Pretransplant lymphocyte count predicts the incidence of infection during the first two years after liver transplantation.

Patients with end-stage liver disease (ESLD) show a low absolute number of peripheral blood lymphocyte subpopulations (PBLSs). We investigated if the baseline PBLS could categorize orthotopic liver transplantation (OLT) recipients into groups at high or low risk for infection after transplantation. PBLSs were prospectively studied in 63 consecutive patients (42 males; mean age +/- standard deviation: 53.5 +/- 10.3 years) with ESLD prior to OLT. Thirty-five patients (55.6%) developed a total of 79 infectious episodes during the first 2 years post-OLT. The median total lymphocyte count and PBLS levels [CD3+ T cells, CD4+ T cells, memory (CD45RO+) CD4+ T cells, T cell receptor alphabeta+ and gammadelta+ subsets, and CD19+ B cells] at baseline were significantly lower in patients with an infection compared with those without one (P < 0.05). There was a significant correlation between the risk of development of a post-OLT infection and a baseline total lymphocyte count < 1.00 x 10(3)/microL (P = 0.001), a baseline CD3+ T cell count < 0.75 x 10(3)/microL (P = 0.009), and a baseline CD4+ T cell count < 0.5 x 10(3)/microL (P = 0.008). In the multivariate analysis, this association between the baseline total lymphocyte level and infection remained significant (odds ratio: 10.1; 95% confidence interval: 1.9-39.5). In conclusion, the pre-OLT total lymphocyte count identifies a subset of patients at high risk for infection. PBLS monitoring prior to OLT may offer an opportunity for surveillance, tapering of immunosuppression, and preemptive therapy.

Long-term follow-up of donor chimerism and tolerance after human liver transplantation.

We aimed to quantify peripheral donor chimerism (DC) and to analyze its association with graft and recipient outcome. Forty-two liver transplant recipients and their respective donors were studied, providing a total of 148 posttransplantation serum samples. DC was assessed with real-time quantitative polymerase chain reaction (qPCR) to detect polymorphic markers. DC did not decrease with time post-transplantation and was higher in child recipients versus adults and in recipients of deceased donor liver transplants versus recipients of live donor liver transplants. Higher levels of DC were detected in Rh-positive blood group donors, in O blood group recipients versus A blood group recipients, and in recipients with hepatitis C virus versus recipients with alcoholic cirrhosis. High DC was associated with patients with organ damage due to recurrent disease and rejection. Stable, high levels of DC, in the absence of other major clinical events, may thus be a marker of transplantation tolerance, and this knowledge may help to tailor immunosuppressive treatment. In conclusion, qPCR is a useful technique for DC follow-up in liver transplantation, although the evolution of DC levels should be analyzed in accordance with the clinical outcome of the patient.

Incidence, risk factors, and outcome of chronic rejection during antiviral therapy for posttransplant recurrent hepatitis C.

Antiviral therapy for recurrent hepatitis C in liver transplantation has been associated with the development of chronic rejection. The aim of this study was to assess the incidence, evolution, and risk factors associated with the development of chronic rejection during posttransplant hepatitis C virus antiviral therapy. Seventy-nine patients with posttransplant recurrent hepatitis C who were treated with pegylated interferon and ribavirin were prospectively followed. Liver biopsy was performed before antiviral therapy was initiated and when liver tests worsened during therapy. Pretransplant and posttransplant factors were analyzed as potential risk factors for the development of chronic rejection. Seven of 79 patients (9%) developed chronic rejection during antiviral therapy. The mean time from the start of treatment to the development of chronic rejection was 5.8 months (3-12 months). An analysis of factors associated with the development of chronic rejection showed that the use of cyclosporine as immunosuppression therapy (6 of 19 patients who received cyclosporine developed chronic rejection in comparison with only 1 of 57 patients who received tacrolimus; P = 0.0013), achievement of sustained virological response (P = 0.043), and ribavirin discontinuation (P = 0.027) were associated with the development of chronic rejection. In conclusion, the development of chronic rejection during posttransplant pegylated interferon and ribavirin therapy is a severe complication. The use of cyclosporine, ribavirin discontinuation, and viral infection elimination seem to be associated with the development of this complication. Liver Transpl 15:948-955, 2009. (c) 2009 AASLD.

Valganciclovir preemptive therapy for the prevention of cytomegalovirus disease in high-risk seropositive solid-organ transplant recipients.

BACKGROUND: The role of valganciclovir in the prevention of cytomegalovirus (CMV) disease in high-risk seropositive transplant patients is not known. METHODS: We prospectively followed 301 seropositive solid organ transplant recipients to assess the efficacy and safety of valganciclovir (VGCV) in the prevention of CMV disease in high-risk patients. Asymptomatic patients with an antigenemia test >or=25 positive cells/2x10(5) polymorphonuclear cells received valganciclovir 900 mg twice a day as preemptive therapy until resolution of antigenemia (minimum 14 days). Additionally, patients treated with antilymphocytic drugs for more than 6 days received prophylaxis with VGCV 900 mg once a day during 90 days. Mean follow-up was 14 months (range 6-20 months). RESULTS: Thirty-eight patients received VGCV; 24 as preemptive therapy and 14 due to the use of antilymphocytic drugs. No patient developed CMV disease during the follow-up. Viral load (antigenemia) decreased a mean of 78% from baseline after 7 days of VGCV therapy (P=0.024) and 98% at day 14 (P=0.029). Two patients showed a relapse of the antigenemia test >or=25 positive cells and were successfully treated with a repeated course of VGCV. Leukopenia (<2500/mm3) developed in 3/24 (12.5%) recipients in the preemptive therapy group and required to discontinuing the drug in one of them. CONCLUSIONS: VGCV is safe and highly efficacious in the prevention of CMV disease in high-risk seropositive organ transplant recipients.

Quantitative ultrasound of the calcaneus in long-term liver or cardiac transplantation patients.

Bone loss is one of the most common complications after solid-organ transplantation, but it is frequently under-diagnosed. Our purpose was to evaluate quantitative ultrasound of calcaneus (QUS) in comparison with dual-energy X-ray absorptiometry (DXA) to identify transplant recipients with osteoporosis. We have cross-sectionally evaluated 140 transplant recipients (85 liver and 55 cardiac transplantations; mean age: 53.6 years, time since transplantation: 67.9 months). Devices used were Hologic 4500 QDR for DXA measurements and Sahara Clinical Sonometer (Hologic Inc, Bedford, MA) for calcaneal QUS. Quantitative ultrasound index (QUI) was calculated from speed of sound (m/s) and broadband ultrasonic attenuation (dB/MHz). QUI T-score and bone mineral density (BMD) T-score (spine and hip) were obtained from Spanish normative data. According to World Health Organization criteria, defined either at lumbar spine or femoral neck, 61% of the females had osteopenia and 32% had osteoporosis, whereas 52% of the males had osteopenia and 11% had osteoporosis. Calcaneal QUS parameters (speed of sound, broadband ultrasonic attenuation, and QUI) were positively correlated with lumbar and femoral BMD (p<0.001). In receiver operator characteristic analysis, a T-score QUI

Is transarterial chemoembolization necessary before liver transplantation for hepatocellular carcinoma?

BACKGROUND: Transarterial chemoembolization (TACE) before liver transplantation (LT) for hepatocellular carcinoma (HCC) has been proposed to prevent tumor progression, thus decreasing tumor recurrence and increasing survival. METHODS: We studied 46 patients undergoing LT for HCC who were divided in 2 groups--group A with pretransplant TACE (18 patients [39.1%]) and group B without pretransplant TACE (28 patients [60.9%])--and compared postoperative and long-term results between the 2 groups. RESULTS: There were no statistical differences in morbidity, transfusion needles, and postoperative time between-and no acute arterial or portal complication in-the 2 groups. There were no statistical differences in tumor recurrence (16.7 % vs 36.4 %, P=.16) with regard to pathway (mainly extrahepatic) or time. In group A patients, mean survival was 89.3+/-21.7 months with 1-, 3-, and 5-year actuarial survival rates of 83.3%, 60.5%, and 60.5%, respectively. In group B patients, mean survival was 75.1+/-19.1 months with 1-, 3-, and 5-year actuarial survival rates of 77.2%, 58.7%, and 38.1%, respectively. The differences in mean survival were not statistically significant (PX .56), nor was 5-year disease-free survival, which was 54% in group A and 39.5% in group B (P=.8). CONCLUSIONS: TACE is a safe procedure for candidates on the wait list who are scheduled for LT to treat HCC. Although TACE does not correlate with increased intraoperative difficulties or postoperative complications, it does not significantly improve tumor recurrence and survival.

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 microg/kg/week) and ribavirin (800-1,000 mg/day) for 12 months. Follow-up was based on biochemical (ALT), virological (RNA-HCV), and histological (liver biopsy) examinations. Follow-up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low gamma-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG-IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy.

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation.

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)-infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis-free, severe hepatitis-free and HCV-related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post-transplant increased with donors aged > or =50 years (RR = 1.34) and donors aged > or =70 years (RR = 1.61). Five-year severe hepatitis-free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut-off points above which the evolution of HCV-infected recipients worsens.