High Viremia,Prolonged Lamivudine Therapy and Recurrent Hepatocellular Carcinoma Predict Posttransplant Hepatitis B Recurrence†

Hepatitis B virus (HBV) recurrence following orthotopic liver transplantation (OLT) is generally preventable by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM). However, HBV recurrence sometimes develops despite prophylaxis. This study assessed posttransplant outcomes and identified predictors of HBV recurrence. We analyzed the outcomes of 209 consecutive patients positive for hepatitis B surface antigen who underwent OLT, who received either combination prophylaxis with HBIG and LAM (89.0%) or HBIG monoprophylaxis (11.0%). The median follow‐up was 36.8 months (range, 1.0–84.4). Posttransplant HBV recurrence occurred in 22 patients (10.5%), including 13 patients with drug‐resistant mutations. HBV recurrence was observed in six patients after hepatocellular carcinoma (HCC) recurrence. Independent predictors of HBV recurrence were recurrent HCC (p < 0.001), LAM therapy >1.5 years (p = 0.001) and high HBV DNA titers (≥10⁵ copies/mL) at OLT (p = 0.036). In conclusion, high viremia at OLT and prolonged exposure to LAM should be further stressed as main predictors of HBV recurrence.     

Prophylactic use of low-dose, on-demand, intramuscular hepatitis B immunoglobulin and lamivudine after liver transplantation

The combination of hepatitis B immunoglobulin (HBIG) and antivirals (nucleos[t]ide analogs) has extended the applicability of orthotopic liver transplantation (OLT) for patients with hepatitis B virus (HBV)-related liver disease. However, HBIG administrations have an extremely high cost. Herein, we evaluated our results with low-dose, on-demand, intramuscular HBIG plus lamivudine (LAM) prophylaxis after OLT. The HBV DNA status in 40 patients at the time of OLT determined the treatment: group A (n = 22), HBV DNA (-), no antiviral pretreatment; group B (n = 11), HBV DNA (-), after LAM; group C (n = 3), HBV DNA (+) after LAM (LAM resistance/Adefovir [ADV] unavailable); group D (n = 2), HBV DNA (+), no antiviral pretreatment; and group E (n = 2), HBV DNA (-) after LAM + ADV (LAM resistance/ADV available). Five patients died within 12 months after OLT unrelated to HBV infection. The remaining 35 patients were followed for a median duration of 16 months (range, 6-93 months). Only two recipients from group C, who were transplanted despite LAM resistance + no ADV pretreatment, revealed recurrent HBV infections at 14 and 16 months posttransplantation; they were then treated successfully with ADV as it became available. The third group C recipient had undetectable HBV DNA at 18 months after OLT. The mean cumulative doses of HBIG administered within the first, second, and third years were 34,014, 5258, and 5090 IU, respectively. In conclusion, low-dose, on-demand, intramuscular HBIG plus (LAM +/- ADV) prophylaxis is a safe, efficient, and cost-effective regimen to prevent recurrent HBV infection following OLT. OLT despite untreated LAM resistance may require sustained higher serum HBsAb levels after surgery.     

肝移植术后HBV再感染的治疗

目的分析肝移植术后乙型肝炎病毒（HBV）再感染患者的抗病毒治疗与乙肝病毒基因变异情况。方法317例HBV相关终末期肝病患者肝移植术后15例单独使用LAM，302例使用小剂量乙肝免疫球蛋白（hepatitis B immune globulin，HBIG）和拉米夫定（lamivudine，LAM）（或adefovir dipivoxil，ADV）联合预防HBV再感染，同时检测HBV血清标志物、血清HBV DNA、YMDD区变异、及肝活检组织乙型肝炎标记物。结果术后LAM组有4例术前HBV DNA阳性患者术后HBV再感染，LAM＋HBIG联合用药组16例HBV再感染，两组术后HBV再感染差异有统计学意义（26．7％VS．5．30％，P〈0．01）。317例患者术后12例发生YMDD变异，发生率为3．79％，再感染病例60％（12／20）。经加用ADV治疗后5例HBV DNA转阴性，4名患者HBV DNA滴度下降，肝功能显著改善，3例发生纤维淤胆性肝炎，2例死亡，1例经再次肝移植治愈。结论小剂量HBIG＋LAM可以有效地预防肝移植术后HBV再感染；在小剂量HBIG＋LAM用药基础上HBV再感染可能产生YMDD（tyrosine，methionine，aspartate，aspartate）变异；ADV可作为LAM耐药后用药，对于发生突破性感染的患者应采取以ADV为主的综合治疗。     

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.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

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.     

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.     

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.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

拉米夫定预防肝移植术后乙型肝炎病毒再感染的研究

目的 探讨和评价拉米夫定预防原位肝移植术后乙型肝炎病毒（HBV）再感染的效果。方法 41例患者，术前诊断为肝炎后肝硬化（失代偿期）者22例，慢性重型肝炎并肝炎后肝硬化（失代偿期）者12例，慢性重型肝炎者7例，其中HBVDNA阳性16例。41例患者均采用背驮式原位肝移植，术前15例给予拉米夫定治疗，术后41例患者均服用拉米夫定。结果 10例患者术后出现HBV再感染，其中9例为YMDD变异毒株感染，术后1、2年的HBV再感染率分别为9．8％（4／41）、24．4％（10／41）。术前血清HBVDNA阴性者术后HBV再感染率（12．0％，3／25）明显低于HBVDNA阳性者（43．8％，7／16）。术前长期服用（超过6个月）拉米夫定者和未服用拉米夫定者术后HBV再感染率分别为66．7％、23．1％，均明显高于术前短期（未超过6个月）服用拉米夫定者（0，P〈0．05）。结论 术前服用拉米夫定可降低乙型肝炎患者肝移植后HBV再感染率，但服药时间不宜超过6个月；长期、单一的应用拉米夫定易导致病毒变异而出现耐药毒株感染。     

New era of liver transplantation for hepatitis B: a 17-year single-center experience

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.     

"大三阳"乙肝病人肝移植后抗HBV治疗远期效果分析

目的 通过长期观察大三阳乙肝病人肝移植后在LAM或(和)HBIG预防下其体内HBV标志物的变化.探讨乙肝复发的可能机制,为预防复发及个体化治疗寻找切人点.方法 ELISA、HBV-DNA荧光定量、免疫组化定期检测术前术后各期血清及其供肝活检组织,回顾性观察55例大三阳病人随访中HBV标志物的变化.结果 平均随访69.14个月,共12例乙肝再感染/复发,LAM+HBIG组乙肝复发比率为4.8%(2/42),而LAM组为76.9%(10/13)(P=0.000).联合组1、2、3、4年生存率分别为100%、97.1%、92.7%、92.7%;单用组1、2、3、4年生存率分别为76.9%、69.2%、53.8%、46.2%(P=0.000);前者2年内乙肝复发率<3%,后者1、2、3、4年复发率分别为16.1%、41.3%、66.4%、66.4%(P=0.000).结论 HBIG联合核苷(酸)类似物作为当前最佳的乙肝复发预防方案明显地降低了复发率,治疗依从性差及病毒的自身状态是中国肝移植后乙肝再感染/复发的主要原因.根据治疗过程中病毒自身状态的变化及时调整用药将有助于进一步减少术后乙肝复发.     

Posttransplantation Hepatitis B Prophylaxis with Combination Oral Nucleoside and Nucleotide Analog Therapy

Liver transplant recipients are at risk of developing recurrent hepatitis B after liver transplantation for hepatitis B virus (HBV)‐related liver disease. We evaluated the efficacy of a new hepatitis B prophylaxis regimen involving conversion from at least 12 months of HBIg with lamivudine to combination therapy with an oral nucleoside and nucleotide analog. Between June 2008 and May 2010, a total of 61 liver transplant recipients were converted to a combination of a nucleoside and nucleotide analog. The mean (±standard deviation) follow‐up time after conversion was 15.0 (±6.1) months. Recurrent HBV occurred in two (3.3%) patients at 3.1 and 16.6 months after HBIg cessation. The overall person time incidence rate for HBV recurrence after HBIg cessation was 2.7 cases per 100 person‐years. The estimate of HBV recurrence was 1.7% at 1 year after HBIg cessation. HBIg cessation a minimum of 12 months after liver transplantation with subsequent combination therapy with a nucleoside and nucleotide analog provides effective prophylaxis against recurrent HBV infection. The clinical implications of HBsAg detection without clinical, biochemical or molecular manifestations of recurrent hepatitis B require further study.     

No hepatitis recurrence using combination prophylaxis in HBV-positive liver transplant recipients with YMDD mutants

Recurrence of hepatitis B impairs the outcome of liver transplantation (OLT). In serum hepatitis B virus (HBV)-DNA-positive recipients, prophylaxis using lamivudine and immunoglobulins (HBIg) reduces the risk of recurrence, but it is undefined whether this regimen also protects candidates with YMDD mutants. Seventeen OLT viraemic candidates received pre-emptive lamivudine followed by post-OLT prophylaxis with lamivudine and HBIg. Both sera and liver biopsies were prospectively collected and high-sensitive polymerase chain reaction (PCR) assay was applied for HBV-DNA detection. Finally, the presence of YMDD mutants was explored in all PCR-positive samples. All patients remained hepatitis B recurrence-free after a mean follow up of 32 months. By PCR, serum HBV-DNA was detectable in 64.3% of cases at OLT-baseline, in 64.7% under combined prophylaxis and in 58.8% in patients (70.5% of the total) with a minimum follow up of 24 months. At OLT-baseline, YMDD mutants were found in 44.4% of patients. After OLT, mutants were present in 50% of patients but only in 16.6% of cases in the long period. Although 41% of the native livers and 42.8% of the analysed grafts harboured HBV-DNA, YMDD mutants were detected in 57% of the native positive livers. YMDD mutants were largely detected both at OLT-baseline and post-OLT, but their presence decreased over time. Regardless of the presence of YMDD mutants, no hepatitis B recurrence was observed in our OLT recipients using pre-emptive lamivudine followed by continuous prophylaxis with lamivudine and HBIg.     

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.     

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.     

Impact of Virologic Breakthrough and HBIG Regimen on Hepatitis B Recurrence After Liver Transplantation

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre‐OLT and HBIG regimens post‐OLT. Data from the NIH HBV‐OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1–81) post‐OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log₁₀ copies/mL, 74% were receiving antiviral therapy. Twenty‐five patients experienced virologic breakthrough before OLT. Post‐OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high‐dose, IV low‐dose, intramuscular low‐dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre‐OLT as long as rescue therapy is administered pre‐ and post‐OLT.     

High Genetic Barrier Nucleos(t)ide Analogue(s) for Prophylaxis From Hepatitis B Virus Recurrence After Liver Transplantation: A Systematic Review

The combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues [NA(s)] is considered as the standard of care for prophylaxis against HBV recurrence after liver transplantation (LT), but the optimal protocol is controversial. We evaluated the efficacy of the newer NAs with high genetic barrier (hgbNA) [i.e. entecavir (ETV) or tenofovir (TDF)] with or without HBIG as prophylaxis against HBV recurrence after LT. In total, 519 HBV liver transplant recipients from 17 studies met the inclusion criteria and they were compared to those under lamivudine (LAM) and HBIG who had been selected in our previous review. Patients under HBIG and LAM developed HBV recurrence (115/1889 or 6.1%): (a) significantly more frequently compared to patients under HBIG and a hgbNA [1.0% (3/303), p < 0.001], and (b) numerically but not significantly more frequently compared to the patients who received a newer NA after discontinuation of HBIG [3.9% (4/102), p = 0.52]. The use of a hgbNA without any HBIG offered similar antiviral prophylaxis compared to HBIG and LAM combination, if the definition of HBV recurrence was based on HBV DNA detectability [0.9% vs. 3.8%, p = 0.11]. Our findings favor the use of HBIG and a hgbNA instead of HBIG and LAM combined prophylaxis against HBV recurrence after LT.     

Clinical study on prevention of HBV re-infection by entecavir after liver transplantation

Cai C‐j, Lu M‐q, Chen Y‐h, Zhao H, Li M‐r, Chen G‐h. Clinical study on prevention of HBV re‐infection by entecavir after liver transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01448.x.
© 2011 John Wiley & Sons A/S. Abstract: Purpose: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re‐infection after liver transplantation (LT). Methods:  A retrospective matched case‐control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. Results: Two hundred and fifty‐two patients were enrolled. The average duration of follow‐up was 38.5 and 41.2 months (LAM and ETV groups) (p > 0.05). Duration of pre‐operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p > 0.05). The HBV DNA level decreased from 3.89 × 10⁶ to 5.31 × 10⁵ copies/mL before LT in the LAM group, and decreased from 8.74 × 10⁶ to 5.49 × 10⁴ copies/mL in the ETV group (p < 0.05). Eighteen patients in LAM group developed HBV re‐infection and 0 in ETV group. Conclusion: ETV is superior to LAM for preventing HBV re‐infection following LT.     

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.