Long-term follow-up ABO-incompatible adult living donor liver transplantation in cirrhotic patients

ABO-incompatible liver transplantation is usually contraindicated. The presence in the recipient of preformed anti-A/B antibodies located on endothelial cells raises the risk of antibody-mediated humoral rejection of the graft. We describe four successful cases of steroid withdrawal in adult patients who had living-donor liver transplantation from ABO-incompatible donors. Antirejection therapy included multiple perioperative plasmapheresis, splenectomy, and a triple immunosuppressive regimen with tacrolimus, methylprednisolone (MPSL), and cyclophosphamide or mycophenolate mofetil (MMF). The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1) was used. As a result, all four patients were able to achieve long-term graft survival without steroid use. They all have good liver function and are leading normal lifestyles. Our experience with these four patients suggests the feasibility of controlling humoral rejection and other complications in adult ABO-incompatible living donor liver transplantations with intrahepatic arterial infusion of PGE1, splenectomy, and plasmapheresis with a regular base of immunosuppression protocol to prevent antibody-mediated humoral rejection.     

ABO-incompatible adult living donor liver transplantation for hepatocellular carcinoma

Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the need for pretransplantation treatment may be eliminated, which may reduce overall morbidity. In this article, we have described 8 adult HCC patients who successfully underwent LDLT from ABO-incompatible donors. Antirejection therapy included multiple preoperative plasmaphereses, splenectomy, and an immunosuppressive regimen with tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of the ABO-identical cases. In addition, we also performed intrahepatic arterial infusion of prostaglandin E1. In 5 patients, we administered a single dose of rituximab, a chimeric CD20 monoclonal antibody. As a result of this treatment, 6/8 patients are still alive. Our experience has shown that it is possible to control antibody-mediated humoral rejection and other complications in adult ABO-incompatible LDLT.     

Successful case of adult ABO-incompatible liver transplantation: beneficial effects of intrahepatic artery infusion therapy: a case report

BACKGROUND: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However, <30% are cases involving adults. The difficultly of ABO-incompatible liver transplantation is associated with the high frequency of humoral rejection and local disseminated intravascular coagulation (DIC), leading to many postoperative complications. We report a successful case of adult ABO-incompatible liver transplantation with the use of an intrahepatic artery infusion. METHODS: A 36-year-old man with Wilson disease, underwent living donor liver transplantation from an ABO-incompatible donor. The immunosuppressive therapy included multiple perioperative plasmaphereses, splenectomy, and treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and blood level of tacrolimus were the same as in ABO-compatible cases. In addition to these therapies, we administered an intrahepatic arterial infusion with prostaglandin (PG) E1 alone. RESULTS: After perioperative plasmapheresis and cyclophosphamide, antidonor blood group antibody titers remained undiluted and without vascular complications throughout the postoperative course, but there was a tendency for bleeding that continued for 10 days after transplantation. On postoperative day 10, a reexploration was performed for intraabdominal bleeding. During another operation on postoperative day 59 a biloma was found and drained. The patient has now survived for 120 days after transplantation with normal liver function. CONCLUSIONS: Beneficial effect of intrahepatic artery infusion with PGE1 seems to be useful in adult ABO-incompatible liver transplantation.     

Adult ABO-incompatible liver transplantation by intraportal transfusion of donor-specific antigen: a case report

A 55-year-old-woman suffering from fluminant hepatitis owing to autoimmune hepatitis underwent ABO-incompatible liver transplantation (LRLD) of blood type A to B. In this study, we investigated whether a new immunosuppressive strategy by intraportal transfusion of donor-specific leukocytes (DSLT) separated from whole blood would yield immunological benefit in adult ABO-LRLD. The operative course was uneventful; she was discharged at 46 days postoperatively without humoral or cellular rejection. On immunologic analysis, 54.6% intrahepatic macrochimerism of donor type CD56+ T cells was recognized at 1 month after transplantation. The interleukin-10 Th2 cytokine level was increased on postoperative day 1. Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with our strategy of immunosuppression by intraportal administration of DSLT. Donor type CD56+ NKT cells may induce tolerance by a veto mechanism and/or an anti-idiotype network. ABO-incompatible liver transplantation may be improved by this strategy.     

New protocol of immunosuppression for liver transplantation across ABO barrier: the use of Rituximab, hepatic arterial infusion, and preservation of spleen

INTRODUCTION: An ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) is a challenge. Until 2000 systemic multidrug immunosuppression and splenectomy was the gold standard with poor results. Application of local administration with prostagrandin E1 (PGE1) and steroids via a portal vein (PV) catheter dramatically improved the survival from 20% to 60% but PV thrombus became a problem (35%). To solve it, an hepatic arterial (HA) catheter was used instead of a PV catheter and splenectomy was omitted. Although the PV thrombus problem was resolved, the ABO antibody titers significantly increased, and two cases of uncontrollable humoral rejection (HR) were experienced. In this study, Rituximab was introduced instead of splenectomy to decrease the antibody. We report the efficacy of prophylaxis with Rituximab for ABO-I LDLT. METHODS: Eight patients received. Rituximab at 2 to 14 days before LDLT. During the operation, the spleen was preserved. Methylpredonisolone and PGE1 were administered via an HA catheter for 2 to 3 weeks after LDLT in addition to an immunosuppressive regimen consisting of tacrolimus and steroids. Antibody titers were measured serially. RESULT: There was no clinical HR. Two patients died of complications unrelated to HR. The antibody titer decreased compared to patients without splenectomy/rituximab. B cells (CD19) were depleted from peripheral blood for up to 3 months. Cytomegalovirus infections were decreased compared to patients with splenectomy (P = .085). CONCLUSION: Rituximab prophylaxis and HA infusion therapy prevented clinical HR, which may provide a breakthrough to overcome the ABO blood-type barrier in liver transplantation.     

ABO-incompatible liver transplantation with no immunological graft losses using total plasma exchange,splenectomy, and quadruple immunosuppression: Evidence for accommodation

ABO-incompatible liver transplants (LTX) have been associated with a high risk of antibody-mediated rejection, poor patient and graft survival, and a high risk of vascular thrombosis and ischemic bile duct complications. We used pretransplantation and posttransplantation double-volume total plasma exchange (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or mycophenolate mofetil, prednisone, cyclosporine or tacrolimus, and OKT3 induction) in 14 patients receiving ABO-incompatible LTX between June 1992 and February 2001: A₁ to O (seven), B to O (two), B to A (two), A to B (one), AB to A (one), and AB to O (one). Actuarial 1- and 5-year patient and graft survival rates are 71.4% and 61.2 % and 71.4% and 61.2%, respectively, with a mean follow-up of 62.9 ± 39.4 months. Ten acute cellular rejections occurred, and the mean time to the first episode was 62 ± 33 days. All were steroid sensitive. No antibody-mediated rejection or vascular thromboses occurred. Pretransplantation pre-TPE immunoglobulin (Ig) G mean isohemagglutinin titers were 262 ± 326, compared with pretransplantation post-TPE titers of 65 ± 103 (P = .04). Eight of nine patients with measurable titers before and after TPE achieved a reduction in titers. The mean number of posttransplantation TPE was 5.5 ± 4.1 (range, 0 to 12), and the last TPE was on postoperative day 9.4 ± 5.3. IgG isohemagglutinin titers 2 weeks posttransplantation had increased to 153 ± 309 (P = .03 compared with pretransplantation pre-TPE IgG). ABO-incompatible liver transplantations can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple immunosuppression. Recovery of isohemagglutinin antibody levels without humoral rejection suggests that accommodation may be the protective mechanism preventing late antibody-mediated rejection. (Liver Transpl 2003;9:22-30.)     

A Comparison of splenectomy versus intensive posttransplant antidonor blood group antibody monitoring without splenectomy in ABO-incompatible kidney transplantation

BACKGROUND: Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. METHODS: We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). RESULTS: Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. CONCLUSIONS: Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.     

Clinical outcomes of liver transplantation for HBV-related hepatocellular carcinoma: data from the NIH HBV OLT study

Han SH, Reddy KR, Keeffe EB, Soldevila‐Pico C, Gish R, Chung RT, Degertekin B, Lok ASF. Clinical outcomes of liver transplantation for HBV‐related hepatocellular carcinoma: data from the NIH HBV‐OLT study.
Clin Transplant 2011: 25: E152–E162. © 2010 John Wiley & Sons A/S. Abstract: Background: Hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV‐related HCC is increasing, while the number of patients listed for HBV‐related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long‐term outcome of patients transplanted for HBV‐related HCC in the National Institutes of Health (NIH) HBV OLT Study Group. Results: Ninety‐eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV‐related HCC. With a mean follow‐up of 36.5 months post‐OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre‐OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre‐OLT in predicting HCC recurrence. Serum alpha‐fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p = 0.003). HCC recurrence was significantly associated with decreased post‐OLT survival. Conclusion: HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence.     

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.     

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.     

Transplantation of ABO-incompatible and living unrelated donor-recipient combinations

INTRODUCTION: According to the Japanese renal transplant registry 2005, 834 transplantations were performed using living donors. Among them 199 (23.9%) kidneys were donated from spouses (husband/wife) and 174 (20.9%) from ABO-incompatible donors. This study summarized our experience of ABO-incompatible and living unrelated, especially spousal kidney transplantation. PATIENTS AND METHODS: We performed 44 cases of living donor kidney transplantation (LKT) between April 2003 and July 2007, including 14 (31.8%) from spouses (unrelated donor) who were divided into two groups: six patients (group 1; G1) from ABO-incompatible donors and eight patients (group 2; G2) from ABO-compatible donors. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were used for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In all G1 patients plasmapheresis was performed to remove anti-AB antibodies prior to LKT, and splenectomy performed at the time of or before LKT. RESULTS: Among G1, no patient died. Among G2, one patient died with a functioning graft due to a traumatic subdural hematoma. Graft survival rate was 100% in both groups. The incidence of acute rejection was 33.3% and 25.0% in G1 and G2, respectively. No patient experienced a lethal infectious complication. CONCLUSIONS: Our results demonstrated that transplantation from an ABO-incompatible spousal donor was equivalent to transplantation from an ABO-compatible spousal donor. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan.     

Indication for splenectomy in the era of living-donor liver transplantation

Although end-stage liver disease (ESLD) is often associated with splenomegaly and thrombocytopenia, splenectomy is not necessary in liver transplantation (OLT) except in special situations. In this paper, we examined the indications for splenectomy in the era of living-donor living transplantation. Six of 46 patients underwent splenectomies. Among them, one received a cadaveric graft. Three splenectomies were performed at 6, 7, and 44 days after OLT because of a huge spleen, massive ascites, or impaired liver function. The other two patients received simultaneous splenectomy during OLT to prevent rejection of ABO-incompatible grafts with a positive anti-T-cell test; and one, for postoperative therapy of hepatitis C. All six patients had a good response to splenectomy. We concluded that splenectomy may be indicated for recipients with severe thrombocytopenia, small-for-size syndrome, ABO incompatibility with positive anti-T/B-cell tests and post-OLT therapy for hepatitis C.     

Outcomes of hepatitis B virus recurrence after liver transplantation

The introduction of high doses of hepatitis B immune globulin (HBIG) and lamivudine for liver transplantation (OLT) prophylaxis has reduced the risk of hepatitis B recurrence and improved the survival of patients transplanted for hepatitis B virus (HBV)-related liver disease. But, posttransplant prophylaxis strategies to treat the recurrence of HBV have not yet been standardized. We analyzed 23 patients with HBV recurrence among 340 HBV-associated liver transplants performed from September 1996 to April 2004 (6.7%). Nine patients underwent deceased donor OLT and 14, living donor OLT. Mean follow-up was 37 months. Seroconversion after recurrence was observed in 6 of 23 patients (26%). Mean time to HBV recurrence tended to be shorter among the seroconversion (+) patients compared to seroconversion (-) patients (10 months vs 19.7 months; P = .062). Seroconversion rate after HBIG and lamivudine combination therapy for patients with HBV recurrence was 37.5% and time to seroconversion after HBV recurrence was 1.7 months. Seroconversion was best achieved when the pretransplant HBV DNA level was high and HBeAg was positive. Also, seroconversion rate was increased when HBV DNA level was low and the alanine transferase level high at the time of recurrence and when the time to recurrence after transplantation was short. Seroconversion after HBV recurrence, which was observed in 26%, may be increased in selected cases. Accordingly, aggressive treatment should be undertaken after HBV recurrence.     

肝移植治疗乙肝相关疾病

目的 总结原位肝移植（OLT）治疗乙肝相关疾病的疗效,并评价了拉米夫定对肝移植术后乙肝复发的防治作用。方法 自1993年4月-2000年12月,中山医科大学器官移植中心为54例乙肝相关疾病患者实施了肝移植,其中乙肝坏死后肝硬化17例,为第1组,25例同时合并肝癌者为第2组、其余12例暴发性肝功能衰竭患者为3组。回顾性地分析了3组患者术后存活率、早期死亡原因以及拉米夫定对术后乙肝复发的防治情况。结果 乙肝相关疾病患者肝移植术后早期存活率为75.9%,暴发性肝衰组患者术后早期并发症发生率明显高于其它2组;OLT对小肝癌患者的疗效明显优于大肝癌患者;拉米夫定防治乙肝复发辣效好且未发现副作用。结论 结合拉米夫定,OLT是治疗暴发性乙肝、乙肝肝硬化及小肝癌甚或某些选择性大肝癌患者的有效手段。     

Impact of Intraportal Donor-Specific Leukocyte Transfusion for Adult ABO-Incompatible Liver Transplantation

Introduction

We have reported that repeated donor-specific leukocyte transfusions (DSLT) via the portal vein allow rapid reduction of immunosuppressants and decrease the occurrence of acute cellular rejection. Herein, we examined the immunological benefits of DSLT in adult ABO-incompatible living donor liver transplantation (LDLT).

Materials and Methods

Ten adult patients (MELD score, 19.4 ± 7.3; range, 12-29) underwent LDLT from ABO-incompatible donors from August 2003 to November 2007. The antirejection therapy included multiple perioperative plasmaphereses, splenectomy, and quadruple immunosuppression. In addition to these conventional approaches, we performed 4 intraportal administrations of DSLT after transplantation.

Results

There was no humoral rejection in any patient. Two patients experienced mild cellular rejection requiring steroid pulse therapy. Both donor-specific immunoglobulin (Ig)M and IgG A/B antibodies in all patients decreased following transplantation by 16 fold. By flow cytometry, donor type of CD56+NK T cells existed in the liver graft showing macrochimerism at 1 month after liver transplantation. Furthermore, interleukin (IL)-10 production of Th2 type cytokines was up-regulated after transplantation. Three patients died of sepsis and infection. The 5-year survival rate was 70% by the Kaplan-Meier method.

Conclusion

Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection using intraportal administration of DSLT. Donor type CD56+NK T cells may induce tolerance by a veto or an anti-idiotype network mechanism.     

ABO-incompatible liver transplantation: a new therapeutic option for patients with acute liver failure in Chile

Different ways have been suggested to expand donor numbers for liver transplantation. Transplantation using ABO-incompatible hepatic grafts has recently been a controversial issue due to the high risk of hyperacute rejection mediated by preformed anti-ABO antibodies. We report three patients with acute liver failure who were transplanted with ABO-incompatible livers: A to O in two patients and A to B in one case. We used pre- and posttransplant total plasma exchange, splenectomy, and triple immunosuppression. All three patients are alive; one graft was lost, probably secondary to thrombotic microangiopathy with low isohemagglutinin titers of 1:8. One patient developed acute cellular rejection that was reversed with a bolus of methylprednisolone. No antibody-mediated rejection occurred. Financial and infectious considerations have to be considered. In our series, the final liver transplantation cost was higher than average for acute liver failure. Plasmapheresis has the highest cost of all the additional procedures. ABO-incompatible liver transplantation, because of the splenectomy it requires, has been associated with more infections due to encapsulated organisms. However, with splenectomy in our three patients, none had infections due to these bacteria. In our country, we do not consider ABO-incompatible liver transplantation as a first-line option, except for highly selected patients.     

Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation

HYPOTHESIS: Hepatic allografts from donors positive for antibody to hepatitis B core antigen (anti-HBc) frequently transmit hepatitis B virus (HBV) infection to recipients. Therefore, most transplantation centers will not use these organs for orthotopic liver transplantation (OLT). Although it is expensive and not always efficacious, hepatitis B immune globulin (HBIG) has been used routinely for indefinite periods to prevent HBV infection in liver allograft recipients. We assessed the effectiveness of long-term use of a nucleoside analog, lamivudine, in preventing HBV transmission by anti-HBc-positive allografts. DESIGN: Retrospective study. SETTING: A tertiary care center. PATIENTS: Twelve patients received hepatic allografts from anti-HBc-positive donors at Loyola University Medical Center, Chicago, between February 23, 1998, and March 13, 2001. INTERVENTION: All patients received 10 000 U/d of intravenous HBIG for 7 days. In addition, they received 300 mg/d of lamivudine in divided doses. Their liver biopsy specimens were tested for HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb). Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody (HBsAb). MAIN OUTCOME MEASURE: The incidence of HBV infection in recipients who received HBcAb-positive donor livers and lamivudine prophylaxis. RESULTS: All recipients were anti-HBc negative before OLT. Five of the recipients had HBsAb titers greater than 150 U at the time of OLT. Three of the donor livers were HBV DNA positive and 2 were hepatitis B core antigen positive at the time of OLT. Donor serum was HBcAb positive in all 12 donors. None of the recipients have become infected with HBV with a follow-up of 2 to 38 months. CONCLUSION: Perioperative use of HBIG combined with long-term use of lamivudine can prevent HBV infection in recipients who receive hepatic allografts from HBcAb-positive donors.     

Experiences and problems pre-operative anti-CD20 monoclonal antibody infusion therapy with splenectomy and plasma exchange for ABO-incompatible living-donor liver transplantation

BACKGROUND: ABO-incompatible living-donor liver transplantation (LDLT) requires a reduction of the anti-ABO antibody titer to <16 before transplantation, which is usually achieved by pre-operative plasma exchange (PE) or double-filtration plasmapheresis. ABO-incompatible transplantations have been performed after a splenectomy with heavy drug immunosupression plus B-cell-specific drugs. Here, we evaluated a pre-transplantation infusion protocol with an anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible LDLT. METHODS: Between March 2002 and December 2005, 73 adult patients underwent LDLT without retransplantation in our institution. Among these cases, 57 were ABO-identical, 11 were ABO-compatible and five were ABO-incompatible. The rituximab infusion protocol consisted of a weekly infusion of rituximab (375 mg/m(2)) for three wk, which was administered to three of the five ABO-incompatible LDLT patients. All three patients underwent a pre-operative PE, as well as a splenectomy during the operation. A triple immunosuppression protocol of tacrolimus, low-dose steroids and mycophenolate mofetil (1500 mg/d) was administered post-operatively. In addition, the patients received a continuous intra-arterial infusion of prostaglandin E(1) and methylprednisolone, and a continuous intra-portal infusion of a protease inhibitor for three and two wk after transplantation, respectively. RESULTS: After the first rituximab infusion, the peripheral blood CD19(+) B cell count rapidly decreased to <1%. All three patients treated with rituximab subsequently received an ABO-incompatible LDLT, with donor/recipient blood groups of B/O, A(1)/B and A(1)/O. In two cases, the ABO-antibody level transiently increased post-operatively, then decreased and remained low. Rituximab infusion therapy did not develop any direct side effect except for mild allergic reaction to the first infusion, but post-operatively all three patients suffered a cytomegalovirus and were successfully treated with ganciclovir, and one patient had a MRSA-positive intra-abdominal abscess. Two patients are currently alive at 20 and 18 months respectively, and show normal graft-liver function. But one patient died of sepsis because of intra-abdominal abscess. CONCLUSIONS: Although the protocol of rituximab administration is a conventional and safe regimen with no major side effects, the development of a new protocol is needed for prevention of the infection with bone suppression.     

Experiences in liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Beside surgical resection, orthotopic liver transplantation (OLT) is not only effective but also the only potentially curable treatment in selected cases of small tumors. We report our experience in 11 male patients transplanted for HCC from August 1998 to July 2002. Selection criteria for OLT were unresectability of the hepatic tumor and severity of the underlying liver disease. The tumor diagnosis was confirmed by histology, imaging techniques, and tumor markers. All patients received an orthotopic liver allograft using a modified piggyback technique. Six of the 11 patients are alive; one died due to acute rejection and four died from recurrent disease. In all four patients with recurrent disease, vascular invasion was shown histologically, whereas only one patient without evidence of recurrence showed vascular invasion. To prevent recurrence after OLT the immunosuppressive regime was adjusted to the underlying disease by early cessation of prednisolone and reduction in the long-term exposure to immunosuppressive drugs. Patients were screened for recurrence by ultrasound and computed tomography. Recurrent HCC were treated symptomatically. OLT is an effective treatment for subgroups of patients with HCC. It might be possible to downstage the liver tumor by chemoembolization and/or radiofrequency ablation and allow the patients to wait for a suitable donor. After OLT the early withdrawal of prednisolone and the reduction of other immunosuppression is feasible. In conclusion, OLT can be a potentially curative therapy for HCC.     

70例原位肝脏移植

目的总结肝脏移植治疗不同终末期肝病的经验,探讨肝移植在治疗肝细胞癌(HCC)和重症乙型肝炎(乙肝)的疗效,以及评价拉米夫定对预防乙肝复发的价值.方法回顾性分析了自1993年4月～2000年12月实施的70例肝移植患者的临床资料.肝移植的主要指征是原发性肝癌(26例)、肝硬化(21例)、重症乙型肝炎(12例)、硬化性胆管炎(4例)以及其它终末期肝病(7例).对12例重症乙型肝炎患者应用拉米夫定治疗.采用多元回归分析确定影响肝移植预后的危险因素.结果54例患者存活1个月以上,16例患者在移植术后30d内死亡,院内存活率为77.1%,肝功能属ChildA级和B级的患者院内存活率明显高于ChildC级患者(P＜0.05),小肝癌患者的疗效优于大肝癌患者.移植前APACEⅢ评分,腹水量以及血肌酐水平与肝移植预后有密切关系.在重症乙肝患者中,9例仍存活、存活时间为2～24个月,拉米夫定可有效地预防肝移植术后乙肝复发,且无明显的副作用.结论本研究结果表明原位肝移植可使部分HCC患者获得治愈,部分病例可获得良好的姑息疗效,病例选择对肝癌肝移植的预后极其重要;结果还提示肝移植是治疗各种终末期肝病的有效手段.同时认为拉米夫定是一种疗效肯定,副作用小的预防肝移植术后乙肝病毒复发的药物.