tacrolimus and Hepatitis-B

Clinical liver transplantation became an established therapy of end-stage liver disease since the first at least medium-term successful liver transplantation in 1967. Clinical studies have played a major part in improving peri- and postoperative therapy in liver transplantation. In this article clinical studies of major impact are presented. Main topics are studies dealing with immunosuppressants, improvements in surgical techniques, viral infections and tumor diseases. Controlled randomized multicentric studies are rare; most of the studies are unicentric. Further studies in the fields of reducing side effects of immunosuppression, the introduction of monoclonal antibodies and improvement of the therapy of viral hepatitis would be helpful. These studies should be controlled, randomized and multicentric.

Topics: Carcinoma, Hepatocellular; Cyclosporine; Cytomegalovirus Infections; Double-Blind Method; Hepatitis B; Hepatitis C; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Neoplasms; Liver Transplantation; Multicenter Studies as Topic; Postoperative Complications; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Tacrolimus

Legionella micdadei (Pittsburgh pneumonia agent) is the second most common cause of Legionella pneumonia, and occurs predominantly in immunocompromised hosts. L micdadei is the cause of nosocomial pneumonia in renal transplant recipients, but has not been described in other adult solid organ transplant recipients. This report describes the first case of L micdadei pneumonia in an adult liver transplant recipient on immunosuppressive therapy. Importantly, this case highlights the difficulties in establishing the diagnosis, as the Legionella urinary antigen is negative, and special culture conditions are required. Furthermore, this case illustrates several atypical clinical features of L micdadei pneumonia in a transplant recipient, including a community acquired mode of transmission, occurrence several years after organ transplantation, and lung abcess formation. The patient was successfully treated with limited surgical resection and quinolone antimicrobial monotherapy.

Topics: Adult; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Ciprofloxacin; Diabetes Mellitus, Type 2; Hepatitis B; Humans; Immunosuppressive Agents; Legionellosis; Liver Transplantation; Lung Abscess; Male; Pneumonia, Bacterial; Postoperative Complications; Tacrolimus; Tomography, X-Ray Computed

Topics: Child; Cyclosporine; Graft Survival; Hepatitis B; Hepatitis C; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Recurrence; Survival Rate; Tacrolimus

Topics: Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Liver Diseases, Alcoholic; Liver Transplantation; Tacrolimus; Tissue Donors

HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection.. We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF). Immunosuppressive Drug Resistant Armored TCR-T cells of desired specificity (HBV or Epstein-Barr virus) were then engineered by concomitantly electroporating mRNA encoding specific TCRs and mutated variants of calcineurin B (CnB) and inosine-5'-monophosphate dehydrogenase (IMPDH), and their function was assessed through intracellular cytokine staining and cytotoxicity assays in the presence of TAC and MMF. Liver transplanted HBV-HCC patients receiving different immunosuppressant drugs exhibited varying levels of activated (CD39. We engineered TCR-T cells of desired specificities that transiently escape the immunosuppressive effects of TAC and MMF. This finding has important clinical applications for the treatment of HBV-HCC relapses and other pathologies occurring in organ transplanted patients.

Topics: Carcinoma, Hepatocellular; Coculture Techniques; Drug Resistance; Graft Rejection; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Humans; Immunotherapy, Adoptive; Liver; Liver Neoplasms; Liver Transplantation; Mycophenolic Acid; Neoplasm Recurrence, Local; Protein Engineering; Receptors, Antigen, T-Cell; T-Lymphocytes; Tacrolimus

Adefovir dipivoxil has activity against wild-type and lamivudine-resistant hepatitis B virus (HBV) and is frequently used to manage HBV infection in transplant recipients. Calcineurin inhibitors are a central component of immunosuppressive therapy.. Study GS-02-531 was an open-label, multicentre drug interaction trial to examine potential drug interactions between adefovir and tacrolimus in stable post-transplant recipients.. Sixteen non-HBV-infected post-transplant recipients with median age 45.5 years (69% male, 44% Caucasian, 50% Hispanic and 6% Black) and stable hepatic and renal function on a stable daily dose of tacrolimus (2-10 mg total daily dose) were studied before (tacrolimus alone) and after co-administration of adefovir 10 mg daily for 14 days (Days 1-14). Pharmacokinetic (PK) analyses utilized non-compartmental methods.. The median elimination half-life of tacrolimus was 14.47 and 12.59 h for Day 0 and Day 14 respectively. The geometric mean ratios for tacrolimus on Day 14 vs Day 0 were 105.2% [90% confidence interval (90% CI): 89.8-123%] for C(max) and 106.4% (90% CI: 92.9-122%) for AUC(tau). Both 90% CIs for the ratios were contained within the predefined lack of interaction bounds of 80 and 125% (i.e. within the bounds for the equivalence assessment), indicating that these PK parameters of tacrolimus are not significantly altered by co-administration of adefovir. Similarly, the observed adefovir PK parameters after 14 days of co-administration with tacrolimus were comparable to historical data in non-transplant patients receiving adefovir alone. Serum creatinine values were stable during the study period.. There is no significant PK interaction between tacrolimus and adefovir co-administered to liver transplant recipients for 14 days.

Topics: Adenine; Adolescent; Adult; Aged; Antiviral Agents; Drug Interactions; Drug Therapy, Combination; Female; Half-Life; Hepatitis B; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Organophosphonates; Tacrolimus; Young Adult

Topics: Adult; Anti-Infective Agents; Azathioprine; Contraindications; Creatinine; Dose-Response Relationship, Drug; Drug Resistance; Female; Follow-Up Studies; Ganciclovir; Graft Rejection; Graft Survival; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Muromonab-CD3; Steroids; Tacrolimus; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Brain; Cyclosporine; Drug Therapy, Combination; Electroencephalography; Hepatitis B; Hepatitis C; Humans; Immunosuppression Therapy; Incidence; Liver Transplantation; Magnetic Resonance Imaging; Neurotoxins; Survival Rate; Tacrolimus; Tomography, X-Ray Computed

Topics: DNA, Viral; Graft Survival; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C, Chronic; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; RNA, Viral; Tacrolimus; Treatment Outcome

We aimed to evaluate the efficacy and safety of an immunosuppressive regimen without steroids after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).. Sixty-six HCC patients who underwent an immunosuppressive regimen without steroids after LT were enrolled in the steroid-free group. The preoperative characteristics and postoperative outcomes of these patients were compared with those of 132 HCC recipients who were placed on an immunosuppressive regimen using steroids (steroid group). The incidence of acute rejection, HBV recurrence, infection, and new-onset diabetes mellitus and the overall and tumor-free survival rates were compared between the two groups.. Differences were not observed in the 1-year (83.3% vs 97.0%, p=0.067), 3-year (65.4% vs 75.8%, p=0.067) or 5-year (56.3% vs 70.7%, p=0.067) patient survival rates or in the 1-year (62.1% vs 72.7%, p=0.067), 3-year (49.8% vs 63.6%, p=0.067) or 5-year (48.6% vs 63.6%, p=0.067) tumor-free survival rates between the two groups, respectively. In the steroid-free group, the patients who fulfilled the Milan criteria had higher overall and tumor-free survival rates than those in the steroid group (p<0.001). The prevalence of HBV recurrence (3.0% vs 13.6%, p=0.02) was significantly lower in the steroid-free group compared with the steroid group.. After LT, an immunosuppressive regimen without steroids could be a safe and feasible treatment for HBVrelated HCC patients, thus resulting in the reduction of HBV recurrence. Based on the observed survival rates, patients who fulfill the Milan criteria may derive benefits from teroidfree immunosuppression.

Topics: Antibodies, Monoclonal; Basiliximab; Carcinoma, Hepatocellular; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Hepatitis B; Hepatitis B virus; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Neoplasms; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Postoperative Period; Prednisolone; Recombinant Fusion Proteins; Tacrolimus; Treatment Outcome

We report a case of a 27-year-old man diagnosed with the infection of HBV delta in the 8th month of life. The treatment complied with evidence-based medical guidelines, comprising neoadiuvant chemotherapy and surgery. Liver transplantation from a deceased donor followed by chemotherapy was performed when the patient was 16 years 9 months of age because of recurrent HCC tumor. The patient qualified for immunosuppressive treatment (rapamycin, tacrolimus), lamivudine, anti-HBs globulin intravascular infusion, and anti-HBV vaccination as a prophylaxis against reinfection with HBV. In conclusion, this case demonstrates the importance of a postoperative follow-up of patients with HCC, even years after liver transplantation.

Topics: Adult; Antiviral Agents; Carcinoma, Hepatocellular; Hepatitis B; Hepatitis B virus; Humans; Immunosuppressive Agents; Lamivudine; Liver Neoplasms; Liver Transplantation; Male; Neoplasm Recurrence, Local; Recurrence; Tacrolimus; Tissue Donors; Treatment Outcome

Calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF) and steroid is mainly used as immunosuppressive therapy after the living-donor liver transplantation (LDLT). However, the nephrotoxicity caused by CNI remains a critical problem for patients with chronic renal failure, especially on early postoperative period. A 62-year-old woman with decompensated liver cirrhosis secondary to hepatitis B (Child-Pugh C, MELD score 11 points) and chronic renal failure due to diabetic nephropathy (Cr 1.56 mg/dl, GFR 27 ml/min/1.73 m2) experienced LDLT. During the reconstruction of hepatic vein, the supra-and infra-hepatic vena cava was totally clamped. The estimated right lobe liver graft volume was 540 g, representing 51.3% of the standard liver volume of the recipient. Because of the perioperative renal dysfunction due to diabetic nephropathy and the total clamping the vena cava which induced the congestion kidney, MMF (1500 mg/day) and steroid (250 mg/day converted into predonisolone) were mainly introduced as an immunosuppressive therapy after LDLT. The low-dose CNI, tacrolimus also induced the nephrotoxicity and was given for only a short time. Finally, according to the postoperative renal function, the low-dose CNI, cyclosporin (50 mg/day) was able to be added to the introduced immunosuppressive therapy. After having left the hospital, MMF (1500 mg/day), steroid (20 mg/day converted into predonisolone) and cyclosporin (75 mg/day) continued to be given as the immunosuppressive therapy and neither acute graft rejection nor drug-induced renal dysfunction was occurred. This is a case report of introducing with mainly MMF and steroid as an immunosuppressive therapy after LDLT for a patient with perioperative renal dysfunction.

Topics: Cyclosporine; Diabetic Nephropathies; Female; Hepatitis B; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Liver Cirrhosis; Liver Transplantation; Living Donors; Middle Aged; Mycophenolic Acid; Prednisolone; Tacrolimus; Treatment Outcome

Topics: Anti-HIV Agents; Carcinoma, Hepatocellular; Cyclohexanes; Drug Interactions; Hepatitis B; HIV Infections; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Maraviroc; Middle Aged; Plasma; Tacrolimus; Treatment Outcome; Triazoles

Tacrolimus is widely used as an immunosuppressive drug in liver transplant recipients with a narrow therapeutic range and variable individualized pharmacokinetics. Tacrolimus is a substrate of cytochrome P-450 3A enzyme and the drug transporter, P-glycoprotein.. We determined the genotypic frequencies of cytochrome P-4503A5 (rs776746), and ABCB1 (rs1045642), single nucleotide polymorphisms in a population of 100 Iranian liver transplant patients, and investigated the influence of the above-mentioned single nucleotide polymorphisms on tacrolimus concentrations. At 7 and 30 days after transplant, tacrolimus dosages (mg/kg/d), trough blood levels (T0), and dose-adjusted concentrations (concentration/dosage ratio) were determined. Polymerase chain reaction, followed by restriction fragment length polymorphism analysis, was used for genotyping cytochrome P-4503A5*3 [6986A>G] as well as ABCB1 [3435C>T].. Ninety-five percent of the population showed a cytochrome P-4503A5*3/*3 genotype. ABCB13435TT genotype was observed in 33 cases (33%); whereas 51 cases (51%) carried 3435CT, and 16 cases (16%) carried 3435CC. With regard to the ABCB1 and cytochrome P-4503A5, they showed no influence on tacrolimus dosing requirements at 1 week or 1 month after transplant. No association of any genetic variant with the acute rejection rate was found.. Finally, as the liver donor genotype influences tacrolimus pharmacokinetics with regard to expression of cytochrome P-4503A5, far more than the genotype of the recipient; therefore, it should be considered before recommending any personal immunosuppressive treatment based on pharmacogenetics.

Topics: Adolescent; Adult; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Child; Child, Preschool; Cholangitis, Sclerosing; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Female; Genotype; Hepatitis B; Humans; Immunosuppressive Agents; Infant; Liver Failure; Liver Transplantation; Male; Middle Aged; Polymorphism, Single Nucleotide; Retrospective Studies; Tacrolimus; Tissue Donors; Transplantation; Young Adult

Steroids have been the mainstay of immunosuppressive regimen in liver transplantation. However, the use of steroids is associated with various post-transplant complications. This study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids (steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant recipients.. Seventy-six patients in line with the selection criteria were enrolled in this prospective study. All patients received anti-IL-2 receptor antibody induction and tacrolimus-based maintenance therapy. The recipients were divided into two groups according to the duration of steroid use: 40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination group. Recipient survival, post-operative infections, biopsy-proven acute rejection and steroid-resistant acute rejection, non-healing wound, recurrence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), de novo diabetes, hyperlipidemia and hypertension were assessed in the two groups.. There was no significant difference in patient survival, incidence of acute rejection episodes and hyperlipidemia, and recurrence of HBV and HCC between the two groups. However, the incidence rates of post-transplant infection, non-healing wound, de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group (all P values <0.05).. Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance, steroid elimination within 24 hours post-transplant is associated with reduced steroid-related complications without increasing the risk of rejection.

Topics: Antibodies, Anti-Idiotypic; Carcinoma, Hepatocellular; China; Follow-Up Studies; Graft Rejection; Hepatitis B; Humans; Immunosuppressive Agents; Incidence; Liver Neoplasms; Liver Transplantation; Prospective Studies; Receptors, Interleukin-2; Recurrence; Steroids; Survival Rate; Tacrolimus; Time Factors; Treatment Outcome; Withholding Treatment

To provide a basis for improved prevention and treatment of hepatitis B virus (HBV) re-infection after liver transplantation, variations in the S and P genes of HBV under immunosuppression in vitro and their association with patient prognosis were investigated. For the in vitro study, HepG2.2.15 hepatocellular carcinoma cells stably producing HBV particles were treated with the immunosuppressants methylprednisolone (MP) and tacrolimus (FK506) at doses found to be non-toxic by the methylthiazolyl tetrazolium (MTT) cell viability assay. MP dose-dependently inhibited HBV DNA expression in HepG2.2.15 cells, while FK506 did not, as determined by quantitative real-time PCR (qRT-PCR). By gene sequencing, both MP and FK506 were found to cause variations in HBV S, P, and S/P overlapping regions. MP- but not FK506-induced mutations were common in the glucocorticoid response element of the P region, while both immunosuppressants caused mutations outside the nucleoside analogue resistance sites. For the in vivo study, 14 patients with HBV-related end-stage liver disease re-infected after liver transplantation, and 20 cases without HBV re-infection as controls, were studied. Seventy-five percent of re-infected recipients showed multi-loci amino acid mutations at different sites besides lamivudine (LAM)-resistant loci in the P region, including in the glucocorticoid response element. Fifty percent of re-infected recipients had mutations in the "a" determinant region and flanking sequences. Re-infection was associated with negative serum hepatitis B immunoglobulin (HBIG), as measured by a microparticle capture enzyme immunoassay. Nucleotide mutations in the S region caused missense or synonymous mutations, which caused synonymous mutations in the overlapping P region. These results showed that effects of immunosuppressants on HBV genes in vitro were different from those in clinical recipients. Positive HBV DNA and gene mutations pre-transplantation were factors affecting re-infection post-transplantation. Multiple mutations found in the P and S genes suggest that the formation of quasispecies contributes to HBV re-infection after liver transplantation.

Topics: Adult; Aged; Base Sequence; Cell Line, Tumor; DNA Replication; Female; Gene Products, pol; Genetic Variation; Genome, Viral; Hep G2 Cells; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Mutation; Recurrence; Sequence Analysis, DNA; Tacrolimus

Topics: Acute Disease; Antiviral Agents; Colon; Colonoscopy; DNA, Viral; Enzyme Inhibitors; Ganciclovir; Hepatitis B; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Thrombotic Microangiopathies

Liver transplantation is the only curative treatment in patients with end-stage liver disease. Neurological complications (NC) are increasingly reported to occur in patients after cadaveric liver transplantation. This retrospective cohort study aims to evaluate the incidence and causes of NC in living donor liver transplant (LDLT) patients in our transplant center. Between August 1998 and December 2005, 121 adult LDLT patients were recruited into our study. 17% of patients experienced NC, and it occurred significantly more frequently in patients with alcoholic cirrhosis (42%) and autoimmune hepatitis (43%) as compared with patients with hepatitis B or C (9/10%, P = 0.013). The most common NC was encephalopathy (47.6%) followed by seizures (9.5%). The choice of immunosuppression by calcineurin inhibitor (Tacrolimus or Cyclosporin A) showed no significant difference in the incidence of NC (19 vs. 17%). The occurrence of NC did not influence the clinical outcome, since mortality rate, median ICU stay and length of hospital stay were similar between the two groups. Most patients who survived showed a nearly complete recovery of their NC. NCs occur in approximately 1 in 6 patients after LDLT and seem to be predominantly transient in nature, without major impact on clinical outcome.

Topics: Brain Diseases; Cohort Studies; Cyclosporine; Female; Hepatitis B; Hepatitis C; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Incidence; Liver Cirrhosis, Alcoholic; Liver Diseases; Liver Transplantation; Male; Middle Aged; Nervous System Diseases; Retrospective Studies; Seizures; Tacrolimus; Treatment Outcome

Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors.. We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus.. Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5-13.5) in comparison with those of group A (median, 4.6; range, 1.8-9.1) (P=0.0001).. By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.

Topics: Adrenal Cortex Hormones; Adult; Aged; Carcinoma, Hepatocellular; Cohort Studies; Disease-Free Survival; Drug Administration Schedule; Female; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Neoplasm Recurrence, Local; Risk Factors; Sirolimus; Survivors; Tacrolimus; Young Adult

Cytomegalovirus (CMV) infection is not only a common complication after liver transplantation but also a significant contributing factor to morbidity and mortality. We investigated whether preemptive therapy can prevent CMV syndrome or tissue-invasive CMV disease in an endemic area. Preemptive therapy was initiated when more than 10 positive CMV pp65 antigen-positive cells per 400,000 white blood cells were detected, regardless of clinical manifestations. Intravenous ganciclovir as preemptive therapy was administered daily for 10 to 14 days until negative results were achieved. The incidence of initial CMV antigenemia and CMV syndrome during the posttransplantation period was 49.7% (353/710) and 5.2% (37/710), respectively. One hundred eight-two patients (51.6%) received ganciclovir as preemptive therapy. Patients with CMV antigenemia who received preemptive therapy had high Model for End-Stage Liver Disease score, repeat operation, renal dysfunction, infection, low hemoglobin concentration, low platelet count, low albumin concentration, high international normalized ratio, high total bilirubin value, high aspartate transaminase concentration, and high CMV peak titer. Cytomegalovirus syndrome and tissue-invasive CMV disease were more common in these patients. The survival curve in patients without CMV syndrome was better than that in those with CMV syndrome (P=.000). Patients with more than 10 pp65 antigen-positive cells per 400,000 white blood cells should be treated aggressively with an antiviral agent as preemptive therapy because CMV infection is common in CMV-endemic areas and patients with CMV syndrome demonstrate poor survival rates.

Topics: Adult; Cadaver; Cyclosporine; Cytomegalovirus; Cytomegalovirus Infections; Endemic Diseases; Female; Graft Rejection; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Korea; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Tissue Donors

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal; cirrhosis develops in up to 30% of cases. Currently there is interest in the midterm outcomes of HCV patients with concomitant hepatitis B virus (HBV) infection among OLT recipients. We therefore retrospectively analyzed our database of patients who underwent OLT for HCV-HBV-related cirrhosis. Between April 1992 and December 2008, 350 patients underwent OLT, including 20 (5.7%) transplanted for HBV-HCV cirrhosis. We assessed patient and graft survivals at 1 and 5 years, as well as the progression of fibrosis. Protocol liver biopsies were available yearly after OLT. The survival curves were analyzed by the Kaplan-Meier approach and chronic hepatitis evaluated according to the Ishak scoring system. At a median follow-up of 68.4 +/- 53 months, the 1- and 5-year patient and graft survival rates were 80% and 70%, respectively. The 5-year fibrosis progression rate was 0.17 +/- 0.08 units of fibrosis. The only patient who developed histologic cirrhosis within 10 years of follow-up showed a lamivudine-resistant HBV recurrence. Patients transplanted for HBV-HCV coinfection showed a lower fibrosis progression rate compared with HCV monoinfected subjects.

Topics: Azathioprine; Cyclosporine; Graft Survival; Hepatitis B; Hepatitis C; Humans; Immunoglobulins; Immunosuppressive Agents; Liver Transplantation; Prednisone; Retrospective Studies; Survival Rate; Tacrolimus; Treatment Outcome

Cytomegalovirus (CMV) infection represents one of the most frequent opportunistic infections following solid-organ transplantation. The incidence and severity of CMV infection depend on the immunosuppressive regimen, the CMV serostatus of donor and recipient, and the type of transplant.. We evaluated CMV infection rates during the last 2 years in our center: March 2007 to March 2009. We enrolled 55 patients-13 females and 42 males-who underwent liver transplantation (OLT) due to hepatitis C virus (HCV) cirrhosis (n = 9), hepatitis B virus (HBV) cirrhosis (n = 5) HCC both on HCV and HBV cirrhosis (n = 37), or autoimmune disease (n = 4). Fifty percent of the patients received tacrolimus (TRL) and the others cyclosporine (CsA), both dosed according to weight. All patients received oral acyclovir (400 mg/td or less, adapted to renal function) as herpes simplex prophylaxis for 6 months. CMV prophylaxis prescribed CMV- hyperimmunoglobulin on postoperative days 1 and 7. CMV infection was monitored using polymerase chain reaction (PCR <1000 IU/mL) according to the following schedule: every week for the first month, every 2 weeks from month 2 to 3 and monthly from month 4 to 6. Patients were treated when three positive PCR results not affected by immunosuppressive dose reduction or when the PCR showed DNA greater than three times the limit of detection. CMV treatment stipulated valgancyclovir (900 mg twice daily) until three consecutive PCRs were negative or for 3 months dosed according to renal function. PCR was measured every 2 weeks during treatment.. Among the patients who were all D(+)/R(+) (CMV-Immunoglobulin G [IgG](+)/IgG(+)). 10 required treatment (18%) within 3 months from OLT. There subjects were prescribed TRL (n = 4) or CsA (n = 6). No renal impairment was observed among treated patients. Of those having the infection, one died due to other causes-sepsis from candida at 5 months after OLT.. CMV-hyperimmunoglobulin on postoperative days 1 and 7 did not confer protection for CMV among OLT patients. Preemptive treatment with intravenous gancyclovir plus valgancyclovir per os seemed to be useful and safe in infected patients requiring treatment.

Topics: Acyclovir; Antiviral Agents; Corticosterone; Cyclosporine; Cytomegalovirus Infections; Female; Graft Rejection; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Retrospective Studies; Tacrolimus

This study aimed to (1) identify the variables that affect graft and patient survival in recipients transplanted for hepatitis B virus (HBV) disease; and (2) assess factors associated with an increased risk of graft cirrhosis at 5 years after liver transplantation (LT).. A total of 104 chronically infected HBV patients were considered for this study and all received tacrolimus- or cyclosporine A (CSA)-based immunosuppressive regimens. The overall 5-year patient and graft survival rates were 80% and 73%, respectively. Univariate Cox proportional hazards regression analysis indicated that older recipient age and higher body mass index (BMI) at LT, LT more than or equal to 1998, arterial hypertension, hyperlipidemia, and CSA-based immunosuppression correlated with decreased patient survival. In the multivariate model, advanced recipient age, higher BMI, CSA-based immunosuppressive therapy, and increasing cold ischemia time were associated with worse patient survival. Recipient age and BMI at time of LT and posttransplant hypertriglyceridemia also affected graft survival. Log-rank analysis showed that a viral load of more than 10 copies/mL and antiviral therapy at LT, post-LT biliary complications, HBV recurrence, nucleos(t)ide analogue monoprophylaxis (without hepatitis B immunoglobulin), and short-term (< or = 1 year) mycophenolate mofetil therapy were significant risk factors for graft cirrhosis within 5 years of LT.. Various recipient factors at the time of LT and post-LT virological status, antiviral prophylaxis, cholestasis, cardiovascular risk profile, and immunosuppressive regimen affect the outcome of HBV patients after LT. Prospective studies are warranted to define optimal immunosuppression for recipients transplanted for hepatitis B.

Topics: Adult; Aged; Cardiovascular Diseases; Cyclosporine; Female; Graft Survival; Hepatitis B; Humans; Immunoglobulins; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Recurrence; Regression Analysis; Risk Factors; Survival Analysis; Survivors; Tacrolimus; Treatment Outcome; Young Adult

Most reported data on posttransplantation diabetes mellitus (PTDM) are from Western countries with patients who underwent deceased donor liver transplantation. A retrospective study was performed to assess the prevalence and predictive factors of PTDM in the context of living donor liver transplantation (LDLT) in the Chinese population using the definition of PTDM proposed in 2003 by the World Health Organization and the American Diabetes Association. The prevalence of DM after LDLT in our study was 25% (21/84), and the incidence of PTDM was 14.9% (11/74) with 64% of cases diagnosed within 3 months after LDLT; 9.5% were observed to show impaired fasting glucose postoperatively. Multivariate analysis identified body mass index >or= 25 kg/m(2) before LDLT as the only independent risk factor for developing PTDM. Only one patient was operated for hepatitis C virus (HCV) infection. Hepatitis B virus (HBV)-related diseases were common in our study population, accounting for 78.6% of all patients. Both HCV and HBV infection status were not independent risk factors for developing PTDM. In addition, a greater tacrolimus trough blood level in the PTDM group versus no-DM group was observed at 3 months post-LDLT (11.03 ng/mL vs 4.87 ng/mL). The mean tacrolimus dose was not significantly different between the two groups. In conclusion, PTDM was prevalent among Chinese LDLT recipients.

Topics: Adult; Blood Glucose; China; Diabetes Mellitus; Female; Glucose Intolerance; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Incidence; Liver Transplantation; Living Donors; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Postoperative Complications; Prevalence; Retrospective Studies; Risk Factors; Tacrolimus

Diabetes mellitus (DM) is a frequent and serious complication in patients with liver diseases. We aimed to assess the prevalence and consequences of post-transplant DM (PTDM) in Chinese patients with HBV-related liver diseases and to determine the possible risk factors.. Altogether 165 patients with HBV infection and undergoing cadaveric related liver transplantation (LT) were enrolled. The clinical data of patients with (PTDM group) and without PTDM (non-PTDM group) were compared.. Of the 165 patients, 28 had DM and 12 had impaired fasting glucose (IFG) before LT. Patients with pre-transplant DM or IFG had a survival rate similar to that of the others. Forty patients (24.2%) developed PTDM with a mean time of 36+/-17 days (range 2-300 days) after LT. Of those, 32 developed PTDM within 3 months post-LT and 29 needed insulin treatment. Pre-transplant hepatic encephalopathy and tacrolimus application were found more frequently in the PTDM group than in the non-PTDM group. The plasma tacrolimus levels were notably higher at 1 and 3 months post-LT in the PTDM group than those in the non-PTDM group. Compared to the non-PTDM group, the PTDM group showed remarkably poorer survival and tumor-free survival in patients with hepatocellular carcinoma, and significantly higher incidence of sepsis, fungal infection, chronic kidney diseases and biliary complications after LT.. Pre-transplant DM did not affect the patient survival after LT. Since PTDM is common, it has a negative impact on outcome and may contribute to tumor recurrence. Pre-transplant hepatic encephalopathy, a tacrolimus-based regimen, and high levels of tacrolimus are clearly associated with the occurrence of PTDM.

Topics: Adolescent; Adult; Aged; China; Diabetes Mellitus; Female; Hepatic Encephalopathy; Hepatitis B; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Liver Transplantation; Male; Middle Aged; Prevalence; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors; Young Adult

Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is associated with poor graft- and patient-survival. Treatment with HBV-specific immunoglobulins (HBIG) in combination with nucleos(t)ide analogs is effective in preventing HBV reinfection of the graft and improving OLT outcome. However, the role of HBV-specific cellular immunity in viral containment in immune suppressed patients in general and in OLT recipients in particular is unclear. To test whether or not OLT recipients maintain robust HBV-specific cellular immunity, the cellular immune response against HBV was assessed in 15 OLT recipients and 27 individuals with chronic and 24 subjects with self-limited HBV infection, respectively; using an overlapping peptide set spanning the viral nucleocapsid- and envelope-protein sequences. The data demonstrate that OLT recipients mounted fewer but stronger clusters of differentiation (CD)8 T cell responses than subjects with self-limited HBV infection and showed a preferential targeting of the nucleocapsid antigen. This focused response pattern was similar to responses seen in chronically infected subjects with undetectable viremia, but significantly different from patients who presented with elevated HBV viremia and who mounted mainly immune responses against the envelope protein. In conclusion, virus-specific CD4 T cell-mediated responses were only detected in subjects with self-limited HBV infection. Thus, the profile of the cellular immunity against HBV was in immune suppressed patients similar to subjects with chronic HBV infection with suppressed HBV-DNA.

Topics: Antibody Specificity; Cyclosporine; DNA, Viral; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Immunosuppressive Agents; Liver Transplantation; Lymphocytes; Nucleocapsid; Recurrence; T-Lymphocytes; Tacrolimus; Viral Load

We retrospectively analyzed the impact of sirolimus addition (SRL) with a 25% dosing reduction in calcineurin inhibitors on liver function among patients with or without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.. Forty-eight renal transplant recipients (HBsAg-positive, n = 5; anti-HCV-positive, n = 7) with allograft dysfunction (serum creatinine: mean 2.7, median 2.0 mg/dL) and normal liver function were enrolled. The duration of the SRL add-on therapy was 8.0 +/- 3.6 months. SRL trough levels were maintained within 6.5 +/- 3.7 ng/mL. The trough levels of tacrolimus and the 2-hour cyclosporine postdose levels were tapered to 4.6 +/- 1.9 ng/mL (24.6% reduction) and 650 +/- 170 ng/mL (24.3% reduction), respectively. SRL-related hepatitis was defined as a rise in liver transferase or alkaline phosphatase or bilirubin over twice the upper limit of normal. Thirty-six HBsAg-negative and anti-HCV-negative patients served as the controls.. Hepatotoxicity developed in 6 (12.5%) of the 48 patients and in 3 (8.3%) of 36 control subjects. One (20.0%) of five HBsAg-positive patients (P = .959) and two (28.6%) of seven anti-HCV-positive patients (P = .496) developed hepatotoxicity, respectively. Three (25.0%) of the 12 HBsAg-positive or anti-HCV-positive patients developed hepatotoxicity (P = .420).. Patients with seropositivity of HBsAg or anti-HCV had an insignificantly higher percentage of hepatitis. Use of SRL in the HBV/HCV patients is not contraindicated, but needs monitoring for HBV/HCV activation.

Topics: Adult; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis C; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Transplantation; Lamivudine; Liver; Male; Middle Aged; Monitoring, Immunologic; Mycophenolic Acid; Retrospective Studies; Sirolimus; Tacrolimus

To evaluate the outcome of pediatric patients who underwent liver transplantation between Oct. 2002 and May 2005 in the Pediatric Hospital.. Eight cases aged from 4 to 67 months who underwent liver transplantation were analyzed retrospectively. Four of the patients were boys and 4 girls, whose body weight at the time of liver transplantation was 6-19 kg. The underlying diseases were biliary atresia, congenital cholestasis, drug-induced cholestatic cirrhosis and cryptogenic cirrhosis. These patients had been followed up for blood routine examinations, liver and renal function, serum electrolytes and blood concentration of tacrolimus for 16 to 43 months after liver transplantation. Results of serological studies for viral etiology, liver biopsy, growth and mental development were also recorded.. One-year survival rate was 75.0% with the longest survival time being 43 months after transplantation. One patient died from renal failure due to postoperative bleeding 24 hours after the surgery and another case died of variceal hemorrhage 8 months after transplantation. Posttransplantation complications included acute cellular rejection, viral infection and hypoalbuminemia. Viral infections included cytomegalovirus infection in 3 cases, Epstein-Barr virus infection in 1 and hepatitis B virus infection in 1. Surgical complications of portal vein thrombosis and stenosis of inferior vena cava and hepatic vein occurred in 2 cases respectively. Side effects of tacrolimus including hypertension, renal damage, liver damage and diarrhea were observed. Significant growth-retardation was not often seen. A self-reported high quality of life was common.. Close follow-up and management of patients after liver transplantation may significantly increase the survival rate and improve quality of life in children with end-stage liver diseases.

Topics: Biliary Atresia; Child; Child, Preschool; Constriction, Pathologic; Female; Graft Rejection; Hepatitis B; Herpesvirus 4, Human; Humans; Hypertension; Immunosuppressive Agents; Liver Cirrhosis; Liver Failure; Liver Transplantation; Male; Pediatrics; Postoperative Complications; Survival Rate; Tacrolimus; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis

De novo hepatitis B was diagnosed in a 47-year-old man 15 months after liver transplantation for end-stage alcoholic cirrhosis. Serum antibodies to hepatitis B core antigen (anti-HBc) were negative, and remained undetectable over 20 months of follow-up. The possible causes of negative serum anti-HBc despite of active hepatitis B virus infection are reviewed. Immunosuppression may underlie this phenomenon in similar cases.

Topics: Antibody Formation; DNA, Viral; False Negative Reactions; Follow-Up Studies; Graft Rejection; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Antigens; Hepatitis B virus; Humans; Immunosuppressive Agents; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Postoperative Complications; Tacrolimus; Viremia

Vaccines containing hepatitis B surface antigen (HBsAg) induce antibody to HBsAg (anti-HBs) in most normal individuals and protects them from hepatitis B virus (HBV) infection. However, these vaccines are not efficient at inducing anti-HBs in immunosuppressed individuals, especially in immunosuppressed HBV carriers. The aim of this study was to prepare and to assess the efficacy of a dendritic cell (DC)-based vaccine in an immunosuppressed HBV transgenic mouse (HBV-Tg), an animal model of the HBV carrier state. In order to prepare immunosuppressed HBV-Tg, HBV-Tg were injected with FK-506, an immunosuppressive agent, once daily, intraperitoneally for 15 days. Spleen cells of immunosuppressed HBV-Tg expressed very little mRNAs for interleukin-2 and interferon-gamma. DCs were isolated from the spleen of immunosuppressed HBV-Tg and cultured with HBsAg (100 microg) for 48 h to prepare HBsAg-pulsed DCs. Immunosuppressed HBV-Tg expressing HBsAg in the sera were administered with HBsAg-pulsed DCs or unpulsed DCs or HBsAg in adjuvant for different durations. Immunosuppressed HBV-Tg (n = 8) twice administered with HBsAg-pulsed DCs expressed anti-HBs in the sera within 6 weeks of first injection. Seven of eight immunosuppressed HBV-Tg remained positive for anti-HBs in the sera for the next 12 weeks of observation in spite of receiving daily injection of FK-506 for the entire duration. However, immunosuppressed HBV-Tg administered with unpulsed DCs or HBsAg in adjuvant did not express anti-HBs in the sera. The data show that DCs from immunosuppressed HBV-Tg can be loaded with HBsAg to prepare immunogenic HBsAg-pulsed DCs. HBsAg-pulsed DCs induced anti-HBs in immunosuppressed HBV-Tg. This approach may be of use to induce and maintain anti-HBs in immunosuppressed human HBV carriers.

Topics: Animals; Dendritic Cells; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Immunosuppression Therapy; Immunosuppressive Agents; Mice; Tacrolimus

Members of the Hepadnaviridae family have been isolated from birds, rodents, and primates. A new hepadnavirus isolated from the woolly monkey, a New World primate, is phylogenetically distinct from other primate isolates. An animal model has been established for woolly monkey hepatitis B virus (WMHBV) by using spider monkeys, since woolly monkeys are endangered. In this study, a greater-than-genome length construct was prepared without amplification by using covalently closed circular DNA extracted from the liver of an infected woolly monkey. Transfection of the human liver cell line Huh7 with WMHBV DNA resulted in the production of viral transcripts, DNA replicative intermediates, and secreted virions at levels similar to those obtained with an infectious human HBV clone, demonstrating that the host range restriction of WMHBV is not at the level of genome replication. WMHBV particles from the medium of transfected cultures initiated an infection in a spider monkey similar to that obtained with virions derived from woolly monkey serum. In an attempt to adapt the virus for higher levels of replication in spider monkeys, immunosuppressed and newborn animals were inoculated. Neither procedure produced persistent infections, and the level of viral replication remained several logs lower than that observed in persistently infected woolly monkeys. These data demonstrate the production of an infectious clone for WMHBV and extend the characterization of the spider monkey animal model.

Topics: Animals; Cebidae; Cloning, Molecular; Disease Models, Animal; Hepatitis B; Hepatitis B virus; Humans; Immunosuppression Therapy; Molecular Sequence Data; Tacrolimus; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Viremia; Virus Replication

Topics: Bile Duct Diseases; Bile Ducts, Intrahepatic; Carbamazepine; Child, Preschool; Cholestasis; Hepatitis B; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Methylprednisolone; Pancreatitis; Stevens-Johnson Syndrome; Tacrolimus

We report the course of thrombotic thrombocytopenic purpura (TTP) in a patient receiving tacrolimus (FK506) immunosuppression for an ABO mismatched second liver graft. A Chinese woman with fulminant hepatitis-B reactivation failed a living-related orthotopic liver transplantation (OLT) due to portal vein thrombosis. An ABO mismatched cadaveric OLT (group A to O) was performed, with peri-operative plasmapheresis to reduce anti-A hemagglutinin titers. On day 30, she developed fever, hemolysis, thrombocytopenia and neurologic dulling. Prominent microangiopathic features in peripheral blood film, and characteristic brain lesions on magnetic resonance imaging confirmed TTP. She responded initially to intensive plasmapheresis with cryosupernatant replacement, and withdrawal of FK506. An attempted reintroduction of FK506 for threatened rejection led to TTP exacerbation. This was controlled with prolonged plasmapheresis and a ten-day infusion of prostacyclin. Immunosuppression was changed to mycophenolate mofetil. By day 53, the peripheral film and lactate dehydrogenase level had returned to baseline and plasmapheresis was stopped.

Topics: ABO Blood-Group System; Adult; Blood Grouping and Crossmatching; Epoprostenol; Female; Hepatitis B; Humans; Liver Transplantation; Plasmapheresis; Purpura, Thrombotic Thrombocytopenic; Salvage Therapy; Tacrolimus

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.

Topics: Adult; Aged; Antiviral Agents; Ascites; Carcinoma, Hepatocellular; Female; Hepatic Encephalopathy; Hepatitis B; Humans; Immunization, Passive; Immunoglobulins; Immunosuppressive Agents; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Middle Aged; Tacrolimus

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Cyclosporine; Data Collection; Drug Therapy, Combination; Europe; Hepatitis B; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Postoperative Complications; Renal Insufficiency; Tacrolimus

Topics: Antigens, CD; CD4-CD8 Ratio; Cyclosporine; Follow-Up Studies; Hepatitis B; HLA-DR Antigens; Humans; Immunosuppressive Agents; Liver Neoplasms; Liver Transplantation; Lymphocyte Subsets; Postoperative Complications; Recurrence; Retrospective Studies; Tacrolimus; Time Factors

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Azathioprine; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Muromonab-CD3; Postoperative Complications; Retrospective Studies; Tacrolimus; Time Factors

Topics: Carcinoma, Hepatocellular; Cyclosporine; Follow-Up Studies; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Lymphoma; Neoplasms; Postoperative Complications; Retrospective Studies; Tacrolimus; Time Factors

Topics: Adult; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Cyclosporine; DNA, Viral; Female; Follow-Up Studies; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Prednisolone; Prednisone; Survival Rate; Tacrolimus

Topics: Azathioprine; Cyclosporine; Follow-Up Studies; Graft Survival; Hepatitis B; Hepatitis C; Humans; Interferon-alpha; Kidney Transplantation; Pilot Projects; Retrospective Studies; Tacrolimus; Time Factors

Hepatitis B viral liver disease (HBVLD) is a major worldwide health problem. It is estimated over 300 million people have had hepatitis B virus infection and that one-third of these have chronic HBVLD. Little effective therapy exists for HBVLD even though high dose interferon (IFN) has been advocated. For those who either are untreated or do not respond to IFN, HBVLD is steadily progressive and orthotopic liver transplantation (OLTx) is the only available therapy. Until quite recently, all OLTx recipients received cyclosporine (CyA) and prednisone. The consequence of OLTx for HBV disease in individuals immunosuppressed with tacrolimus has not previously been reported. A total of 78 consecutive patients with HBV-related liver diseases who were transplanted between January 1, 1990, and December 31, 1991, and treated with tacrolimus were studied. The clinical records of these patients were reviewed retrospectively. HBV disease recurrence was documented with serologic and histologic methods. As of April 1, 1993, 57 of 78 (73%) of the patients were still alive. Thirty-one of the alive patients have documented HBV recurrence. Eighteen of these 31 patients, however, have normal liver function. With a median follow-up of 24 months, 8 patients (10.9%) have died of recurrent HBVLD. Seven of 8 patients, who preoperatively were HBeAg+, developed recurrence and 4 of these patients have already died of recurrence. Patients who were HBsAg+ rarely recurred (1 of 16 patients). The use of HBIG did not prevent recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Female; Graft Rejection; Graft Survival; Hepatitis B; Humans; Immunosuppression Therapy; Liver Transplantation; Male; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Tacrolimus

Topics: Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Cyclosporine; Drug Administration Schedule; Graft Rejection; Graft Survival; Hepatitis B; Hepatitis B Surface Antigens; Humans; Immunosuppression Therapy; Liver Failure; Liver Transplantation; Postoperative Complications; Prednisolone; Receptors, Interleukin-2; Recurrence; Reoperation; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors; Treatment Outcome

Topics: Cyclosporine; Drug Monitoring; Graft Rejection; Hepatitis B; Hepatitis C; Humans; Immunosuppression Therapy; Incidence; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Cirrhosis, Biliary; Liver Transplantation; Muromonab-CD3; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors

Liver transplantation has become an extraordinarily valuable and useful operation, but one that is not perfect and that has not been exploited to anything like its full potential. Better immunosuppression may become available soon as exemplified by developments with the Japanese drug, FK506. Improved preservation with the UW solution is already here. With these advantages, liver transplantation is certain to become far more widely used than at any time in the past. Examples were cited of innovative approaches using liver transplantation for the treatment of hepatic malignancies.

Topics: Animals; Azathioprine; Cyclosporins; Graft Survival; Hepatitis B; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Pyridines; Tacrolimus; Tissue Preservation