Tsung-Han Wu

Feasibility of split liver transplantation for 2 adults in the model of end-stage liver disease era.

Objective: To examine the results of split liver transplantation for 2 adults in the model of end-stage liver disease (MELD) era. Background: In the MELD era, liver allografts are first allocated to recipients with the highest MELD scores. However, the application of split liver transplantation for 2 adults in urgent condition has doubled and has become a matter of concern. Methods: Twenty-one deceased liver grafts were split into full right and full left lobes for 42 adult recipients. One of the hemiliver grafts was allocated to the recipient with the highest MELD score in the waiting list. The results of split liver transplantation were examined and compared with those of living donor liver transplantation. Results: Among 42 recipients, 24 (57.1%) had MELD scores higher than 20. The median (interquartile) MELD score for the recipients with split liver transplantation was 22 (15–30), which was higher than that for the recipients with living donor liver transplantation (P < 0.001). The 1-, 3-, and 5-year survival rates for split liver transplantation were comparable with those of living donor transplantation (P = 0.489). Nevertheless, 10 of 42 split liver recipients died within 3 months after transplantation. By receiver operating characteristic curve analysis, the safe graft-recipient weight ratio was better more than 1% to avoid early patient death for split liver transplantation. Conclusions: Although most of the recipients with split liver transplantation had high MELD scores, the results were comparable with those of living donor liver transplantation. Split liver transplantation for 2 adults is still feasible in the MELD era.

Application of cryopreserved vein grafts as a conduit between the coronary vein and liver graft to reconstruct portal flow in adult living liver transplantation.

Abstract:u2002 Adult‐to‐adult living donor liver transplantation is an alternative to donation from a deceased individual, and can help relieve the shortage of liver donations available for adult patients in Asian countries. When transplant candidates have thrombosis and deterioration of the portal vein, living donor liver transplantation is relatively contraindicated because portal veins in the grafts are short and vein grafts may not be available to reconstruct the portal vein. From June 2003 to May 2007, 82 adult living donor liver transplantations were performed at Chang‐Gung Memorial Hospital. Three patients had portal vein thrombosis and marked fibrosis of the portal vein and cryopreserved vein grafts were used to reconstruct portal flow from the engorged coronary vein to the graft portal vein. All vein grafts are patent and all patients have normal liver function at 21–36u2003months after transplantation. When cryopreserved vein grafts are available, adult living donor liver transplantation can be successfully performed in patients with marked deterioration of the portal vein. The short distance from the engorged coronary vein to the graft portal vein may decrease the incidence of re‐thrombosis of the venous conduit.

The Preference for Anterior Approach Major Hepatectomy: Experience Over 3 Decades and a Propensity Score-Matching Analysis in Right Hepatectomy for Hepatocellular Carcinoma.

AbstractSurgical treatment for primary hepatocellular carcinoma (HCC) has progressed enormously over time. The aim of this study was to analyze the evolution of surgical techniques and outcomes of patients undergoing major right hepatectomy (RH) over the last few decades.A retrospective review of 557 consecutive patients who had undergone RH for HCC between January 1982 and December 2011 was performed. Patients were categorized into subgroups and analyzed according to period and surgical approach to hepatectomy. Based on a propensity score-matching model, the surgical approach in patients in the second period was also analyzed in terms of anterior approach (AA) and conventional approach (CA)-RH.Tumor factors remained the most important prognostic factors related to postoperative HCC recurrence throughout the 2 periods examined in this study. Comparison of patients selected by a propensity score-matching model showed that AA-RH led to significantly better outcomes including recurrence-free survival (RFS) (Pu200a=u200a0.011) and overall survival (OS) (Pu200a=u200a0.012) in patients with HCC as compared with CA-RH. The 5-year RFS and OS were 33.4% and 52.2% after AA-RH, and 21.0% and 36.5% after CA-RH.Major hepatectomy has evolved into a safe procedure that can be performed with confidence. RH by an AA has shown several advantages over CA-RH, and can thus be recommended as the standard procedure for liver resection in patients who require right hepatectomy.

Adult Living Donor Liver Transplantation Across ABO-Incompatibility

Abstract The objective of this study was to evaluate the results of adult ABO-incompatible living donor liver transplantation (LDLT). ABO-incompatible LDLT is an aggressive treatment that crosses the blood-typing barrier for saving lives from liver diseases. Although graft and patient survival have been improved recently by various treatments, the results of adult ABO-incompatible LDLT require further evaluation. Two regimens were designed based on isoagglutinin IgG and IgM titers and the time course of immunological reactions at this institute. When isoagglutinin IgG and IgM titers were ⩽64, liver transplantation was directly performed and rituximab (375u200amg/m2) was administrated on postoperative day 1 (regimen I). When isoagglutinin titers were >64, rituximab (375u200amg/m2) was administered preoperatively with or without plasmapheresis and boosted on postoperative day 1 (regimen II). Immunosuppression was achieved by administration of mycophenolate mofetil, tacrolimus, and steroids. Forty-six adult ABO-incompatible and 340 ABO-compatible LDLTs were performed from 2006 to 2013. The Model for End-Stage Liver Disease scores for ABO-incompatible recipients ranged from 7 to 40, with a median of 14. The graft-to-recipient weight ratio ranged from 0.61% to 1.61% with a median of 0.91%. The 1-, 3-, and 5-year survival rates were 81.7%, 75.7%, and 71.0%, respectively, for ABO-incompatible LDLT recipients, compared to 81.0%, 75.2%, and 71.5% for ABO-C recipients (Pu200a=u200a0.912). The biliary complication rate was higher in ABO-incompatible LDLT recipients than in the ABO-compatible recipients (50.0% vs 29.7%, Pu200a=u200a0.009). In the rituximab era, the blood type barrier can be crossed to achieve adult ABO-incompatible LDLT with survival rates comparable to those of ABO-compatible LDLT, but with more biliary complications.

Inhibition of allogenic T-cell cytotoxicity by hepatic stellate cell via CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in vitro.

BACKGROUNDnThe liver is considered to be an immune-privileged organ. Several types of liver cells have been implicated in the induction of immunologic tolerance. Hepatic stellate cells (HSCs) seem to participate in hepatic fibrosis and to display immunological properties.nnnMATERIALS AND RESULTSnIn this study, HSCs isolated from C3H mice were highly positive for GFAP (98.4%) and α-SMA (95.4%). After stimulation by interferon-γ (IFN-γ), HSCs were more active in morphology with enhanced expression of H2-K(K), I-A(K), CD80, and CD54, similar to mature myelogenic dendritic cells (MDCs). Through allogeneic stimulation, C3H HSCs induced proliferation of both CD8(+) and CD4(+) T cells in B6 mice. However, the T cells activated by allogeneic HSCs produced less INF-γ, interleukin (IL)-4, IL-10, and IL-17, but large amount of transforming growth factor-β. These T cells expressed immunoregulatory rather than effector functions. Naïve T cells stimulated by allogeneic HSCs expressed Foxp3 compared with MDCs (8.67% vs 2.14%, P < .05). CD8(+) T cells activated by HSCs lost their allogeneic cytotoxicity, and CD4(+) T cells activated in this fashion suppressed the allogeneic cytotoxicity of CD8(+) T cells activated by MDCs.nnnCONCLUSIONnHSCs seem to act as liver-resident antigen-presenting cells instructing the generation of Foxp3(+) regulatory T cells, a property suggestion of induction of immunologic tolerance.

Risk factors for early mortality after hepatectomy for hepatocellular carcinoma.

AbstractDespite advances in surgical technique and medical care, liver resection for hepatocellular carcinoma (HCC) remains a high-risk major operation. The present study evaluated the risk factors for early mortality after hepatectomy.We retrospectively reviewed records of patients undergoing liver resection for HCC between 1983 and 2015. A point score (Risk Assessment for early Mortality (RAM) score) for hepatectomy was developed based on multivariate analyses.Three hundred eighty-three patients (11.3%) expired within 6 months after the operation. Logistic regression analyses identified that operative duration >270u200aminutes and blood loss >800u200acc were significant predictors of major surgical complications (P = 0.013 and 0.002, respectively). On the other hand, diabetes mellitus, albumin ⩽3.5u200ag/dL, &agr;-fetoprotein (AFP) >200u200ang/mL, major surgical procedure, blood loss >800u200acc, and major surgical complications were independent risk factors for early mortality after hepatectomy (P = 0.019, <0.001, <0.001, 0.006, 0.018, and <0.001, respectively). Risk Assessment for early Mortality score (RAM score) identified 3 subgroups of patients with distinct 6-month mortality rate, with Class III (score 10) having highest risk of early mortality.Our study demonstrated that meticulous surgical techniques to minimize blood loss and avoid prolonged operative time may help decrease the occurrence of major surgical complications. In addition to major surgical complications, diabetes mellitus, hypoalbuminemia, high AFP, massive blood loss, and major surgical procedure are also associated with early mortality after liver resection. Further study is warranted to validate the utility of RAM score as a bedside scoring system to predict postoperative outcome.

Split-Liver Transplantation in 2 Adults: Significance of Caudate Lobe Outflow Reconstruction in Left Lobe Recipient: Case Report

Split-liver transplantation is a well-known procedure for increasing the donor pool. The procedure is commonly used in 1 adult and 1 child, but is less commonly performed in 2 adults because of technical difficulty and poor outcome in left-lobe recipients. Preservation of caudate lobe function is important in recipients with borderline graft-recipient weight ratio to achieve better results. Herein, we report a case in which caudate lobe outflow was reconstructed in a left lobe with a caudate lobe graft in split-liver transplantation in 2 adults.

Validation of the Model for End-Stage Liver Disease Score Criteria in Urgent Liver Transplantation for Acute Flare Up of Hepatitis B

AbstractAcute flare up of hepatitis B in noncirrhotic liver with rapid liver function deterioration is a critical condition. This flare up of hepatitis B may be subsided under medical treatments, otherwise urgent liver transplantation is needed. However, the necessity of urgent liver transplantation is hard to decide. In this institute, the indications of urgent liver transplantation for acute flare up of hepatitis B in noncirrhotic liver were settled according to the model for end-stage liver disease (MELD) scores: once upon MELD scores ≥35 (criterion 1) or MELD scoreu200a<u200a35 at beginning and increased in the subsequent 1 to 2 weeks (criterion 2). This study was to examine whether MELD score criteria for liver transplantation were valid in such an urgent condition. Eighty-three patients having acute flare up of hepatitis B virus with total bilirubin ≥17.5u200amg/dL were included in this study. Among 83 patients, 20 patients met criterion 1. Five patients were transplanted and 15 patients died of liver failure with a median survival of 17 days. Fifty-one patients met criterion 2. Nineteen were transplanted, 30 patients died of liver failure with a median survival of 23.5 days, and 2 patients recovered from this critical condition. The other 12 patients did not meet criteria 1 and 2, and urgent liver transplantation was spared although 5 patients needed liver transplantation in subsequent 2 to 3 months. Therefore, the sensitivity of MELD score criteria for urgent liver transplantation was 100% and specificity was 85.7%. In conclusion, determination of urgent liver transplantation for hepatitis B with acute liver failure is crucial. MELD score criteria are valid to make a decision of urgent liver transplantation for hepatitis B patients with acute flare up and liver failure.

Microscope-assisted Hepatic Artery Reconstruction in Adult Living Donor Liver Transplantation - A Review of 325 Consecutive Cases in A Single Center

Despite the technical and medical improvements in the recent years, hepatic artery thrombosis (HAT) remains a devastating complication after living donor liver transplantation (LDLT). We described our surgical techniques and monitoring protocols for hepatic artery reconstruction. We reported one of the lowest incidence rates of HAT in the literature.

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

BACKGROUNDnThe 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.nnnMETHODSnThis retrospective study reviewed 268 recipients with MELD scorexa0<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.nnnRESULTSnThe 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)3xa0< 93.2 (count/μL), CD4/CD8xa0<2.4, fungal infection, and more than one site of fungal colonization significantly influenced survival (Pxa0= .0003, Pxa0= .002, Pxa0= .04, Pxa0= .004, Pxa0< .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%.nnnCONCLUSIONSnOlder 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 scoresxa0<30 LTx groups for long-term survival. Patients in these groups with any of the three factors had inferior long-term survival results.