聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎初治与再治患者的回顾性研究

目的评价聚乙二醇干扰素联合利巴韦林对慢性丙型肝炎初治与再治患者的疗效。方法2008年1月至2012年2月回顾性分析上海市公共卫生临床中心慢性丙型肝炎病例67例,以是否为初治将患者分为初治组与再治组,初治组35例,再治组32例,分析两组患者病毒学应答之间的差异及影响因素。结果①初治组患者获得快速病毒学应答（RVR）、早期病毒学应答（EVR）比率明显高于再治组[60％（21例）比28％（9例）,77％（27例）比53％（17例）;均P〈0．05],但两组治疗结束时病毒学应答（ETR）、持续病毒学应答（SVR）的比率差异无统计学意义[86％（30例）比72％（23例）,77％（27例）比56％（18例）;均P〉0．05];②再治组慢性丙型肝炎患者治疗结束后复发率高于初治组[22％（5例）比10％（3例）],但差异无统计学意义（P〉0．05）;③既往有干扰素抗病毒治疗史的患者再次以聚乙二醇干扰素联合利巴韦林治疗后获得RVR、EVR、ETR、SVR的差异无统计学意义（均P〉0．05）;④再治者SVR低于初治者[56％（18例）比77％（27例）],基因1型SVR低于非l型[54％（13例）比74％（32例）],经多因素分析,OR值分别为0．29,0．26（均P〈0．05）。结论慢性丙型肝炎初治患者较再治患者获得较高病毒学应答率,复发率较低;既往治疗方案采用普通干扰素或聚乙二醇干扰素对再治慢性丙型肝炎患者获得病毒学应答无影响;再治与基因1型是慢性丙型肝炎患者获得SVR的危险因素。     

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

Objective

This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated.

Methods

Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day) for 24 - 48 weeks in one of four treatment arms: HIV-negative (A), HIV-positive without HAART (B) and HIV-positive on HAART (C). Patients within arm C were randomized to receive open label either a nucleoside containing (C1) or a nucleoside free HAART (C2).

Results

168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy) were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000). Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708). Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209).

Conclusions

Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.     

不同剂量利巴韦林联合干扰素治疗慢性丙型肝炎快速及早期病毒学应答的疗效观察

目的观察不同剂量利巴韦林（Ribavirin）联合普通干扰素（INFα-1b）治疗慢性丙型肝炎（CHC）快速及早期病毒学应答的疗效。方法二组均应用INFα-1b治疗,对照组33例患者加用利巴韦林10mg/（kg.d）;治疗组35例患者加用利巴韦林15mg/（kg.d）,观察二组的快速病毒学应答（RVR）及早期病毒学应答（EVR）。结果对照组RVR、EVR病例数分别为7例（21.21%）、18例（54.55%）;治疗组RVR、EVR病例数分别为10例（28.57%）、30例（85.71%）。二组RVR差异无统计学意义,而EVR差异有统计学意义（P〈0.05）。结论利巴韦林15mg/（kg.d）联合INFα-1b治疗CHC,可提高EVR,进一步可预测提高持续病毒学应答（SVR）。     

聚乙二醇干扰素联合利巴韦林标准方案治疗慢性丙型肝炎36例临床观察

目的评价聚乙二醇干扰素（Peg—IFN）联合利巴韦林（RBV）标准方案治疗慢性丙型病毒性肝炎（CHC）的疗效与不良反应。方法采用Peg～IFN—ct2a联合RBV标准方案治疗CHC患者36例,疗程为48周,疗程结束后均随访24周。定期观察血常规、肝功能、丙型肝炎病毒（HCV）定量、甲状腺功能及临床症状变化。结果快速病毒学应答（RVR）者10例（27．8％,10／36）,其中2例基因型为3型、2例为2a型;完全早期病毒学应答（complete early virological response,cEVR）者24例（66．7％,24／36）;部分早期病毒学应答（partial early virological response,pEVR）者2例（5．6％,2／36）,其基因型均为1b型。复发1例（2．8％,1／36）,基因型为1b型,其余均达持续病毒学应答（sustained virological response,SVR）。1例发生较严重的银屑病,于16周停药,无复发;1例反复严重口腔溃疡,RBV未全程坚持,复发。结论Peg—IFN联合RBV标准方案治疗CHC疗效较满意,可以达到较高SVR,不良反应常见,但较少影响疗程的完成,联合RBV对获得较高的SVR十分重要。     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的评价聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效。方法聚乙二醇干扰素α-2a（派罗欣）联合利巴韦林（800-1200mg／d）治疗58例慢性丙型肝炎患者,疗程48周,分别于治疗4、12、24和48周及治疗结束后24周评价疗效,并观察药物副作用。结果RVR：36例（62.1％）EVR：18例（31.0％）,SLVR：3例（5.2％）,ETVR54例（93.1％）,SVR：52例（89.7％）;HCVRNA高水平组和低水平组之闻持续应答率分别为66.7％和50.0％,差异有统计学意义（P〈0.05）。结论在慢性丙型肝炎患者的治疗中SVR54（93.1％）,HCV-RNA低水平组的疗效优于高水平组。     

A real world cost effectiveness analysis of interferon-based therapy for HCV naïve super-responders

Background

A direct-acting antiviral (DAA) era in hepatitis C virus (HCV) treatment is fast approaching; unfortunately, the availability and affordability of DAAs in Asia–Pacific areas vary, making it difficult to develop universal HCV practice guidelines appropriate for the all Asian populations. This study aimed to evaluate the real-world cost-effectiveness of IFN-based therapy according to the current strategies with PegIFN/RBV for “easy-to-treat” to provide a reference for application of future DAA development for IFN-eligible, treatment naïve HCV patients.

Apolipoprotein E gene polymorphisms and serum cholesterol in healthy Irish adults: a proposed genetic marker for coronary artery disease risk

Background

The apolipoprotein (Apo) E gene, and thus its gene product, plays a central and pervasive role in lipid metabolism by serving as a ligand for lipoprotein receptors. Polymorphisms of this gene have been associated with variation in lipid phenotypes in some Caucasian and Asian populations, but not in others. No such study has been carried out in a resident Irish population.

Aim

A study was designed to examine the relationship between serum cholesterols and Apo E genotype in a cohort of healthy Irish adults.

Methods

One hundred healthy Irish adults, aged 19–65 years, were recruited from the Cork City area. Two fasting blood samples were collected from each subject. One was assayed for serum cholesterols — total and low-density lipoprotein (LDL), and high-density lipoprotein (HDL) — while the other sample was used for isolation of genomic DNA and determination of Apo E genotype.

Results

While the E2 (12%) was the least prevalent, E3 was the most prevalent Apo E genotype (66%) in this group of healthy Irish adults. A significant Apo E gene-dosage effect was evident, whereby individuals with the Apo E2 genotype had a lower level of total cholesterol, E3 had intermediate levels, and E4 had a higher level. Moreover, those with the Apo E4 genotype had a significantly higher level of LDL cholesterol compared to E2 or E3 genotypes. There was no significant difference in mean serum adjusted HDL-cholesterol levels between the three Apo E genotypes.

Conclusion

These findings suggest that healthy Irish adults with the Apo E4 genotype have higher serum total and LDL-cholesterol levels than those with E2 or E3 Apo E genotypes and therefore may have a higher risk of atherosclerotic coronary artery disease and coronary heart disease in later life.     

Acute hepatitis C in persons infected with the human immunodeficiency virus (HIV): The "Real-life Setting" proves the concept

Objectives

Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations.

Methods

HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks.

Results

Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99%) patients were of caucasian origin, 296 (93%) declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1%) cases. Median age at HCV diagnosis was 40 years (range 20-69 years). Median HCV viral load was 1.2 × 10⁶ IU/mL, 222 patients (70%) had HCV genotype 1, 59 (18%) genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years). Median HIV viral load was 110 copies/mL (range 25 to 10 × 10⁶ copies/mL). The median CD 4 count was 461 cells/mm³ (range 55- 1331 cells/mm³). Two hundred and fourty-six patients (77%) received anti-HCV treatment, and 175 (55%) had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9). 93 of the 175 treated patients (53%) reached a sustained virological response (SVR). In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p < 0.0001). Seventy-three patients (23%) did not receive anti-HCV treatment. In 19 of the untreated patients (26%) the hepatitis C virus was cleared spontaneously.

Conclusions

Our findings confirm that acute hepatitis C in HIV infected patients affects mainly MSM who acquire HCV sexually. Patients had a short duration of HIV infection and a stable immunological situation. In this real-life setting from urban regions in northern Germany, treatment rates appear to be high and effective.     

宿主IL28B基因型联合病毒基因型对慢性丙型肝炎抗病毒疗效的预测

目的综合分析宿主IL28B基因型和丙型肝炎病毒（HCV）基因型对慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林抗病毒治疗疗效的影响。方法对120例慢性丙型肝炎患者进行全程联合治疗,其中92例患者完成了治疗后24周随访,同时分析HCV基因型及宿主IL28B基因型对治疗结束时应答（ETR）及持续病毒学应答（SVR）的影响。结果 IL28B基因CC型在这组慢性丙型肝炎患者中占89%。在HCV基因1b型患者中,IL28B基因CC型患者可以获得比非CC（N-CC）型更高的ETR率（P=0.001 4）和SVR率（P=0.000 7）,但在HCV基因非1b（N-1b）型患者中,CC型与N-CC型患者间的抗病毒疗效差异无统计学意义;在IL28B基因N-CC型患者中,HCV基因N-1b可以获得比1b型更高的ETR率（P=0.035 0）和SVR率（P=0.022 2）,但在CC型患者中,HCV基因N-1b与1b型间的疗效差异无统计学意义。结论 HCV基因型及宿主IL28B基因型对我国慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林抗病毒治疗疗效具有重要影响。联合检测宿主IL28B基因型和病毒基因型可以更加科学、准确地预测抗病毒疗效,为真正实现个体化治疗提供依据。     

Elective surgery: a comparison of in-patient versus day surgery practices in Ireland

Background

Currently, there is a paucity of research which has assessed practices at the point of care for day surgery patient.

Aim

To outline the patient journey from first referral for surgery and identify structures and processes which facilitate or constrain the provision of day surgery.

Method

A retrospective medical charts review of 200 consecutively presenting patients undergoing elective surgery in two Irish teaching hospitals. Data collection was completed from January 2009 to March 2009. This analysis spanned from first referral to the hospital until discharge and follow up.

Results

Great variability was noted in practices between the two hospitals. While some of the differences in practice become barriers to increased rates of day surgery, others did not have an impact.

Conclusion

This study echoes findings of other similar studies in that management of patients undergoing elective surgery which varies significantly across Irish hospitals.     

HIV/HCV双重感染者抗HCV治疗时机的探讨

目的探讨HIV/HCV双重感染者抗HCV治疗的时机。方法根据基线CD4+T淋巴细胞计数将HIV/HCV双重感染者分为A、B、C 3组,A组19例(CD4+T淋巴细胞计数>350个/μl)采用聚乙二醇干扰素α-2a(PEG-IFNα-2a)135或180μg皮下注射,1次/周,利巴韦林900～1 200 mg口服,1次/d,48周为1个疗程;B组14例(CD4+T淋巴细胞计数200～350个/μl)先给予高效抗反转录病毒治疗(HAART)治疗8周,再采用A组相同的方案治疗;C组30例(CD4+T淋巴细胞计数<200个/μl)先给予HAART,复查CD4+T淋巴细胞计数>200个/μl并持续8周以上再采用A组相同方案治疗。分别在基线及治疗后12周、24周、48周、72周复查患者丙型肝炎病毒RNA(HCV-RNA)和CD4+T淋巴细胞计数。结果 3组患者中早期病毒学应答(EVR)29例(46.03%),持续病毒学应答(SVR)28例(44.44%)。A+B组的EVR(69.70%)和SVR(66.67%)均高于C组(EVR为20.00%、SVR为20.00%)。结论 CD4+T淋巴细胞计数>200个/μl是HIV/HCV双重感染者抗HCV治疗的最佳时机,其疗效和单纯丙肝患者相近,但CD4+T淋巴细胞计数<200个/μl者疗效较差。     

慢性丙型肝炎直接抗病毒药物治疗进展

丙型肝炎（丙肝）是全球面临的公共卫生问题,约有1.8亿丙肝病毒（HCV）感染者,每年新增病例300万~400万。国际公认的聚乙二醇干扰素（pegylated interferon,PEG-IFN）α联合利巴韦林（ribavirin,RBV）标准方案（standard of care,SOC）治疗基因1型慢性丙型肝炎（chronic hepatitis C,CHC）的持续病毒学应答（sustained virological response,SVR）率为40%~50%[1]。此外,临床上有30%~40%的CHC患者不能耐受SOC不良反应而影响治疗,导致丙肝进展。     

Difficulties with percutaneous endoscopic gastrostomy (PEG): a practical guide for the endoscopist

Background

Percutaneous endoscopic gastrostomy (PEG) is a widely used and effective means of providing long-term nutrition in patients with inadequate oral intake. The demand for this intervention has risen steadily since the early 1990s. Endoscopists who perform PEG insertion have become increasingly concerned about inappropriate use of this intervention.

Aims

This review addresses the particular areas of difficulty, namely, dementia, stroke, aspiration pneumonia and use of PEG to facilitate discharge from hospital.

Methods

A Pubmed literature search and the author’s personal experience.

Conclusions

Strategies for improving patient selection and a practical approach to difficult decisions are described.     

The advent of successful organ transplantation in the Irish HIV positive cohort

Background

Liver disease is an increasing cause of morbidity and mortality in Human immunodeficiency virus (HIV) positive patients.

Aim

To describe the first cases of organ transplantation in HIV positive patients in Ireland.

Method

We report the Irish patients with HIV who received liver transplantation and performed a chart review.

Result

Two patients received liver transplantation for end stage liver disease caused by Hepatitis C, with survival at 2?years of 100%.

Conclusion

Liver transplantation is a feasible treatment for patients with HIV and end stage liver disease. The success of transplantation in the HIV positive population should encourage the provision of other medical and surgical interventions previously not offered to patients with HIV.     

索磷布韦维帕他韦治疗不同基因型慢性丙型肝炎患者和HCV/HIV合并感染患者的临床疗效与安全性

  目的  观察索磷布韦维帕他韦治疗慢性丙型肝炎患者和HCV/HIV合并感染患者的临床疗效和安全性。  方法  将2018年6月至2020年6月就诊于云南省昆明市第三人民医院的419例慢性丙型肝炎患者和56例HCV/HIV合并感染患者纳入到研究中。观察治疗4周、12周、治疗后随访12周持续病毒学应答（SVR12）、生化学应答、肝纤维化改善和治疗期间的不良反应。  结果  停药12周后，单纯HCV患者的基因1（genotype，GT1）型的SVR12率为97.56%，GT2型的SVR12率为98.97%，3型的SVR12率为97.54%，6型的SVR12率为97.85%，P = 0.870；对于HCV/HIV合并感染患者（除抗HIV治疗外给予索磷布韦维帕他韦抗HCV治疗）治疗12周后，GT1型患者的SVR12为85.71%，GT3型患者的SVR12为92.11%，GT6型患者的SVR12为90.91%，P = 0.862；单纯HCV患者抗病毒治疗后的AST、ALT、ALB生化学指标明显好转，肾功能明显改善；单纯HCV患者的肝纤维化指标在治疗后，纤维化程度明显改善；不良反应发生的患者中GT3型出现腹泻、恶心、呕吐、乏力，其他基因型别的患者和HCV/HIV合并感染患者以乏力、头痛为主。  结论  索磷布韦维帕他韦对于治疗初治慢性丙型肝炎患者、HCV/HIV合并感染患者的抗病毒治疗有效且有较高安全性。     

Inappropriate use of proton pump inhibitors

Background

Proton pump inhibitors (PPIs) are widely used expensive medications.

Aims

We performed a cross-sectional study to determine the extent and indication of PPI use in Irish acute medical wards.

Methods

Fifty-five medical charts were reviewed at the beginning and end of 1 month.

Results and conclusions

Thirty-three patients were prescribed PPIs; 26 prior to admission. The prescribing of PPIs was concordant with guideline recommendations in only 30% of cases. Two-thirds of PPI use was unlicensed.     

HCV1b亚型ISDR变异影响PEG-IFN/RBV抗病毒疗效的新特点分析

目的 探讨HCV干扰素敏感决定区(ISDR)氨基酸(aa)序列变异度对聚乙二醇干扰素(PEG-IFN)联合利巴韦林(RBV)治疗1b亚型慢性丙型肝炎(CHC)疗效的影响.方法 58例HCV 1b亚型慢性感染者采用PEG-IFN/RBV联合方案治疗48周,并随访24周.定量检测血清HCV RNA,逆转录-聚合酶链反应扩增治疗前血标本中HCV ISDR片段并测序,MEGA 4分析氨基酸序列变异度;二分类Logistic回归分析各变量与持续病毒学应答(SVR)之间的关系.结果 治疗前血清HCV的ISDR氨基酸序列与HCVJ株比较,15例为野生型(未突变),42例为中间型(1-3个突变),1例为突变型(≥4个突变).其中2218位点突变最多,约为60.3％(35/58).dSDR aa突变数目与SVR关系密切(P=0.000),ISDR aa突变数≥2的CHC组所获得的EVR和SVR明显高于aa突变数＜2的CHC组(P=0.041/P=0.012).结论 华南HCV 1b亚型ISDR突变型(氨基酸变异≥4)极少.ISDR aa变异能够预测SVR;采用PEG-IFN/RBV联合方案治疗,对SVR有预测价值的ISDR aa突变数可由4个减少为2个.     

Intensive care in a general hospital: demographics,utilization and outcomes

Introduction

Intensive care units (ICU) in Irish academic centres are known to fare as well as their international counterparts. Our aim in this study was to characterise the role and outcomes of an ICU in a smaller Irish hospital and to compare these to international best practice.

Methods

We reviewed admissions of patients to the ICU of St. Luke’s Hospital, Kilkenny. Patient demographics, indications for admission, and outcomes were all recorded and analysed. Sequential organ failure assessment (SOFA) scores were calculated.

Results

Forty-three patients were included in our study, 33 (76.7 %) of which were emergency admissions. Median length of stay was 2 days. The observed mortality rate in our cohort was 20.9 %. The median SOFA score in patients admitted was 7. Higher median SOFA scores on admission were predictive of mortality. The ICU occupancy rate during the duration of our study was 98 %, with only 15 (35.7 %) of admissions to ICU occurring within core working hours.

Conclusion

Critical care can be provided safely and in line with current best practice in smaller Irish hospitals. There is a cohort of patients for whom care may be best provided in a tertiary centre, how best to provide for these patients will likely be achieved by early identification (e.g. with SOFA score). Bed capacity issues remain problematic.     

Effectiveness of interferon alfa-2b/ribavirin combination therapy for chronic hepatitis C in a clinic setting

AIM: To determine effectiveness of treatment for hepatitis C outside clinical trials, by testing the hypothesis that apparent effectiveness and tolerability of interferon alfa-2b/ribavirin combination therapy would be less in a hospital liver clinic setting. DESIGN: Retrospective analysis of all patients in one centre commencing interferon alfa-2b/ribavirin therapy, but not in clinical trials, between 1998 and 2000. MAIN OUTCOME MEASURES: Effectiveness as sustained virological response (SVR); tolerability as premature discontinuation of treatment. RESULTS: The 121 patients had similar demographic and viral characteristics as those in Australian trials (age, 44 +/- 10 years; males, 66%; genotype 1, 44%; genotype 3, 36%), but 38% had advanced fibrosis, including 17% with cirrhosis. Sixty (50%) were previously untreated, 38 (31%) had relapsed after initial response (response relapse) and 23 (19%) were non-responders to interferon monotherapy. Sustained viral response (SVR) was achieved in 53% of patients overall: 47% of patients with genotype 1 HCV, 71% of patients with genotype 3. For patients with genotype 1 HCV, SVR was 43% in those previously untreated, 63% in response relapsers, and 38% in non-responders. Corresponding SVRs for genotype 3 were 65%, 87% and 33%. These results are similar to those obtained in published trials. Only 7% of our patients discontinued treatment because of adverse effects, fewer than reported in most clinical trials. Dose reduction was required in 18% of patients. CONCLUSIONS: In a hospital clinic setting the effectiveness of interferon alfa-2b/ribavirin combination therapy appears equivalent to published results from clinical trials.