聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎及其合并人类免疫缺陷病毒感染者的疗效

目的观察人类免疫缺陷病毒（HIV）／丙型肝炎病毒（HCV）合并感染者及HCV单一感染者聚乙二醇干扰素（Peg_INF）联合利巴韦林抗HCV疗效。方法70名HIV／HCv合并感染者（合并感染组）及60例HCV单一感染者（单一感染组），均给予Peg-INFoa-2a联合利巴韦林抗HCV治疗，于治疗0、4、12、24、48周及停药后24周行HCVRNA载量检测。PCR加测序法获得HCV基因型及IL-28B基因rs8099917、rsl2979860及rsl2980275位点基因型。分析两组患者疗效，并分析HCV基因型及IL-28B基因型对疗效的影响。数据采用SPSS16．0软件进行分析。离散型分类计数资料使用x2检验，计量资料使用重复测量数据方差分析、方差分析；独立样本的均数比较采用t检验；对非正态分布数据采用参数检验统计分析。结果持续病毒学应答（SVR）率合并感染组为32．9％，单一感染组为71．7％，两组比较，p=0．000，差异有统计学意义。合并感染组中，HCV-1型和HCV-非1型患者SVR率分别为30．8％和33．3％，P=1．000，差异无统计学意义。单一感染组中，HCV-1型和HCV-非1型患者SVR率分别为86．1％和50．0％，P=0．002，差异有统计学意义。SVR率在HCV-1型单一感染组为86．1％，合并感染组为30．8％，P=0．000，差异有统计学意义。不同IL-28B基因型的疗效，差异无统计学意义。结论单一感染组Peg-INFa-2a联合利巴韦林疗效优于合并感染组；HCV基因1型合并感染组疗效比单一感染组差；IL-28B基因型并不影响Peg-INFa-2a联合利巴韦林疗效。

《圣经》文学视野中的《母亲利巴的哀歌》

《旧约·耶利米哀歌》是戏剧家向培良(1905—1961)创作独白剧《母亲利巴的哀歌》(1930)的最主要原型。本文在《圣经》文学的视野中,详细分析了《母亲利巴的哀歌》是如何对《旧约·撒母耳记》中的相关历史事件进行改写、挪置与扩充的,试图阐释中西文学中的"哀歌"与"哀吊"这一文类的相似性及其特质,并希望向培良的这部无人问津的短剧能够引起中国现代文学研究者的足够关注。

国内外多轴向经编设备的研发状况

阐述了多轴向经编技术的发展现状以及多轴向经编机的工作原理。分别介绍了国外的利巴(Liba)Copcentra MAX 3 CNC型设备和卡尔.迈耶(Karl Mayer)Malimo Multiaxial型设备,以及国内的常州润源RCD-l型多轴向经编机和常州第八纺机GE2-M2型多轴向经编机的性能特点。指出:多轴向编织正在朝着自动化、人性化、铺纬准确等方向发展。我国多轴向经编设备的生产企业及从业人员要积极应对,努力开发具有高附加值、高技术含量的有自主知识产权的多轴向经编机。

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.

Ischemic colitis during interferon-ribavirin therapy for chronic hepatitis C:A case report

Ischemic colitis is a rare complication of interferon administration.Only 9 cases in 6 reports have been described to-date.This report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis C,and includes a review of the relevant literature.A 48-year-old woman was treated with pegylated interferon-2a and ribavirin for chronic hepatitis C,genotype Ib.After 19 wk of treatment,the patient complained of severe afebrile abdominal pain with hematochezia.Vital signs were stable and serum white blood cell count was within the normal range.Abdominal computed tomography showed diffuse colonic wall thickening from the splenic flexure to the proximal sigmoid colon,which is the most vulnerable area for the development of ischemic colitis.Colonoscopy revealed an acute mucosal hyperemic change,with edema and ulcerations extending from the proximal descending colon to the sigmoid colon.Colonic mucosal biopsy revealed acute exudative colitis.Polymerase chain reaction and culture for Mycobacterium tuberculosis were negative and the cultures for cytomegalovirus,Salmonella and Shigella species were negative.After discontinuation of interferon and ribavirin therapy,abdominal pain and hematochezia subsided and,following colonoscopy showed improvement of the mucosal ulcerations.Ischemic colitis cases during interferon therapy in patients with chronic hepatitis C reported so far have all involved the descending colon.Ischemic colitis is a rarely encountered complication of interferon administration in patients with chronic hepatitis C and should be considered when a patient complains of abdominal pain and hematochezia.

Current progress in the treatment of chronic hepatitis C

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.

Current treatment options and response rates in children with chronic hepatitis C

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children.The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol (PEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age.In five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15 mg/kg per day) or PEG-interferon α-2a with ribavirin.Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk.Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients.Stratified for genotype;120/234 (51%) with genotype 1,68/73 (93%) with genotype 2/3,and 6/11 (55%) with genotype 4 showed SVR.Relapse rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis C in children and adolescents,a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/3.Thus,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

Treatment modalities for hypersplenism in liver transplant recipients with recurrent hepatitis C

Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.

Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

Telaprevir/boceprevir era: From bench to bed and back

Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.

Hepatitis C Virus Experimental Model Systems and Antiviral drug Research

An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.

Impact of ribavirin dose on retreatment of chronic hepatitis C patients

AIM: To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients. METHODS: Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-2a or-2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed. RESULTS: An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%). CONCLUSION: Retreatment with PEG-IFN/RBV is effective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.

Ketoprofen,peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C:A phaseⅡ study

AIM:To evaluate the safety of adding ketoprofen to pegylated-interferon(PEG-IFN)with or without ribavirin and the effect on viral kinetics,STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS)in genotype 1 chronic hepatitis C in a phaseⅡstudy. METHODS:Forty-five patients were studied:fifteen were randomized to PEG-IFN plus ribavirin(PR),16 to PEGIFN plus ketoprofen and 14 to PR and ketoprofen.Themolecular study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS:The combination of ketoprofen and PEG- IFN with or without ribavirin was safe and well tolerated.An early activation of STAT1 was observed in ke-toprofen-treated patients,but this activation was less sustained over time.Conversely,ketoprofen plus PEG- IFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th wk.These data are consistent with the clinical results,showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin. CONCLUSION:The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.

Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C

AIM： To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon plus ribavirin for chronic hepatitis C. METHODS： Five hundred and sixty-one Japanese patients with hepatitis C virus genotype lb who had received combination treatment were enrolled and as- signed randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection poly- merase chain reaction. Factors influencing significant anemia （hemoglobin concentration 〈 10.0 g/dL at week 4 of treatment） and significant hemoglobin decline （declining concentrations 〉 3.0 g/dL at week 4） were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors. RESULTS： Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline： hemoglobin decline at week 2 [P = 3.29× 10^4, odds ratio （OR） = 7.54 （g/dL）], estimated glomerular filtration rate [P = 2.16× 10^4, OR = 0.962 （ml/min/1.73 m2）], rs1127354 （P = 5.75 × 10^4, OR = 10.94） and baseline hemoglobin [P = 7.86 × 10^4, OR = 1.50 （g/alL）]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia. CONCLUSION： Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.

Pure red cell aplasia caused by pegylated interferon-α-2a plus ribavirin in the treatment of chronic hepatitis C

Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA may be congenital or acquired.To our knowledge,there is only one case report in the English literature of PRCA after pegylated interferon combination therapy for chronic hepatitis C.We report a second case of PRCA after pegylated interferon combination treatment for chronic hepatitis C.The diagnosis of PRCA was confirmed by the typical findings of bone marrow biopsy.The possible etiologies of our case are also discussed in this paper.

Impact of Land-Use Practices on Sediment Yield in the Dhrabi Watershed of Pakistan

Soil erosion by water is one of the most important land degradation processes in the sloping rainfed lands in Pakistan. A study was conducted in the Dhrabi watershed of Pakistan to evaluate sediment yield associated with rainfall-runoff under various land-use practices. Five sub-catchments with sizes varying from 1.5 to 350 ha were selected for measurement of rainfall, runoff and sediment yield. Soil conservation techniques were also introduced to reduce the soil erosion. All runoff events occurred in the summer especially during monsoon season （July-September）. Sediment yield of two small gully catchments ranged from 4.79 to 8.34 t/ha/yr in 2009, a relatively dry year. In 2010, the annual sediment yield was 8.15 to 12.31 t/ha. Terraced catchment with arable crops produced annual 4.1 t/ha of sediment as compared to 12.31 t/ha by the adjacent gully catchment showing high potential of terraces in reducing erosion. Runoff coefficients calculated for these catchments vary from 0.09 to 0.75. The macro and micro nutrients present in the sediment indicate that these nutrients are being depleted due to soil erosion.

Bell’s palsy and choreiform movements during peginterferon α and ribavirin therapy

Neuropsychiatric side effects of long-term recombinant interferon-α therapy consist of a large spectrum of symptoms. In the literature, cranial neuropathy, especially Bell's palsy, and movement disorders, have been reported much less often than other neurotoxic effects. We report a case of Bell's palsy in a patient with chronic hepatitis C during peginterferon-α and ribavirin therapy. The patient subsequently developed clinically inapparent facial nerve involvement on the contralateral side and showed an increase in choreic movements related to Huntington's disease during treatment.