Over the last decade, the standard of care for the treat- ment of chronic hepatitis C has been the combination of pegylated-interferon-alfa （PEG-IFN） and ribavirin （RBV） which results in sustained virological resp...Over the last decade, the standard of care for the treat- ment of chronic hepatitis C has been the combination of pegylated-interferon-alfa （PEG-IFN） and ribavirin （RBV） which results in sustained virological response （SVR） rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Cur- rently, there are rapid and continuous developments of numerous new agents against hepatitis C virus （HCV）, which are the focus of this review. Boceprevir and tela- previr, two first-generation NS3/4A HCV protease inhibi- tors, have been recently licensed in several countries around the world to be used in combination with PEG- IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, com- pared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naTve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-na＇ive patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events （anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir）, new drug interactions and increasing dif- ficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG- IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well toler- ated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.展开更多
文摘目的:观察以化瘀解毒益气法为治则的中药消痞颗粒对慢性萎缩性胃炎(chronic atrophic gastritis,CAG)伴异型增生大鼠胃黏膜细胞增殖和凋亡的影响。方法:以MNNG癌诱变剂灌胃为主多因素联合建立CAG伴Dys大鼠模型,按体质量随机分成自然恢复组、维酶素组与中药组,分别给予生理盐水、维酶素悬浊液、消痞颗粒灌胃,并与正常对照组大鼠对照。干预阶段持续12周,观察各组大鼠胃黏膜病理变化、免疫组化检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)水平、末端脱氧核苷酸转移酶介导的d UTP缺口末端标记测定[terminal dexynucleotidyl transferase(Td T)-mediated d UTP nick end labeling,TUNEL]法检测胃黏膜上皮细胞凋亡状况。结果:中药组治疗后与自然恢复组胃黏膜病理存在显著差异(P<0.05),维酶素组与自然恢复组无明显差异(P>0.05);消痞颗粒组凋亡指数显著低于自然恢复组和维酶素组(P<0.01,P<0.05)。自然恢复组和维酶素组间无显著性差异;消痞颗粒组PCNA表达的阳性比与维酶素组、自然恢复组间均存在显著差异(P<0.05,P<0.01);而维酶素组与自然恢复组间并无显著性差异(P>0.05)。结论:消痞颗粒可改善CAG伴Dys大鼠胃黏膜的病理变化,降低其凋亡指数及PCNA表达。
文摘Over the last decade, the standard of care for the treat- ment of chronic hepatitis C has been the combination of pegylated-interferon-alfa （PEG-IFN） and ribavirin （RBV） which results in sustained virological response （SVR） rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Cur- rently, there are rapid and continuous developments of numerous new agents against hepatitis C virus （HCV）, which are the focus of this review. Boceprevir and tela- previr, two first-generation NS3/4A HCV protease inhibi- tors, have been recently licensed in several countries around the world to be used in combination with PEG- IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, com- pared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naTve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-na＇ive patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events （anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir）, new drug interactions and increasing dif- ficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG- IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well toler- ated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.
