Portal vein thrombosis(PVT)is one of the most common serious complications in patients with liver cirrhosis.The occurrence of PVT not only aggravates the condition of liver cirrhosis but can also cause several serious...Portal vein thrombosis(PVT)is one of the most common serious complications in patients with liver cirrhosis.The occurrence of PVT not only aggravates the condition of liver cirrhosis but can also cause several serious complications,such as portal hypertension,esophagogastric variceal bleeding,and refractory ascites.All these factors have a serious impact on patients’quality of life and prognosis.This article evaluates the current evidence on the management of PVT in cirrhosis and explores the role of direct oral anticoagulants,but data on individualized anticoagulation strategies are limited and lacking for the treatment of PVT in cirrhosis,and it is hoped that it will inform a broad range of clinicians on the treatment of cirrhosis combined with PVT.展开更多
Chronic hepatitis C virus(HCV)infection is the principal etiology of cirrhosis and,ultimately,hepatocellular carcinoma(HCC).At present,approximately 71 million people are chronically infected with HCV,and 10%–20%of t...Chronic hepatitis C virus(HCV)infection is the principal etiology of cirrhosis and,ultimately,hepatocellular carcinoma(HCC).At present,approximately 71 million people are chronically infected with HCV,and 10%–20%of these are expected to develop severe liver complications throughout their lifetime.Scientific evidence has clearly shown the causal association between miRNAs,HCV infection and HCC.Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development,variations in miRNA patterns have been described in different liver diseases,including HCC.Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis.In this Review,we aim to summarize current knowledge on the association between miRNA,HCV and HCC from a diagnostic point of view,and also the potential implications for therapeutic approaches.展开更多
Hepatitis C virus(HCV) affects about 3% of the world'spopulation, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution(highest in developing c...Hepatitis C virus(HCV) affects about 3% of the world'spopulation, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution(highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.展开更多
Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the pres...Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5 A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-totreat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.展开更多
Hepatitis C virus(HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endp...Hepatitis C virus(HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminarydata, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals(DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.展开更多
AIM To evaluate the efficacy of direct-acting antivirals(DAAs) in Kanto Rosai Hospital. METHODS All patients with hepatitis C virus(HCV) who underwent DAA prescription were enrolled in this study. The present study wa...AIM To evaluate the efficacy of direct-acting antivirals(DAAs) in Kanto Rosai Hospital. METHODS All patients with hepatitis C virus(HCV) who underwent DAA prescription were enrolled in this study. The present study was a single center retrospective analysis using patients infected with HCV genotype 1 or 2. Resistance analysis was performed by using direct sequencing and cycleave PCR in genotype 1 patients treated with interferon(IFN)-free DAA. The primary endpoint was sustained virologic response at 12 wk after therapy(SVR12).RESULTS A total of 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + IFN + ribavirin and all achieved SVR. Of the 119 patients who received IFN-free DAA(in different combinations), 102 achieved SVR and 9 failed(7/9 were on daclatasvir/asunaprevir and 2/9 on ledipasvir/sofosbuvir). Efficacy analysis was done only for 43 patients who received daclatasvir/asunaprevir. From this analysis, Y93 resistance-associated substitutions were significantly correlated with SVR.CONCLUSION The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5 A resistance-associated substitutions that are selected by HCV NS5 A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.展开更多
BACKGROUND Direct-acting antiviral(DAA)therapy regimens are highly effective at eliminating hepatitis C virus(HCV)infection but rates of sustained virologic response(SVR)are lower in patients with decompensated cirrho...BACKGROUND Direct-acting antiviral(DAA)therapy regimens are highly effective at eliminating hepatitis C virus(HCV)infection but rates of sustained virologic response(SVR)are lower in patients with decompensated cirrhosis or hepatocellular carcinoma.Since many of these patients will be referred for liver transplant,they will require retreatment after transplantation.Sofosbuvir/velpatasvir/voxilaprevir(SOF/VEL/VOX)is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data.CASE SUMMARY We present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant.CONCLUSION This case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting.Treatment was successful with all patients achieving SVR,it was well tolerated,and there were minimal drug-drug interactions with their immunosuppressants.展开更多
Hepatitis B and C viruses(HBV and HCV), both cause serious chronic infections leading to fatal liver diseases. The prototype therapy for both HBV and HCV was based on IFN-α with or without ribavirin. The advent of di...Hepatitis B and C viruses(HBV and HCV), both cause serious chronic infections leading to fatal liver diseases. The prototype therapy for both HBV and HCV was based on IFN-α with or without ribavirin. The advent of direct-acting antivirals(DAA) for both HBV and HCV has remarkably improved the standard of treatment for both infections. While HCV can be eliminated following combination DAA therapy, HBV persists even after treatment, requiring life-long therapy with DAAs. Treatment with DAAs is also associated with high cost, the development of resistance and side effects. There is ample published evidence that both HBV and HCV can be eliminated from infected host cells through noncytolytic immune mechanisms. We need to identify the mechanisms behind this successful elimination of replicating viruses and develop them into novel immunotherapeutic regimens. Moreover, a synergy of, chemo- and immuno-therapeutic strategies will be necessary to eradicate HBV or HCV from a host.展开更多
BACKGROUND Hepatitis C virus(HCV)infection is a major global public health problem.In the Republic of Cyprus,the estimated prevalence of chronic hepatitis C(CHC)among the general population is 0.6%,while the CHC preva...BACKGROUND Hepatitis C virus(HCV)infection is a major global public health problem.In the Republic of Cyprus,the estimated prevalence of chronic hepatitis C(CHC)among the general population is 0.6%,while the CHC prevalence among people who inject drugs(PWID)is estimated at 46%.Direct-acting antivirals that can eliminate HCV are not yet widely available in the Republic of Cyprus.However,when direct-acting antivirals become available,a long-term strategic plan to guide elimination efforts will be needed to maximize the effect of treatment.AIM To determine the programmatic targets to eliminate HCV in the Republic of Cyprus.METHODS A dynamic,stochastic,individual-based model of HCV transmission,disease progression,and cascade of care was calibrated to data from Cyprus.The model stratifies the population into the infected general population and the PWID population.A variety of test,prevention,and treatment strategies concerning the general population,PWID,or both were examined.The time horizon of the analysis was until 2034.RESULTS Under the status quo scenario,the model predicted that 75(95%confidence interval(CI):60,91)and 575(95%CI:535,615)liver-related deaths and new infections would occur by 2034,respectively.Launching an expanded treatment program,without screening interventions,would cause modest outcomes regarding CHC prevalence(16.6%reduction in 2034 compared to 2020)and liverrelated deaths(10 deaths would be prevented compared to the status quo scenario by 2034).Implementing a test and treat strategy among the general population but without any intervention in the PWID population would suffice to meet the mortality target but not the incidence target.To achieve HCV elimination in Cyprus,3080(95%CI:3000,3200)HCV patients need to be diagnosed and treated by 2034(2680 from the general population and 400 from PWID),and harm reduction coverage among PWID should be increased by 3%per year(from 25%in 2020 to 67%in 2034).CONCLUSION Elimination of HCV is a demanding public health strategy,which requires significant interventions both among the general population and high-risk groups.展开更多
基金Supported by the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_2067Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH123009-079.
文摘Portal vein thrombosis(PVT)is one of the most common serious complications in patients with liver cirrhosis.The occurrence of PVT not only aggravates the condition of liver cirrhosis but can also cause several serious complications,such as portal hypertension,esophagogastric variceal bleeding,and refractory ascites.All these factors have a serious impact on patients’quality of life and prognosis.This article evaluates the current evidence on the management of PVT in cirrhosis and explores the role of direct oral anticoagulants,but data on individualized anticoagulation strategies are limited and lacking for the treatment of PVT in cirrhosis,and it is hoped that it will inform a broad range of clinicians on the treatment of cirrhosis combined with PVT.
文摘Chronic hepatitis C virus(HCV)infection is the principal etiology of cirrhosis and,ultimately,hepatocellular carcinoma(HCC).At present,approximately 71 million people are chronically infected with HCV,and 10%–20%of these are expected to develop severe liver complications throughout their lifetime.Scientific evidence has clearly shown the causal association between miRNAs,HCV infection and HCC.Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development,variations in miRNA patterns have been described in different liver diseases,including HCC.Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis.In this Review,we aim to summarize current knowledge on the association between miRNA,HCV and HCC from a diagnostic point of view,and also the potential implications for therapeutic approaches.
文摘Hepatitis C virus(HCV) affects about 3% of the world'spopulation, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution(highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.
文摘Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5 A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-totreat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.
文摘Hepatitis C virus(HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminarydata, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals(DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.
基金Supported by research funds to promote the Hospital functions of the Japan Organization of Occupational Health and SafetyNo.359
文摘AIM To evaluate the efficacy of direct-acting antivirals(DAAs) in Kanto Rosai Hospital. METHODS All patients with hepatitis C virus(HCV) who underwent DAA prescription were enrolled in this study. The present study was a single center retrospective analysis using patients infected with HCV genotype 1 or 2. Resistance analysis was performed by using direct sequencing and cycleave PCR in genotype 1 patients treated with interferon(IFN)-free DAA. The primary endpoint was sustained virologic response at 12 wk after therapy(SVR12).RESULTS A total of 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + IFN + ribavirin and all achieved SVR. Of the 119 patients who received IFN-free DAA(in different combinations), 102 achieved SVR and 9 failed(7/9 were on daclatasvir/asunaprevir and 2/9 on ledipasvir/sofosbuvir). Efficacy analysis was done only for 43 patients who received daclatasvir/asunaprevir. From this analysis, Y93 resistance-associated substitutions were significantly correlated with SVR.CONCLUSION The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5 A resistance-associated substitutions that are selected by HCV NS5 A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.
文摘BACKGROUND Direct-acting antiviral(DAA)therapy regimens are highly effective at eliminating hepatitis C virus(HCV)infection but rates of sustained virologic response(SVR)are lower in patients with decompensated cirrhosis or hepatocellular carcinoma.Since many of these patients will be referred for liver transplant,they will require retreatment after transplantation.Sofosbuvir/velpatasvir/voxilaprevir(SOF/VEL/VOX)is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data.CASE SUMMARY We present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant.CONCLUSION This case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting.Treatment was successful with all patients achieving SVR,it was well tolerated,and there were minimal drug-drug interactions with their immunosuppressants.
文摘Hepatitis B and C viruses(HBV and HCV), both cause serious chronic infections leading to fatal liver diseases. The prototype therapy for both HBV and HCV was based on IFN-α with or without ribavirin. The advent of direct-acting antivirals(DAA) for both HBV and HCV has remarkably improved the standard of treatment for both infections. While HCV can be eliminated following combination DAA therapy, HBV persists even after treatment, requiring life-long therapy with DAAs. Treatment with DAAs is also associated with high cost, the development of resistance and side effects. There is ample published evidence that both HBV and HCV can be eliminated from infected host cells through noncytolytic immune mechanisms. We need to identify the mechanisms behind this successful elimination of replicating viruses and develop them into novel immunotherapeutic regimens. Moreover, a synergy of, chemo- and immuno-therapeutic strategies will be necessary to eradicate HBV or HCV from a host.
基金the Onisilos Funding Scheme of the University of Cyprus.
文摘BACKGROUND Hepatitis C virus(HCV)infection is a major global public health problem.In the Republic of Cyprus,the estimated prevalence of chronic hepatitis C(CHC)among the general population is 0.6%,while the CHC prevalence among people who inject drugs(PWID)is estimated at 46%.Direct-acting antivirals that can eliminate HCV are not yet widely available in the Republic of Cyprus.However,when direct-acting antivirals become available,a long-term strategic plan to guide elimination efforts will be needed to maximize the effect of treatment.AIM To determine the programmatic targets to eliminate HCV in the Republic of Cyprus.METHODS A dynamic,stochastic,individual-based model of HCV transmission,disease progression,and cascade of care was calibrated to data from Cyprus.The model stratifies the population into the infected general population and the PWID population.A variety of test,prevention,and treatment strategies concerning the general population,PWID,or both were examined.The time horizon of the analysis was until 2034.RESULTS Under the status quo scenario,the model predicted that 75(95%confidence interval(CI):60,91)and 575(95%CI:535,615)liver-related deaths and new infections would occur by 2034,respectively.Launching an expanded treatment program,without screening interventions,would cause modest outcomes regarding CHC prevalence(16.6%reduction in 2034 compared to 2020)and liverrelated deaths(10 deaths would be prevented compared to the status quo scenario by 2034).Implementing a test and treat strategy among the general population but without any intervention in the PWID population would suffice to meet the mortality target but not the incidence target.To achieve HCV elimination in Cyprus,3080(95%CI:3000,3200)HCV patients need to be diagnosed and treated by 2034(2680 from the general population and 400 from PWID),and harm reduction coverage among PWID should be increased by 3%per year(from 25%in 2020 to 67%in 2034).CONCLUSION Elimination of HCV is a demanding public health strategy,which requires significant interventions both among the general population and high-risk groups.
