Pre-Transplantation Immune Cell Distribution and Early Post-Transplant Fungal Infection Are the Main Risk Factors of Liver Transplantation Recipients in Lower Model of End-Stage Liver Disease.

BACKGROUND: The prognosis of patients after liver transplantation (LTx) with high Model of End-Stage Liver Disease (MELD) score (>30) is predicted, but patients with lower MELD scores (<30) have no conclusive studies of pre- and post-transplant risk factors that influence the long-term outcome. METHODS: This retrospective study reviewed 268 recipients with MELD score <30, from 2008 to 2013 in our institution, for evaluation of pre-transplant risk factors including patients' clinical background data, pre-transplant lymphocyte subpopulation, and early post-transplant infection complication as predictors for long-term survival after LTx. RESULTS: The post-transplant patients' survival estimates were 90.7%, 85.1%, and 83.6% at 1, 3, and 5 years, respectively. In multivariate analysis, age >55years, presence of ascites, cluster of differentiation (CD)3 < 93.2 (count/µL), CD4/CD8 <2.4, fungal infection, and more than one site of fungal colonization significantly influenced survival (P = .0003, P = .002, P = .04, P = .004, P < .0001, and P > .0001, respectively). We also noticed that these five factors accumulatively influence the long-term survival rate; this means that in the presence of any two risk factors, the 5-year survival can still be 88.4%, whereas in the presence of any three risk factors, the survival rate dropped to only 57.1%. CONCLUSIONS: Older patients in the presence of pre-transplant low immune cell number and ascites in association with post-transplant fungal infection are the independent risk factors in MELD scores <30 LTx groups for long-term survival. Patients in these groups with any of the three factors had inferior long-term survival results.

Application of CD8+ Cells Count as a Guide of Immunosuppressive Regimen Introduction for Very Sick Patients Undergoing Liver Transplantation.

BACKGROUND: Immunosuppression (IS) protocols should be individualized according to the individual recipient's immunity to minimize adverse effects. The aim of this study was to determine whether preoperative levels of CD8+ T lymphocytes could be used as a guide for the introduction of IS. METHODS: Sixteen adult liver transplantations in our institute were retrospectively analyzed. The immunosuppressive agents were temporarily withheld for 8 patients with a lower (<10%) preoperative percentage of CD8+ cells after transplant (classified as group A). In this group, postoperative immunosuppressive agents had never been used until acute rejection was suspected. Another 8 patients receiving classic IS were classified as group B. We collected their demographic features and analyzed the clinical courses. RESULTS: The postoperative IS-free period of group A was 5 to 120 days (median, 31 days). Our data showed an inverse correlation between CD8+ levels and the severity of liver disease. Although the IS-free protocol did not present a lower incidence of infection-related events, most of them were effectively treated with antibiotics. The 1-, 3-, and 5-year overall patient survival rates were not different between those with a short-term IS-free period and those with regular IS (87.5% vs 100%, 75% vs 100%, and 62.5% vs 87.5%; P = .468). No patient died of graft failure due to acute rejection. CONCLUSIONS: Postoperative immunosuppressive agents can be safely withheld for a period of time to preserve proper immune responses against infections in very sick recipients guided by using the CD8+ levels.

Outcomes of liver resection for hepatocellular carcinoma in liver transplantation era.

AIMS: Surgical treatment for early-stage hepatocellular carcinoma (HCC) is toward transplantation. However, liver resection remains the major surgical treatment for HCC in Asia. This study is to examine the results of liver resection when liver transplantation became an option of treatment for early-stage HCC. METHODS: In this retrospective cohort study, 1639 patients with resectable HCC were reviewed and divided into two groups. In the 1st period (2002-2005), all 679 patients received liver resection. In the 2nd period (2006-2010), 916 patients had liver resection and 44 patients jointed liver transplantation program. The results of treatment in these two periods were analyzed. RESULTS: The characteristics of tumors were the most important factors of tumor recurrence after liver resection. Liver function reserve, characteristics of tumors, and surgeons' endeavor were all independent factors for overall survival after liver resection. When the patients with oligo-nodular tumors or portal hypertension with low platelet count had liver transplantation rather than liver resection in the 2nd period, the survival rates in the 2nd period were improved. When the patients in the 1st period with low platelet count (≤105 × 10(3)/uL) were subtracted, the 5-year survival rate of the patients with one-segmentectomy for small-sized HCC in the 1st period was similar to those in the 2nd period and transplant patients. CONCLUSIONS: The outcomes of liver resection were improved while liver transplantation was performed for the patients with suspicious portal hypertension. Platelet count, 105 × 10(3)/uL, could be a watershed for early stage HCC patients to undergo liver resection or liver transplantation.

Risk factors and clinical outcomes of ventilator-associated pneumonia in patients on the liver transplant waiting list.

BACKGROUND: Prolonged intubation results in ventilator-associated pneumonia (VAP), which contributes to significant mortality among patients on the waiting list. The aim of this study was to determine the risk factors for and clinical outcomes of VAP among patients into the intensive care unit (ICU). METHODS: We enrolled 50 consecutive critically ill patients with end-stage liver disease admitted to the ICU from January 2005 through December 2010. All patients were intubated for more than 4 days; no definite infection was found initially. We evaluated potential risks factors for VAP and clinical outcomes. RESULTS: Smoking, underlying liver disease, and lobar focal consolidations were significant factors for patients with versus without VAP. Fourteen-day mortality rates were 61.5% for VAP versus 40.5% for patients without VAP. Twenty-eight-day mortality rates for both groups were 92.3% and 86.5%, respectively. Multivariate analysis failed to identify independent predictors of early 14-day mortality. CONCLUSIONS: Underlying liver disease and lobar focal consolidations were risks factors for VAP in patients with prolonged intubation. Patients with prolonged intubation have a dismal prognosis even without VAP. The clinical outcomes of patients with versus without VAP were similar. However, early liver transplantation (<14 days of intubation) improves the chance to rescue patients before development of VAP.

The risk factors for early infection in adult living donor liver transplantation recipients.

OBJECTIVE: The high rate of early major infections in liver transplantation recipients is due to their compromised immune-system. We examined the risk factors of early major infection in living donor liver transplantation (LDLT). MATERIALS AND METHODS: From January 2004 to December 2010, 242 patients undergoing LDLT were enrolled in the prospective cohort. We prospectively collected their clinical and demographic variables, operative details, and posttransplant complications. RESULT: One hundred thirty-nine patients (57.7%) experienced 252 episodes of early infection posttransplantation: bloodstream septicemia (n = 46, 18.3%), urinary tract (n = 34; 14.1%), pneumonia (n = 64; 25.4%), peritonitis (n = 62; 25.7%), and catheter related (n = 46; 19%). The most frequent Gram-positive bacteria were coagulase-negative staphylococci (n = 52; 16.9%), followed by Staphylococcus aureus (n = 32; 10.4%). The most common Gram-negative bacteria were Escherichia coli (n = 27; 8.8%); Acinetobacter baumannii (n = 29; 9.4%), Pseudomonas aureos (n = 18; 5.8%), and Sternotrophomonas maltophilia (n = 18; 5.8%). Upon multivariate logistic regression analysis, the risk factors for early major infection were a high creatinine level (odds ratio = 1.481), a long anhepatic arterial phase (1.01), a reoperation (6.417), young age (1.040), and non-hepatocellular carcinoma recipient (2.141). CONCLUSION: Early major infection after LDLT was high with Gram-positive bacteria, the most common etiologies. Prolonged anhepatic arterial phase, renal insufficiency, and reoperation were risk factors for an early major infection.

Bortezomib is effective to treat acute humoral rejection after liver transplantation.

INTRODUCTION: Acute humoral rejection (AHR), a rare complication in orthotopic liver transplantation (OLT), responds poorly to conventional therapies. Bortezomib, a proteasome inhibitor, has been shown to be effective in treating plasma cell-derived tumors and acute rejection episodes after renal transplantation. Herein, we have reported our clinical experience with bortezomib as a novel approach to treat AHR after OLT. METHODS: We retrospectively analyzed the 247 adult OLTs performed from January 2007 to April 2011. Patients with AHR who were treated with steroid pulses, rituximab (375 mg/m2), and plasmapheresis (PP) were assigned to group A. Group B subjects were prescribed steroid pulses, rituximab, PP, and bortezomib (1.3 mg/m2), after March 2009. RESULTS: Among the 9 patients (3.6%) diagnosed with AHR, all subjects in group A (n=3) died within several days after AHR, whereas 4/6 (66.7%) group B patients were rescued and 3 (50%) survived at a mean follow-up 22.3 months (range, 18-26). CONCLUSION: Proteasome inhibitor-based therapies provide a more effective strategy to treat AHR after OLT.

"Left at right" adult liver transplantation: the feasibility of heterotopic implantation of left liver graft.

Left liver grafts have been widely utilized in adult liver transplantation (LT) and yielded acceptable results. However, the conventional orthotopic implantation of a left liver graft imposes the potential risk of perioperative vascular complications. We report herein an alternative modified technique for adult left liver LT and evaluate its feasibility in LT. In this study, 10 recipients had their left liver graft rotated 180°, and heterotopically implanted at the right subphrenic space, which we termed "left at right" liver transplantation (LAR-LT). The sequence of vascular and biliary reconstruction was performed as standard techniques, and no perioperative vascular complications related to LAR-LT were encountered. There were two mortalities in this series, one due to a small-for-size graft dysfunction and the other due to postoperative internal hemorrhage. Two recipients had biliary strictures that were successfully managed by percutaneous biliary dilatation and Roux-en-Y hepaticojejunostomy. The clinical characteristics and outcomes of patients undergoing LAR-LT were also compared with patients undergoing conventional orthotopic left liver LT (n = 14). Although the results showed no significant difference between the two groups, according to our experience, the satisfactory outcome and easier technical reconstruction suggest that the LAR-LT modification could be a feasible alternative to left liver LT.