Long‐term outcome of patients with lamivudine after early cessation of hepatitis B immunoglobulin for prevention of recurrent hepatitis B following liver transplantation

Yuefeng M, Weili F, Wengxiang T, Ligang X, Guiling L, Hongwei G, Wencai L, Xiaoguang W, Wei M, Zhongyi F. Long‐term outcome of patients with lamivudine after early cessation of hepatitis B immunoglobulin for prevention of recurrent hepatitis B following liver transplantation.
Clin Transplant 2011: 25: 517–522. © 2010 John Wiley & Sons A/S. Abstract: Background: The aim of this study is to examine the efficacy of long‐term prophylaxis with lamivudine (LAM) after a course of post‐operative hepatitis B immunoglobulin (HBIG) in patients who underwent liver transplantation (LT) for hepatitis B virus (HBV)‐related disease. Result: The medical records of HBV‐infected patients who underwent a LT in our institution between July 2001 and May 2005 were reviewed. There were 15 liver transplant recipients who were administered HBIG for <18 months and used LAM as a maintenance prophylaxis regime enrolled in this study. At enrollment, all patients were hepatitis B surface antigen (HBsAg) positive and three patients were HBeAg positive. There were 13 patients who were HBV DNA positive with a mean viral load of 5.4 log copies/mL, and among them, 12 recipients were on antiviral therapy with LAM (100 mg/d orally) for 12–168 d, resulting in HBV DNA negative levels in nine patients prior to their transplant. HBV recurrence post‐LT was noted in two patients who had very high‐HBV DNA levels pre‐LT. Both of these patients showed LAM‐resistant mutation at the time of recurrence. The 11 patients who were HBV DNA negative before LT (low‐risk patients) had no HBV recurrence during a follow‐up at a median of 58 months post‐LT. This included five patients who had intermittent low‐level HBV DNA post‐LT (HBsAg negative), of whom two had YMDD mutation and these two were given adefovir in addition to LAM. Conclusion: Our retrospective study demonstrated excellent long‐term outcomes in the low‐risk patients treated with LAM after a short course of HBIG.     

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.     

Virologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV‐HBV Coinfected Transplant Recipients

Liver transplantation (LT) is the treatment of choice for end‐stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV‐hepatitis B virus (HBV) coinfected patients transplanted between 2001–2007; outcomes including survival and HBV clinical recurrence were determined. Twenty‐two coinfected patients underwent LT; 45% had detectable HBV DNA pre‐LT and 72% were receiving anti‐HBV drugs with efficacy against lamivudine‐resistant HBV. Post‐LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow‐up 3.5 years. Low‐level HBV viremia (median 108 IU/mL, range 9–789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow‐up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono‐ versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV‐HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low‐level HBV DNA is detectable in ～50% of recipients.     

The long‐term efficacy of nucleos(t)ide analog plus a year of low‐dose HBIG to prevent HBV recurrence post‐liver transplantation

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long‐term nucleos(t)ide analog in combination with one yr of low‐dose HBIG. One hundred and fifty‐two adults with HBV‐related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long‐term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow‐up post‐transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long‐term follow‐up, demonstrates that short course of low‐dose HBIG (without anti‐HBs monitoring) combined with the use of long‐term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.     

Liver transplant from Anti‐HBc‐positive,HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature

Avelino‐Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti‐HBc‐positive, HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature.
Clin Transplant 2010: 24: 735–746. © 2010 John Wiley & Sons A/S. Abstract: Introduction: After liver transplant (LT) from Anti‐HBc+/HBsAg? donors into HBsAg? recipients, transmission of hepatitis B virus (HBV) may occur (de novo HBV infection). This study analyzes the incidence of de novo HBV infection in HBsAg? recipients of Anti‐HBc+/HBsAg? LT with respect to: (i) the recipients’ HBV serology and (ii) the type of preventive therapy adopted. Methods: A systematic review of the literature using the electronic database Medline. Results: Five hundred and fifty‐two LT in 36 articles were selected. Lamivudine, Hepatitis B immune globulin (HBIG), revaccination, and combined therapies were employed in multiple strategies as preventive interventions. Naïve recipients had a high risk of de novo HBV infection, with smaller incidences when HBIG and lamivudine were used, either alone or in association. Vaccinated recipients or those with isolated hepatitis B core antibodies (Anti‐HBc) and previous HBV infection had lower risks of viral transmission, additionally reduced by any prophylaxis adoption. Discussion: LT from Anti‐HBc+/HBsAg? donors into HBsAg? recipients is apparently safe, as long as the recipient is vaccinated or presents an isolated Anti‐HBc or previous HBV infection and some prophylaxis is employed. Currently lamivudine seems the best alternative; other nucleoside analogs and revaccination strategies should be considered in future studies. Follow‐up and preventive therapies should be maintained for five yr or preferably throughout the recipients’ life span.     

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.     

Low prevalence of HBV DNA in the liver allograft from anti‐HBc‐positive donors: a single‐center experience

Pan J‐J, Oh S‐H, Soldevila‐Pico C, Nelson DR, Liu C. Low prevalence of HBV DNA in the liver allograft from anti‐HBc‐positive donors: a single‐center experience.
Clin Transplant 2011: 25: 164–170. © 2010 John Wiley & Sons A/S. Abstract: Allografts from donors positive for antibody to hepatitis B core antigen (anti‐HBc⁺) can transmit hepatitis B virus (HBV) to the recipients. We aimed to study the prevalence of HBV DNA in liver allografts from anti‐HBc⁺ donors. Between January 2003 and December 2008, this retrospective study identified 18 patients who received a liver from an anti‐HBc⁺ donor. Pre‐ and post‐transplantation HBV serology and serum HBV DNA level of the study subjects were reviewed. DNA extracted from liver biopsy tissue was used for PCR assay. Immunohistochemistry was also performed to determine viral protein expression. We observed a low prevalence of HBV DNA in allografts from anti‐HBc⁺ donors even among patients who did not receive prophylaxis. Only one of 18 patients had detectable HBV DNA in the liver allograft. This recipient was seronegative for HBV before transplantation and did not receive prophylaxis after transplantation, and developed de novo hepatitis B. Of the five patients who were positive for both antibody to hepatitis B surface antigen and anti‐HBc before transplantation and did not receive prophylaxis after transplantation, none developed HBV infection. Prophylaxis for HBV is important for seronegative recipients receiving a liver from an anti‐HBc⁺ donor. Such prophylaxis may not be necessary for recipients who do not have detectable HBV DNA in the liver allograft.     

Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation

BACKGROUND: Mortality or graft loss after renal transplantation might be influenced by hepatitis virus infection. METHODS: Sera from time of transplantation of 927 renal transplant recipients were tested for hepatitis C (HCV) and hepatitis B virus (HBV) in order to investigate the impact of hepatitis virus infection on graft loss and mortality over an observation period of 20 yr. RESULTS: One hundred and twenty three of 927 patients were HCV positive, 30 patients HBV positive and seven patients HBV and HCV positive. The observation period was 9.2 +/- 4.4 yr. Mortality was significantly higher in patients with hepatitis B (p = 0.0005), as well as in patients with concomitant B and C hepatitis (p < 0.0001) and in those who acquired HCV infection after transplantation (n = 30, p = 0.0192) compared with non-infected patients. Patients with replicating HBV infection (HBeAg positive) had the worst prognosis (p < 0.0001). In the multivariate analysis the presence of HBeAg (p < 0.0001), patients' age (p < 0.0001) and HCV infection after transplantation (p = 0.0453) were predictors for death. Graft survival was significantly shorter in patients with concomitant hepatitis B and C (p = 0.0087) as well as in HBeAg positive patients (p = 0.002). HCV infection or HBs antigenemia did not have a significant impact on graft survival compared with non-infected patients. CONCLUSION: HCV infection after transplantation is associated with a high mortality whereas chronic HCV infection before trans plantation does not have a significant impact on mortality. Patients with replicating HBV infection or concomitant HBV and HCV infection have a high risk of graft loss and mortality.     

Occult hepatitis B virus infection in liver transplant recipients with recurrent hepatitis C: relationship with donor age and fibrosis progression

Abstract:  Liver transplantation (OLT) recipients who receive a graft from donors positive for hepatitis B virus (HBV) anti-core antibodies may develop overt " de novo " HBV infection. The study was undertaken to explore how often HBV infection may remain occult after OLT for hepatitis C, and whether it may represent a factor of graft fibrosis progression. We studied 30 consecutive patients transplanted for hepatitis C liver disease. Specimens from the native liver and from the graft were searched for occult HBV infection (O-HBV). In the native liver, 8/30 patients had detectable O-HBV; during the follow-up, O-HBV infection was demonstrated in 14 graft specimens. Graft O-HBV was associated with older donor age (≥50 yr; 8/9 vs. 6/21, p < 0.005). Recipients with graft O-HBV and no O-HBV in the native liver who received their grafts from donors aged >40 yr had faster fibrosis progression than recipients with no post-transplant O-HBV, whose grafts came from donors aged >40 yr and recipients whose grafts came from donors aged ≤40 yr (4/7 vs. 1/7 vs. 2/16, p < 0.05). In OLT recipients, O-HBV is more likely to occur when grafts are obtained from aged donors and may affect the rate of fibrosis progression because of recurrent hepatitis C.     

Beneficial Effects of Short-Term Lamivudine Treatment for de novo Hepatitis B Virus Reactivation After Liver Transplantation

Clearance of hepatitis B surface antigen (HBsAg) by lamivudine is achieved in only a small proportion of patients with chronic hepatitis B virus (HBV) infection. We investigated the effect of lamivudine on de novo HBV reactivation after living-donor liver transplantation when the number of HBV was expected to be very small. Thirty-eight HBV-naive recipients who received liver grafts from antibodies to core antigen-positive donors receiving hepatitis B immunoglobulin (HBIG) were studied. HBsAg appeared in nine cases (23.7 %) despite receiving HBIG for 12-71 months (mean: 35.1 months) after transplantation. Lamivudine treatment was started in six recipients during the acute phase of HBV reactivation. Five of the six recipients achieved complete clearance of HBsAg in sera at a median of 4.6 months (ranging from 21 to 330 days) after lamivudine administration. Although lamivudine was stopped in four cases, all remained negative for HBsAg. Our findings suggested that short-term lamivudine treatment during acute phase of HBV reactivation could achieve complete clearance of HBsAg in a significant number of liver transplant recipients.     

Kidney Transplantation from Hepatitis B Surface Antigen Positive Donors into Hepatitis B Surface Antibody Positive Recipients: A Prospective Nonrandomized Controlled Study from a Single Center

The number of patients on renal transplant waiting list is increasing rapidly in many countries, exacerbating the shortage of organs. We conducted a study to evaluate the safety and efficacy of deceased-donor kidney transplantation from hepatitis B surface antigen (HBsAg)-positive (+) donors into hepatitis B surface antibody (anti-HBs)-positive (+) recipients. Sixty-five patients received grafts from HBsAg(+) donors, and 308 subjects received grafts from HBsAg-negative(−) donors. Posttransplantation, recipients with HBsAg(−) grafts or HBsAg(+) grafts received 400 U of hepatitis B immunoglobulin once and twice, respectively. The seven recipients who received grafts from hepatitis B virus (HBV) DNA(+) donors were treated with hepatitis B immunoglobulin 400 U weekly for 3 months and lamivudine 100 mg daily for 6 months. All patients were monitored for liver function and hepatitis B viral status. The follow-up period was 38.7 ± 15.4 months. Although two recipients developed de novo HBV infection, neither patient developed severe liver dysfunction nor died. The incidence of liver injury (39/65 vs. 207/308, chi-square test, p > 0.05) and survival (log-rank test, p > 0.05) did not differ between the groups. We conclude that anti-HBs(+) recipients receiving HBsAg(+) grafts did as well as those receiving HBsAg(−) grafts.     

Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single‐center Asian experience

Sun C‐K, Chen C‐L, Concejero AM, Wang C‐C, Wang S‐H, Liu Y‐W, Yang C‐H, Yong C‐C. Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single‐center Asian experience.
Clin Transplant 2011: 25: 47–53. © 2010 John Wiley & Sons A/S. Abstract: From March 1984 to November 2008, we performed 539 primary liver transplantations (LTs). Nineteen (19, 3.5%) were transplanted for end‐stage liver disease secondary to primary biliary cirrhosis (PBC). There were 17 (89%) female and 2 (11%) male recipients. The overall mean age was 50.3 ± 6.3 yr. The mean model for end‐stage liver disease, and Child–Turcotte–Pugh scores were 20.7 ± 2.1, and 11.0 ± 0.5, respectively. There were 2 (11%) United Network for Organ Sharing status 3, 16 (84%) 2B, and 1 (5%) 2A patients. Fourteen patients (14, 73.7%) underwent living donor LT, and five patients (26.3%) received deceased donor LT. The primary immunosuppression consisted of cyclosporine (n = 5) and tacrolimus (n = 14). Liver function returned to normal one month after transplantation. The overall mean follow‐up was 5.8 ± 0.8 yr (range, four months to 15.7 yr). The overall one‐, three‐, and five‐yr survival rates were 94.7%, 89.2%, and 89.2%, respectively. Without hepatitis B virus (HBV) prophylaxis, one patient acquired de novo HBV infection after receiving a graft from an anti‐HBc(+) donor. Another patient developed recurrent hepatitis C infection and expired 25 months after transplantation. Our results showed that HBV prophylaxis was effective not only against de novo infection, but it also worked on pre‐transplant HBV carrier with PBC and helped in virus clearance.     

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.     

Hepatitis B virus vaccination of recipients and donors of allogeneic peripheral blood stem cell transplantation

Abstract: Background: The aim of this study was to determine the role of hepatitis B virus (HBV) vaccination as defined by the seroconversion to hepatitis B surface antibody (anti‐HBs) positivity in peripheral blood stem cell transplants. Methods: A total of 65 recipients and their donors were enrolled in this study. Recipients were divided into four distinct groups. Group 1 consisted of individuals who were vaccinated, group 2 consisted of individuals who were naturally immunized, group 3 consisted of individuals who were HBs‐Ag positive, and group 4 consisted of individuals who were HBV naïve and not vaccinated. Results: Eighty‐eight percent of the HBV‐vaccinated recipients (14 of 16), who had vaccinated‐donors, seroconverted to anti‐HBs positivity. Eighty‐three percent of HBV‐naïve recipients (five of six), who received stem cells from HBV‐immune donors, seroconverted to anti‐HBs positivity. Two of the four HBs‐Ag positive recipients with HBV‐immune donors seroconverted to anti‐HBs positivity after transplantation. Fifty‐seven percent of previously vaccinated‐recipients (eight of 14) lost detectable anti‐HBs antibody following transplantation. Finally, 31% of HBV‐naïve recipients with HBV‐naïve donors acquired a de novo HBV infection. Conclusions: (i) Hepatitis B virus immunization of recipients of allogeneic hematopoietic cell transplantation results in an effective antibody response. (ii) The HBV‐immune status of the donor plays an important role in post‐transplantation HBs‐Ab on seroconversion. (iii) Systematic re‐immunization of recipients will be necessary to maintain HBV immunity in long‐term serving recipients.     

Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC,United States, 2014‐2017

We evaluated clinical outcomes among organ recipients with donor‐derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti‐HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti‐HCV and HCV RNA. Donor risk behaviors were abstracted from next‐of‐kin interviews and medical records. During 2014‐2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow‐up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow‐up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next‐of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.     

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.     

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.     

Transplantation of hepatitis B surface antigen-positive livers into hepatitis B virus-positive recipients and the role of hepatitis delta coinfection.

The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)-carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Combination prophylaxis schemes against HBV post-liver transplantation (LT) recurrence are currently available; the efficacy of those schemes in HBV-related cirrhosis and HCC must be assessed. This report describes the allocation of HBsAg-positive grafts in three HBsAg-positive recipients, with HBV-related cirrhosis and evolving HCC lesions, two of them with hepatitis Delta virus (HDV) coinfection. Patients were administered anti-hepatitis B immunoglobulins (HBIGs) and lamivudine in order to prevent HBV recurrence. In spite of anti-HBV prophylaxis, HBV infection did persist after LT in all patients (no serum clearance of HBsAg). HBV replication assessed by serum HBV deoxyribonucleic acid (DNA) presence was detected in the first month after LT in the 3 recipients. A prompt HDV reinfection with a clinical and histological pattern of hepatitis was observed in the 2 HBV / HDV coinfected recipients. In 1 of them, an evolving chronic hepatitis required a second LT. The non-HDV-infected patient showed an uneventful follow-up, but the lack of the neutralizing effect of HBIGs and the high risk of escape mutants forced the addition of adefovir-dipivoxil to lamivudine, in order to prevent viral variants and hepatitis recurrence. In conclusion, allografts from HBsAg-positive donors in HBsAg-positive recipients are associated with the persistence of the HBsAg after LT due to the failure of HBIG prophylaxis, even if lamivudine does inhibit virion production. This condition favors HDV replication and HDV hepatitis recurrence in coinfected patients. The allocation of HBsAg-positive grafts in HBsAg-positive recipients could be justified only in recipients without HDV coinfection and a combined prophylaxis with lamivudine and adefovir-dipivoxil is currently the best way to manage escape mutants in these recipients.     

Outcome of renal transplantation in hepatitis B surface antigen-positive patients after introduction of lamivudine.

BACKGROUND: In end-stage renal disease patients with hepatitis B surface antigen (HBsAg), the risk of hepatic dysfunction after immunosuppression represents a large barrier in renal transplantation. Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. We retrospectively investigated the outcome of HBsAg-positive renal transplantation recipients after lamivudine had become available. METHODS: From July 1994 to August 2000, seventeen HBsAg-positive patients (M:F=15:2) received renal allografts (13:4=living:cadaveric donors). Liver function tests at the time of transplantation were normal in all patients. Pre-transplant liver biopsies performed in 15 patients demonstrated minimal inflammatory histology, except in three patients showing pathological and clinical signs of active hepatitis. Lamivudine was started pre-operatively in these three subjects. Another seven patients were treated with lamivudine for post-operative hepatic dysfunction. The remaining seven patients did not develop hepatic dysfunction after transplantation. RESULTS: Lamivudine was initially effective in decreasing serum HBV DNA titres, and in normalizing hepatic enzymes. Lamivudine was well tolerated without significant side effects for 35.5+/-8.9 months after initiation of treatment. HBV DNA became negative in nine patients but remained positive in one patient. Among the nine patients with initial negative conversion of HBV DNA, two developed transient positive conversion of HBV DNA and two demonstrated persistent positive conversion. Among the patients with normal liver histology in the pre-transplant period, 41.6% (5/12) developed liver pathology progression after immunosuppression. All 17 patients had functioning grafts, except for one patient who developed relapsed IgA nephropathy. CONCLUSIONS: Our data showed relatively favourable outcomes in hepatitis B-positive renal transplant recipients receiving lamivudine treatment, even though two patients developed lamivudine resistance.     

Liver transplantation for HBsAg‐positive recipients using grafts from HBsAg‐positive deceased donors

This study reports our experience using deceased donor liver grafts from HBsAg‐positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg‐positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26–64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(?) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46–76) at LT. Post‐LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow‐up period was 25.5 months (range: 14–82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV‐unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow‐up biopsies. This experience shows that LT using grafts from deceased HBsAg‐positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.