Factors Related to Hepatocellular Carcinoma Recurrence After Liver Transplantation-A Brazilian Multicenter Study.

BACKGROUND: Liver transplantation (LT) is a curative treatment option for hepatocellular carcinoma (HCC); recurrent HCC after liver transplantation (HCC-R) is diagnosed in 9%-16%. The objective of this study was to evaluate which factors are associated with R-HCC after liver transplantation. METHODS: This retrospective real-life study analyzed 278 LTs from 3 reference centers (2,093 LTs) in Brazil from 1988 to 2015. HCC-R with histologic confirmation was seen in 40 patients (14.4%). RESULTS: Most of them were male with cirrhosis secondary to viral hepatitis. Only 37.5% underwent chemoembolization, and 50% had cold ischemia time >8 hours. From the explant analysis, most of the patients were outside Milan criteria and 37.5% had microvascular invasion. The donors were mostly male, and the median intensive care unit time was >3 days. The Kaplan-Meier survival was lower according to alpha-fetoprotein (AFP) >200 ng/dL (P = .02), and older donors and more blood transfusions were risk factors for HCC-R death. CONCLUSION: AFP >200 ng/mL was associated with lower survival, and older donors and more blood transfusions were risk factors for death after HCC-R. A trend to lower survival was observed in patients who did not have chemoembolization and had cold ischemia times >8 hours.

Can pre-liver transplantation renal insufficiency using a creatinine clearance calculator predict long-term survival?

INTRODUCTION: Renal insufficiency can be associated with poor long-term survival of liver transplant recipients. OBJECTIVE: The objective of this study was to study renal insufficiency observed pretransplantation and its long-term impact after liver transplantation. METHODS: We analyzed retrospectively an electronic database collected prospectively including transplant records from June 1994 to October 2010 using piggyback venous reconstruction. The exclusion criteria were chronic kidney disease, acute hepatic failure, children up to 12 years of age, and retransplantations. Renal insufficiency was defined by the creatinine clearance (CCr) calculated using the Cockcroft-Gault method. Patients were distributed into 3 groups: CCr >90, between 90 and 60, and >60 mL/min/1.73 m(2). The survival rate was calculated using the Kaplan-Meier method and proportional hazards Cox regression analysis using death and CCr as stratifying variables evaluated predictive factors for survival. The groups were compared using the Kruskal-Wallis test with significant differences at P < .05. RESULTS: Among the 305 patients those who showed preoperative and postoperative CCR of >90 were 187/59.9% and 82/26.3%, 60 to 90 were 77/24.7% and 74/23.7%, or <60 mL/min/1.73 m(2) were (41/13.1% and 149 (47.7%). Patients with preoperative CCr <60 mL/min/1.73 m(2) showed worse short- and long-term survivals as well as the longest intensive care unit and hospital stays (P = .034). The only predictive donor factor was age older than 40 years namely, the greatest hemotransfusion needs and postoperative liver and renal dysfunction (Chi square = 100.6064; P = .00001). The area under the curve (AUC) obtained using an receiver operating characteristic (ROC) analysis was 0.563 (95% CI 0.498-0.627) with a cut off of 30.25. CONCLUSION: Pre-liver transplantation renal insufficiency seemed to be a predictive factor for long-term survival.

Prognostic factors for hepatocellular carcinoma recurrence: experience with 83 liver transplantation patients.

INTRODUCTION: Orthotopic liver transplantation (OLT) is a rational therapeutic option for early-stage hepatocellular carcinoma (HCC) providing a potential cure and improving survival. METHODS: This retrospective study of a longitudinal cohort used an electronic database collected prospectively from September 1997 to May 2010. The variables were gender, age (years), and alpha-fetoprotein (AFP) level (ng/mL). In explanted livers we observed: microvascular or macrovascular invasion, number of nodules and their largest size, Edmondson-Steiner histological differentiation, incidental tumor transarterial chemoembolization (TACE), Milan criteria, and previous down-staging. RESULTS: Five of 83 (6.0%) subjects including 68 (82%) males with a mean time to diagnosis of 9 months experienced tumor relapses. Mean patient age at HCC recurrence was 55.3 years for male and 44.6 years for female subjects. Vascular invasion was detected in 17/83 (20.5%) subjects, namely 2% of macrovascular invasion, and 52.5% with expanded Milan criteria due to an increased number and size of nodules in the explanted livers. An incidental tumor was observed in 29.5% of cases. Preoperative TACE treatment was performed in 13 (15.6%) patients. None of the patients who had a HCC recurrence had undergone TACE. AFP level at the time of recurrence was around 1,900 ng/mL. The predictive factor for mortality was nodule size (P=.04; hazard ratio=0.0269; confidence interval [CI], 95% 0.0094-0.299). CONCLUSION: Patients with relapses showed the worst survival and tumor size was a predictive factor for recurrence.

Correlations between A/H1N1 influenza and acute cellular rejection in liver transplantation patients.

INTRODUCTION: Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. CASE REPORTS: From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. CONCLUSION: A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes.

Survival before and after model for end-stage liver disease score introduction on the Brazilian liver transplant waiting list.

INTRODUCTION: To examine whether the official adoption of Model for End-Stage Liver Disease (MELD) as a criterion for organ allocation was effective, we studied risk factors for patient deaths and the accuracy of the MELD score to predict mortality. METHODS: Patients on the waiting list for liver transplantation were divided into two periods depending on whether they were on the waiting list before (period 1) or after (period 2) the MELD introduction in Brazil. The Kaplan-Meier method with log-rank tests were used to study patient survivals. Predictive factors were identified using the Cox regression method. A receiver operating characteristic (ROC) curve was used to analyze Child-Turcotte-Pugh (CTP) and MELD accuracy. RESULTS: We analyzed 295 patients in period 1 and 240 in period 2. The survivals after 3, 6, 9, and 12 months in periods 1 and 2, were 95.6%, 90.5%, 84.9%, and 69.6% vs 95.7%, 92.1%, 85.3%, and 83.3%, respectively (P = NS). Multivariate analysis showed CTP, MELD-Na, and albumin levels, besides spontaneous bacterial peritonitis (SBP), to be independent factors related to survival in period 1. In period 2, CTP, creatinine levels, international normalized ratio, besides spontaneous bacterial peritonitis, were the independent factors. The ROC curve for CTP was 0.676 and for MELD, 0.644 (P = .4) in period 1. In period 2, the ROC curve for CTP was 0.680 and for MELD, 0.718 (P = .4). CONCLUSION: Patient survival on the waiting list for liver transplantation did not change at 1 year after the introduction of the MELD.

Changes in serological markers of hepatitis B virus after renal transplantation.

An estimated 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Immunosuppression after renal transplantation seems to enhance viral replication and increase the risk of developing cirrhosis and hepatocellular carcinoma. This retrospective study was performed to assess the prevalence among and serological status of HBV infection after renal transplantation at a single university Brazilian center. Thirty six (4.2%) patients among 850 kidney recipients showed positive HBsAg for more than 6 months; 31 were hepatitis B surface antigen (HBsAg) positive at transplantation. Of the 15 hepatitis B e antigen (HbeAg) positive patients, six had spontaneous HBeAg seroconversion and three also had HBsAg clearance. An additional two showed HBeAg clearance with Lamivudine without seroconversion. Among 15 HBeAg-negative patients, three developed HBeAg reversion with no elevation of alanine transferase (ALT) levels and one had HBsAg clearance. Only one patient had acute exacerbation of hepatitis B (ALT > 20 times normal range) but remained HbeAg negative. During follow-up, five patients became HBsAg positive; two reactivations of resolved hepatitis B, two with previous anti-HBS induced by vaccination, and one with no serological marker for HBV. Lamivudine was prescribed for 16 patients, two of whom had HbeAg clearance without seroconversion and five who developed viral resistance to Lamivudine after a mean of 29.2 months. No hepatocellular carcinoma or deaths related to hepatitis B were seen in this group. In summary, prevalence of HBV in kidney transplant patients was 4.2%. Immunosuppression after renal transplantation in HBV infection led to an increased risk of liver complications and changes in HBV serological status.

Elderly donors for HCV(+) versus non-HCV recipients: patient survival following liver transplantation.

INTRODUCTION: Chronic liver failure due to hepatitis C virus (HCV)-related cirrhosis is the leading indication for liver transplantation. Inferior long-term results have been reported for liver transplantation in HCV(+) patients, especially when marginal donor livers are utilized. AIM: The aim of this study was to analyze retrospectively the outcome of liver transplantation patients from elderly donors in the case of HCV(+) versus non-HCV recipients. METHODS: Among 330 liver transplantations performed from January 1994 to December 2006, we selected 244 excluding acute hepatic failure, children, and retransplants. Among these patients we analyzed 232 subjects who underwent the piggyback technique. Donor risk index (DRI) as described by Feng et al was applied using 1.7 as a cutoff value. We used Kaplan-Meier survival and Cox hazard regression analyses. We studied 14 donor variables using descriptive statistical tests. RESULTS: There were 148 (63.8%) HCV(+) recipients and 84 (36.2%) non-HCV liver transplant recipients. Among HCV(+) recipients, 130/148 (87.8%) patients received livers, from donors less than 50 years old, and 18/148 (12.2%), over 50 years. The descriptive statistics of patient categorical variables are shown in Table 1, and continuous variables in Table 2. The cumulative proportional survival curves are shown in Figs 1 and 2. Mortality predictive factors in HCV(+) liver transplant recipients with donor age > 50 years old as determined by Cox hazard regression showed that death risk was increased with hazard ratios for warm ischemia = 1.01 (P = .001); for red blood cell intraoperative requirements = 2.63 (P = .003); for Child-Turcotte-Pugh classification points = 2.25 (P = .04), and for DRI > 1.7 = 2.19 (P = .03). In conclusion, advancing donor age, as well as the use of nonideal donors, intraoperative bleeding, and prolonged warm ischemia, had an adverse influence on patient survival for HCV(+) recipients.