Seroconversion to Human Herpesvirus 6 following Liver Transplantation Is a Marker of Cytomegalovirus Disease

Dockrell, David H.; Prada, José Antonio Vázquez de; Jones, Mary F.; Patel, Robin; Badley, Andrew D.; Harmsen, William S.; Ilstrup, Duane M.; Wiesner, Russell H.; Krom, Ruud A.F.; Smith, Thomas F.; Payá, Carlos V.

doi:10.1086/514104

Cited by 120 publications

(92 citation statements)

References 34 publications

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“…Indeed, reactivation of HHV6 in transplant recipients experiencing primary CMV infection has been reported. [67][68][69] However, we found that this was not the case in our patient population. Although many of the eight samples with high CMV levels also demonstrated detectable EBV and/or HHV7 virus, they were present at low levels.…”

Section: Predictive Value Of Quantitative Pcrcontrasting

confidence: 71%

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Bai

Rogers

Harkins

et al. 2000

The Journal of Molecular Diagnostics

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Human herpesviruses can cause significant morbidity and mortality in pediatric solid organ transplant recipients. It was hypothesized that viral burden quantification by polymerase chain reaction using an internal calibration standard could aid in distinguishing between viral disease and latency. Here we report the results of a 2-year prospective study of 27 pediatric solid organ (liver, kidney, or heart) transplant recipients in which multiple samples were analyzed for levels of all eight human herpesviruses by internal calibration standard-polymerase chain reaction. Herpes simplex viruses 1 and 2, varicella-zoster virus, and Kaposi's sarcoma-associated herpesvirus were not detected in any of these samples. Human herpesvirus types 6 and 7 were detected in half of the patients, but were present at low levels, similar to those found in reference populations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were detected in 89% and 56% of the patients, respectively. Viral burden analysis suggested distinct patient populations for CMV, with a natural cutoff of 10,000 viral targets/ml blood strongly associated with disease. In some cases, a dramatic increase in CMV levels preceded clinical evidence of disease by several weeks. EBV viral burden was relatively high in the only patient presenting with an EBV syndrome. However, two other patients without evidence of EBV disease had single samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred with antiviral treatment. These data suggest that viral burden analysis using internal calibration standard-polymerase chain reaction for CMV, and possibly other herpesviruses, is an effective method for monitoring pediatric transplant patients for significant herpesvirus infection and response to therapy.

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Section: Predictive Value Of Quantitative Pcrcontrasting

confidence: 71%

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Bai

Rogers

Harkins

et al. 2000

The Journal of Molecular Diagnostics

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“…As a result of several in vitro analyses, HHV-6 has been demonstrated to have immunomodulatory effects such as impaired T cell activation, decreased cytokine synthesis, and impaired dendritic cell functions. [37][38][39][40] Although several investigators have suggested that HHV-6 infection is positively associated with CMV disease 15,17,18 and fungal infection 7 in liver transplant recipients, a definitive association between HHV-6 infection and these opportunistic infections remains unclear. This study showed no association between HHV-6 reactivation and CMV antigenemia or fungal infection.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to cytomegalovirus (CMV), a well-known pathogen in immunocompromised patients, it has been proposed that human herpesvirus 6 (HHV-6) is also an opportunistic pathogen in liver transplant recipients. 1,2 Many investigators have studied the clinical features of HHV-6 infection in liver transplant recipients, using viral isolation, [3][4][5][6][7][8][9] antigenemia assay, [10][11][12][13][14] serological analysis, 15,16 and molecular analysis such as real-time polymerase chain reaction (PCR). [17][18][19][20][21][22] Several clinical features, including fever, 5,6,8,10 encephalitis, 7,23 CMV disease, 15,17,18 fungal infection, 7 graft dysfunction, 10,11,22 and hepatitis C virus (HCV) recurrence 9,19 after transplantation, have been suggested as clinical manifestations due to HHV-6 infection.…”

mentioning

confidence: 99%

Human herpesvirus 6 infection in adult living related liver transplant recipients

et al. 2007

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To analyze human herpesvirus 6 (HHV-6) infection in adult living related liver transplantation, we performed a virological analysis, including viral isolation, serological assay, and real-time polymerase chain reaction, of serially collected blood samples from 67 recipients. In addition, cytokine levels were measured to determine their role in viral reactivation. HHV-6 was isolated from only 4 recipients (6.0%), and viral DNA was detected in 15 (22.4%) of the 67 recipients. A significant increase in HHV-6 immunoglobulin G antibody titers was observed in 19 (28.4%) of the 67 recipients. Finally, 26 recipients (38.8%) had HHV-6 reactivation 2-6 weeks after transplantation. HHV-6 associated clinical features were analyzed in the 17 recipients presenting with either viremia or DNAemia. Two recipients with viremia and 3 recipients with DNAemia had unexplained fever at the time of viral infection. An increase in aminotransferase levels was observed in 2 recipients with viremia and 3 recipients with DNAemia. Recipients with liver cirrhosis caused by hepatitis B virus or hepatitis C virus infection as the underlying disease were more likely to have HHV-6 infection (P ϭ 0.025). Mortality at the last follow-up in recipients with HHV-6 reactivation was significantly higher than in those without viral reactivation (P ϭ 0.0118). Plasma interleukin-6 levels were significantly higher in the recipients with HHV-6 viremia than in the recipients without viremia at 4 weeks post-transplant (P ϭ 0.0411). Moreover, tumor necrosis factor ␣ levels were also higher in recipients with HHV-6 viremia (P Ͻ 0.0001) or reactivation (P ϭ 0.0011) than in recipients without viremia or reactivation 4 weeks post-transplant.

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“…However, it was lymphocytopenia (predominantly less CD4 + T lymphocytes) rather than severe acute GVHD that was related to the development of CMV diseases. 28 Dockrell et al 29 have reported that seroconversion to HHV-6 after liver transplantation can be a marker of CMV disease. Likewise, active CMV infection was related to HHV-6 isolation after allogeneic BMT.…”

Section: Discussionmentioning

confidence: 99%

Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation

Wang

Linde

Dahl

et al. 1999

Bone Marrow Transplant

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Summary:Human herpesvirus 6 (HHV-6) infection and the HHV-6-specific lymphocyte proliferation response were studied longitudinally in 24 patients in the first 3 months after allogeneic stem cell transplantation (allo-SCT). HHV-6 DNAemia was analyzed by a nested PCR method, and the HHV-6-specific lymphocyte proliferation responses were evaluated with a standard lymphocyte proliferation assay. All patients who responded to HHV-6 GS (variant A) antigen also responded to HHV-6 Z29 (variant B) antigen, and a response to HHV-6 Z29 antigen was detected more often than to HHV-6 GS antigen after allo-SCT (P = 0.048). HHV-6 DNA was detected in more patients after than before transplantation (P = 0.01) and in more patients with acute GVHD grades II-IV than those without (P = 0.009). An HHV-6-specific proliferative response was more often detected in patients without, than in those with persistent HHV-6 infection (three consecutively positive PBL samples; P Ͻ 0.001). Patients with persistent HHV-6 infection had lower lymphocyte counts from the 8th week after transplantation than those without (P = 0.03). No HHV-6-specific proliferation responses were detected in the three patients who developed HHV-6 disease. HHV-6 infection was associated with persistent lymphocytopenia and might thereby inhibit immune function.

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Seroconversion to Human Herpesvirus 6 following Liver Transplantation Is a Marker of Cytomegalovirus Disease

Cited by 120 publications

References 34 publications

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Human herpesvirus 6 infection in adult living related liver transplant recipients

Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation

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