Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors

BACKGROUND: Liver transplantation from hepatitis B core-antibody (HBcAb)-positive donors to hepatitis B surface-antigen (HBsAg)-negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long-term lamivudine monotherapy to prevent development of HBV infection in HBsAg-negative recipients of liver allografts from HBcAb-positive donors. METHODS: From 315 cadaveric adult liver transplantations performed at our unit between July 1999 and March 2005, 18 recipients (5.7%) received liver allografts from HBcAb-positive donors, 13 of whom were HBsAg-negative pre-transplantation. The recipients consisted of four females and 14 males, age range 28-65 yr (median 49.5 yr). Post-transplantation, HBsAg-negative recipients were administered lamivudine 100 mg daily long term. HBsAg-positive recipients were administered low-dose hepatitis B immunoglobulin (HBIg) and lamivudine according to our usual protocol. Standard post-transplantation immunosuppression was given. Recipients were followed up regularly (range 2-69 months, median 21 months) for development of de novo HBV infection. RESULTS: Ten HBsAg-negative recipients received long-term lamivudine. One patient (HBcAb and HBsAb positive pre-transplant) did not receive lamivudine and, in two patients, lamivudine was discontinued following urgent re-transplantation for primary graft non-function. All 13 of the HBsAg-negative recipients were still alive, with no evidence of HBV infection at the end of follow-up. CONCLUSION: Long-term lamivudine monotherapy was effective in preventing development of HBV infection in HBsAg-negative liver transplant recipients from HBcAb-positive donors.     

Safe use of livers from donors with positive hepatitis B core antibody

Thirty-five patients received liver transplants using liver donors who had positive test results for the hepatitis B core antibody (HBcAb). In the same time frame, 195 patients received HBcAb-negative liver donors. Mean follow up for patients receiving HBcAb-positive donors was 25 months. All patients receiving HBcAb-positive donors were monitored for recurrence of hepatitis B (HBV) with HBV DNA assays. There was no de novo HBV in recipients of HBcAb-negative grafts. In the group of patients receiving HBcAb-positive donors, 4 of 35 patients died within 3 months after transplant with no evidence of HBV recurrence at time of death. Four patients were transplanted for HBV-related disease and were postoperatively placed on lamivudine and hepatitis B immune globulin (HBIG). HBV recurrence was seen in one of these patients. Of the remaining 27 patients, three of three mismatched patients (HBcAb-positive donor to HBcAb-negative recipient) developed de novo HBV (100%). Of 24 matched patients (HBcAb-positive donor to HBcAb-positive recipient), only two (7%) developed recurrent HBV allograft reinfection. All de novo and recurrent HBV infections were successfully managed with HBIG and lamivudine therapy. Survival for this subgroup of patients receiving HBcAb-positive donors for non-HBV–related liver disease was 100%. We conclude that the judicious use of HBcAb-positive donors is reasonably safe and associated with low morbidity and mortality, with the appropriate follow-up protocols. Additionally, lamivudine use can be reserved for those cases with de novo or recurrent HBV in the liver allograft, or, selectively, as prophylaxis in those recipients patients who are naı̈ve to HBV and receive an HBcAb-positive donor. (Liver Transpl 2002;8:556-561.)     

Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.

BACKGROUND: The shortage of donor organs occasionally mandates the use of hepatic allografts from anti-HBc+ donors in recipients who are susceptible to de novo hepatitis B virus (HBV) infection. The efficacy of hepatitis B immune globulin and lamivudine to prevent de novo HBV infection in anti-HBs negative recipients of allografts from anti-HBc+ donors has not been investigated. METHODS: After liver transplantation with an allograft from a donor positive for anti-HBc, recipients who were anti-HBs-, HbsAg- received hepatitis B immune globulin (HBIG) 10,000 IU i.v. daily for 7 days and monthly for 6 months. After 6 months, 1000 IU of HBIG was given IM. every 2 weeks for 18 months. Patients transplanted after 4/1/97 were given lamivudine 150 mg daily starting postoperative day 1. RESULTS: Between 8/14/96 and 6/10/98, 264 orthotopic liver transplants were performed and 16 anti-HBs-, HbsAg- patients received an hepatic allograft from a donor positive for anti-HBc. HBIG mono-therapy was administered to one patient. HBIG and lamivudine combination therapy was administered to 15 patients. Of the 16 patients, 8 were positive only for anti-HBc before transplant, and 8 were naive (anti-HBs-, anti-HBc-). The single patient who received HBIG monotherapy became HbsAg+ at 6 months. All patients receiving combination therapy with HBIG and lamivudine have remained HbsAg-. The average follow-up is 459 days (range 170-754). Two patients died from unrelated causes. CONCLUSIONS: Combination therapy with HBIG and lamivudine may prevent de novo HBV infection in anti-HBs-, HbsAg- recipients of hepatic allografts from anti-HBc+ donors.     

Living donor liver transplantation from hepatitis B core antibody positive donors

Liver allografts from donors previously exposed to hepatitis B virus (HBV) carry the risk of transmission of HBV infection to immunosuppressed recipients. However, exclusion of donor candidates with the serologic evidence of resolved hepatitis B-HBV surface antigen (HbsAg) negative and HBV core antibody (anti-HBc) positive-is not feasible in countries endemic for HBV. AIM: Our aim was to assess the safety of living donor liver transplantation from anti-HBc positive donors. MATERIALS AND METHODS: In our institution, 152 transplants were performed between June 1999 and April 2004. Fifty-six (37%) of the living donors were anti-HBc positive. Twenty of these liver grafts were transplanted to HbsAg-negative recipients. We excluded four HBsAg negative recipients who died because of early complications after transplantation. Lamivudine (100 mg/day) was given for prophylaxis of de novo HBV infection. RESULTS: The mean follow-up time for 16 HBsAg-negative recipients was 21.7 (7-48) months. None of them experienced de novo HBV infection. CONCLUSION: The use of liver allografts from anti-HBc-positive living donors is reasonably safe in HBsAg-negative recipients under lamivudine prophylaxis.     

Risk of de novo hepatitis in liver recipients from hepatitis-B core antibody-positive grafts - a systematic analysis

Skagen CL, Jou JH, Said A. Risk of de novo hepatitis in liver recipients from hepatitis‐B core antibody‐positive grafts – a systematic analysis.
Clin Transplant 2011: 25: E243–E249. © 2011 John Wiley & Sons A/S. Abstract: Many transplant programs utilize liver grafts from hepatitis‐B core antibody (HBcAb)‐positive and hepatitis‐B surface antigen (HBsAg)‐negative donors. However, there is risk for de novo hepatitis B (DNH) in recipients of these grafts. We reviewed 26 studies reporting the rates of DNH in recipients receiving HBcAb‐positive liver grafts. Four hundred and sixty‐two donor–recipient pairs were included to evaluate the risk of DNH stratified by the recipient’s immune status to hepatitis B and type of prophylactic therapy given, if any. The rate of DNH was highest (58%) in the stratum of hepatitis‐B (HBV) naïve recipients who did not receive prophylaxis. In HBV naïve recipients, prophylactic therapy (lamivudine and/or hepatitis‐B immunoglobulin – HBIG) reduced DNH to 11% (odds ratio [OR] = 11.1, 95% CI 4.98–25, p < 0.0001 for DNH without prophylaxis). Recipients with hepatitis‐B surface antibody (HBsAb) positivity had DNH rates of 18% without prophylaxis and 0% with prophylaxis (OR = 9.2, 95% CI 1.1–83.3, p = 0.039). Recipients with both HBsAb and HBcAb positivity had DNH rates of 4% without prophylaxis and 3% with prophylaxis (p = 1.00), while recipients with HBcAb positivity alone had DNH rates of 14% without prophylaxis and 3% with prophylaxis (p = 0.21). There was no significant difference between the types of HBV prophylaxis received whether lamivudine, HBIG or both. However, in the subgroup who received HBIG alone, rates of DNH were higher after cessation of HBIG prophylaxis compared to DNH rates with indefinite HBIG (p = 0.0002). In summary, the risk of DNH is highest for HBV naïve liver recipients from HBcAb‐positive donors. Recipients who are HBV naïve as well as those recipients with isolated HBsAb positivity derive significant benefit from HBV prophylaxis after transplantation with a HBcAb‐positive graft. The ideal prophylactic regimen for prevention of DNH is unclear, but based on our analysis of the literature, antivirals alone may suffice. More data are needed with the newer antivirals for hepatitis B.     

Case Report of Lamivudine-Resistant Hepatitis B Virus Infection Post Liver Transplantation from a Hepatitis B Core Antibody Donor

The use of allografts from donors with hepatitis B core antibody in liver transplantation (LT) is associated with the risk of de novo hepatitis B virus (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and lamivudine alone or in combination has been reported. Yet, there are no standardized regimens and long-term efficacy is not known. We report a case of a patient who underwent LT for alcoholic liver disease who received an allograft from a donor with Hepatitis B core antibody. The patient had no previous exposure to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface antibody present in serum before and 6 months after transplantation. Prophylaxis with short-term HBIg (1 week) and indefinite lamivudine was given. De novo HBV infection developed more than 3 years after LT with a lamivudine-resistant polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the risk of de novo post-LT HBV infection in recipients of livers from hepatitis B core antibody positive donors. High risk were HBV naïve recipients, moderate risk recipients had isolated hepatitis B surface antibody (anti-HBs) or hepatitis B core antibody (anti-HBc), while low-risk recipients had both anti-HBs and anti-HBc. We reviewed prophylaxis protocols reported in the literature and made recommendations for management.     

Prevention of de novo hepatitis B virus infection by vaccination and high hepatitis B surface antibodies level in children receiving hepatitis B virus core antibody-positive living related donor liver: case reports

Transmission of hepatitis B virus (HBV) infection from donors negative for hepatitis B surface antigen (HBsAg) but positive for antibody to hepatitis B core antigen (anti-HBc) have been reported. The aim of our study was to evaluate the outcomes of recipients who received liver grafts from living related donors with serological evidence of previous exposure to hepatitis B virus (HBsAg-negative/anti-HBc-positive) after recipient vaccination against HBV before and after liver transplantation.     

Safety of using hepatitis B virus core antibody or surface antigen-positive donors in kidney or pancreas transplantation

Hepatitis B virus core antibody (HBcAb) or surface antigen (HBsAg)-positive organ donors have the potential to transmit infection to transplant recipients. We investigated the safety of using HBcAb(+) or HBsAg(+) donors in kidney or pancreas transplant recipients with 1 yr lamivudine prophylaxis. While HBsAb(-) recipients of HBcAb(+) donors received prophylaxis, HBsAb(+) recipients did not. HBsAg(+) organs were only used in patients who were both HBcAb and HBsAb(+). Forty-six patients received HBcAb(+) and four received HBsAg(+) organs (47 kidney, two pancreas, and one kidney/pancreas). All but one recipient were HBsAg(-), 25 were HBsAb(+), and 19 HBcAb(+). During a median 36 months of follow-up (range 6-66 months), with 43 of a total 50 patients having at least 1 yr follow-up and were off lamivudine, and none of the patients developed hepatitis B viremia or seroconversion to HBsAg or HBsAb(+). These results suggest that HBcAb(+) or HBsAg(+) organs can be used safely in selected recipients with lamivudine prophylaxis without requiring hepatitis B immunglobulin.     

Use of hepatitis B core antibody-positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and Lamivudine

INTRODUCTION: With the shortage of donor organs, increasing number of hepatitis B core antibody (HBcAb)-positive [HBcAb(+)] liver allografts are being used for liver transplantation (LTx) in patients who are HBcab-negative [HBsAb(-)]. This study was aimed at assessing outcomes for hepatitis C virus (HCV)-positive [HCV(+)] and HCV-negative [HCV(-)] patients who received HBcAb(+) liver grafts from deceased donors and also received a short course of hepatitis B immunoglobulin (HBIg) with long-term lamivudine therapy after LTx. MATERIALS AND METHODS: From February 1995 through February 2003, 28 patients (mean age 53.8 +/- 10.2 years, 19 men and nine women, 16 HCV[-]; 12 HCV[+]) received HbcAb(+) liver allografts. All recipients received a short course of HBIg prophylaxis (10,000 units/day for 4 days) and long-term lamivudine 100 mg/d after LTx in addition to a tacrolimus-based immunosuppressive regimen. RESULTS: Seven (25%) of the 28 recipients died during follow-up and three recipients required retransplantation. Three recipients (10.7%) developed HBV infection during follow-up, one of whom died 36 months after LTx and the other two had YMDD mutant HBV. The overall 6-year actuarial patient survival after transplantation was 74.4% and those for HCV(-) and HCV(+) recipients were 81.3% and 66.6%, respectively (P = .46). The overall 6-year actuarial graft survival was 63.9% and those for HCV(+) and HCV(-) recipients were 68.8% and 57.1%, respectively (P = .6). CONCLUSION: We conclude that HBcAb(+) liver grafts can be used for both HCV(+) patients and HCV(-) patients who are critically ill, have early hepatocellular carcinoma, or have been exposed to HBV in the past. A short course of HBIg-lamivudine combination therapy provides effective prophylaxis against HBV infection in 89% of recipients of HBcAb(+) grafts.     

Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool

The use of livers from anti-hepatitis B core (HBc) positive donors can alleviate donor shortage. Nineteen of 367 (6%) adults receiving anti-HBc positive allografts [three were hepatitis B antigen (HBsAg) negative, hepatitis B antibody (HBsAb) positive; four were HBsAg positive and 12 were not exposed to hepatitis B viral (HBV) infection] were retrospectively reviewed. In HBsAg negative recipients, immunoprophylaxis (IP) was guided by viral serology and immunohistochemistry (IH) of day 0 and day 7 liver biopsies. If IH was negative, IP was stopped. None of three HBsAg negative, HBsAb positive recipients infected; one (replicating) of four HBsAg positive recipients reinfected and seven of eight (87.5%) HBsAg, HBsAb negative recipients, who did not receive long-term IP, infected after a median time of 2 years (range 1-5); one patient died of liver failure. Four HBsAg, HBsAb negative recipients, receiving life-long IP, remained infection free. Anti-HBc positive donor livers must be directed selectively first to HBsAg positive recipients, next to recipients having HBV antibodies and finally to HBV-naive recipients. Identification of both donor and recipient risk factors for HBV infection before transplantation allows indiscriminate use of antiviral prophylaxis. The necessity for IP therapy should be guided by HBV-DNA testing of donor liver tissue and serum. IH of early liver biopsies is an unreliable marker for predicting antiviral treatment requirements.     

Frequent detection of hepatitis B core antibodies in heart transplant recipients without preceding hepatitis B infection

It is unclear whether heart donors positive for hepatitis B core antibodies (anti-HBc) can transfer hepatitis B virus (HBV) infection to immunosuppressed heart recipients, or whether passive transfer of anti-HBc simulates a hepatitis B infection. Therefore, we performed a case-controlled study in 46 heart recipients who all tested negative for hepatitis B antigen (HbsAg), antiHBc, and hepatitis B surface antibodies before heart transplantation. Twenty-three patients (group 1) received hearts from anti-HBc-positive donors, while 23 other patients (group 2) received hearts from anti-HBc-negative donors. After heart transplantation, anti-HBc were present in 65.0% of blood samples among group 1 and 47.8% of the blood samples among group 2 (P > .05). HbsAg was undetectable in blood samples of all patients of both study groups. The immunoglobulin preparation that we regularly use for immune suppression immediately after heart transplantation contained a relatively high concentration of anti-Hbc antibodies. The nearly identical presence of anti-HBc in both study groups indicated that passive transfer via immunoglobulin preparations rather than HBV infection is the cause for the anti-HBc detected in heart recipients. Since only a small volume of blood is transferred with the donor heart, it seems to be rather unlikely that the donor heart might be the source of anti-HBc. In summary, we observed no evidence for HBV infection in those heart recipients who received organs from anti-HBc-positive donors. Moreover, our data demonstrated that the presence of anti-HBc in heart recipients frequently occurs but does not necessarily indicate a preceding HBV infection.     

Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors

Exclusion of liver grafts from hepatitis B core antibody (anti-HBc) positive donors to prevent de novo hepatitis B virus (HBV) infection after liver transplantation is not feasible in areas highly endemic for HBV virus like Taiwan, where approximately 80% of adults are anti-HBc(+). The efficacy of lamivudine monotherapy to prevent de novo HBV infection after living donor liver transplantation (LDLT) using grafts from anti-HBc(+) donors remains to be elucidated. From June 1994 to August 2000, LDLT was performed in 42 recipients. Twenty-four of the 42 donors were anti-HBc(+) (57%). Pre-transplant HBV vaccination was given to all recipients irrespective of anti-HBc status at monthly intervals for 3 months. Until December 1997, eight recipients received liver grafts from anti-HBc(+) donors without prophylaxis. Since January 1998, prophylaxis with lamivudine monotherapy was given to 16 recipients receiving liver grafts from anti-HBc(+) donors. De novo HBV infection occurred in three of the eight recipients (37.5%) who did not receive prophylaxis, while none of the 16 recipients given lamivudine developed de novo HBV infection after a mean follow-up of 25 months. Two of the three recipients with de novo HBV infection were anti-HBs(-) and one recipient was anti-HBs(+). Lamivudine was well tolerated, and no side effects were noted. These results suggest that lamivudine monotherapy for recipients receiving anti-HBc(+) liver grafts is a simple, relatively inexpensive and effective prophylactic regimen for prevention of de novo HBV infection. The additive protection provided by vaccine-induced or natural immunity is uncertain.     

Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation.

Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.     

Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients with HBcAb-positive liver grafts

We followed the efficacy of long-term lamivudine monotherapy in preventing development of de novo hepatitis B (DNHB) in a large cohort of hepatitis B surface antigen (HBsAg)-negative recipients with grafts from hepatitis B core antibody (HBcAb)-positive donors. Recipients were observed over a long follow-up. Between July 1999 and December 2008, 45 patients (median age 54, range 19-67) who were HBsAg negative before transplantation were included in the study of monoprophylaxis with lamivudine starting on post-operative day 1, and continuing for life. Mean follow-up: 37.9 months; median 32.1 months (range 2.4-117). No suspension of therapy was reported during the study. Post-transplantation, no DNHB was observed in follow-up: all 45 HBsAg-negative recipients remained HBsAg and HBV DNA negative. Thirty-four of these HBsAg-negative recipients were alive at conclusion of the study. A total of 11 patients died, five of HCV recurrence, two of hepatocellular carcinoma (HCC) recurrence, two of disseminated KSV infection, and two of multiorgan failure because of early graft dysfunction. Patient and graft survival of HBsAg-negative recipients with HBcAb-positive donor grafts (45 cases) were not significantly different from those of the HBsAg-negative recipients with HBcAb-negative donor grafts (302 cases). In our experience, lamivudine monoprophylaxis provided complete protection against HBV reactivation and showed long-term efficacy.     

Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis

BACKGROUND: The present scarcity of organ donors requires consideration of grafts from sources not previously used. Several studies have addressed the use of grafts from donors who have antibodies to the hepatitis B core antigen (anti-HBc+). The aim of this study was to evaluate the impact of the use of anti-HBc+ grafts in patients transplanted for hepatitis B virus (HBV)-related cirrhosis. METHODS: Recipients of first hepatic transplants from donors with antibodies to HBV were identified retrospectively. All patients who had serology suggestive of active HBV and were negative for hepatitis C and D were included in the analysis. The Kaplan-Meier method was used to assess the actuarial recurrence-free survival on patients with graft survival longer than 1.5 months. The stepwise Cox regression model was used to identify independent predictors of HBV recurrence. RESULTS: One thousand seven hundred seventeen first liver transplants were performed at the Thomas E. Starzl Transplantation Institute from September 1, 1990, to December 31, 1999. HBV was the cause of cirrhosis in 112 patients (6.5%). Thirty-three patients had coexistent viral infection (23 HCV and 10 HDV). Fourteen donors (17.2%) were positive for HBV markers, with nine anti-HBc+ and with five both anti-HBc+ and anti-HB surface-positive; of these, 13 anti-HBc+ organ recipients had long-term survival. Nine (69.2%) of these cases were reinfected versus 20 (35.7%) in the group that received grafts from HBV- donors (P<0.05, Fisher's exact test). The mean time to reinfection was shorter in the anti-HBc+ group (2.9 yr vs. 6.4 yr, P<0.005). There were no statistical differences in graft or patient survival between the two groups. HBV prophylaxis with combined lamivudine and hepatitis B immunoglobulin (HBIG) significantly reduced the reinfection rate (P<0.03). Hepatitis Be (Hbe) antigen-positive recipients trended to faster reinfection (not significant). Cox regression analysis revealed that both anti-HBc graft donor status (RR, 2.796; P=0.020) and combination of lamivudine/HBIG (RR, 0.249; P=0.021) are independently associated with reinfection. CONCLUSIONS: The use of anti-HBc+ liver grafts does not affect graft or patient survival. However, patients who receive these organs are 2.5 times more likely to develop HBV recurrence. Lamivudine and HBIG combination decreases HBV recurrence 4-fold.     

Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine

BACKGROUND: The increasing demand for transplantation has resulted in a trend toward using virologically compromised donors. We reviewed our experience with liver grafts from hepatitis-B surface antigen (HBsAg)(-), antibody to core antigen (anti-HBc)(+) donors. METHODS: Sixty-two liver transplants using HBsAg(-), anti-HBc(+) donors were studied. The decision to use prophylaxis was based on the presence or absence of donor and recipient risk factors for posttransplant hepatitis-B virus (HBV) transmission or reinfection. If the donor or recipient showed positive HBVDNA, hepatitis-B immunoglobulin (HBIg) and lamivudine were used. If both donor and recipient HBVDNA were negative, a choice between lamivudine and no prophylaxis was made on the basis of presence or absence of HBsAg and antibody to the surface antigen (anti-HBs) in the recipient. RESULTS: No death or graft loss could be ascribed to HBV. Mild HBV infection occurred in two patients who were not taking the recommended prophylaxis. Among the other 60 patients, 1 showed positive e antigen (HBeAg) early after transplantation, and 2 (1 with recurrent cancer, 1 with HIV infection) showed HBsAg(+). None of the three patients had any other evidence of HBV infection. Forty-seven patients underwent liver biopsies. Changes consistent with hepatitis were observed in 26, and 24 had HCV infection; immunostains for HBV antigens were negative in all cases, and 7 showed positive HBVDNA. CONCLUSIONS: A selective protocol based on donor and recipient risk factors for post-liver transplant HBV infection can prevent hepatitis-B infection and avoid unnecessary administration of antiviral prophylaxis in recipients of HBsAg(-), anti-HBc(+) liver allografts.     

Failure of reactivation of hepatitis B after liver transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients

BACKGROUND: Hepatitis B virus (HBV) infection after liver transplantation may occur in patients previously not exposed to the virus, but who receive an organ from a surface antigen (HBsAg)-negative, core antibody (HBcAb)-positive donor. The risk of HBV reactivation after liver transplantation in recipients that are HBsAg negative and HBcAb positive requires definition, because reactivation in kidney and bone marrow transplant patients has occurred. PATIENTS AND METHODS: A total of 409 HBsAg-negative patients underwent transplantation between April 1994 and June 1999. Pretransplantation sera were tested subsequently for HBcAb and HBsAb and posttransplantation sera for HBsAg. RESULTS: Of the 55 recipients who were positive for HBcAb, 48, who were immunosuppressed predominantly using tacrolimus, showed no evidence of HBV reactivation as shown by the absence of HBsAg (mean follow up 21.3+/-13.5 months). The remaining seven died within 6 months. CONCLUSIONS: In our experience, HBV reactivation did not occur in HBsAg-negative, HBcAb-positive recipients after liver transplantation, most of whom were immunosuppressed with tacrolimus. We would not, therefore, currently recommend HBV prophylaxis in these patients.     

Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients

INTRODUCTION: The rate of hepatitis B virus transmission via organs from with isolated hepatitis B virus core antibody-positive (HBcAb+) donors in kidney transplant recipients seems very low. PATIENTS AND METHODS: Over 4 years, we performed 36 transplants from Ig HBcAb+, hepatitis B surface antigen (HBsAg)-negative donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination (28 patients) and in recipients who were not immunized and received a pretransplant prophylaxis with hepatitis B immunoglobulins. We examined the HBV-related outcomes in these 36 patients in comparison with 40 recipients of allografts from HBcAb- donors. RESULTS: No patient receiving an allograft from an HBcAb+ donor developed clinical HBV infection or HBSAg positivity. The rate of seroconversion was 14.2% in immunized patients, 12.5% in nonimmunized patients, and 0% in the control group. The 17.8% of immunized patients developed elevated transaminases after transplant, in comparison with 25% and 10% in the nonimmunized patients and the control group, respectively. Graft and patient survival was 93% and 93% for immunized patients, 100% and 100% for nonimmunized patients, and 98% and 95% for the control group, respectively. CONCLUSION: The use of anti-HBc antibody-positive kidneys was associated with no risk of transmission of HBV infection, without affecting graft and patient survival, and could be considered a safe way to expand the donor pool. Our preliminary results suggest that such kidneys could be safely transplanted even in not immunized patients who underwent a prophylaxis with hepatitis B immunoglobulins.     

Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage

While the number of cadaveric organ donors remains relatively stable, the number of patients awaiting transplantation continues to increase, creating a shortage of donor organs. To address this imbalance, there is interest in transplanting organs formerly considered marginal or undesirable. Thus, more organs are currently transplanted from living donors, older donors, hemodynamically unstable donors, non-heart-beating donors and donors with markers of prior hepatitis B virus (HBV) infection. A large number (up to 93.8%) of liver transplant seronegative recipients from anti-HBc antibody positive donors have acquired HBsAg after liver transplantation in the absence of immunoprophylaxis. Based on experience in liver transplantation programs, transmission of HBV from donors without HBsAg but with antibody to HBV core antigen (anti-HBc), although conventionally defined as evidence of resolved infection, can have adverse consequences on both graft and recipient. On the contrary, HBV appears to be in-frequently transmitted from HBsAg negative/anti-HBcAb positive kidney donors: the incidence of de novo HBsAg seropositivity after renal transplantation ranges between 0 and 5.2%. A significantly higher incidence of anti-HBc antibody seroconversion (without developing HBsAg) after renal transplantation with anti-HBc antibody positive donors was seen. However, anti-HBc antibody positive renal allografts should be considered, especially for recipients who have been successfully immunized with HBV vaccine. Prospective long-term studies are in progress to assess the risk of de novo HBV infection (HBsAg seroconversion) in renal transplant recipients who have not been successfully immunized with vaccine against HBV.     

Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation

BACKGROUND: The use of hepatitis B core antibody (HBcAb+) and hepatitis C antibody (HCV Ab+) positive donors represents one strategy to increase available donor organs, but this remains controversial because of concern for viral transmission to recipients. We hypothesized that isolated HBcAb+ donors represent minimal risk of viral transmission in vaccinated lung transplant (LTx) recipients. METHODS: A retrospective study was performed of LTx recipients who received HBcAb+ or HCV Ab+ pulmonary allografts. We analyzed liver function studies, viral hepatitis screening tests, quantitative polymerase chain reaction for hepatitis B viral DNA (HBV DNA) and hepatitis C viral RNA (HCV RNA), freedom from bronchiolitis obliterans syndrome, acute rejection, and survival. RESULTS: Between April 1992 and August 2003, 456 LTx operations were performed. Twenty-nine patients (HB group) received HBcAb+ allograft transplants with a median posttransplant follow-up of 24.5 months. Three critically ill patients (HC group) received HCV Ab+ allografts with a median follow-up of 21.5 months. One-year survival for the HB group is 83% versus 82% for all patients who received non-HB organs (P=0.36). No patient in the HB group developed clinical liver disease because of viral hepatitis, and all patients alive (n=21) at follow-up are, to date, HBV DNA and/or HBcAb negative. All patients in the HC group tested HCV RNA positive; one patient died of liver failure at 22 months. CONCLUSIONS: Risk of viral transmission with HCV Ab+ allografts seems high after LTx. However, the use of HBcAb+ pulmonary allografts in recipients with prior hepatitis B vaccination seems to be a safe and effective strategy to increase organ availability.