Milljae Shin

Safety of small-for-size grafts in adult-to-adult living donor liver transplantation using the right lobe.

The problem of graft size is one of the critical factors limiting the expansion of adult‐to‐adult living donor liver transplantation (LDLT). We compared the outcome of LDLT recipients who received grafts with a graft‐to‐recipient weight ratio (GRWR) < 0.8% or a GRWR ≥ 0.8%, and we analyzed the risk factors affecting graft survival after small‐for‐size grafts (SFSGs) were used. Between June 1997 and April 2008, 427 patients underwent LDLT with right lobe grafts at the Department of Surgery of Samsung Medical Center. Recipients were divided into 2 groups: group A with a GRWR < 0.8% (n = 35) and group B with a GRWR ≥ 0.8% (n = 392). We retrospectively evaluated the recipient factors, donor factors, and operative factors through the medical records. Small‐for‐size dysfunction (SFSD) occurred in 2 of 35 patients (5.7%) in group A and in 14 of 392 patients (3.6%) in group B (P = 0.368). Graft survival rates at 1, 3, and 5 years were not different between the 2 groups (87.8%, 83.4%, and 74.1% versus 90.7%, 84.5%, and 79.4%, P = 0.852). However, when we analyzed risk factors within group A, donor age and middle hepatic vein tributary drainage were significant risk factors for graft survival according to univariate analysis (P = 0.042 and P = 0.038, respectively). Donor age was the only significant risk factor for poor graft survival according to multivariate analysis. The graft survival rates of recipients without SFSD tended to be higher than those of recipients with SFSD (85.3% versus 50.0%, P = 0.074). The graft survival rates of recipients with grafts from donors < 44 years old were significantly higher than those of recipients with grafts from donors ≥ 44 years old (92.2% versus 53.6%, P = 0.005). In conclusion, an SFSG (GRWR < 0.8%) can be used safely in adult‐to‐adult right lobe LDLT when a recipient is receiving the graft from a donor younger than 44 years. Liver Transpl 16:864–869, 2010.

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.

Living donor liver transplantation: the Asian perspective.

Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. Hepatic steatosis, a common finding in living liver donors, not only influences the outcome of liver transplantation for the recipient but also affects the recovery of the living donor after partial hepatectomy. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but it is invasive, and results are vulnerable to sampling error. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. This article describes potential clinical applications for liver fat quantification of imaging methods for fat detection and quantification, with an emphasis on the advantages and limitations of ultrasonography, computed tomography, and magnetic resonance imaging for quantifying liver fat.

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.

Risk factors for posttransplant lymphoproliferative disorder in pediatric liver transplant recipients with cytomegalovirus antigenemia.

Epstein-Barr virus (EBV) infections, associated with posttransplant lymphoproliferative disorder (PTLD) are known to develop in cytomegalovirus (CMV)-infected transplant recipients due to the indirect effects of CMV. This study evaluated risk factors for PTLD among pediatric liver transplant recipients with CMV infections. We reviewed the medical records of 119 patients<or=18 years old who underwent liver transplantation between September 1996 and April 2009. Sixty-six subjects (55.5%) displayed CMV antigenemia during the study period; 15 (12.6%) developed PTLD. Of these, 10 developed PTLD after CMV antigenemia. The other patients (n=5) were excluded due to negative CMV antigenemia. The incidence of PTLD influenced by CMV infection was not significantly different from the incidence of PTLD without underlying CMV (P=.258). There were no differences in age, gender, antiviral prophylaxis, type of liver transplantation, or acute rejection episodes in the incidence of between patients with versus without PTLD. EBV but not CMV high-risk groups were a predictor for the development of PTLD (P=.035). CMV syndrome, tissue-invasive CMV disease, and CMV peak titer were not associated with an increased risk of PTLD. The primary risk factor for PTLD was EBV high-risk patients (donor positive/recipient negative). CMV disease was not associated with PTLD in pediatric liver transplant recipients with CMV infections.

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.

Patients With Unresectable Hepatocellular Carcinoma Beyond Milan Criteria: Should We Perform Transarterial Chemoembolization or Liver Transplantation?

Patients with unresectable, beyond Milan criteria, hepatocellular carcinoma (HCC) invariably undergo palliative transarterial chemoembolization (TACE). The aim of this study was to compare the outcomes of conventional TACE versus liver transplantation (LT) in unresectable (beyond Milan criteria) HCC. Twelve patients underwent LT and 86 TACE for unresectable, beyond Milan criteria HCC. The inclusion criteria were a single tumor<or=6.5 cm or <or=5 tumors and all tumors<or=5 cm based on initial radiologic findings. We excluded patients with double primary cancers, age>60 years, vascular invasion, or extrahepatic spread. Survival rates were calculated using the Kaplan-Meier method. Multivariate analysis showed that TACE was a prognostic factor for survival (hazard ratio, 16.66, P=.000). The LT group showed significantly better survival than the TACE cohort. Two cases (16.7%) in the LT group recurred at a median time of 13.5 months. Survival rates at 1, 3, and 5 years were 100%, 88.9%, and 76.2% in the LT group, and 85.6%, 45.6%, and 21.4% in the TACE group, respectively. Patients with unresectable, beyond Milan criteria HCC should be given the option to receive LDLT, because LT offers a significantly better likelihood of survival than TACE.

Advances in endoscopic management of biliary complications after living donor liver transplantation: Comprehensive review of the literature

Apart from noticeable improvements in surgical techniques and immunosuppressive agents, biliary complications remain the major causes of morbidity and mortality after living donor liver transplantation (LDLT). Bile leakage and stricture are the predominant complications. The reported incidence of biliary complications is 15%-40%, and these are known to occur more frequently in living donors than in deceased donors. Despite the absence of a confirmed therapeutic algorithm, many approaches have been used for treatment, including surgical, endoscopic, and percutaneous transhepatic techniques. In recent years, nonsurgical approaches have largely replaced reoperation. Among these, the endoscopic approach is currently the preferred initial treatment for patients who undergo duct-to-duct biliary reconstruction. Previously, endoscopic management was achieved most optimally through balloon dilatation and single or multiple stents placement. Recently, there have been significant developments in endoscopic devices, such as novel biliary stents, as well as advances in endoscopic technologies, including deep enteroscopy, the rendezvous technique, magnetic compression anastomosis, and direct cholangioscopy. These developments have resulted in almost all patients being managed by the endoscopic approach. Multiple recent publications suggest superior long-term results, with overall success rates ranging from 58% to 75%. This article summarizes the advances in endoscopic management of patients with biliary complications after LDLT.

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.