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1.
Liver transplant candidates and recipients with hepatitis C virus(HCV)-related liver disease greatly benefit from an effective antiviral therapy. The achievement of a sustained virological response before transplantation can prevent the recurrence of post-transplant HCV disease that occurs universally and correlates with enhanced progression to graft cirrhosis. Previous standard-of-care regimens(e.g.,pegylated-interferon plus ribavirin with or without first generation protease inhibitors,boceprevir and telaprevir) displayed suboptimal results and poor tolerance in liver transplant recipients. A new class of potent direct-acting antiviral agents(DAA) characterized by all-oral regimens with minimal side effects has been approved and included in the recent guidelines for the treatment of liver transplant recipients with recurrent HCV disease. Association of sofosbuvir with ribavirin and/or ledipasvir is recommended in liver transplant recipients and patients with decompensated cirrhosis. Other regimens include simeprevir,daclatasvir,and combination of other DAA. Possible interactions should be monitored,especially in coinfected human immunodeficiency virus/HCV patients receiving antiretrovirals.  相似文献   

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Summary. By mathematically describing early hepatitis C virus (HCV) RNA decay after initiation of interferon (IFN)‐based antiviral therapy, crucial parameters of the in vivo viral kinetics have been estimated, such as the rate of production and clearance of free virus, and the rate of loss of infected cells. Furthermore, by suggesting mechanisms of action for IFN and ribavirin mathematical modelling has provided a means for evaluating and optimizing treatment strategies. Here, we review recent modelling developments for understanding complex viral kinetics patterns, such as triphasic HCV RNA declines and viral rebounds observed in patients treated with pegylated interferon and ribavirin. Moreover, we discuss new modelling approaches developed to interpret the viral kinetics observed in clinical trials with direct‐acting antiviral agents, which induce a rapid decline of wild‐type virus but also engender a higher risk for emergence of drug‐resistant variants. Lastly, as in vitro systems have allowed a better characterization of the virus lifecycle, we discuss new modelling approaches that combine the intracellular and the extracellular viral dynamics.  相似文献   

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BACKGROUND/AIMS: In France, two recent studies enabled modeling of the impact of viral eradication on HCV mortality. METHODS: The French HCV population was simulated from infection to death using a computer-based model. We took into account the impact of alcohol, present screening and antiviral therapy to predict 2006-2025 HCV mortality and to assess the impact of viral eradication. RESULTS: In 2006, the model estimated that among HCV-RNA+, 55% were F0-F1, 18% F2, 22% F3-F4 and 6% had liver complications. The mortality ratio was 11-fold higher in alcoholic patients 40-65 years old. Current therapy will save 14,400 (95% CI, 13,900-15,000) lives compared to absence of therapy. Sensitivity analyses did not change the main results. Contrary to guidelines, if patients F<2 were treated in the same proportions as those with F2, 700 (95% CI, 700-750) lives would be saved. If screening were to reach 75% in 2010, 4 years earlier than model expectation, 950 (95% CI, 900-1000) lives would be saved. If a new molecule improving eradication for genotype 1/4 by 40% were to become available in 2010, 1500 (95% CI, 1400-1600) lives would be saved. CONCLUSIONS: Current therapy is reducing HCV mortality. Therapeutic guidelines must take into account their impact on HCV mortality.  相似文献   

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Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.  相似文献   

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Background/Aims: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation.Methods: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LCTM assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection.Results: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p = 0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3–63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection.Conclusions: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.  相似文献   

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Chronic hepatitis C virus (HCV) infection increases all-cause mortality, rates of cirrhosis, hepatocellular carcinoma, liver transplantation and overall health care utilization. Morbidity and mortality disproportionately affect individuals born between 1945 and 1975. The recent development of well-tolerated and highly effective therapies for chronic HCV infection represents a unique opportunity to dramatically reduce rates of HCV-related complications and their costs. Critical to the introduction of such therapies will be well-designed provincial programming to ensure immediate treatment access to individuals at highest risk for complication, and well-defined strategies to address the global treatment needs of traditionally high-risk and marginalized populations. HCV practitioners in New Brunswick created a provincial strategy that stratifies treatment according to those at highest need, measures clinical impact, and creates evaluation strategies to demonstrate the significant direct and indirect cost savings anticipated with curative treatments.  相似文献   

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The authors of this study note that in liver transplantation (LT), the survival rates of hepatitis C virus (HCV)-positive donors and HCV-negative receivers are comparable to those of HCV-negative donors and recipients. Direct-acting antiviral (DAA) therapies have nearly 100% effectiveness in treating HCV. Between 2006 and 2016, the percentages of HCV-positive patients on the waiting list and HCV-positive LT recipients fell by 8.2 percent and 7.6 percent, respectively. Records from April 1, 2014, in which the donor and receiver were both at least 18 years old and had a positive HCV status, were the only ones eligible for the study. The analysis for this study was restricted to the first transplant recorded for each patient using a data element that documented the number of prior transplants for each recipient, although some recipients appeared multiple times in the data set. HCV-positive recipients or people with fulminant hepatic failure were the main beneficiaries of primary biliary cirrhosis among HCV-positive donors. However, there is still a reticence to use HCV-positive donor organs in HCV recipients due to clinical and ethical considerations. Similar survival rates between HCV-positive donors and recipients and HCV-negative donors and receivers illustrate the efficacy of these DAA regimens.  相似文献   

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《Digestive and liver disease》2018,50(11):1133-1152
Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation.  相似文献   

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正直接抗病毒药物(direct-acting antiviral agents,DAAs)对丙型肝炎的治疗效果已取得突破性进展,持续病毒学应答(sustained virologic response,SVR)高达90%~95%~([1])。目前,DAAs主要包括NS3/4A蛋白酶抑制剂、核苷类NS5B聚合酶抑制剂、非核苷类NS5B聚合酶抑制剂、NS5A抑制剂。自  相似文献   

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BACKGROUNDIn the last few years we have witnessed a revolution in the treatment of hepatitis C virus (HCV) infection. With the introduction of direct-acting antiviral agents (DAAs), sustained virological response (SVR) is achieved in more than 95% of the patients. The focus is now being turned to the global targets set by the World Health Organization, with the aim of achieving HCV elimination by 2030. Prison inmates constitute one of the high-risk groups, and receive treatment less frequently due to several barriers in access to health care.AIMTo describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting, where tertial referral liver center specialists locally provide, on-site assessment and treatment for the prisoners.METHODSA prospective observational study was conducted from April 2017 to March 2020, which included all HCV monoinfected prison inmates in the largest Northern Portugal prison. Demographic, clinical, and laboratory data, as well as transient elastography measurements, were collected onsite by the medical team and prospectively recorded. Patients were treated with DAA according to international guidelines. The primary endpoint was SVR at post-treatment week 12. RESULTSThere were 98 monoinfected HCV male inmates (mean age, 42.7 ± 8.6 years) included in the analysis. Injecting drugs or tattooing were reported in 74.5%, with 38.8% of the latter being done in prison. Alcohol consumption of more than 30 g/d was referred in 69.4%. The most prevalent genotype was 1a (54.1%), followed by 3 (27.6%), 4 (9.2%) and 1b (6.1%). Pretreatment fibrosis degree was mild-to-moderate (F0-F2) in 77.6% and severe in 22.4% (F3-F4). Treatment regimens chosen were: 45.9% elbasvir/grazoprevir, 29.6% sofosbuvir/velpatasvir, and 12.2% sofosbuvir/ledispavir and glecaprevir/pibrentasvir. No major adverse events were observed. SVR at post-treatment week 12 was 99%.CONCLUSIONIn a population considered to be both hard-to-access and a cornerstone for HCV elimination, the onsite evaluation and treatment of HCV-infected prisoners, achieved an exceptional highly effective success rate. This type of collaborative program should be considered to be expanded, to support hepatitis C elimination efforts.  相似文献   

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庄焱  卢捷  谢青  林兰意 《肝脏》2020,(3):249-253
目的了解丙型肝炎肝硬化患者直接抗病毒药物(DAA)治疗现状、短期预后和影响因素。方法选取2015年1月至2019年11月期间于瑞金医院感染科诊治的丙型肝炎肝硬化患者,收集其数据,研究基线特征、DAA方案及疗效和预后的关系。结果共入组161例,DAA治疗者149例;代偿组122例,失代偿组27例;两组在年龄、性别、HCV基因型及干扰素治疗史等方面无显著性差别;两组疗效与安全性均良好,其中SVR12率(99.17%比96.25%,P=0.325)和SVR24率(96.64%比92.0%,P=0.614)均无明显差异;基线肝硬化失代偿期患者中发生肝病进展的比例明显高于代偿期患者(50%vs.13.75%,P=0.000);基线肝硬化失代偿是DAA治疗后短期预后的独立危险因素(HR 6.765,95%Cl:2.866~15.969,P=0.000)。结论基线肝硬化失代偿是DAA治疗后短期预后的独立预测因素。  相似文献   

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The goal of therapy in chronic hepatitis C virus (HCV) infection is sustained virological response (SVR) which reflects HCV eradication. Treatment against HCV has dramatically improved with the recent availability of direct-acting antivirals (DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. Carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant (LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with Child C cirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 mL/min. Drug-drug interactions may still occur with the current DAAs particularly in post-LT patients, in whom simeprevir should not be co-administered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase II clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HCV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplant patients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.  相似文献   

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目的通过对肝移植术后丙型肝炎复发患者进行抗病毒治疗,研究抗病毒治疗效果以及对肝纤维化进展的影响。方法对本院2005年6月至2012年12月收治的23例肝移植术后丙型肝炎复发患者进行干扰素联合利巴韦林抗病毒治疗,观察病毒学应答情况、不良反应以及治疗前后肝组织病理情况。计数资料以例数表示,不同抗病毒疗效组间肝纤维化情况比较采用等级资料秩和检验。结果 12例患者因不良反应终止治疗。23例患者共获得结束时病毒学应答(ETVR)18例,其中6例获得持续病毒学应答(SVR),12例出现反跳。19例患者完成前后肝组织病理检查,SVR组肝纤维化减轻3例、持平1例、进展0例;停药后反跳组肝纤维化减轻2例、持平3例、进展5例;无应答组肝纤维化减轻0例、持平1例、进展4例;3组间抗纤维化效果比较,差异有统计学意义(χ2=7.330,P=0.026)。结论肝移植术后丙型肝炎复发患者抗病毒治疗SVR率较低,有效的抗病毒治疗可延缓肝纤维化进展,取得SVR的患者肝纤维化改善效果最佳。  相似文献   

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Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles.Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed.ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree.ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.  相似文献   

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目的:探讨直接抗病毒药物(direct-acting antiviral agent,DAA)治疗慢性丙型肝炎肝硬化患者实现持续病毒学应答(sustained virologic response, SVR)后的预后及转归。方法:回顾性分析2014年1月至2017年6月于天津市第二人民医院临床诊断为慢性丙型肝炎肝硬化的...  相似文献   

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Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.  相似文献   

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BACKGROUND Infection by the hepatitis C virus(HCV) is currently considered to be a global health issue, with a high worldwide prevalence and causing chronic disease in afflicted individuals. The disease largely involves the liver but it can affect other organs, including the skin. While leukocytoclastic vasculitis has been reported as one of the dermatologic manifestations of HCV infection, there are no reports of this condition as the first symptom of HCV recurrence after liver transplantation.CASE SUMMARY We report here a case of leukocytoclastic vasculitis in a liver transplant recipient on maintenance immunosuppression. The condition presented as a palpable purpura in both lower extremities. Blood and urine cultures were negative and all biochemical tests were normal, excepting evidence of anemia and hypocomplementemia. Imaging examination by computed tomography showed a small volume of ascites, diffuse thickening of bowel walls, and a small bilateral pleural effusion. Skin biopsy showed leukocytoclasia and fibrinoid necrosis.Liver biopsy was suggestive of HCV recurrence in the graft, and HCV polymerase chain reaction yielded 11460 copies/mL and identified the genotype as 1 A. Treatment of the virus with a 12-wk direct-acting antiviral regimen of ribavirin, sofosbuvir and daclatasvir led to regression of the symptoms within the first 10 d and subsequent complete resolution of the symptoms.CONCLUSION This case highlights the difficulties of diagnosing skin lesions caused by HCVinfection in immunosuppressed patients.  相似文献   

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