Sanghyun Song

Donor morbidity including biliary complications in living-donor liver transplantation: single-center analysis of 827 cases.

Background Because of the shortage of deceased-donor livers for transplantation, living-donor liver transplantation (LDLT) has become an indispensible treatment strategy for end-stage liver disease. The critical prerequisite for LDLT is the maximal safety of healthy donors. Methods From June 1996 to November 2010, a total of 827 completed donor hepatectomies were performed in our center. We analyzed donor morbidity associated with LDLT. Results There was no donor mortality. No complications were observed in 744 (90.0%) donors, and 83 (10.0%) donors experienced complications. Wound complications were most common, occurring in 48 (5.8%) patients. According to a modified Clavien classification, grade I, grade II, grade IIIa, and grade IIIb complications were experienced in 56 (67.5%), 2 (2.4%), 15 (18.1%), and 10 (12.0%) donors, respectively. Surgical or interventional management was successful in all grade IIIa and grade IIIb donors. The incidence of biliary complications was significantly higher in younger donors. Donor morbidity did not decrease below the attained level even after time had passed. Conclusions This study demonstrates the safety of donor hepatectomy. Complications were relatively minor and easily controlled. The incidence of biliary complications and donor age was inversely correlated. The procedural experience of the surgeons was not associated with the donor complication rate.

Is cytomegalovirus infection dangerous in cytomegalovirus-seropositive recipients after liver transplantation?

Cytomegalovirus (CMV) infections contracted after liver transplantation put patients at an increased risk of morbidity and mortality. We analyzed the effects of CMV infection by time of onset, mortality, and graft failure risk factors in liver recipients who were CMV donor‐positive/recipient‐positive (D+/R+). We reviewed 618 medical records for consecutive adult liver transplant cases. CMV pp65 antigenemia assays to determine patient CMV status were administered monthly. The incidences of CMV infection and disease were 55.7% (344 of 618 records) and 5.5% (34 of 618 records), respectively. The differences in patient survival and graft failure rates for CMV‐infected and CMV‐uninfected patients were not significant (P = 0.707 and P = 0.973), but the rates were lower in patients with CMV disease than in CMV‐uninfected patients (P = 0.005 and P = 0.030, respectively). The recurrence of hepatitis B virus and hepatocellular carcinoma, hepatic dysfunction, infection, numerous pp65‐staining cells, and CMV disease were found to be the risk factors for mortality and graft failure in CMV D+/R+ adult liver transplant patients. In conclusion, the occurrence of CMV disease, and not asymptomatic CMV infection, was a risk factor for mortality and graft failure in adult liver transplant recipients with CMV D+/R+. Liver Transpl, 2011.

Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression

BACKGROUND AIMS Mesenchymal stromal cells (MSC) from several tissues have immunomodulatory properties that involve various immunosuppressive molecules. An example is human leukocyte antigen (HLA)-G, a non-classical major histocompatibility complex (MHC) class I molecule that induces tolerance via interactions with inhibitory receptors present on major immune effector cells. Recently, the molecular mechanisms that regulate MSC-mediated immunosuppression have come under investigation. Our goal was to determine whether HLA-G plays a crucial role in immunosuppression and whether human adipose tissure (hAT) MSC can be used as a tool for biologic immunosuppression with HLA-G in transplantation. METHODS MSC were characterized by fluorescence-activated cell sorting (FACS) analysis, reverse transcriptase (RT)-polymerase chain reaction (PCR) and staining for differentiation. The immunogenicity and immunomodulatory effects of MSC were monitored by peripheral blood mononuclear cell (PBMC) proliferation assay with or without phytohemagglutinin (PHA) stimulation. Stable expression of HLA-G1 in MSC was done using a lentiviral system. Results. MSC from different tissues had similar morphology, immunophenotypic characters and differentiation potential. We also found that the immunosuppressive effect of MSC was monitored along with their endogenous HLA-G mRNA and protein levels. Stable expression of HLA-G1 appeared to enhance the immunosuppressive effect of hAT MSC, and the function of HLA-G1 was significantly decreased by HLA-G antagonistic antibody in PBMC proliferation assays. CONCLUSIONS Although the HLA-G molecule is not the sole factor for MSC-mediated immunosuppression, our data provide evidence that HLA-G plays an important role in immunosuppression and that hAT MSC can be used as a tool for biologic immunosuppression during transplantation procedures.

The prognosis and treatment outcomes of patients with recurrent hepatocellular carcinoma after liver transplantation.

Liver transplantation (LT) is performed in patients with hepatocellular carcinoma (HCC), but recurrent HCC after LT remains a problem. We retrospectively reviewed the data from 63 patients with recurrent HCC who underwent LT at a single institution between September 1996 and March 2011 to determine the prognosis of patients with recurrent HCC after LT. A survival analysis was performed with the preoperative data, histological findings, patterns of recurrence, and treatment methods. Univariate and multivariate analyses were performed to determine the factors associated with early (<1 yr) cancer‐related death. The independent prognostic factors, according to the multivariate analysis, were recurrence within six months (hazards ratio [HR] = 4.557, p = 0.021) and initial multiple‐organ involvement (HR = 5.494, p = 0.015). The survival rates of patients differed according to the treatment type. The combined treatment with local and systemic treatment resulted in increased survival even in patients with HCC recurrences involving multiple organs.

Effectiveness of Intraportal Prostaglandin E1 Administration after Liver Transplantation

PURPOSE Prostaglandin E1 (PGE1) has been used to improve hepatic blood flow and to reduce ischemia reperfusion injuries of allografts in liver transplantation. However, PGE1 undergoes extensive metabolic clearance in the pulmonary and splanchnic circulation during intravenous administration. We analyzed the effect of intraportally administered PGE1. METHODS Sixty living-donor liver transplant recipients received continuous infusions of PGE1 for 10 days immediately after the reperfusion of the allografts. Of them, 40 recipients received PGE1 intravenously (IV group) via the internal jugular vein, and 20 recipients received PGE1 intraportally (IP group) through a catheter in the inferior mesenteric vein. Data were collected for 3 weeks postoperatively. RESULTS The IP group exhibited lower initial aspartate aminotransferase and alanine aminotransferase levels compared with the IV group. However, no apparent differences were recognized in the serum albumin, total bilirubin, alkaline phosphatase, r-glutamyl transpeptidase, or prothrombin time levels between the 2 groups. Chylorous ascites were observed more frequently in the IP group. There was no difference in portal venous flow measured by Doppler sonogram between the 2 groups during the first postoperative week. CONCLUSION This study demonstrated that intraportal administration of PGE1 had a better cytoprotective effect against hepatocellular damage than intravenous administration, although it did not have additional benefits for perihepatic hemodynamics.

Antiviral Treatment for Hepatitis B Virus Recurrence Following Liver Transplantation

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV‐related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty‐seven LTs were performed for HBsAg‐positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow‐up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 105 IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV‐recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre‐transplant HBV viremia and an effective post‐transplant HBV prophylaxis.

Serial ImmuKnow assay in stable kidney transplant recipients

Objectives The ImmuKnow assay (cylex Inc., Columbia, MD) has been reported to measure the global immune monitoring tool for organ transplantation recipients. We assess immuKnow ATP values in stable kidney transplant patients. Material and methods Patients who were kidney transplanted between September 2008 and May 2011 were enrolled in the prospective serial ImmuKnow assay study. The criteria of inclusion were living donor kidney transplantation (KT), no evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and PRA less than 50%. ImmuKnow assay monitoring was performed at one day before operation, post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. We excluded patients who had undergone infectious syndrome or rejection episodes during the follow-up period. Results Among 71 patients who were enrolled in prospective serial ImmuKnow assay monitoring, 37 patients were proven to stable KT patients during the follow-up period. Two hundred and twenty-four samples from 37 patients were collected. ImmuKnow value and immunosuppression drug level were compared in post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. The value of ImmuKnow assay was significantly different depending on the length of time after transplant (p = 0.038). Interestingly, the pre-transplant ImmuKnow values were lower than those of the immediate post-transplant period. Conclusions The ImmuKnow value of stable KT recipients is different according to “time after transplant”. Therefore, “time after transplant” should be considered when applying an ImmuKnow assay in clinical practice.

The Effect of Human Fetal Liver-Derived Mesenchymal Stem Cells on CD34+ Hematopoietic Stem Cell Repopulation in NOD/Shi-scid/IL-2Rãnull Mice

Mesenchymal stem cells (MSCs) are progenitors that are capable of differentiating into mesenchymal tissues. They are known to support allogeneic hematopoietic stem cell transplantation by facilitating engraftment without increasing the risk of graft-versus-host disease. We optimized culture conditions for human fetal liver-derived MSCs (hFL-MSCs) to investigate the role of hFL-MSCs on repopulation of hematopoietic stem cells in NOD/Shi-scid/IL-2Rγ(null) (NOG) mice using CD34(+) hematopoietic stem cells (HSCs) derived from umbilical cord blood (UCB). FL-MSCs and CD34(+) HSCs were prepared from fetal liver and UCB, respectively. Twenty-four hours after irradiation, CD34(+) HSCs and hFL-MSCs were injected intravenously and intratibially into NOG mice. During 24 weeks posttransplantation, engraftment levels of human cells were analyzed in bone marrow, peripheral blood, and spleen of transplanted mice by flow cytometry. hFL-MSCs showed a fibroblast-like morphology and immunophenotypic characteristics appropriate for MSCs. hFL-MSCs prolonged the survival of NOG mice that had been cotransplanted with UCB CD34(+) cells. Fluorescence-activated cell-sorting analysis showed that engraftment of human cells was increased by cotransplantation of hFL-MSCs. However, significant enhancement of human cell engraftment was not detected in NOG mice regardless of the number of cotransplanted MSCs. Although survival of repopulating NOG mice and engraftment of human cells were prolonged by cotransplantation of hFL-MSCs, 8.0 × 10(6) MSCs were not sufficient to increase HSC engraftment in irradiated NOG mice in vivo.

Clinical Significance of Proteinuria at Posttransplant Year 1 in Kidney Transplantation

PURPOSE Proteinuria in the nontransplant population is a progressive renal disease. We analyzed the prevalence and clinical significance of proteinuria as well as factors related to its degree at posttransplant year 1 among kidney transplant recipients. METHODS We measured protein in a 24-hour urine among 644 recipients from January 1996 to December 2010. RESULTS Among 372 male and 272 female recipients, the mean amount of urinary protein was 424.4 ± 1010 mg/d (range, 13.88-8691) including 388 (60.2%) subjects with microproteinuria and the other 256 (39.8%) with overt proteinuria. Nephrotic range proteinuria was observed in 17 (2.6%) and nonnephritic range proteinuria, in 239 (37.1%) recipients. The latter cohort was categorized into low-grade proteinuria (n = 224; 34.8%) and high-grade proteinuria (n = 15; 2.3%). Proteinuria at posttransplant 1 year highly correlated with serum creatinine values at posttransplant years 1 and 2 as well as estimated glomerular filtration rate but not creatinine clearance at postoperative year 2. A greater incidence of graft loss was observed among recipients with more severe proteinuria. Males, recipients with anti-hepatitis C virus antibody, unrelated donors, anti-thymocyte immunoglobulin at the time of reperfusion, maintenance immunosuppression with cyclosporine or without mycophenolate mofetil were strongly associated with the amount of proteinuria. CONCLUSION This study demonstrated the prevalence of proteinuria in kidney transplant recipient to be high. The presence as well as level of proteinuria were predictive markers for inferior allograft function.

A new technique for complete portal vein and superior mesenteric vein thrombosis in a liver transplant recipient.

We describe a deceased-donor liver transplant recipient with grade 3 complete portal vein and superior mesenteric vein thromboses, which was successfully managed with an extensive thrombectomy through the venotomy site of superior mesenteric vein. In this case report, we suggest our method as an option for grade 3 portal vein thromboses, and discuss other options available for recipients with portal vein thromboses.