Hepatitis B virus reactivation after heart transplant: Incidence and clinical impact

Vitrone, Martina; Iossa, Domenico; Rinaldi, Luca; Pafundi, Pia Clara; Molaro, Rosa; Parrella, Antonio; Andini, Roberto; Ragone, Enrico; Maiello, Ciro; Zampino, Rosa; Durante‐Mangoni, Emanuele

doi:10.1016/j.jcv.2017.09.011

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…After removing 212 duplicates, 2,117 were excluded based on title and abstract screening, and 20 were excluded after full-text screening (Fig 1). Finally, 16 studies were included in the final meta-analysis [7,8,14,15,[22][23][24][25][26][27][28][29][30][31][32][33]. The inter-reviewer agreement was excellent, with a kappa statistic of 0.94.…”

Section: Resultsmentioning

confidence: 99%

Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis

Yin

Zhang

et al. 2023

PLoS Med

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Background Current guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients with resolved HBV infection, even in anti-hepatitis B surface antigen (anti-HBs)-negative recipients and those receiving intense immunosuppression. This systematic review and meta-analysis aimed to determine the incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver SOT recipients. Methods and findings Three databases (PubMed, Embase, and Cochrane Library) were systematically searched up to December 31, 2022. Clinical studies reporting HBV reactivation in non-liver SOT recipients were included. Case reports, case series, and cohort studies with a sample size of less than 10 patients were excluded. Random-effects analysis was used for all meta-analyses. We included 2,913 non-liver SOT recipients with resolved HBV infection from 16 retrospective cohort studies in the analysis. The overall HBV reactivation rate was 2.5% (76/2,913; 95% confidence interval [95% CI 1.6%, 3.6%]; I2 = 55.0%). Higher rates of reactivation were observed in recipients with negative anti-HBs (34/421; 7.8%; 95% CI [5.2%, 10.9%]; I2 = 36.0%) by pooling 6 studies, experiencing acute rejection (13/266; 5.8%; 95% CI [2.3%, 14.5%]; I2 = 63.2%) by pooling 3 studies, receiving ABO blood type-incompatible transplantation (8/111; 7.0%; 95% CI [2.9%, 12.7%]; I2 = 0%) by pooling 3 studies, receiving rituximab (10/133; 7.3%; 95% CI [3.4%, 12.6%]; I2 = 0%) by pooling 3 studies, and receiving anti-thymocyte immunoglobulin (ATG, 25/504; 4.9%; 95% CI [2.5%, 8.1%]; I2 = 49.0%) by pooling 4 studies. Among recipients with post-transplant HBV reactivation, 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) developed HBV-related hepatic failure, and 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) had HBV-related death. Negative anti-HBs (crude odds ratio [OR] 5.05; 95% CI [2.83, 9.00]; p < 0.001; I2 = 0%), ABO blood type-incompatible transplantation (crude OR 2.62; 95% CI [1.05, 6.04]; p = 0.040; I2 = 0%), history of acute rejection (crude OR 2.37; 95% CI [1.13, 4.97]; p = 0.022; I2 = 0%), ATG use (crude OR 3.19; 95% CI [1.48, 6.87]; p = 0.003; I2 = 0%), and rituximab use (crude OR 3.16; 95% CI [1.24, 8.06]; p = 0.016; I2 = 0%) increased the risk of reactivation. Adjusted analyses reported similar results. Limitations include moderate heterogeneity in the meta-analyses and that most studies were conducted in kidney transplant recipients. Conclusions Non-liver SOT recipients with resolved HBV infection have a high risk of HBV-related hepatic failure and HBV-related death if HBV reactivation occurs. Potential risk factors for HBV reactivation include rituximab use, anti-thymocyte immunoglobulin use, anti-HBs negative status, acute rejection history, and ABO blood type-incompatible transplantation. Further research on monitoring and routine antiviral prophylaxis of non-liver SOT recipients at higher risk of HBV reactivation is required.

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Section: Resultsmentioning

confidence: 99%

Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis

Yin

Zhang

et al. 2023

PLoS Med

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“…In certain cases, histological diagnosis is difficult to establish in a viral infection that is associated with inflammation and necrosis, especially when there are no microorganisms directly associated with the infection. Sometimes it is difficult to differentiate a virus-induced lesion from an acute rejection (26,27). In these instances the results of the initial biopsy (with differential diagnosis difficulties) are compared with the results of subsequent biopsies, performed after specific treatment for the infection have already been administered.…”

Section: Discussionmentioning

confidence: 99%

Essentials in the diagnosis of postoperative myocardial lesions similar to or unrelated to rejection in heart transplant

Dumitru

Zazgyva

Habor

et al. 2021

Revista Romana De Medicina De Laborator

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Background, objectives: Histological diagnosis of control biopsies in patients with heart transplant represents a significant step of monitoring, with a great influence on adjusting immunosuppressive treatment. Histological lesions are usually related to ischemia and reperfusion, with varying degrees of intensity. This study aimed to highlight the most important aspects of the histological diagnosis and differential diagnosis of postoperative myocardial lesions associated or unrelated to rejection in heart transplant. Materials and Methods: This retrospective study involved 53 patients who received cardiac transplant between 2000 and 2017. Patients were monitored by lesion quantification of endomyocardial biopsies, with diagnoses established based on biopsy material in the early, medium and late post-transplant periods. Hematoxylin eosin, Masson’s trichrome, and Van Gieson stains were used; immunohistochemical determinations used CD4, CD20, CD45, CD68, HLA-DR, VEGF and CD31. Results: Ischemia and reperfusion lesions were diagnosed on all biopsies in the first 6 weeks post-transplant. Nine cases of the Quilty effect were identified, and in 12 cases, the biopsies were performed on the same spot as previous biopsies. A significant number of transplanted patients presented cytomegalovirus that was difficult to diagnose on endomyocardial biopsies. Conclusions: The detailed study of ischemia and reperfusion lesions, as well as of changes un-related to rejection becomes a major objective in the short, medium and late post-transplant period. Overdiagnosis of rejection induces changes of the immunosuppressive therapeutic protocol, with alarming repercussions on cytomegalovirus reactivation, and risks of potentiating inflammation, myocyte destruction and the recurrence of disorders related to both inducing and aggravating heart failure.

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“…In contrast, virological events of uncertain significance (VEUS, ie, intermittently positive HBV‐DNA only with high‐sensitivity qualitative nested PCR) were observed in five of the remaining 10 recipients. The single patient with definite HBV reactivation was treated with entecavir before ALT elevation, while the other subjects were only followed up and none of them developed clinical signs of liver injury . Although the clinical significance of such VEUS appeared to be negligible in our patients, they could imply persistence of covalently closed circular HBV‐DNA (cccDNA) within hepatocytes.…”

Section: Introductionmentioning

confidence: 86%

“…Hepatitis B virus (HBV) reactivation in immunosuppressed HBsAg−/anti‐HBc+/HBV‐DNA− patients has been described in various clinical settings. We recently analyzed this phenomenon in 11 heart transplant recipients with markers of prior HBV infection (anti‐HBc+/±anti‐HBs+/HBVDNA−, thereafter referred to as “past HBV”), searching HBV‐DNA by high‐sensitivity qualitative nested PCR in sera obtained before transplant and for a median period of 30 months after transplant …”

Section: Introductionmentioning

confidence: 99%

Hepatitis B core‐related antigen to detect hepatitis B virus (HBV) reactivation in heart transplant recipients with past HBV infection: A pilot study

Iossa

Vitrone

Liotti

et al. 2019

Clinical Transplantation

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Hepatitis B virus (HBV) reactivation in immunosuppressed HBsAg−/anti-HBc+/HBV-DNA− patients has been described in various clinical settings. We recently analyzed this phenomenon in 11 heart transplant recipients with markers of prior HBV infection (anti-HBc+/±anti-HBs+/HBVDNA−, thereafter referred to as "past HBV"), searching HBV-DNA by high-sensitivity qualitative nested PCR in sera obtained before transplant and for a median period of 30 months after transplant. 1 A definite HBV reactivation (HBV-DNA detectable in serum with standard, commercially available methods) was observed in only one of these 11 past HBV recipients. In contrast, virological events of uncertain significance (VEUS, ie, intermittently positive HBV-DNA only with high-sensitivity qualitative nested PCR) were observed in five of the remaining 10 recipients. The single patient with definite HBV reactivation was treated with entecavir before ALT elevation, while the other subjects were only followed up and none of them developed clinical signs of liver injury. 1 Although the clinical significance of such VEUS appeared to be negligible in our patients, they could imply persistence of covalently closed circular HBV-DNA (cccDNA) within hepatocytes. Recently, cccDNA was found to correlate with a novel serological marker of HBV infection, named hepatitis B core-related antigen (HBcrAg). HBcrAg derives from denatured hepatitis B e antigen (HBeAg), HBV core antigen and a core-related protein (p22cr). SerumHBcrAg levels correlate mostly with serum HBV-DNA 2 and cccDNA, but also with quantitative HBsAg (QT-HBsAg). 3 Thus, HBcAg could be used to monitor intrahepatic viral status 2 in different phases of the natural history of HBV infection 4 and to early detect HBV reactivation after discontinuing antiviral therapy or when immune suppression occurs. 5 However, no data are available regarding the significance of HBcrAg in solid organ transplant recipients with past HBV infection.Accordingly, we designed this study to assess whether HBcrAg levels could be used as a measure of HBV reactivation after heart transplant.Our aims were to study the dynamics of this novel marker of HBV replication in such immunosuppressed past HBV-infected patients and assess its possible correlation with QT-HBsAg and HBV-DNA detected by high-sensitivity PCR. AbstractHepatitis B core-related antigen (HBcrAg) has been proposed as a new marker of hepatitis B virus (HBV) replication. We analyzed HBcrAg dynamics in 15 heart transplant recipients with active or prior HBV infection and correlated it with quantitative (QT)-HBsAg and HBV-DNA pre-and post-transplant. Serum HBcrAg was detected in HBsAg/HBV-DNA-positive subjects but not in recipients with past HBV infection. HBcrAg levels correlated with QT-HBsAg in pre-and post-transplant samples.In prior HBV infection, HBcrAg levels were unrelated to HBV-DNA positivity. In heart transplant recipients with prior HBV infection, HBcrAg does not correlate with viral replication and cannot be applied to detect HBV reactivation during follow-up. ...

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Hepatitis B virus reactivation after heart transplant: Incidence and clinical impact

Cited by 7 publications

References 32 publications

Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis

Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis

Essentials in the diagnosis of postoperative myocardial lesions similar to or unrelated to rejection in heart transplant

Hepatitis B core‐related antigen to detect hepatitis B virus (HBV) reactivation in heart transplant recipients with past HBV infection: A pilot study

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