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Abstract: Purpose: We evaluated the clinical utility of peritransplant in vitro assays of immune cell function in adult living donor liver transplant (LDLT) recipients. Methods: In particular, we measured immune cell function, using the ImmuKnow assay, in 107 adult LDLT recipients and 200 potential living liver donors (control group) admitted to our center between July 2008 and January 2009. Results: In the control group, the mean proportion of T-helper/inducer cells was 36.8% ± 8.2%. The degree of immune response was strong in 12%, moderate in 77%, and low in 11%. In the study group, the degree of immune response within the first month was strong in 4.6%, moderate in 38.2%, and low in 57.2%, thus significantly lower than in the control group (P < .001). ImmuKnow results and tacrolimus levels did not show a significant correlation (r 2 = .002, P = .392). Although six patients showed biopsy-proven acute cellular rejection, none showed a strong immune response. Patients with overt infection showed a lower immune response. Conclusions: These results indicate that peritransplant assessment of immune response using the ImmuKnow assay does not reliably predict the occurrence of acute rejection. Additional studies are necessary to accurately assess the clinical utility of immune response monitoring. [Copyright &y& Elsevier]

Background Abnormal serum lipid profiles are an issue in chronic kidney disease (CKD), but the clinical ramifications of dyslipidemia in live kidney donors are unclear. Thus, we explored the relationship between serum lipids and residual renal function in living donors post-nephrectomy. Methods Charts of living donors who underwent nephrectomy between January 2010 and March 2013 were reviewed, targeting those with 6-month follow-up examinations at minimum. Altogether, 282 donors were studied, examining total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels assayed before donation by standard techniques. Median follow-up time was 14 months. The relationship between postoperative renal function and allograft biopsy results was assessed. Recursive partitioning was applied to identify optimal cut-off points for each parameter. Results Median (interquartile range) serum TC, TG, LDL, and HDL levels were 183 (161–205) mg/dL, 86 (63–131) mg/dL, 108 (92–128) mg/dL, and 53 (44–62) mg/dL, respectively. The glomerular filtration rate at last follow-up was associated with TC (r = −0.187; P = .002) and LDL (r = −0.172; P = .005) levels, but showed no correlation with TG and HDL. Root nodes of TC and LDL determinations in recursive partitioning were 170.5 mg/dL and 80.5 mg/dL, respectively, serving as thresholds for further evaluation. On logistic regression analysis, the likelihood of CKD (glomerular filtration rate < 60 mL/min/1.73 m 2 ) at last follow-up was greater in donors with elevated TC and LDL levels (odds ratio = 1.96 and 3.33; P = .021 and .029, respectively). Conclusion Kidney donors with serum TC and LDL elevations require close observation, given their demonstrable predisposition to CKD after donation. [ABSTRACT FROM AUTHOR]

We devised a hepatic vein clamping method to assess the amount of hepatic venous congestion (HVC) before liver transection. From February 2003 to May 2003, this method was applied to 5 of 58 living donor livers especially to assess donor safety. The left portal vein and proper hepatic artery as well as the middle hepatic vein (MHV)–left hepatic vein (LHV) trunk were clamped simultaneously to assess the HVC in the remnant right lobe before performing extended left lobectomy. As three donors demonstrated the extent of the HVC equivalent to about 40% of the right lobe volume (RLV), their operations proceeded according to the preoperative plan. The territory of HVC after liver transection was the same as that observed with direct clamping of the hepatic vein. However, one donor showed massive HVC more than 50% of RLV and the operative plan was adjusted to harvest only the left lobe without the MHV trunk for donor safety. To assess the HVC in the remnant left lobe, the isolated LHV trunk was occluded after clamping the donor''s proper hepatic artery. The whole left lobe except for a small area at the anterior portion of the medial segment became discolored on LHV clamping: the opposite demarcation appeared on MHV clamping. The amount of HVC was so small that we harvested the right lobe with the MHV trunk. All donors and recipients recovered uneventfully. We believe that this direct clamping method makes the assessment of HVC feasible before parenchymal transection of a donor liver. [Copyright &y& Elsevier]

Abstract: Background: After > 2000 adult living donor liver transplants (LDLTs), we observed minimization of the complication rate using case-by-case modification of venous outflow reconstruction in right liver graft (RLG), standardization seeking intend to provide a hemodynamic- based, regeneration-compliant hepatic outflow reconstruction. Methods: We retrospectively examined 100 consecutive adult LDLT using modified RLG before and after application of RLG standardization to compare the 6-month incidences of vascular outflow complications. Result: The right hepatic vein stenting rate for first 6 months was 5% in the customized group and 1% in the standardized group (P = .212). The middle hepatic vein stenting rate for first 6 months was 9% in the customized group and 4% in the standardized group (P = .373). The inferior right hepatic vein stenting rate for first 6 months was 12.8% in the customized group and 7.1% in the standardized group (P = .472). The overall 6-month patient survival rate was 94% in the customized group and 95% in the standardized group (P = .867). The overall incidence of significant RLG venous outflow complications was 19% in the customized group and 8% in the standardized group (P = .023). Conclusion: Standardization as a universal graft model seemed to be more effective and feasible than conventional graft customization requiring individualized case-by-case modification. [Copyright &y& Elsevier]

Background Acute graft-vs-host disease (GVHD) is a rare but life-threatening complication of orthotopic liver transplantation (OLT). We present 6 cases of GVHD after OLT. Methods Among our 4294 OLT recipients, we identified 6 patients (0.14%) who were diagnosed with GVHD. Their medical records were reviewed retrospectively. Results Liver graft types included deceased donor whole liver graft (n = 3) and right liver graft from son (n = 3). Mean recipient and donor ages were 57.2 ± 6.6 years and 32.7 ± 10.8 years, respectively. Onset of GVHD symptoms occurred 14 to 32 days after OLT, and initial symptoms were skin rash (n = 5) and fever (n = 1). GVHD was pathologically confirmed by skin or rectal biopsy. Chimerism of donor lymphocytes was identified in all 3 patients who underwent the short tandem repeat polymerase chain reaction assay. Attempts were made to treat the GVHD in all 6 patients by corticosteroids with or without low-dose calcineurin inhibitor, but we had to stop early or reduce these agents due to aggravation of pancytopenia and septic complications. Ultimately, 5 patients died 6 to 106 days after the onset of GVHD, and only 1 patient recovered. This surviving patient was diagnosed earlier and had been administered the recommended dosage of corticosteroid for a longer period with aggressive infection prophylaxis compared to the other cases. Conclusions Because of very poor outcomes of GVHD after OLT, early diagnosis and vigorous treatment should be emphasized, although no effective treatment modality has been established yet. We strongly suggest performing aggressive infection prophylaxis during GVHD treatment. [ABSTRACT FROM AUTHOR]

Background Donor safety is the most important aspect in living-donor liver transplantation (LDLT). Gilbert syndrome is an autosomal recessive condition that is a common cause of isolated unconjugated hyperbilirubinemia, and its prevalence is not negligibly low in the general population. This study intended to assess donor safety and recipient liver function after LDLT with the use of right liver grafts from living donors with Gilbert syndrome. Methods Among 2,140 right liver transplantations performed from January 2002 to December 20113 at our institution, we identified 12 living donors (0.6%) who showed a preoperative serum total bilirubin level of ≥2 mg/dL. These donors were clinically diagnosed with Gilbert syndrome. The clinical outcomes of these donors and their recipients were analyzed retrospectively. Results The mean donor age was 24.6 ± 7.1 years, and 11 donors were male. All subjects met the preoperative evaluation conditions for right liver donation except for the level of unconjugated hyperbilirubinemia. The mean serum total bilirubin level of the donors was 2.23 ± 0.20 mg/dL before and 1.79 ± 0.61 mg/dL 1 year after right liver donation. The preoperative donor direct bilirubin level was 0.43 ± 0.19 mg/dL. The preoperative indocyanine green retention rate at 15 minutes was 8.2 ± 2.8%. All donors and recipients recovered uneventfully and were alive at the time of writing. The recipient serum total bilirubin level was 1.29 ± 0.47 mg/dL 1 year after LDLT. Conclusions We suggest that LDLT with living donors with Gilbert syndrome can be safely performed, but that a meticulous preoperative evaluation is vital to maximize donor safety. [ABSTRACT FROM AUTHOR]

Purpose This study reviewed the past and present status of liver transplantation (LT) and outlooks for the future of LT in Korea. Method The first LT in Korea was successfully performed using a deceased donor graft in 1988. Pediatric and adult living donor liver transplantations (LDLTs) were initiated in 1994 and 1997, respectively. From 1988 to 2013, 10,581 LTs were performed at 40 centers, whereas LDLT accounted for 76.5% of all LTs. Results In the early 1990s, the deceased organ donation rate was less than 1.5 per million population (PMP) per year, but it increased to 5 PMP beginning in 2008. Despite the increasing number of deceased donor liver transplantations (DDLTs), high prevalence of hepatitis B virus (HBV)-induced cirrhosis and hepatocellular carcinoma (HCC) has provoked persistent performance of adult LDLT with technical advancement including middle hepatic vein (MHV) reconstruction of right lobe graft and dual graft LDLT with 1 nationwide donor mortality. Conclusion The number of LTs in Korea in 2010 was 23.2 PMP (1042 LTs/45 million population), lower than 23.5 PMP of Spain, but higher than 20 PMP of the United States. However, future LT numbers may decrease because of lowering the HBV carrier rate (neonatal HBV universal vaccination began in 1992), new potent anti-HBV agents, and lowest birth rate (1.22 children per family) with a decrease of potential live donors. [ABSTRACT FROM AUTHOR]

Introduction Optimization of kidney donor selection is critical to ensure recovery of the donor. The goal of this study was to determine the influence of metabolic syndrome on renal histology and perioperative renal function in living kidney donors. Patients and Methods Between January 2010 and March 2013, a total of 363 living kidney donors who underwent donor nephrectomy at our institution were enrolled. Metabolic syndrome was diagnosed in patients according to the National Cholesterol Education Program's Adult Treatment Panel III, and renal histology of implantation biopsy specimens and perioperative renal function were compared in participants with or without metabolic syndrome. Using multivariate regression analysis, the goal was to identify which component of metabolic syndrome induces chronic histologic changes and delayed renal function recovery. Results We identified 30 donors (8.45%) with metabolic syndrome. Donors with metabolic syndrome were older (48.4 ± 9.2 years vs 39.7 ± 11.4 years; P < .001) and more likely to have chronic histologic changes (36.8% vs 9.7%; P = .001) than subjects without metabolic syndrome. Results of the multivariate regression analysis indicated that obesity, hyperglycemia, and hypertriglyceridemia were independently associated with chronic histologic changes. Perioperative renal function was correlated with the presence of metabolic syndrome rather than with chronic histologic changes, and patients with metabolic syndrome were more likely to experience delayed renal function recovery. Linear regression models found that the sum of the metabolic components correlated with renal function 6 months postoperatively, but among all risk factors, only obesity was significantly associated with the occurrence of delayed renal function recovery (odds ratio, 2.67; P = .001). Conclusions Although metabolic syndrome in living kidney donors is characterized by chronic histologic changes, perioperative renal function is affected by the syndrome itself rather than by the histologic changes. Obesity is the most important metabolic factor for predicting delayed renal function recovery in living kidney donors, providing an important clinical indicator of postoperative renal function in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: De novo malignancy is not uncommon after liver transplantation (OLT). We have compared the incidence of novo malignancy following OLT with those among the general Korean population. Methods: Between January 1998 and December 2008, 1952 adult OLT were performed, including 1714 living donor and 238 deceased donor grafts whose medical records were retrospectively reviewed. Results: Among the 1952 patients, 44 (2.3%) showed de novo malignancies after a mean posttransplant period of 41 months. Among the 14 types of malignancy the most frequent was stomach cancer (n = 11; 25.0%), colorectal cancer (n = 9; 20.5%), breast cancer (n = 4; 9.1%), and thyroid cancer (n = 3; 6.8%). These patients underwent aggressive treatment, including surgery, chemotherapy, and radiotherapy, except for one patient with an aggressive primary liver cancer. Over a mean follow-up of 45 months after diagnosis of de novo malignancy, 13 patients (29.5%) died; the overall 3-year patient survival rate was 67.5%. The relative risk of malignancy following OLT was 7.7-fold higher in men and 7.3-fold higher in women than the Korean general population. Conclusions: OLT recipients must be checked periodically for de novo malignancy throughout their lives, especially for cancers common in the general population. [Copyright &y& Elsevier]

Abstract: Purpose: This study analyzed the effects of a recent increase in deceased donors on the pattern of adult liver transplantation (OLT) in a high-volume center in Korea. Methods: OLT patterns relative to pretransplant recipient status were analyzed for 112 deceased donor LTs (DDLT) and 743 living donor OLT (LDLT) in a single center as compared to nationwide Korean data over 3 years from 2006 to 2008. Results: During the study period, the annual proportion of institutional urgent OLT was relatively invariable (20% to 25.2%), but the annual proportion of DDLTs to all OLT increased from 8.9% to 19.9%, as did the annual rate of DDLTs among those undergoing urgent OLT, from 18.6% to 65.8%, with a reciprocal decrease in the proportion of urgent LDLTs. Korean nationwide data also showed a noticeable increase in deceased liver graft allocation for urgency from 39.8% to 62.2% over the same time period. Conclusion: An increase in deceased donors up to 5 per million enabled an increase in urgent adult DDLTs, alleviating the need for urgent adult LDLTs in Korea. [Copyright &y& Elsevier]

Abstract: Purpose: Following implantation into adult recipients, living donor liver grafts usually undergo liver regeneration. This regeneration process may provoke the growth of occult hepatocellular carcinoma (HCC) cells in the recipient body. To assess the risk of HCC recurrence, we analyzed the influence of graft–recipient weight ratio (GRWR). Methods: The 181 recipients with HCC within the University of California at San Francisco (UCSF) criteria were divided into four groups according to GRWR: low GRWR (<0.8; n = 30), mid GRWR (0.8–1.0; n = 65), high GRWR (>1.0; n = 64), and whole liver graft group (>1.5; n = 22). Results: There were no differences in overall patient survival (P = .105) and recurrence-free survival (P = .406) among these four groups. GRWR <0.8 was not a significant risk factor for HCC recurrence. Similar outcomes were obtained in HCC patients who met the Milan criteria (n = 170). Conclusions: We think that small living donor liver graft and subsequent liver regeneration do not increase the risk of posttransplant HCC recurrence when HCC is within the Milan or UCSF criteria. [Copyright &y& Elsevier]

Abstract: Objective: The cosmetic aspects of abdominal skin incisions are a matter of concern for both live liver donors and surgeons. We performed a prospective comparative study on the use of minilaparotomy to perform right liver graft harvests with and without hand-assisted laparoscopic surgery (HALS). Methods: Young donors were indicated for surgery using minilaparotomy with or without HALS. In the non-HALS group (n = 20), a 10–12-cm-long right subcostal incision was used for right liver graft harvest. In the HALS group (n = 20), an 8-cm-sized right subcostal incision was used for hand assistance and 3 laparoscopic holes made for manipulation. The retrohepatic inferior vena cava (IVC) was initially laparoscopically dissected while using air inflation. The skin incision was extended to 10–12 cm, and then hilar dissection and hepatic transection were performed through the skin incision. Results: In all 40 donors in the study cohort, safe uneventful harvesting of the right liver grafts was successfully achieved through the minilaparotomy incisions. The HALS group required an additional 30 minutes for laparoscopic preparation and dissection compared with the non-HALS group. HALS facilitated retrohepatic IVC dissection, and the remaining part of the surgery was the same as that for minimal-incision surgery. The minimal skin incision for the delivery of the liver from the abdomen was an average 10 cm for grafts <500 g and 12 cm for grafts ≥700 g. Compared with the patient profiles, there were no differences regarding donor age, body mass index, graft weight, intraoperative blood loss, postoperative increase in peak liver enzymes, total hospital stay, and incidence of postoperative complications. Conclusions: HALS facilitates the performance of donor hepatectomy with the use of a minimal incision, which probably allows for a wider selection of living donors. [Copyright &y& Elsevier]

Abstract: Although hepatitis A virus (HAV) infection is usually self-limited, it may induce fulminant hepatitis. We present an unusual case of a 40-year-old, otherwise healthy man with intractable recurrent HAV infection requiring retransplantation after primary liver transplantation for HAV-associated fulminant liver failure. After the first living-donor liver transplantation, allograft function recovered uneventfully; however, beginning at 35 days, his serum total bilirubin concentration increased, reaching 40 mg/dL, with a slight increase in liver enzymes. Detection of genomic HAV RNA in serum at the time of graft dysfunction led to a diagnosis of recurrent HAV infection. Fifty-one days after the first transplant, he underwent a deceased donor retransplantation. His allograft function recovered; the patient was discharged from the hospital. Sixty-five days later, however, he was readmitted for colitis-like symptoms and was again treated for acute rejection, but died owing to overwhelming sepsis and persistence of HAV infection. These findings indicate that patients who undergo liver transplantation for HAV-associated liver disease may be at risk of HAV reinfection, particularly if they require anti-rejection therapy. Routine measurements of anti-HAV immunoglobulin M and HAV RNA during the early posttransplant period in HAV-associated liver transplant recipients may differentiate reinfection from an acute cellular rejection episode. [Copyright &y& Elsevier]