穿琥宁治疗小儿流行性腮腺炎疗效观察

目的:评价穿琥宁治疗小儿流行性腮腺炎的疗效。方法:流行性腮腺炎患儿96例,随机分为两组,治疗组49例静滴穿琥宁10mg/(kg·d),对照组47例给予利巴韦林10～15mg/(kg·d),6d为一个疗程。结果:总有效率治疗组95.5%,对照组80.9%,两组比较差别有显著意义(P<0.05)。结论:穿琥宁治疗小儿流行性腮腺炎有明显疗效。     

Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients with chronic hepatitis C

Background/Aims

Sustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients.

Methods

This was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860.

Results

Overall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR.

Conclusions

The SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.     

丙型肝炎肝硬化的“分级”及聚乙二醇干扰素α-2a联合利巴韦林的抗病毒治疗

目的观察丙型肝炎肝硬化不同条件下抗病毒治疗的临床效果,拟定丙型肝炎肝硬化的分级规范治疗标准。方法选择确诊为丙型肝炎肝硬化的患者82例,以32例慢性丙型肝炎（CHC）患者为对照,根据肝硬化程度、脾功能亢进情况以及抗病毒治疗的耐受分为不同抗病毒治疗组：在采取造血因子刺激、脾栓塞或脾切除治疗后,观察患者脾功能亢进的缓解情况,解决脾功能亢进后,以标准治疗方案为基础,采取＂分级＂抗病毒治疗策略,可以实施更为主动的个体化治疗方案;分析不同组别的抗病毒治疗效果,并随访患者肝功能恢复状况。结果经过治疗后,各组患者白细胞及血小板计数显著升高,在给予抗病毒治疗后,脾栓塞及脾切除治疗组均有约60%患者获得早期病毒学应答（EVR）,而其持续病毒学应答（SVR）比率分别为59.3%与63.6%,丙氨酸氨基转移酶（ALT）水平显著下降。结论丙型肝炎肝硬化＂分级＂抗病毒治疗策略,通过采取不同的抗病毒治疗方案,可以延缓病情进展,提高患者生活质量。     

Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control

Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients’ serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.     

长效干扰素联合利巴韦林治疗慢性丙型肝炎患者疗效及其对静息能量消耗和营养状态的影响*

目的 探讨应用长效α-干扰素联合利巴韦林治疗慢性丙型肝炎(CHC)患者疗效及静息能量消耗和营养状态的变化。方法 2017年4月～2019年4月我院收治的CHC患者48例,采用随机数字表法分为观察组24例和对照组24例,分别给予聚乙二醇干扰素α-2a(peg-IFNα-2a)和利巴韦林治疗或干扰素α-2a(IFNα-2a)联合利巴韦林治疗48 w。测量静息能量消耗(REE)和预测静息能量消耗(pREE),常规检测血清前白蛋白(PA)和白蛋白(ALB)水平,计算体质指数(BMI)。结果 在治疗48 w结束和随访6 m时,观察组完全应答率分别为62.5%和54.2%,显著高于对照组的37.5%和29.2%,差异有统计学意义(P＜0.05);在观察组,用药前REE和pREE分别为(1504.6±481.5)kcal/d和(1432.3±229.3)kcal/d,在治疗结束时显著增加至(1822.1±546.7)kcal/d和(1241.8±208.6)kcal/d,对照组用药前REE和pREE分别为(1505.2±482.1)kcal/d和(1433.5±231.2)kcal/d,在治疗结束时,显著增加至(1824.4±547.6)kcal/d和(1243.1±208.8)kcal/d, 但两组之间REE和pREE变化无显著性差异(P>0.05);治疗前,观察组BMI及血清PA和ALB水平分别为(19.2±2.0)kg/m²、(161.5±45.2)mg/L和(38.4±4.2)g/L,在治疗结束时分别降为(17.1±1.5)kg/m²、(135.8±40.2)mg/L和(34.2±3.2)g/L,治疗前对照组BMI及血清PA和ALB水平分别为(19.3±2.1)kg/m²、(161.3±45.0)mg/L和(38.5±4.4)g/L,在治疗结束时分别降为(17.2±1.5)kg/m²、(136.3±40.2)mg/L和(34.2±3.1)g/L,但两组之间这些指标的变化无显著性差异(P>0.05)。结论 相对于IFNα-2a与利巴韦林联合,应用peg-IFNα-2a与利巴韦林联合治疗CHC患者能够获得更好的治疗效果,但无论何种治疗方案,均增加了能量消耗,降低了体质量和血清白蛋白水平,提示标准方案抗病毒治疗的不良反应还是值得重视的。     

Ribavirin uptake by human erythrocytes and the involvement of nitrobenzylthioinosine-sensitive (es)-nucleoside transporters

1. The major toxicity associated with oral therapy with ribavirin is anaemia, which has been postulated to occur as a result of accumulation of ribavirin triphosphate interfering with erythrocyte respiration. The objective of this study was to determine the mechanism by which ribavirin enters into erythrocytes.
2. Entry into human erythrocytes was examined by measuring influx rates of [³H]-ribavirin alone and with the inhibitor nitrobenzylthioinosine (NBMPR), and by investigating the inhibitory effects of nucleoside and nucleobase permeants on ribavirin transport, by use of inhibitor oil-stop methods. Transport mechanisms were further characterized by assessment of substrates to cause countertransport of ribavirin in preloaded erythrocytes, and by measuring the effects of ribavirin on [³H]-NBMPR binding to erythrocyte membranes.
3. Human erythrocytes had a saturable influx mechanism for ribavirin (K_m at 22°C of 440±100 μM) which was inhibited by nanomolar concentrations of NBMPR (IC₅₀ 0.99±0.15 nM). Nucleosides also inhibited the influx of ribavirin (adenosine more effective than uridine) but the nucleobases hypoxanthine and adenine had no effect. In addition, uridine caused the countertransport of ribavirin in human erythrocytes. Entry of ribavirin into horse erythrocytes, a cell type that lacks the NBMPR-sensitive (es) nucleoside transporter, proceeded slowly and via a pathway that was resistant to NBMPR inhibition. Ribavirin was a competitive inhibitor of adenosine influx (mean K_i 0.48±0.14 mM) and also inhibited NBMPR binding to erythrocyte membranes (mean K_i 2.2±0.39 mM).
4. These data indicate that ribavirin is a transported permeant for the es nucleoside transporter of human erythrocytes. There was no evidence for ribavirin entering cells via a nucleobase transporter.

     

索磷布韦、达拉他韦联合或不联合利巴韦林对基因1b型慢性丙肝患者HCVRNA转阴率的影响

目的 分析索磷布韦、达拉他韦联合或不联合利巴韦林对基因1b型慢性丙型肝炎(CHC)患者丙型肝炎病毒(HCV)-RNA(HCV RNA)转阴率的影响。方法 将本院收治的82例基因1b型CHC患者作为研究对象,根据患者治疗方法的不同,分为A组(36例)给予达拉他韦+索磷布韦+利巴韦林治疗,B组(46例)给予达拉他韦+索磷布韦治疗。比较两组患者治疗后HCV RNA转阴率,治疗结束后第4、12周HCV RNA不可测(SVR4、SVR12)及不良反应发生情况等差异。结果 在治疗4、8周时,两组患者HCV RNA转阴率有所增加;但治疗后12周时,两组患者HCV RNA转阴率并未继续升高,与治疗后8周时的转阴率持平。结果显示,两组患者在治疗4、8、12周时HCV RNA转阴率的比较,均无显著性差异(P>0.05)。两组患者SVR4、SVR12的比较,亦无显著性差异(P>0.05)。A组治疗期间出现贫血、皮疹、头痛、疲劳、恶心及心悸等不良反应发生率较B组明显升高(P<0.05)。结论 达拉他韦、索磷布韦联合或不联合利巴韦林对基因1b型CHC患者的临床疗效相当,均具有较高的HCV RNA转阴率,但联合利巴韦林可能存在不良反应增加的风险,且达拉他韦+索磷布韦联合治疗基因1b型CHC患者可尝试将疗程缩短为8周。     

Peginterferon and ribavirin in HCV: Improvement of sustained viral response

Peginterferon alfa in combination with ribavirin is and will remain for the next years the current standard for treatment of chronic hepatitis C. The new antivirals currently investigated in phase II of III trials may augment the overall response rates but require peginterferon/ribavirin as backbone. The cure rate of peginterferon/ribavirin treatment can be improved by better education of treating physicians to identify and treat conditions which negatively influence the final outcome of therapy. Specific focus is the prevention and/or early treatment of common side effects of therapy including anaemia, cytopenia and depression. Measuring the viral response at various time points during treatment allows individualization of treatment duration. Based on these recent findings the treatment algorhytms for chronic hepatitis C will be reformulated (Figure 2 and Figure 3). The soon to be released German consensus statement for treatment of chronic hepatitis C will incorporate these recommendations.

1. Peginterferon/ribavirin is and will remain for the foreseeable future the standard of care for the treatment of chronic hepatitis C.

2. Sustained viral elimination (‘cure’) can be reached in about 50% of patients with genotypes 1 and 4, and in 70–80% of patients with genotypes 2 and 3. The major limitations for successful treatment in virologic responders are the well-known side effects of therapy. They may lead to decreased drug exposure or even early discontinuation of therapy.

3. Better education of treaters will improve side effect management and thus augment response rates.

4. Adaptation of treatment duration according to the rapidity of viral response is an important step for further improvement of outcome.

5. The impact of the new antiviral agents currently under investigation is unknown, but there is a great expectation that far more patients can be cured in future.

利巴韦林治疗小儿病毒性感染合并白细胞减少症的临床分析

目的探讨临床应用利巴韦林治疗小儿病毒性感染合并白细胞减少症是否安全可行。方法将86例病毒性感染合并白细胞减少症的小儿,分别用利巴韦林、其他抗病毒药物进行随机分组治疗,从两组患儿在用药后外周血白细胞升至正常的时间、利巴韦林组是否出现白细胞进行性减少、两组病人抗病毒药物费用等方面进行探讨分析。结果发现正常剂量的利巴韦林在治疗小儿病毒性感染合并白细胞减少症疗效确切,没有出现其本身可能导致白细胞减少的副作用,与其他抗病毒药物比较临床疗效无差异性,并且价格低廉,可减轻患儿经济负担。结论治疗小儿病毒性感染合并白细胞减少症可以选用利巴韦利。