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Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir

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World Journal of Clinical Cases 2023年第34期11卷 8139-8146页

作者： Gui-Cai Yuan Ai-Zhen Chen Wei-Xin Wang Xu-Lan Yi Long Tu Fang Peng Zhi-Hong Qiu Department of Infectious Diseases Yichun University Second Affiliated HospitalYichun 336000Jiangxi ProvinceChina

BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to *** alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil *** To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to *** A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNAresponse(HBV DNA levelresponse was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two *** of the patients developed genotypic resistance to ETV or *** drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse *** significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either *** TAF group had a significantly lower decrease in bone mine

关键词： Entecavir Tenofovir alafenamide Chronic hepatitis B Virologic response Renal and bone toxicity suboptimal response

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Optimization therapy for the treatment of chronic hepatitis B

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World Journal of Gastroenterology 2014年第19期20卷 5730-5736页

作者： En-Qiang Chen Hong Tang Center of Infectious Diseases West China Hospital of Sichuan University Division of Infectious Diseases State Key Laboratory of BiotherapySichuan University

Chronic hepatitis B (CHB) is currently medically managed with either interferon-alpha or one of the five nucleos(t)ide analogs. However, there are still a large number of CHB patients whose response to the above therapies remains less than satisfactory, and their incomplete or non-response to antiviral therapies has plagued clinicians worldwide. In recent years, a newly proposed optimization therapy has provided us with a new approach to solve this problem. The key points in this optimization therapy are to initiate antiviral therapy with an appropriate agent at the correct time point, and to adjust treatments in patients with poor early responses by adding a second agent or switching to another more potent agent. In this review, we summarize recent developments in optimization therapy for the treatment of CHB, and provide an outlook for future research in this field. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

关键词： Chronic hepatitis B Nucleos(t)ide analog Interferon suboptimal response Optimization therapy

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Micheliolide exerts effects in myeloproliferative neoplasms through inhibiting STAT3/5 phosphorylation via covalent binding to STAT3/5 proteins

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Blood Science 2023年第4期5卷 258-268页

作者： Huijun Huang Jinqin Liu Lin Yang Yiru Yan Meng Chen Bing Li Zefeng Xu Tiejun Qin Shiqiang Qu Liang Wang Gang Huang Yue Chen Zhijian Xiao State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China MDS and MPN Centre Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinChina State Key Laboratory of Medicinal Chemical Biology College of ChemistryNankai University94 Weijin RoadTianjinChina Department of Cell System&Anatomy the University of Texas Health Science Center at San AntonioSan AntonioTX 78229USA Mays Cancer Center Joe R.&Teresa Lozano Long School of Medicinethe University of Texas Health Science Center at San AntonioSan AntonioTX 78229USA Hematologic Pathology Center Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinChina.

Ruxolitinib is a cornerstone of management for some subsets of myeloproliferative neoplasms(MPNs);however,a considerable number of patients respond ***,we evaluated the efficacy of micheliolide(MCL),a natural guaianolide sesquiterpene lactone,alone or in combination with ruxolitinib in samples from patients with MPNs,JAK2V617F-mutated MPN cell lines,and a Jak2V617F knock-in mouse *** effectively suppressed colony formation of hematopoietic progenitors in samples from patients with MPNs and inhibited cell growth and survival of MPN cell lines in ***-treatment with MCL and ruxolitinib resulted in greater inhibitory effects compared with treatment with ruxolitinib ***,dimethylaminomicheliolide(DMAMCL),an orally available derivative of MCL,significantly increased the efficacy of ruxolitinib in reducing splenomegaly and cytokine production in Jak2V617F knock-in mice without evident effects on normal ***,MCL could target the Jak2V617F clone and reduce mutant allele burden in ***,MCL can form a stable covalent bond with cysteine residues of STAT3/5 to suppress their phosphorylation,thus inhibiting JAK/STAT ***,these findings suggest that MCL is a promising drug in combination with ruxolitinib in the setting of suboptimal response to ruxolitinib.

关键词： Micheliolide Myeloproliferative neoplasms Ruxolitinib STAT3/5 suboptimal response

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