BACKGROUND: Graft cholangiopathy has been recognized as a significant cause of morbidity, graft loss, and even mortality in patients after orthotopic liver transplantation. The aim of this review is to analyze the etiology, pathogenesis, diagnosis and therapeutic strategies of graft cholangiopathy after liver transplantation.
DATA SOURCE: A PubMed database search was performed to identify articles relevant to liver transplantation, biliary complications and cholangiopathy.
RESULTS: Several risk factors for graft cholangiopathy after liver transplantation have been identified, including ischemia/reperfusion injury, cytomegalovirus infection, immunological injury and bile salt toxicity. A number of strategies have been attempted to prevent the development of graft cholangiopathy, but their efficacy needs to be evaluated in large clinical studies. Non-surgical approaches may offer good results in patients with extrahepatic lesions. For most patients with complex hilar and intrahepatic biliary abnormalities, however, surgical repair or re-transplantation may be required.
CONCLUSIONS: The pathogenesis of graft cholangiopathy after liver transplantation is multifactorial. In the future, more efforts should be devoted to the development of more effective preventative and therapeutic strategies against graft cholangiopathy.

BACKGROUND: The low graft-to-recipient weight ratio (GRWR) in adult-to-adult living donor liver transplantation (LDLT) is one of the major risk factors affecting graft survival. The goal of this study was to evaluate whether the lower limit of the GRWR can be safely reduced without portal pressure modulation in right-lobe LDLT.
METHODS: From 2005 to 2011, 317 consecutive patients from a single institute underwent LDLT with right-lobe grafts without portal pressure modulation. Of these, 23 had a GRWR of less than 0.7% (group A), 27 had a GRWR of ≥0.7%, <0.8% (group B), and 267 had a GRWR of more than and equal to 0.8% (group C). Medical records, including recipient, donor, operation factors, laboratory findings and complications were reviewed retrospectively.
RESULTS: The baseline demographics showed low model for end-stage liver disease score (mean 16.3±8.9) and high percentage of hepatocellular carcinoma (231 patients, 72.9%). Three groups by GRWR demonstrated similar characteristics except recipient body mass index and donor gender. For small-for-size syndrome, there were 3 (13.0%) in group A, 1 (3.7%) in group B, and 2 patients (0.7%) in group C (P<0.001). Hepatic artery thrombosis was more frequently observed in group A than in groups B and C (8.7% vs 3.7% vs 1.9%, P=0.047). However, among the three groups, graft survival rates at 1 year (100% vs 96.3% vs 93.6%) and 3 years (91.7% vs 73.2% vs 88.1%) were not different (P=0.539). In laboratory measurements, there was no group difference in total bilirubin and albumin. However, prothrombin time was longer in group A within postoperative 1 week and platelet count was lower in groups A and B within postoperative 1 month.
CONCLUSION: A GRWR lower to 0.7% is safe and does not need to modulate portal pressure in adult-to-adult LDLT using the right-lobe in favorable conditions including low model for end-stage liver disease score.

BACKGROUND: Platelet count reduction in living donors after graft harvesting is very common. The mechanisms and the subsequent adverse consequences are not clear. The present study was to explore the mechanisms and the consequences of platelet count reduction in living donors.
METHODS: We collected data from 231 living liver donor patients who donated at our transplant center between July 2002 and August 2009. Baseline and post-operative platelet counts were collected and analyzed. Multivariate logistic regression analysis was used to compare the risk factors for the persistent decrease in platelet counts. Complications and other post-operative recovery were compared between the donors.
RESULTS: Platelet count decreased differently at each of the follow-up intervals, and the average reduction from baseline evaluation to year 3 was 18.2%. A concomitant decrease in white blood cells was observed with platelet count reduction. All of the splenic volumes at the post-operative follow-up time points were significantly higher than those at baseline (P<0.01). Multivariate logistic regression analysis indicated that the graft-to-donor weight ratio was a risk factor for low post-operative platelet counts in living donors at the three follow-up time points: one week (P=0.047), one month (P=0.034), and three months (P=0.047). At the one week follow-up time, 77 donor platelet counts were higher (group 1) and 151 donor platelet counts were lower (group 2) than baseline levels. Two hemorrhage events (1.3%) were observed in group 2, while three hemorrhage events (3.9%) were observed in group 1 (P=0.211). The overall complication rate was comparable between the two groups (P=0.972).
CONCLUSION: An increase in harvesting graft may decrease platelet counts, but this reduction does not produce short- or long-term damage in living liver donors.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA (miRNA) profiles in ACLF patients may provide new clues to the pathogenesis and management of this syndrome.
METHODS: Genome-wide microarray was performed to compare the different miRNA expression profiles in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF patient and an HBV asymptomatic carrier (AsC). The case-control miRNA profiles were compared and confirmed by quantitative reverse transcription-polymerase chain reaction in 104 ACLF patients and 96 AsCs. A combined computational prediction algorithm was used to predict the potential target genes.
RESULTS: Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and 8.63-fold in ACLF patients compared with that in AsCs, respectively (P<0.001). CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes of hsa-let-7a.
CONCLUSIONS: Our results showed that there is a close relationship between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR-16 and hsa-let-7a may contribute to the development of ACLF.

BACKGROUND: Ischemic preconditioning (IPC) has been shown to decrease liver injury and to increase hepatic microvascular perfusion after liver ischemia reperfusion. This study aimed to evaluate the effects of IPC on hemodynamics of the portal venous system.
METHODS: Thirty-two rats were randomized into two groups: IPC group and control group. The rats of the IPC group underwent IPC by 10 minutes of liver ischemia followed by 10 minutes of reperfusion before liver ischemia, and the rats of the control group were subjected to 60 minutes of partial liver ischemia. Non-ischemic lobes were resected immediately after reperfusion. The animals were studied at 4 hours and 12 hours after reperfusion. Mean arterial pressure, heart rate, portal vein flow and pressure were analyzed. Blood was collected for the determination of the levels of aspartate aminotransferase, alanine aminotransferase, calcium, lactate, pH, bicarbonate, and base excess.
RESULTS: IPC increased the mean portal vein flow at 4 hours and 12 hours after reperfusion. IPC recovered 78% of the mean portal vein flow at 12 hours after reperfusion. IPC decreased the levels of aspartate aminotransferase, alanine aminotransferase and lactate, and increased the levels of ionized calcium, bicarbonate and base excess at 12 hours after reperfusion.
CONCLUSIONS: This study demonstrated that IPC increases portal vein flow and enhances hepatoprotective effects in liver ischemia reperfusion. The better recovery of portal vein flow after IPC may be correlated with the lower levels of transaminases and with the better metabolic profile.

BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finger and BTB domain-containing protein 20 (ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice.
METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2 (ZHX2), ZBTB20, alpha-fetoprotein (AFP) and glypican 3 (GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function.
RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3.
CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.

BACKGROUND: The high recurrence rate of hepatolithiasis and the high operative risk of right posterior, caudate or multiple lobe hepatectomy are the unsettled problems in hepatobiliary surgery. The present study was to investigate the efficacy of chemical hepatectomy performed via applying sequential embolization of the branches of the bile duct and portal vein to the targeted hepatic lobe.
METHODS: The bile duct and portal vein branches of the median hepatic lobe of rats were treated with: 1) bile duct embolization followed by portal vein ligation (BDE+PVL) and 2) portal vein ligation followed by bile duct embolization (PVL+BDE). The efficacy of chemical hepatectomy in BDE+PVL and PVL+BDE groups was compared with that of sole BDE by histology and Western blotting analysis of collagen I expression.
RESULTS: After six weeks of the chemical hepatectomy, rats in the BDE group showed hepatocyte damages, fibrosis and "self-cut" only in the periphery of the embolized lobe. In contrast, rats in the PVL+BDE and BDE+PVL groups exhibited complete necrosis of hepatocytes and replacement with proliferative ductules and collagen fibers, leading to complete fibrosis and "self-cut" phenomenon in the whole targeted lobe. Collagen I expression in the PVL+BDE group was slightly higher than that in the BDE+PVL group; however, no statistically significant difference was noted.
CONCLUSION: The sequential embolization of the bile duct and portal vein branches to the targeted hepatic lobe may be a feasible and effective approach to acheive the ideal effect of chemical hepatectomy in a short period of time.

BACKGROUND: The development of direct peroral cholangio¬scopy (DPOC) using an ultraslim endoscope simplifies biliary cannulation. The conventional techniques are cumbersome to perform and require advanced skills. The recent introduction of the guidewires and balloons has improved the therapeutic outcomes. Here we describe an effective and easier method for performing DPOC using an ultraslim upper endoscope.
METHODS: Indications for DPOC were the presence of stones on follow-up of patients who had previously undergone complete sphincteroplasty, including endoscopic sphincterotomy or endoscopic papillary large balloon dilatation. Fifteen patients underwent DPOC. An ultraslim endoscope was inserted perorally and was advanced into the major papilla. The ampulla of Vater was visualized by retroflexing the endoscope in the distal second portion of the duodenum, and then DPOC was performed using a wire-guided cannulation technique with an anchored intraductal balloon catheter.
RESULTS: One patient failed in the treatment due to looping of the endoscope in the fornix of the stomach. Fourteen (93.3%) were successfully treated with our modified DPOC technique. Only one patient (6.7%) experienced an adverse event (pancreatitis) who responded well to conservative management. Residual stones of the common bile duct were completely removed in 3 patients.
CONCLUSION: The modified method of DPOC is simple, safe and easy to access the bile duct.

BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor (PPAR)α, PPARγ, liver X receptor α (LXRα), farnesoid X receptor (FXR), ABCG5, ABCG8, and 7α-hydroxylase (CYP7A1) which are directly involved in the cholesterol saturation index in bile.
METHODS: Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARα and PPARγ was measured by Western blotting analysis, and the mRNA expression of LXRα, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR.
RESULTS: In cultured Hep3B cells, pravastatin activated PPARα and PPARγ protein expression, induced stronger expression of PPARγ than that of PPARα, increased LXRα mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRα, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARγ and LXRα pathways, together or independently.
CONCLUSION: Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of  FXR, LXRα and CYP7A1 in human hepatocytes.

BACKGROUND: There are few data on blood group (BG) types and types of pancreatic cancers. The aims of this study were to study BG types and BG-antigens in pancreatic intraductal papillary mucinous neoplasms (IPMNs).
METHODS: BG type and tumor BG-antigen (glycoprotein) expression (studied by immunohistochemistry on tissue microarrays) were analyzed with regard to characteristics of 101 surgically resected pancreatic IPMNs.
RESULTS: Non-O BG type predicted invasive carcinoma independently from high serum CA19-9 and male gender. BG type A was observed more frequently in women than in men. Chronic pancreatitis was more frequently seen in patients with BG type B or AB. Aberrant tumor expression (with regard to BG type) of loss of A antigen expression type occurred in 15.0% of IPMNs and of loss of B antigen expression type in 62.5% of IPMNs. Intraneoplasm BG-antigen expression was not related to dysplasia grade or invasion.
CONCLUSION: The results of the study suggest that in pancreatic IPMN, non-O BG type predicted invasive carcinoma, whereas for intratumor BG-antigen expression no specific patterns were detected with regard to the progression of glandular epithelial dysplasia or invasion.

BACKGROUND: CD74 is known as a type II transmembrane glycoprotein that is associated with the major histocompatibility complex class II α and β chains. Recent studies have demonstrated that the expression of CD74 is also linked to some forms of tumors. The present study was to assess the effect of CD74 expression on the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC).
METHODS: Forty-six patients who had received a curative resection of primary PDAC and postoperative chemotherapy were included in this study. Immunohistochemical staining was conducted of CD74 on paraffin-embedded tumor sample slices. The patients were grouped according to CD74 staining: CD74 (-): CD74 positive tumor cells <25%; and CD74 (+): CD74 positive tumor cells ≥25%. The correlation of CD74 expression level with clinicopathological features and cumulative survival rate was calculated.
RESULTS: The numbers of CD74 (+) and (-) patients were 32 and 14, respectively. CD74 (+) patients showed a high rate of perineural invasion (P=0.007). The 3- and 5-year cumulative survival rates of CD74 (-) patients were significantly higher than those of CD74 (+) patients (62% and 41% vs 9% and 0%, P=0.000). Multivariate analysis showed that CD74 expression and lymphatic permeation were the independent prognostic indicators.
CONCLUSIONS: The overexpression of CD74 is a key factor associated with perineural invasion. Lower-stage (I and II) PDAC patients with CD74 overexpression have a poor prognosis even if they receive a curative resection. CD74 can be used as a prognostic indicator for resectable PDAC.

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer.
METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C (VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry.
RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors.
CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

Loco-regional recurrence after potentially curative resection remains a problem in hilar cholangiocarcinoma. Hilar dissection risks local spillage of tumor cells leading to suboptimal disease free survival. We have developed a new technique of radical resection for hilar cholangiocarcinoma based on the distinctive anatomy of the Rex recess of the liver, which has been assessed in two patients with locally advanced hilar cholangiocarcinoma. This technique included a right hepatectomy with en-bloc resection of the hepatoduodenal ligament and portal venous reconstruction to the left portal vein at the Rex recess. Both patients had R0 resection and have been disease-free for 26 and 38 months, respectively.

Domino liver transplantation has been accepted as a safe procedure to further expand the organ donor pool. The most important technical challenge of the procedure resides in restoring a proper hepatic venous allograft outflow in the familial amyloidotic polyneuropathy-liver recipient. To overcome this issue, combined techniques were used to perform an innovative outflow reconstruction. A domino liver transplantation was successfully performed with reconstruction of complex venous outflow. The inferior vena cava sparing hepatectomy technique in the familial amyloidotic polyneuropathy-donor was used to cut the hepatic vein to the liver parenchyma. To overcome this issue the venous outflow tract was reconstructed using a longitudinally opened iliac vein graft from a post-mortem donor to create a new outflow tract using a diamond patch between the right and middle/left hepatic veins.

Under ultrasound guidance, a blunt suture needle was inserted around the Glissonian pedicle and then sutured. This technique significantly reduced the blood loss and facilitated the procedure of partial hepatectomy. We applied this technique in 182 patients who needed partial hepatectomy. We concluded that this method is simple and easy to occlude the vascular inflow and outflow, and allows an accurate delineation of the anatomic zone and therefore, simplifies the procedure of partial hepatectomy.

BACKGROUND: In order to overcome ABO blood group incompatibility, paired donor interchange has been practised in living donor liver transplantation. Liver transplantations using grafts donated by Samaritan living donors have been performed in Europe, North America, South Korea, and Hong Kong. Such practice is clearly on strong biological grounds although social and psychological implications could be far-reaching. Local experience has been satisfactory but is still limited. As few centers have this arrangement, its safety and viability are still being assessed under a clinical trial setting.
METHODS: Here we report a donor interchange involving an ABO-compatible pair with a universal donor and an ABO-incompatible pair with a universal recipient. This matching was not only a variation but also an extension of the donor interchange scheme.
RESULTS: The four operations (two donor hepatectomies and two recipient operations) were successful. All the two donors and the two recipients recovered well. Such donor interchange further supports the altruistic principle of organ donation in contrast to exchange for a gain.
CONCLUSIONS: Samaritan donor interchange certainly taxes further the ethical challenge of donor interchange. Although this practice has obvious biological advantages, such advantages have to be weighed against the potential increase in potential psychological risks to the subjects in the interchange. Further ethical and clinical evaluations of local and overseas experiences of donor interchange should guide future clinical practice in utilizing this potential organ source for transplantation.