Survival after orthotopic liver transplantation: The impact of antibody against hepatitis B core antigen in the donor
2009; Lippincott Williams & Wilkins; Volume: 15; Issue: 10 Linguagem: Inglês
10.1002/lt.21788
ISSN1527-6473
AutoresLei Yu, Thomas D. Koepsell, Lisa E. Manhart, George N. Ioannou,
Tópico(s)Hepatitis B Virus Studies
ResumoLiver TransplantationVolume 15, Issue 10 p. 1343-1350 Original ArticlesFree Access Survival after orthotopic liver transplantation: The impact of antibody against hepatitis B core antigen in the donor†‡§ Lei Yu, Corresponding Author Lei Yu [email protected] Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA Research Enhancement Award Program, Veterans Affairs Puget Sound Health Care System, Seattle, WA Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA Telephone: 206-650-7942Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356424, Seattle, WA 98195-6424Search for more papers by this authorThomas Koepsell, Thomas Koepsell Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WASearch for more papers by this authorLisa Manhart, Lisa Manhart Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WASearch for more papers by this authorGeorge Ioannou, George Ioannou Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA Research Enhancement Award Program, Veterans Affairs Puget Sound Health Care System, Seattle, WASearch for more papers by this author Lei Yu, Corresponding Author Lei Yu [email protected] Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA Research Enhancement Award Program, Veterans Affairs Puget Sound Health Care System, Seattle, WA Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA Telephone: 206-650-7942Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356424, Seattle, WA 98195-6424Search for more papers by this authorThomas Koepsell, Thomas Koepsell Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WASearch for more papers by this authorLisa Manhart, Lisa Manhart Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WASearch for more papers by this authorGeorge Ioannou, George Ioannou Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA Research Enhancement Award Program, Veterans Affairs Puget Sound Health Care System, Seattle, WASearch for more papers by this author First published: 29 September 2009 https://doi.org/10.1002/lt.21788Citations: 30 † See Editorial on Page 1164 ‡ This research was based on data derived from the United Network for Organ Sharing on January 18, 2007. § The content of this work is the responsibility of the authors alone and does not necessarily reflect the views or policies of the US Department of Health and Human Services. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Liver transplantation using grafts from donors with antibody against hepatitis B core antigen (anti-HBc) increases the recipients' risk of developing hepatitis B virus (HBV) infection post-transplantation. Our aim was to assess whether using such grafts was associated with reduced posttransplantation survival and whether this association depended on recipients' prior exposure to HBV on the basis of their pretransplantation serological patterns. Data were derived from the United Network for Organ Sharing on adult, cadaveric, first-time liver transplants performed between 1994 and 2006. Among recipients who did not have HBV infection before transplantation, those with anti-HBc–positive donors had significantly worse unadjusted posttransplantation patient survival than recipients with anti-HBc–negative donors [hazard ratio, 1.35; 95% confidence interval (CI), 1.21-1.50]. However, after adjustments for other predictors of posttransplantation survival, including donor age, donor race, and recipient underlying liver diseases, patient survival was not significantly different between the 2 groups (hazard ratio, 1.09; 95% CI, 0.97-1.24). Among recipients without antibody against hepatitis B surface antigen (anti-HBs), use of anti-HBc–positive donor grafts was associated with a trend toward worse survival (adjusted hazard ratio, 1.18; 95% CI, 0.95-1.46), whereas no such trend was observed among recipients positive for anti-HBs. In conclusion, in patients without HBV infection before transplantation, using anti-HBc–positive donors was not independently associated with worse posttransplantation survival. Matching these donors to recipients with anti-HBs pre-transplantation may be especially safe. Liver Transpl 15:1343–1350, 2009. © 2009 AASLD. Liver transplantation using grafts from donors positive for antibody against hepatitis B core antigen (anti-HBc) increases the recipients' risk of hepatitis B virus (HBV) infection post-transplantation, as defined by the detection of hepatitis B surface antigen (HBsAg).1-6 The underlying mechanism may be related to the observation that HBV can persist in the liver for many years after initial recovery,7 and it can be reactivated in the setting of immunosuppression.8 There are, however, conflicting data with respect to overall survival among these recipients. Dickson et al.2 reported that 78% (18/23) of recipients with anti-HBc–positive donor grafts developed HBV infection post-transplantation, with significantly decreased 4-year patient survival in comparison with recipients with anti-HBc–negative grafts [hazard ratio, 2.4; 95% confidence interval (CI) 1.4-4.0]. In contrast, Prieto et al.3 did not find a survival difference between the 2 groups despite a similarly high frequency of HBV infection (50%, 15/30) among recipients with anti-HBc–positive grafts. More recent studies have shown effective prophylaxis against HBV infection in recipients with anti-HBc–positive grafts using lamivudine with or without hepatitis B immunoglobulin (HBIG), but few have analyzed patient or graft survival.9-13 All of these studies involved a relatively small number of patients from selected transplant centers. No studies have adjusted for other important predictors of posttransplantation survival such as donor age,14-17 donor race,16, 17 cold ischemia time,18, 19 or recipient markers of liver disease severity.17 Despite these uncertainties, anti-HBc–positive donor livers continue to be used because of the current organ shortage, especially when the recipient is severely ill or has HBV-related cirrhosis.3, 9, 20, 21 With the exclusion of recipients with a pretransplantation diagnosis of HBV, it has been shown that when anti-HBc–positive donor grafts were used in recipients who also harbored anti-HBc with or without antibody against hepatitis B surface antigen (anti-HBs),2, 3, 5, 6 there was a lower incidence of HBV infection post-transplantation. The protective effect of such matching, however, was not complete,2, 6 and the number of patients involved in these studies was too small for firm conclusions to be drawn. It also remains unclear whether posttransplantation survival was affected when anti-HBc–positive donor livers were matched to anti-HBc–positive or anti-HBs–positive recipients. To more carefully examine these questions in a large and representative population, in the current study we aimed to assess whether anti-HBc–positive donor grafts were associated with worse patient and graft survival following liver transplantation after adjustments for other important predictors of posttransplantation survival using data reported to the United Network for Organ Sharing (UNOS) from 1994 to 2006. We also aimed to assess whether this association depended on recipients' prior exposure to HBV or vaccination on the basis of their pretransplantation HBV serological patterns. Abbreviations anti-HBc, antibody against hepatitis B core antigen; anti-HBs, antibody against hepatitis B surface antigen; BMI, body mass index; CI, confidence interval; HBIG, hepatitis B immunoglobulin; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; ICU, intensive care unit; INR, international normalized ratio; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; SD, standard deviation; UNOS, United Network for Organ Sharing. PATIENTS AND METHODS Study Design and Data Source We performed a retrospective cohort study using data compiled by UNOS.22 Transplant centers in the United States are required to submit to UNOS standardized data collection forms, including the Transplant Candidate Registration Form, which contains patient information at the time of listing for liver transplantation, the Deceased Donor Registration Form, which contains information on all consented recovered and nonrecovered donors, the Transplant Recipient Registration Form, which includes the patient status at discharge, pretransplant and posttransplant clinical information, and treatment data, and the Transplant Recipient Follow-Up Form, which is generated 6 months post-transplant and on each subsequent transplant anniversary. The Transplant Recipient Follow-Up Form contains information on patient survival, clinical data, and treatment. After these forms are submitted to UNOS, the data are compiled into a single Standard Transplant Analysis and Research file. A detailed description of the UNOS database has been reported elsewhere.23 We obtained a Standard Transplant Analysis and Research file from UNOS that included all liver transplants performed in the United States through January 18, 2007. Study Population Donor anti-HBc has been recorded on the Deceased Donor Registration form since April 1, 1994; we therefore included liver transplants performed between April 1, 1994 and January 18, 2006. We excluded recipients younger than 18 years of age (n = 6568) and those who had donors under 10 years of age (n = 568), living donors (n = 1961), split-liver donors (n = 717), non–heart-beating donors (n = 816), simultaneous organ transplants (n = 1937), or previous liver transplants (n = 4065). In our main analysis, we also excluded recipients who tested positive for HBsAg pre-transplantation or carried the diagnosis of HBV (n = 2947). We additionally excluded transplants with donors who tested positive for HBsAg (n = 50) or antibody against hepatitis C virus (HCV; n = 850). Among the remaining 37,155 transplants, 4.1% (n = 1535) had missing data on donor anti-HBc, and this left 35,620 transplants in the univariate analyses, including 1270 with positive donor anti-HBc. Patients with the diagnosis of HBV were analyzed separately, and a similar exclusion was applied to them as well. Definition of Outcomes Patient survival was measured in years from transplantation until death from any cause. Patients who remained alive or were lost to follow-up as of January 18, 2007 were censored at the time of last known follow-up for the analysis of patient survival. Graft survival was measured in years from transplantation until liver failure (with or without retransplantation) or patient death from any cause, whichever came first. Patients who remained alive without liver failure or were lost to follow-up as of January 18, 2007 were censored at the time of last known follow-up for the analysis of graft survival. Predictors of Posttransplantation Survival We assessed whether any observed differences in posttransplantation survival between recipients with and without anti-HBc–positive donors were confounded by donor and recipient characteristics known to affect posttransplantation survival.17 These included donor age, gender, and race and recipient age, gender, race, underlying liver diseases, and body mass index (BMI). Underlying liver diseases were based on diagnoses reported to UNOS after liver transplantation. Recipients who received exception scores for hepatocellular carcinoma (HCC) based on the more recent Model for End-Stage Liver Disease allocation system were characterized as having HCC instead of their primary liver disease. We included recipients' serum albumin, total bilirubin, creatinine, and international normalized ratio (INR) at the time of transplantation as markers for liver disease severity. We also adjusted for the cold ischemia time, year of transplantation, and urgency of transplantation. We used recipient location prior to transplantation (intensive care unit, hospital ward, or home) as a surrogate marker for urgency.24 Among recipients of anti-HBc–positive donor grafts for whom data on lamivudine or HBIG use were available (n = 374 in 2004-2006), we also assessed the potential effect of these treatments on patient survival. Effect Modification Among recipients without a pretransplantation diagnosis of HBV, we tested whether any survival difference between recipients with and without anti-HBc–positive donors depended on recipient HBV serological patterns. Routinely tested recipient HBV serological markers include anti-HBc and anti-HBs with 4 potential patterns: (1) anti-HBs–negative and anti-HBc–negative, indicating a lack of evidence of prior HBV exposure; (2) anti-HBs–negative and anti-HBc–positive, indicating possible prior exposure; (3) anti-HBs–positive and anti-HBc–negative, indicating HBV vaccination; and (4) anti-HBs–positive and anti-HBc–positive, indicating recovered HBV infection. We also tested whether any survival difference between recipients with and without anti-HBc–positive donors depended on recipients' diagnosis of hepatitis C infection pre-transplantation. Statistical Analysis Cox proportional hazards regression was used to compare patient and graft survival in recipients with and without anti-HBc–positive donors before and after adjustments for other predictors of posttransplantation survival.25 The assumption of proportional hazards was tested by graphical and weighted residual methods. In the multivariate analysis, we decided a priori to include all predictors of posttransplantation survival except INR, which was not recorded in close to 50% of recipients during the study period. Given that the mean INR was not significantly different between the 2 exposure groups, its inclusion would have resulted in a loss of sample size and precision. All predictors were modeled continuously except for gender, race, underlying liver diseases, pretransplantation location, and transplantation year categories (1994-1997, 1998-2000, 2001-2003, and 2004-2006). Trends in anti-HBc–positive donor use over the 13-year study period were assessed with the chi-square test for trends. The Kaplan-Meier method was used to estimate patient survival at 1 year among recipients who received an anti-HBc–positive graft between 2004 and 2006. For these recipients, the log-rank test was used to compare survival between those who were and those who were not using lamivudine or HBIG. We also performed the same univariate and multivariate analyses among recipients who carried the diagnosis of HBV pre-transplantation (excluded in the primary study population) to assess the effect of anti-HBc–positive donor organs on their survival. All analyses were performed with STATA 9.0 software (Stata Corp., College Station, TX). To simultaneously adjust for multiple predictors of posttransplantation survival in multivariate analyses, we excluded transplants with missing data for the following characteristics: recipient BMI (n = 1007), creatinine (n = 303), total bilirubin (n = 459), albumin (n = 808), and cold ischemia time (n = 3691). We also excluded 659 transplants with very abnormal data (because they might have been recorded erroneously) and 170 transplants with implausible data (almost certainly recorded erroneously), as defined in the next paragraph; this left 28,494 transplants in the multivariate analyses, including 997 with positive donor anti-HBc. Transplants with missing data on both recipient anti-HBc and recipient anti-HBs were further excluded (n = 7465) when we examined their effect on the relationship between donor anti-HBc status and posttransplantation survival. After these exclusions, the distribution of important confounding variables based on donor anti-HBc status, such as recipient age and BMI, donor age, and recipient liver disease etiologies, remained similar to the distribution before these exclusions. Very abnormal values were defined as follows: cold ischemia time, 0.5 to 24 to 48 hours; BMI, 10 to 15 or 55 to 65 kg/m2; serum creatinine, >0 to 15 to 20 mg/dL; serum total bilirubin, >0 to 0 to 6 to 10 g/dL. Implausible data were even more extreme than the very abnormal values. RESULTS Among recipients without a pretransplantation diagnosis of HBV infection, anti-HBc–positive donors accounted for 3.6% (1270/35,620) of adult, cadaveric, first-time liver transplants from 1994 to 2006. This increased significantly from 1.8% in 1994 to 6.0% in 2006 (P < 0.001; Fig. 1). Among 11 UNOS regions, the proportion of transplants involving anti-HBc–positive donors ranged from 1.2% to 8.5% (P < 0.001). Compared to recipients with anti-HBc–negative donors, recipients with anti-HBc–positive donors had similar pretransplantation mean BMI, albumin, creatinine, and INR. The 2 groups, however, had significantly different underlying liver diseases (P < 0.001; Table 1). Most strikingly, recipients with anti-HBc–positive donors had a higher proportion of HCV infection (41.2% versus 32.9%) and HCC (15.5% versus 10.2%) and a lower proportion of cholestatic liver diseases (5.3% versus 12.4%). Recipients with anti-HBc–positive donor grafts were also more likely to harbor anti-HBc themselves with (25.5% versus 9.1%) or without (17.6% versus 8.5%) anti-HBs (P < 0.001; Table 1). Compared to anti-HBc–negative donors, anti-HBc–positive donors were older (mean age, 47.0 ± 15.6 versus 39.3 ± 17.6 years; P < 0.0001) and more likely to be black (26.6% versus 11.5%; P < 0.001). Figure 1Open in figure viewerPowerPoint Proportion of liver transplant recipients who did not have hepatitis B virus infection pre-transplantation with antibody against hepatitis B core antigen–positive donors (April 1994 to January 2006). Table 1. Characteristics of Liver Transplant Recipients Without HBV Infection Pre-Transplantation by Donor Anti-HBc Status Total (n = 35,620) Anti-HBc–Negative Donor (n = 34,350) Anti-HBc–Positive Donor (n = 1270) P Value Age (years, mean ± SD) 50.9 ± 10.3 51.7 ± 10.2 0.005 BMI (kg/m2, mean ± SD) 28.1 ± 5.7 28.1 ± 5.5 0.6 Laboratory studies at transplant Creatinine (mg/dL, mean ± SD) 1.3 ± 1.0 1.3 ± 0.9 0.3 Total bilirubin (mg/dL, mean ± SD) 6.4 ± 8.2 5.9 ± 7.9 0.03 INR (mean ± SD) 1.9 ± 1.8 1.8 ± 1.0 0.1 Albumin (g/dL, mean ± SD) 2.9 ± 0.6 2.9 ± 0.7 0.4 Male (%) 63.4 66.6 0.02 Race (%) <0.001 White 78.3 74.2 Black 7.4 7.2 Hispanic 1.5 2.2 Asian 2.1 4.1 Other 10.8 12.2 Underlying liver disease (%) <0.001 HCV 32.9 41.2 Alcohol 14.5 11.8 NASH 0.9 0.7 Cryptogenic 8.9 7.2 PBC and PSC 12.4 5.3 Autoimmune 4.0 2.1 Heptocellular carcinoma 10.2 15.5 Cholangiocarcinoma 0.3 0.2 Fulminant 6.2 6.5 Other 9.7 9.6 HBV serology (%) <0.001 Anti-HBs–negative, anti-HBc–negative 73.1 46.6 Anti-HBs–negative, anti-HBc–positive 8.5 17.6 Anti-HBs–positive, anti-HBc–negative 9.4 10.4 Anti-HBs–positive, anti-HBc–positive 9.1 25.5 Cold ischemia time (hours, mean ± SD) 8.2 ± 3.1 8.4 ± 3.3 0.003 Causes of death 0.09 Cardiovascular 6.8 6.4 Rejection 1.8 1.2 Infection 17.3 20.0 Malignancy 11.4 12.8 Biliary 0.3 0 Vascular 0.8 1.2 Hepatitis 6.0 9.3 Other 55.6 49.3 Location before transplant (%) 0.06 Home 67.6 65.9 Ward 17.1 16.5 ICU 15.2 17.6 Other 0.1 0 Donor age (years, mean ± SD) 38.7 ± 17.6 47.0 ± 15.6 <0.0001 Donor male (%) 59.1 58.1 0.5 Donor race (%) <0.001 White 75.0 46.7 Black 11.5 26.6 Hispanic 1.8 3.2 Asian 1.4 10.0 Other 9.4 13.5 Transplant year (%) <0.001 April 1994 to December 97 24.6 14.0 January 98 to December 00 25.0 22.8 January 01 to December 03 27.8 33.8 January 04 to January 06 22.5 29.4 Abbreviations: anti-HBc, antibody against hepatitis B core antigen; anti-HBs, antibody against hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; ICU, intensive care unit; INR, international normalized ratio; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; SD, standard deviation. Before adjustments for other predictors of posttransplantation survival, recipients with anti-HBc–positive donors had significantly worse patient survival than those with anti-HBc–negative donors (hazard ratio, 1.35; 95% CI, 1.21-1.50; Table 2). After adjustments for other predictors of posttransplantation survival, patient survival was not significantly different between the 2 groups (hazard ratio, 1.09; 95% CI, 0.97-1.24). Similar results were found for graft survival. Although anti-HBc–positive donor organs appear to affect recipients without HCV infection (hazard ratio, 1.46; 95% CI, 1.27-1.68) more adversely than recipients with HCV infection (hazard ratio, 1.17; 95% CI, 1.00-1.38) in the univariate analysis, this effect was not significant after adjustments for other predictors of survival (hazard ratio, 1.10, and 95% CI, 0.96-1.25 for recipients without HCV; hazard ratio, 1.06, and 95% CI, 0.72-1.56 for recipients with HCV). Table 2. Association Between Donor Anti-HBc Status and Posttransplant Patient and Graft Survival Among Recipients Without HBV Infection Pre-Transplantation Total (n = 35,620) Anti-HBc–Negative Donor (n = 34,350) Anti-HBc–Positive Donor (n = 1270) Follow-up length (patient years) 130,428 3,962 Patient deaths 8,329 345 Mortality per 100 patient years 6.4 9.3 Unadjusted hazard ratio (95% CI) for patient survival 1 1.35 (1.21–1.50) Adjusted hazard ratio (95% CI) for patient survival* 1 1.09 (0.97–1.24) Unadjusted hazard ratio (95% CI) for graft survival 1 1.33 (1.21–1.46) Adjusted hazard ratio (95% CI) for graft survival* 1 1.09 (0.97–1.21) Abbreviations: anti-HBc, antibody against hepatitis B core antigen; CI, confidence interval; HBV, hepatitis B virus. * Adjusted for donor age, gender, and race; recipient age, gender, race, underlying liver diseases, body mass index, serum albumin, creatinine, total bilirubin at the time of transplant, and location before transplant; transplant year; and cold ischemia time. Although using grafts from anti-HBc–positive donors did not significantly influence adjusted patient (Table 3) or graft survival (data not shown) in any subgroup of recipients on the basis of their HBV serological patterns, use of such grafts appeared to affect recipients without anti-HBs more adversely than those with anti-HBs (Table 3). We did not observe a higher matching rate (anti-HBc–positive donors with anti-HBc–positive or anti-HBs–positive recipients) in more recent years (data not shown). Table 3. Association Between Donor anti-HBc Status and Posttransplant Patient Survival in 4 Groups of Recipients Without HBV Infection Pre-Transplantation on the Basis of Their HBV Serology Recipient HBV Serology Anti-HBs–Negative, Anti-HBc–Negative (n = 15,111) Anti-HBs–Negative, Anti-HBc–Positive (n = 1947) Anti-HBs–Positive, Anti-HBc–Negative (n = 1880) Anti-HBs–Positive, Anti-HBc–Positive (n = 2091) Anti-HBc–negative donor (n = 20,273) 14,762 1747 1872 1892 Anti-HBc–positive donor (n = 756) 349 133 75 199 Unadjusted hazard ratio (95% CI) 1.32 (1.08–1.64) 1.43 (1.04–1.97) 1.01 (0.60–1.69) 0.95 (0.69–1.30) Adjusted hazard ratio (95% CI)* 1.18 (0.95–1.46) 1.22 (0.87–1.70) 0.84 (0.50–1.44) 0.86 (0.62–1.20) Abbreviations: anti-HBc, antibody against hepatitis B core antigen; anti-HBs, antibody against hepatitis B surface antigen; CI, confidence interval; HBV, hepatitis B virus. * Adjusted for donor age, gender, and race; recipient age, gender, race, underlying liver diseases, body mass index, serum albumin, creatinine, total bilirubin at the time of transplant, and location before transplant; transplant year; and cold ischemia time. Since 2004, data with respect to the use of lamivudine and HBIG became available in the UNOS database. From January 1, 2004 through January 18, 2006, 374 recipients who did not have a pretransplantation diagnosis of HBV infection received anti-HBc–positive donor grafts. Among them, 24.5% (92/374) received either lamivudine or HBIG. The use of these medications was not associated with recipient anti-HBc or anti-HBs status. One-year survival was not significantly different between those who were using lamivudine or HBIG and those who were not (94.1% versus 88.6% respectively, P = 0.9). Among recipients with HBV infection pre-transplantation (n = 2797), 387 (13.8%) received anti-HBc–positive donor organs. There was no apparent adverse effect on patient survival related to anti-HBc–positive donor organs before (hazard ratio, 0.90; 95% CI, 0.70-1.16) or after (hazard ratio, 1.06; 95% CI, 0.80-1.41) adjustments for other predictors of posttransplantation survival. DISCUSSION Using comprehensive clinical data from UNOS, we did not find a significant association between use of anti-HBc–positive donors and posttransplantation patient or graft survival after adjusting for other predictors of posttransplantation survival. Among recipients without HBV infection pre-transplantation, older donor age,14-17 a higher proportion of donor black race,16 and a higher proportion of recipient HCV and HCC,24 which are known risk factors for decreased posttransplantation survival, likely confounded the association between anti-HBc–positive donors and worse survival observed in the univariate analysis. Among recipients without HBV infection pre-transplantation, a number of small studies have suggested that the rate of posttransplantation HBV infection varies, depending on recipients' HBV serological patterns as indications of prior exposure or vaccination.2, 3, 5, 6 The rate of infection among recipients negative for both anti-HBc and anti-HBs has ranged from 38% (3/8)4 to 100% (3/3)6 versus the range of 0% (0/22 and 0/43) to 13% (2/15)5 among recipients positive for anti-HBc. The protective effect of anti-HBs has been similarly varied, with infection rates ranging from 0% (0/7,5 0/2,3 and 0/136) to 33% (1/3).2 Despite the small number of patients involved, several studies have advocated actively matching anti-HBc–positive donors to recipients with serological evidence of HBV exposure or vaccination.3, 5, 6 The effect of this strategy was evident in the current study, in which recipients with anti-HBc–positive grafts were much more likely to harbor anti-HBc with or without anti-HBs pre-transplantation (Table 1). We wanted to test whether the potential benefit of matching in reducing posttransplantation HBV infection translates into improved patient and graft survival among recipients without HBV infection pre-transplantation. Using a much larger sample than prior studies, we found no significant association between use of anti-HBc–positive donors and posttransplantation survival, regardless of recipients' HBV serological patterns (Table 3). One possibility is that despite the large sample size, we did not have sufficient statistical power to detect small differences in survival, especially in the groups of recipients negative for anti-HBs with or without anti-HBc. In these 2 groups, recipients of anti-HBc–positive donor grafts had approximately 20% worse patient survival after adjustments for important confounders, but this did not reach statistical significance (Table 3). An alternative explanation may be that matching does reduce the risk of posttransplantation HBV, but it does not affect overall survival because effective prophylaxis now exists even when matching is not feasible.9-13 Dodson et al.9 first reported 100% success using a combination of lamivudine and HBIG to prevent posttransplantation HBV infection (0/15) among recipients who received an anti-HBc–positive graft with a mean follow-up of 15 months. Eight of these 15 patients were negative for both anti-HBc and anti-HBs. Yu et al.10 subsequently reported similar success using lamivudine alone with a mean duration of follow-up of 17 months. A study from Taiwan, where the prevalence of anti-HBc–positive donors was 63%, reported an incidence of posttransplantation HBV of 44% (7/16) without lamivudine versus 0% (0/44) with lamivudine among recipients with anti-HBc–positive grafts.26 Even though none of these studies were randomized and there are currently no published guidelines for prophylaxis against HBV infection post-transplantation when anti-HBc–positive grafts are used, these overwhelmingly positive results li
Referência(s)