Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Nucleos(t)ide analogues(NA) are a breakthrough in the treatment and management of chronic hepatitis B.NA could suppress the replication of hepatitis B virus(HBV) and control the progression of the disease.However,drug resistance caused by their long-term use becomes a practical problem,which influences the long-term outcomes in patients.Liver transplantation is the only choice for patients with HBV-related end-stage liver disease.But,the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients.Recently,the multi-drug resistance(MDR) has become a common issue raised due to the development and clinical application of a variety of NA.This may complicate the antiviral therapy and bring poorly prognostic outcomes.Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR,the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy.The future of HBV researches relies on how toprevent the MDR occurrence and develop reasonable and effective treatment strategies.This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

Factor V Leiden mutation in one family of Chinese origin

目的 研究中国人FVLeiden基因突变引起的抗活化蛋白C现象 (APCR)。方法 采用APTT±APC方法、多聚酶链反应 (PCR)、MnLI限制性内切酶分析 ,序列特异性引物 (PCR SSP)和DNA测序方法 ,对中国汉族 30例“正常”无关个体和 2 0例血栓性疾病患者进行APCR测定和FVLeiden基因突变分析。结果 发现一例正常人抗APC敏感值比值 (APC SR)明显减低 (0 8) ,并确诊为FVLeiden基因 (Arg50 6 Gln)突变杂合子 ,其叔祖父、父亲、弟弟和儿子同样确定为FVLeiden基因杂合子 ;有 3例血栓性疾病患者APC SR低于正常 ,但均无FVLeiden基因突变。结论 这是在国内发现的首例四代FVLeiden突变所致的APCR现象的家系。中国人血栓症中APCR的产生是否导致其它未知的基因缺陷 ,尚待进一步研究。