J.R. Fernandez

Management of Hepatocellular Carcinoma Recurrence After Liver Transplantation

UNLABELLED Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months. RESULTS The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 +/- 37.5 and 48 +/- 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 +/- 21.5 versus 11.9 +/- 6.9 months (P = .006). CONCLUSIONS HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies.

Encephalitis Caused by Human Herpesvirus-6 in a Liver Transplant Recipient

Encephalitis Caused by Human Herpesvirus-6 in a Liver Transplant Recipient Miguel Montejo a, Jose Ramon Fernandez b, Milagros Testillano b, Andres Valdivieso c, Koldo Aguirrebengoa a, Carmen Varasd, Alberto Olaizola e Jorge Ortiz De Urbina c Divisions of a Infectious Diseases, bHepatology, cLiver Transplantation Surgery, dDermatology Service, and eEmergency Service, Hospital de Cruces, Bilbao, Spain

Liver transplantation for hepatocellular carcinoma in cirrhotic patients

A consecutive series of 88 patients underwent transplantation for hepatocellular carcinoma with cirrhosis over a 7-year period. Liver transplantation was indicated because of the tumor in 75 cases (85.2%); tumor was an incidental finding in 13 cases (14.8%). One patient was retransplanted due to primary nonfunction. The perioperative mortality was 4.5%. Tumor recurrence was observed in seven patients (7.95%) with incidental tumor recurrence in one case. As in patients with known primary liver tumors pretransplant, a thorough follow-up is advisable to establish an early diagnosis of recurrence. The actuarial survival for nonincidental hepatocellular carcinoma at 1, 3, and 5 year was 92%, 77%, and 75%, respectively. The differences in actuarial survival between hepatitis C negative and positive hepatocellular carcinoma were not significant (log-rank test P=.27), though there was a clear improvement in results (94%, 85%, and 78% vs 90%, 71%, and 71%), at 1, 3, and 5 years meaning that HCV infection is an important prognostic factor. Although transplantation for HCC has the advantages of removing the tumor and the cirrhotic liver, it remains a controversial topic. In our experience patients showing lesions less than 5 cm or three or fewer lesions experience an equivalent survival to transplanted patients who do not have cancer.

Selective immunosuppression with daclizumab in liver transplantation with graft-versus-host disease

GRAFT-VERSUS-host disease (GVHD) is a relatively common complication that appears after bone marrow or hematopoietic stem cell transplantation. The humanized anti-interleukin 2 receptor antibody (daclizumab) has been used successfully in the treatment of GVHD. GVHD is an increasingly common complication of liver transplantation. Two hundred fifty one liver transplantations have been performed in our hospital; only two of these patients had GVHD. We hereby describe one of these patients, who was successfully treated with daclizumab after previous authorization issued by the Spanish Ministry of Health (as daclizumab is currently not approved for liver transplantation in Spain).

Survival and Hepatitis C Virus Recurrence After Liver Transplantation in HIV- and Hepatitis C Virus–Coinfected Patients: Experience in a Single Center

INTRODUCTION Posttransplant hepatitis C virus (HCV) recurrence has been shown to negatively impact graft and patient survivals. It has been suggested that HCV recurrence among HIV- and HCV-coinfected transplant recipients is even more aggressive. OBJECTIVE To compare the histological severity and survival of posttransplant HCV recurrence between HIV- and HCV-coinfected and HCV-monoinfected patients. PATIENTS AND METHODS Among 72 adult patients who underwent primary liver transplantation at our institution for HCV-related cirrhosis between October 2001 and April 2007. We excluded one coinfected patient who died on postoperative day 5 leaving 12 HIV- and HCV-coinfected patients for comparison with 59 monoinfected patients. When listed, all coinfected patients fulfilled the criteria of the Spanish Consensus Document for transplantation in HIV patients. Immunosuppression did not differ between the two groups: all were treated with tacrolimus + steroids (slow tapering). Aggressive HCV recurrence was defined as cholestatic hepatitis and/or a fibrosis grade > or =2 during the first posttransplant year. RESULTS Coinfected patients were younger than monoinfected patients: 45 +/- 6 years vs 55 +/- 9 years (P = .0008). There were no differences in Child score, Model for End-stage Liver Disease score, donor age, graft steatosis, ischemia time, HCV pretransplant viral load or genotype between the groups. Significant rejection episodes were also equally distributed (25% vs 14%; P = .38). Seven coinfected patients and 29 monoinfected patients developed aggressive HCV recurrences (58% vs 49%; P = .75). Median follow-up was 924 days. Global survival at 3 years was 80%. Survivals at 1, 2, and 3 years were 83%, 75%, 62% in the coinfected vs 98%, 89%, 84% in the monoinfected patients, respectively (log-rank test = 0.09). CONCLUSIONS The severity of histological recurrence was similar among HIV- and HCV-coinfected and monoinfected HCV liver recipients in the first posttransplant year. Mortality attributed to recurrent HCV was similar in the groups. There were no short-term (3-year) differences in survival between the two groups of patients.

Advagraf De Novo in Liver Transplantation: A Single-Center Experience

UNLABELLED Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses. METHODS We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo. RESULTS The incidence of biopsy proven acute rejection episodes was 10% (n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% (n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%. CONCLUSION Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.

Risk Factors for Biliary Complications After Orthotopic Liver Transplantation With T-Tube: A Single-Center Cohort of 743 Transplants

BACKGROUND Despite recent advances in organ preservation, surgical procedures, and immunosuppression, biliary reconstruction after orthotopic liver transplantation (OLT) remains as a major source of morbidity. The purpose of this study was to identify risk factors for the development of biliary complications (BCs) after end-to-end choledochocholedochostomy (EE-CC) with a T-tube as the standard technique for biliary reconstruction after OLT. METHODS A total of 833 consecutive liver transplantations that took place from February 1996 to April 2010 were retrospectively reviewed. Patients with concomitant hepatic artery complications were excluded, as were those who underwent urgent retransplantation or died within 1 week after transplantation. Finally, the study group comprised 743 patients. RESULTS The overall BC rate was 9.8% (73 patients), including stricture in 19 patients (2.6%) and bile leakage in 39 patients (5.2%). After univariate analysis, significant risk factors for BCs were surgery time >5 hours, arterial ischemia time >30 minutes, use of a classic transplant technique, transfusion of red blood cells ≥5 units, anti-cytomegalovirus treatment, and period of transplantation between 1996 and 2002. Stepwise logistic regression study was performed, including those variables with a value of P <.200. Multivariate analysis showed that pretransplant serum creatinine (odds ratio = 1.27; 95% confidence interval [CI], 1.03-1.57; P = .025) and arterial ischemia time >30 minutes (odds ratio = 2.44; 95% CI, 1.45-4.12; P = .001) were the only independent risk factors related to the development of BCs after biliary reconstruction with the T-tube. CONCLUSIONS The performance of different variables in predicting occurrence of BCs was assessed with the use of receiver operating characteristic analysis. The area under the receiver operating characteristic curve of our model was 0.637 (95% CI, 0.564-0.710), and therefore we must conclude that other variables not included in our model may have influence in the development of BCs after OLT with an EE-CC with a T-tube as the procedure for biliary reconstruction.