较治疗前降低,且治疗组低于对照组;治疗组PTA较治疗前升高,且治疗组高于对照组(均P<0.05)。治疗组抗病毒治疗后Child-Pugh评分较治疗前降低,且治疗组Child-Pugh评分低于对照组(均P<0.05)。与对照组比较,治疗组在抗病毒治疗后HBV-DNA阴转率升高(P<0.05)。在未行EVL治疗患者中,治疗组食管静脉曲张减轻程度高于对照组(P<0.05)。在接受及未接受EVL治疗的患者中,治疗组消化道出血率低于对照组(均P<0.05)。结论:核苷类似物能够抑制乙型肝炎肝硬化并发食管静脉曲张患者HBV病毒复制,改善肝功能和凝血功能,减轻食管静脉曲张程度,降低消化道出血风险。

一线核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的发生及治疗策略

强效低耐药口服抗病毒治疗可使HBV复制受到强力抑制,但部分患者接受恩替卡韦、替诺福韦酯、丙酚替诺福韦、艾米替诺福韦治疗48周及以上仍存在低病毒血症(LLV)。国内外多项研究结果提示,抗病毒治疗后LLV与慢性乙型肝炎肝纤维化进展、失代偿期肝硬化和肝细胞癌发生风险以及长期生存率降低密切相关。因此,本文聚焦有关一线核苷(酸)类似物治疗后LLV的发生及其危险因素和临床危害以及不同的治疗方案,以期为今后慢性乙型肝炎患者LLV的治疗提供参考。

恩替卡韦、富马酸替诺福韦二吡呋酯及富马酸丙酚替诺福韦治疗慢性乙型肝炎的疗效及安全性分析

目的观察恩替卡韦(entecavir,ETV)、富马酸替诺福韦二吡呋酯(tenofovir disoproxil fumarate,TDF)及富马酸丙酚替诺福韦(tenofovir alafenamide fumarate,TAF)抗病毒治疗慢性乙型病毒性肝炎(慢乙肝)的临床疗效及安全性。方法选择2021年3月—2023年6月我院收治的181例慢乙肝患者,依据抗病毒治疗用药不同分为3组,ETV组(n=66)、TDF组(n=64)及TAF组(n=51)。比较3组患者的血脂、肝功能、HBsAg、HBV DNA、血肌酐及估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)等指标在治疗前后及组间的差异。结果ETV组有效率为86.36%(57/66),TDF组有效率为90.63%(58/64),TAF组有效率为90.20%(46/51),3组比较差异无统计学意义(P>0.05)。治疗后,3组的HBsAg水平、HBV DNA载量均低于治疗前(P均<0.05),且3组间HBsAg水平、HBV DNA载量的变化幅度比较,差异具有统计学意义(P<0.05)。治疗后,3组的ALT、AST水平均低于治疗前(P均<0.05),且3组间ALT、AST水平的变化幅度比较,差异有统计学意义(P<0.05)。治疗后,ETV组的HDL-C、LDL-C均高于治疗前(P均<0.05),TC、TG较治疗前差异均无统计学意义(P均>0.05);TDF组的TC、HDL-C均低于治疗前(P均<0.05),TG、LDL-C较治疗前差异均无统计学意义(P均>0.05);TAF组的TC、TG、HDL-C、LDL-C较治疗前差异均无统计学意义(P均>0.05),但3组间TC、TG、HDL-C、LDL-C的变化幅度比较,差异均有统计学意义(P均<0.05)。治疗后,3组的血肌酐、eGFR较治疗前差异均无统计学意义(P均>0.05),但3组间血肌酐、eGFR的变化幅度比较,差异均有统计学意义(P均<0.05)。结论ETV、TDF、TAF治疗慢乙肝的临床疗效相近,服用TAF不会对血脂造成影响,但服用ETV会引起HDL-C、LDL-C水平升高,服用TDF可降低TC、HDL-C水平,并且均有较好的肾脏安全性。

新型冠状病毒RNA依赖性RNA聚合酶抑制剂研究进展

由严重急性呼吸综合征冠状病毒2型导致的新型冠状病毒感染席卷全球,寻找广谱抗病毒特效药一直是一项重大任务。RNA病毒的RNA依赖性RNA聚合酶是一类不同病毒间在结构和功能上高度保守的关键非结构蛋白,针对该聚合酶为靶点开发新的小分子抑制剂至关重要。本文作者从新型冠状病毒RNA依赖性RNA聚合酶的结构为出发点,详细阐述了该病毒RNA依赖性RNA聚合酶的作用机制以及不同种类抑制剂的特点。着重从药物化学的角度介绍了核苷类似物和非核苷类似物的作用特点和作用机制,综述了多种小分子聚合酶抑制剂化学结构与生物活性之间的关系。

慢性乙型肝炎患者血清HBV RNA水平与核苷(酸)类似物治疗时间的关系

目的检测未治疗和经过治疗的慢性乙型肝炎(CHB)患者血清HBV RNA水平,并分析血清HBV RNA水平与核苷(酸)类似物(NAs)抗病毒治疗时间的关系。方法选取2022年2月—2022年7月间就诊于石河子大学医学院第一附属医院感染科门诊患者中的300例CHB患者为研究对象。收集患者临床资料,根据患者抗病毒治疗时间不同分为未治疗组(n=73)、治疗时间≤1年组(n=91)、治疗时间>1年组(n=136),检测患者血清HBV RNA和HBV DNA载量及HBsAg浓度。计量资料两组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Bonferroni校正法;计数资料用χ^(2)检验,采用Spearman相关分析比较各指标间相关程度。结果HBeAg阳性率18.3%,在HBV DNA阴性者中HBV RNA阳性者占比44.1%(86/195)。HBeAg阳性组和HBeAg阴性组患者血清HBV RNA、HBV DNA、HBsAg水平分布差异均具有统计学意义(Z值分别为10.740、6.300、7.280,P值均<0.05)。未治疗组与治疗时间≤1年组仅有DNA水平分布情况有统计学差异(P<0.05),未治疗组与治疗时间>1年组HBV RNA、HBV DNA水平分布差异均有统计学意义(P值均<0.05),治疗时间≤1年与治疗时间>1年组中HBV RNA、HBV DNA、HBsAg水平分布情况差异均有统计学意义(P值均<0.05)。抗病毒治疗时间与HBV RNA、HBsAg水平呈极弱负相关(r值分别为-0.247、-0.138,P值均<0.05),与HBV DNA水平呈强负相关(r=-0.771,P<0.001)。血清HBV RNA与HBV DNA、HBsAg水平呈低度相关(r值分别为0.360、0.442,P值均<0.001),进一步分层分析显示,在未治疗组中,HBV RNA与HBV DNA水平呈强正相关(r=0.752,P<0.001),与HBsAg水平呈中度正相关(r=0.559,P<0.001);在治疗时间≤1年组中,HBV RNA与HBV DNA、HBsAg水平呈低度正相关(r值分别为0.396、0.388,P值均<0.001);在治疗时间>1年组中,HBV RNA与HBsAg水平呈低度正相关(r=0.352,P<0.001)。结论血清HBV RNA与NAs治疗时间呈负相关,与HBV DNA、HBsAg水平的相关性随着治疗时间的延长逐渐下降,可以在一定程度上作为CHB患者病毒学水平监测的补充指标,尤其在未治疗患者中反映病毒复制水平准确性较高。

慢性乙型肝炎患者接受核(苷)酸类似物抗病毒治疗后血清HBV-DNA的表达及临床意义

目的探讨慢性乙型肝炎(CHB)患者接受核(苷)酸类似物(NAs)抗病毒治疗后血清乙型肝炎病毒脱氧核糖核酸(HBV-DNA)的表达及临床意义。方法回顾性分析2021年1月至2022年10月河南省人民医院83例采用NAs抗病毒治疗的CHB患者临床资料,根据血清学应答标准将其分为应答组(46例)和未应答组(37例)。比较两组基线资料、治疗前及治疗3、6、12个月时血清HBV-DNA水平;绘制受试者工作特征(ROC)曲线,以曲线下面积(AUC)检验血清HBV-DNA对CHB患者NAs抗病毒治疗未应答的预测价值。结果治疗前,应答组和未应答组HBV-DNA比较,差异无统计学意义(P>0.05);两组治疗前至治疗12个月的HBV-DNA呈下降趋势,组间、时点、交互效应有统计学意义(P<0.05)。绘制ROC曲线显示,治疗3个月时HBV-DNA对CHB患者NAs抗病毒治疗未应答的预测价值较低(AUC=0.694,P=0.002),治疗6个月时HBV-DNA对CHB患者NAs抗病毒治疗未应答具有一定预测价值(AUC=0.751,P<0.001)。结论血清HBV-DNA表达在CHB患者NAs抗病毒治疗前后变化明显,且治疗6个月时血清HBV-DNA可作为抗病毒治疗未应答的预测指标。

甘草酸类制剂与核苷(酸)类似物联用对慢性乙型肝炎患者临床疗效与安全性的网状Meta分析

目的:比较与分析甘草酸类制剂与核苷(酸)类似物联用对慢性乙型肝炎(chronic hepatitis B,CHB)患者的临床疗效与安全性。方法:在Pubmed、Embase和中国知网、万方医学网、维普等数据库中,检索建库至2023年10月甘草酸类制剂与核苷(酸)类似物联用对CHB患者临床疗效与安全性的随机对照试验(randomized controlled trial)研究,采用Stata1和Revman等软件进行甘草酸类制剂与核苷(酸)类似物联用对CHB患者的临床疗效与安全性的网状Meta分析。结果:筛选后共纳入文献42篇,共涉及病例3991例;网状Meta分析结果显示,甘草酸类制剂与核苷(酸)类似物联用对CHB患者在丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素等指标上的疗效均优于单用核苷(酸)类似物(P<0.05);在用药安全性方面,甘草酸类制剂与核苷(酸)类似物联用和单用核苷(酸)类似物的药物不良反应发生率经比较其差异无统计学意义(P>0.05)。结论:甘草酸类制剂与核苷(酸)类似物联用对CHB患者的疗效较为肯定,安全性也较高。

Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.