Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increase...Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D+/R-serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specif ic CD4+ and CD8+ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-). However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being performed comparing the展开更多
Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness of...Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferredstrategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/Rliver transplant recipients, and such occurrence of lateonset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach(antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effect展开更多
AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was reviewed and approved...AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus(CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection.RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D^+/R^- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 receivedprophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients(14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16(23.5%) vs n = 3(4.9%), P = 0.003)].CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver transplantation.展开更多
Cytomegalovirus (CMV) is the most common viral pa- thogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often ac com panied by bone marrow suppression, and in some cases, i...Cytomegalovirus (CMV) is the most common viral pa- thogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often ac com panied by bone marrow suppression, and in some cases, invades tissues including the transplanted allog raft. In addition, CMV has been signif icantly asso- ciated with an increased predisposition to allograft re- jection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall pa tient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver trans plant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the preven tion of CMV disease in high-risk recipients [CMV-ser o-negative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylax is has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if fea sible, one should also reduce the degree of immuno-suppression. In one recent controlled clinical trial, val ganc iclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to mo d erate CMV disease in solid organ (including liver) tran splant recipients. In this article, the authors review the current state and the future 展开更多
Cytomegalovirus(CMV)infection is one of the primary causes of morbidity and mortality following liver transplantation(LT).Based on current worldwide guidelines,the most effective strategies for avoiding post-transplan...Cytomegalovirus(CMV)infection is one of the primary causes of morbidity and mortality following liver transplantation(LT).Based on current worldwide guidelines,the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment.CMV-IgG serology is the established technique for pretransplant screening of both donors and recipients.The clinical presentation of CMV infection and disease exhibits variability,prompting clinicians to consistently consider this possibility,partic-ularly within the first year post-transplantation or subsequent to heightened immunosuppression.At annual symposia to discuss CMV prevention and how treatment outcomes can be improved,evidence on the incorporation of immune functional tests into clinical practice is presented,and the results of studies with new antiviral treatments are evaluated.Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation,a consensus reflected in the guidelines has not been formed.Determining the most appro-priate strategy at the individual level appears to be the key to enhancing out-comes.Although prevention strategies reduce the risk of CMV disease,the disease can still occur in up to 50%of high-risk patients.A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients.The objective of this study was to establish a compre-hensive framework for the management of CMV in patients who have had LT.展开更多
Background Despite its widespread use in the management of HIV-related cytomegalovirus （CMV） infection, there have been surprisingly few reports of the use of valganciclovir （VGC） in the post-allotransplant settin...Background Despite its widespread use in the management of HIV-related cytomegalovirus （CMV） infection, there have been surprisingly few reports of the use of valganciclovir （VGC） in the post-allotransplant setting.So far, no multi-center, non-crossover trial data have been available with the use of this drug as the primary pre-emptive.The present study evaluated the efficacy and safety of VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem cell transplantation （HSCT）.Methods From January to April 2007, VGC was adopted in eleven centers in China's Mainland for pre-emptive therapy of CMV infection in consecutive patients undergoing allogeneic HSCT.Allogeneic HSCT recipients were followed weekly via CMV pp65 antigenemia assay or real-time quantitative polymerase chain reaction （PCR） for detection of CMV-DNA.Patients with a positive assay were treated with VGC, 900 mg P.O.twice a day for 14 days followed by 900 mg P.O.once a day for 14 days after a negative result or the CMV-DNA load was lower.Results A total of 54 patients （15 siblings, 28 mismatched related donors, 11 unrelated donors） had a positive assay treated with oral VGC.The seroconversion rate was 89% （48/54） as confirmed by a negative assay; six patients failed oral VGC.No significant toxicity was encountered.No case of CMV disease was diagnosed in the responding patients with a median follow-up of 5.3 months after the drug administration.Conclusion Pre-emptive therapy of CMV viraemia with oral VGC is safe and effective in allogeneic HSCT.展开更多
Cytomegalovirus(CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years,a...Cytomegalovirus(CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years,and clinical guidelines have been recently updated.Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currentlyrecruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries.Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir(AIC246) and brincidofovir(CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.展开更多
文摘Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D+/R-serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specif ic CD4+ and CD8+ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-). However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being performed comparing the
文摘Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferredstrategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/Rliver transplant recipients, and such occurrence of lateonset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach(antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effect
文摘AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus(CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection.RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D^+/R^- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 receivedprophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients(14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16(23.5%) vs n = 3(4.9%), P = 0.003)].CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver transplantation.
文摘Cytomegalovirus (CMV) is the most common viral pa- thogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often ac com panied by bone marrow suppression, and in some cases, invades tissues including the transplanted allog raft. In addition, CMV has been signif icantly asso- ciated with an increased predisposition to allograft re- jection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall pa tient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver trans plant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the preven tion of CMV disease in high-risk recipients [CMV-ser o-negative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylax is has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if fea sible, one should also reduce the degree of immuno-suppression. In one recent controlled clinical trial, val ganc iclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to mo d erate CMV disease in solid organ (including liver) tran splant recipients. In this article, the authors review the current state and the future
文摘Cytomegalovirus(CMV)infection is one of the primary causes of morbidity and mortality following liver transplantation(LT).Based on current worldwide guidelines,the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment.CMV-IgG serology is the established technique for pretransplant screening of both donors and recipients.The clinical presentation of CMV infection and disease exhibits variability,prompting clinicians to consistently consider this possibility,partic-ularly within the first year post-transplantation or subsequent to heightened immunosuppression.At annual symposia to discuss CMV prevention and how treatment outcomes can be improved,evidence on the incorporation of immune functional tests into clinical practice is presented,and the results of studies with new antiviral treatments are evaluated.Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation,a consensus reflected in the guidelines has not been formed.Determining the most appro-priate strategy at the individual level appears to be the key to enhancing out-comes.Although prevention strategies reduce the risk of CMV disease,the disease can still occur in up to 50%of high-risk patients.A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients.The objective of this study was to establish a compre-hensive framework for the management of CMV in patients who have had LT.
文摘Background Despite its widespread use in the management of HIV-related cytomegalovirus （CMV） infection, there have been surprisingly few reports of the use of valganciclovir （VGC） in the post-allotransplant setting.So far, no multi-center, non-crossover trial data have been available with the use of this drug as the primary pre-emptive.The present study evaluated the efficacy and safety of VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem cell transplantation （HSCT）.Methods From January to April 2007, VGC was adopted in eleven centers in China's Mainland for pre-emptive therapy of CMV infection in consecutive patients undergoing allogeneic HSCT.Allogeneic HSCT recipients were followed weekly via CMV pp65 antigenemia assay or real-time quantitative polymerase chain reaction （PCR） for detection of CMV-DNA.Patients with a positive assay were treated with VGC, 900 mg P.O.twice a day for 14 days followed by 900 mg P.O.once a day for 14 days after a negative result or the CMV-DNA load was lower.Results A total of 54 patients （15 siblings, 28 mismatched related donors, 11 unrelated donors） had a positive assay treated with oral VGC.The seroconversion rate was 89% （48/54） as confirmed by a negative assay; six patients failed oral VGC.No significant toxicity was encountered.No case of CMV disease was diagnosed in the responding patients with a median follow-up of 5.3 months after the drug administration.Conclusion Pre-emptive therapy of CMV viraemia with oral VGC is safe and effective in allogeneic HSCT.
文摘Cytomegalovirus(CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years,and clinical guidelines have been recently updated.Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currentlyrecruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries.Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir(AIC246) and brincidofovir(CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.
