BACKGROUND: Minimally invasive spleen-preserving distal pancreatectomy (SPDP) can be performed with either splenic vessel preservation (SVP) or resection [Warshaw procedure (WP)]. The aim of this study was to evaluate the postoperative clinical outcomes of patients undergoing both methods.
DATA SOURCES: Database search of PubMed, Embase, Scopus, Cochrane, and Google Scholar was performed (2000-2014); key bibliographies were reviewed. Qualified studies comparing patients undergoing SPDP with either SVP or WP, and assessing postoperative complications were included. Calculated pooled risk ratio (RR) with the corresponding 95% confidence interval (CI) by random effects methods were used in the meta-analyses.
RESULTS: The search yielded 215 studies, of which only 14 observational studies met our selection criteria. The studies included 943 patients in total; 652 (69%) underwent SVP and 291 (31%) underwent WP. Overall, there was a lower incidence of splenic infarction (RR=0.17; 95% CI: 0.09-0.33; P<0.001), gastric varices (RR=0.16; 95% CI: 0.05-0.51; P=0.002), and intra/postoperative splenectomy (RR=0.20; 95% CI: 0.08-0.49; P<0.001) in the SVP group. There was no difference in incidence of pancreatic fistula (WP vs SVP, 23.6% vs 22.9%; P=0.37), length of hospital stay, operative time or blood loss. There was moderate cross-study heterogeneity.
CONCLUSIONS: SVP is a safe, efficient and feasible technique that may be used to preserve the spleen. WP may be more suitable for large tumors close to the splenic hilum or those associated with splenomegaly. Randomized clinical trials are justified to examine the long-term benefits of SVP-SPDP.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is increasingly recognized as a distinct clinical entity and is associated with a high short-term mortality. The most common cause of ACLF is chronic hepatitis B worldwide. Currently, there is no standardized approach for the management of ACLF and the efficacy and safety of therapeutic modalities are uncertain.
DATA SOURCES: PubMed and Web of Science were searched for English-language articles. The search criteria focused on clinical trials and observational studies on the treatment of patients with HBV-related ACLF.
RESULTS: Therapeutic approaches for ACLF in patients with chronic hepatitis B included nucleos(t)ide analogues, artificial liver support systems, immune regulatory therapy, stem cell therapy and liver transplantation. All of these therapeutic approaches have shown the potential to improve liver function and increase patients' survival rate, but most of the studies were not randomized or controlled.
CONCLUSION: Substantial challenges for the treatment of HBV-related ACLF remain and further basic research and randomized controlled clinical trials are needed.

BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multi-step and complex process. Early diagnosis and effective treatments are of utmost importance. This review summarized the recent studies of oncofetal glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC.
DATA SOURCES: English-language reports published from June 2001 to September 2014 were searched from MEDLINE. The key words searched included: GPC-3, biomarker, target and HCC. The sensitivity, specificity, positive and negative predictive values were extracted, and the effect of GPC-3 targeted therapy on HCC was also evaluated.
RESULTS: GPC-3 plays a crucial role in HCC cell proliferation and metastasis. It mediates oncogenesis involving signaling pathways during hepatocyte malignant transformation. GPC-3 expression is increased in atypical hyperplasia and cancerous tissues. GPC-3 levels in HCC patients are related to HBV infection, TNM stage, periportal cancerous embolus, and extrahepatic metastasis. The diagnostic accuracy of the combination of serum GPC-3 and alpha-fetoprotein in HCC is up to 94.3%. Down-regulation of GPC-3 with specific siRNA or anti-GPC-3 antibody alters cell migration, metastasis and invasion behaviors. The nude mice xenograft tumor growth is inhibited by silencing GPC-3 gene transcription.
CONCLUSION: Oncofetal GPC-3 is a highly specific biomarker for the diagnosis of HCC and a promising target molecule for HCC gene therapy.

BACKGROUND: With improvements in survival, liver transplant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of rejection. 
METHOD: We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cellular rejection (ACR) and various clinical factors. 
RESULTS: Multivariate analysis showed that older age (P=0.04, OR=0.982), chronic hepatitis B virus infection (P=0.005, OR= 0.574), living donor liver transplantation (P=0.02, OR=0.648) and use of interleukin-2 receptor antagonist on induction (P<0.001, OR=0.401) were associated with fewer ACRs. Patients with fulminant liver failure (P=0.004, OR=4.05) were more likely to develop moderate to severe grade ACR. 
CONCLUSIONS: Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver transplantation and use of interleukin-2 receptor antagonist on induction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

BACKGROUND: Once-daily extended-release tacrolimus (Tac-OD) has been introduced as a useful therapeutic option to increase patient adherence to immunosuppressive therapy. This study aimed to evaluate the safety, efficacy and immunosuppressant adherence of conversion from twice-daily tacrolimus (Tac-BID) to Tac-OD in stable adult living donor liver transplant (LDLT) recipients in a single institution. 
METHODS: Between February and May 2013, Tac-BID was converted to Tac-OD in recipients followed up for at least 12 months after transplantation and without previous rejection episodes. The switching policy was based on a dose ratio of 1:1 with dose adjustment target trough levels at 3-5 ng/mL. Tacrolimus trough levels, laboratory parameters, metabolic disorders, and adverse events were assessed. 
RESULTS: A total of 229 patients were enrolled in the study. The median age at conversion was 53 years (range 31-73). The median transplant duration was 35.3 months (range 12.0-95.4). During a median follow-up of 13.5 months after conversion, 9 patients returned to Tac-BID because of adverse events. No acute rejection episodes were observed. Of 214 patients still on Tac-OD at 12 months, 12 (5.6%) received a reduced dose and 95 (44.4%) required an increased dose over baseline. Overall adherence was 82.2% at the end of follow-up. 
CONCLUSION: The conversion from Tac-BID to Tac-OD with similar target trough levels after conversion is safe and effective for long-term stable LDLT patients.

BACKGROUND: Portal vein thrombosis (PVT) is one of the main vascular complications after liver transplantation (LT), especially in pediatric patients with biliary atresia (BA). This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT. 
METHODS: One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultrasound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT (within 1 month following LT) and those without PVT. Receiver operating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT. 
RESULTS: Of the 128 transplant recipients, 41 (32.03%) had a hypoplastic portal vein (PV), 52 (40.63%) had hepatofugal PV flow and 40 (31.25%) had a high hepatic artery resistance index (HARI) of ≥1. Nine cases (7.03%) experienced early PVT. A PV diameter ≤4 mm (sensitivity 88.89%, specificity 72.27%), and a hepatofugal PV flow (sensitivity 77.78%, specificity 62.18%) with a high HARI ≥1 (sensitivity 77.78%, specificity 72.27%) were hepatic hemodynamic risk factors for early PVT. 
CONCLUSIONS: Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter (≤4 mm) and hepatofugal PV flow combined with high HARI (≥1) are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.

BACKGROUND: Steatotic liver grafts, although accepted, increase the risk of poor posttransplantation liver function. However, the growing demand for adequate donor organs has led to the increased use of so-called marginal grafts. Liver X receptor alpha (LXRα) is important in fatty acid metabolism and interrelated with the specific ischemia-reperfusion injury in fatty liver transplantation. This study aimed to investigate whether LXRα RNA interference (RNAi) could improve the organ function of liver transplant recipients. 
METHODS: Fifty Sprague-Dawley rats were fed with a high-fat diet and 56% alcohol. The livers of these animals had greater than 60% macrovesicular steatosis and were used as liver donors. The experimental donors were treated with 7×107 TU LXRα-RNAi-LV of a mixture injection and control donors with negative control-LV vector injection into the portal vein 72 hours before the operation. The effects of LXRα-RNAi-LV were assessed by serum aminotransferases, histology, immunostaining, and protein levels. The transcription of LXRα mRNA was assessed by reverse transcription-polymerase chain reaction. 
RESULTS: Compared with controls, LXRα RNAi inhibited the expression of LXRα at the mRNA (0.53±0.03 vs 0.94±0.02, P<0.05) and protein levels (0.51±0.08 vs 1.09±0.12, P<0.05). LXRα RNAi also decreased the expressions of sterol regulatory element-binding protein 1c (SREBP-1c) and CD36. LXRα RNAi consequently reduced fatty acid accumulation in hepatocytes. Compared with control animals, LXRα RNAi-treated group had lower serum alanine aminotransferase, aspartate aminotransferase, interleukin-1β, and tumor necrosis factor-alpha levels and milder pathologic damages. TUNEL analysis revealed a significant reduction of apoptosis in the livers of rats treated with LXRα-RNAi-LV, and overall survival as determined by the Kaplan-Meier method was improved among rats treated with LXRα-RNAi-LV (P<0.05). 
CONCLUSION: LXRα-RNAi-LV treatment significantly downregulated LXRα expression and improve steatotic liver graft function and recipient survival after a fatty liver transplantation in rats.

BACKGROUND: Liver resection is a major surgery requiring perioperative blood transfusion. Predicting the need for blood transfusion for patients undergoing liver resection is of great importance. The present study aimed to develop and validate a model for predicting transfusion requirement in HBV-related hepatocellular carcinoma patients undergoing liver resection. 
METHODS: A total of 1543 consecutive liver resections were included in the study. Randomly selected sample set of 1080 cases (70% of the study cohort) were used to develop a predictive score for transfusion requirement and the remaining 30% (n=463) was used to validate the score. Based on the preoperative and predictable intraoperative parameters, logistic regression was used to identify risk factors and to create an integer score for the prediction of transfusion requirement. 
RESULTS: Extrahepatic procedure, major liver resection, hemoglobin level and platelets count were identified as independent predictors for transfusion requirement by logistic regression analysis. A score system integrating these 4 factors was stratified into three groups which could predict the risk of transfusion, with a rate of 11.4%, 24.7% and 57.4% for low, moderate and high risk, respectively. The prediction model appeared accurate with good discriminatory abilities, generating an area under the receiver operating characteristic curve of 0.736 in the development set and 0.709 in the validation set. 
CONCLUSIONS: We have developed and validated an integer-based risk score to predict perioperative transfusion for patients undergoing liver resection in a high-volume surgical center. This score allows identifying patients at a high risk and may alter transfusion practices.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease. Hepatocellular carcinoma (HCC) is one of its complications. Although the pathophysiology is unclear, it is reasonable to expect that cryptogenic cirrhosis related HCC (cryptogenic HCC) behaves differently to other types of HCC. This study prospectively compared patients with cryptogenic HCC and those with HCC related to alcoholic cirrhosis. 
METHODS: A total of 150 consecutive patients with HCC (89 cryptogenic HCC and 61 alcohol related HCC) referred to our unit over a 23-month period were studied. Their demographic data, liver function, tumor characteristics and outcomes were compared. 
RESULTS: Alcohol related HCC was seen only in males. Compared with cryptogenic HCC, alcohol related HCC had significantly higher aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (1.7 vs 1.4, P=0.002), model for end-stage liver disease score (13 vs 11, P=0.018) and Child's score (7 vs 6, P=0.037). No significant difference was seen in platelet counts, serum sodium and AST to platelet ratio index. Single nodular tumors were more common in cryptogenic HCC, while diffuse type tumors and macroscopic vascular invasion were common in alcohol related HCC. In patients who could not be offered any treatment because of advanced tumors or poor liver function, alcohol related HCC had a significantly lower median survival (5.3 months) compared with cryptogenic HCC (9.3 months, P=0.034). 
CONCLUSIONS: Compared with cryptogenic HCC, alcohol related HCC had worse liver function and aggressive tumor morphology at presentation, and a higher proportion was untreatable. In patients who could not be treated, median survival was lower in patients with alcohol related HCC than in those with cryptogenic HCC.

BACKGROUND: Golgi protein 73 (GP73) is a promising biomarker of hepatocellular carcinoma (HCC). It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoembolization (TACE) have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients after TACE treatment, and the possible underlying mechanisms in the cell cultures. 
METHODS: Blood samples were collected from 72 HCC patients, before TACE, at day 1 and day 30 after TACE. GP73 levels were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents (5-FU and pirarubicin) on GP73 expression were tested in three HCC cell lines (HepG2, HCCLM3 and MHCC97H). 
RESULTS: The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure (P<0.05). There was no statistical difference between the two time points after TACE, nor correlation between GP73 levels and clinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, significantly increased GP73 expression in three cell lines. 
CONCLUSIONS: Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

BACKGROUND: Because of the diversity of the clinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. 
METHODS: Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis. 
RESULTS: The partial least squares discrimination analysis model (R²Y=0.991, Q²=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and specificity of 100%. Five groups of biomarkers were identified, including bile acids, free fatty acids, phosphatidylcholines, lysolecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy control group. The other biomarkers decreased in the AIH and PBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. 
CONCLUSIONS: The biomarkers identified revealed the pathophysiological changes in AILD and helped to discriminate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

BACKGROUND: Little information is available on the influence of comorbidities on outcomes of older patients with acute pancreatitis. This study aimed to investigate the influence of comorbidities on outcomes of older patients with acute pancreatitis using data from a national Japanese administrative database. 
METHODS: A total of 14 322 older patients (≥70 years) with acute pancreatitis were referred to 1090 hospitals between 2010 and 2012 in Japan. We collected patients' data from the administrative database to compare the in-hospital mortality and length of stay of older patients with acute pancreatitis. The patients were categorized into four groups according to comorbidity level using the Charlson Comorbidity Index (CCI): none (CCI score=0; n=6890); mild (1; n=3874); moderate (2; n=2192) and severe (≥3; n=1366). 
RESULTS: Multiple logistic and linear regression analyses revealed that severe comorbidity was significantly associated with higher in-hospital mortality and longer length of stay [odds ratio (OR)=2.26; 95% confidence interval (CI): 1.75-2.92, P<0.001 and coefficient 4.37 days; 95% CI: 2.89-5.85, P<0.001, respectively]. In addition, cardiovascular and renal diseases were the most significant comorbidities affecting outcomes of the older patients. ORs of cardiovascular and renal diseases for mortality were 1.44 (95% CI: 1.13-1.85, P=0.003) and 2.69 (95% CI: 1.88-3.85, P<0.001), respectively, and coefficients for length of stay were 3.01 days (95% CI: 1.34-4.67, P<0.001) and 3.72 days (95% CI: 1.01-6.42, P=0.007), respectively. 
CONCLUSION: This study demonstrated that comorbidities significantly influenced outcomes of older patients with acute pancreatitis and cardiovascular and renal comorbidities were significant factors affecting outcomes.

BACKGROUND: With the development of new surgical techniques, pancreaticoduodenectomy (PD) with portal vein or superior mesenteric vein (PV/SMV) resection has been used in the treatment of patients with borderline resectable pancreatic cancer. However, opinions of surgeons differ in the effectiveness of this surgical technique. This study aimed to investigate the effectiveness of this approach in patients with pancreatic cancer. 
METHODS: Follow-up visits and retrospective analysis were carried out of 208 patients with pancreatic cancer who had undergone PD (PD group) and PD combined with PV/SMV resection and reconstruction (PDVR group) from June 2009 to May 2013 at our center. Statistical analysis was performed to compare the clinical features, the difference of survival time and risk factors of venous invasion in pancreatic cancer. Factors relating to postoperative survival time of pancreatic cancer were also investigated. 
RESULTS: In the PDVR group, which consisted of 42 cases, the 1-, 2- and 3-year survival rates were 70%, 41% and 16%, respectively and the median survival time was 20.0 months. Among the 166 patients in the PD group, the 1-, 2- and 3-year survival rates were 80%, 52%, and 12%, respectively with the median survival time of 26.0 months. No significant difference in survival time and R0 resection ratio was found between the two groups. Lumbodorsal pain, tumor with pancreatic capsular invasion and bile duct infiltration were found to be independent risk factors for PV invasion in pancreatic cancer. In addition, non R0 resection, large tumor size (>2 cm) and poorly differentiated tumor were independent risk factors for survival time in post-PD. 
CONCLUSIONS: The tumor has a higher chance of venous invasion if preoperative imagings indicate that it juxtaposes with the vessel. Lumbodorsal pain is the chief complaint. Patients with pancreatic cancer associated with PV involvement should receive PDVR for R0 resection when preoperational assessment shows the chance for eradication.

BACKGROUND: Few studies have analyzed the effect of venous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The present study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma (PA) outcomes. 
METHODS: All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histological data at time of diagnosis or within the first 3 months after surgery, including the presence (+) or absence (-) of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism (PE), deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. 
RESULTS: Among 162 PA patients with a median follow-up of 15 (3-92) months after diagnosis, 28 demonstrated VTE (+). PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and history of treatment. The distribution of cancer stages was similar between the two groups VTE (+) and VTE (-). The median duration of survival was significantly worse in the VTE (+) group vs VTE (-) (12 vs 18 months, P=0.010). In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. 
CONCLUSION: VTE (+) at time of diagnosis or within the first 3 months after surgery during treatment is an independent factor of poor prognosis in PA.

The shortage of organs and the increasing median age of deceased donors for orthotopic liver transplantation stimulate transplant centres to accept grafts that otherwise would have been discarded due to severe vascular abnormalities. We encountered a donor with two arterial aneurysms and a left accessory hepatic artery: an arterial aneurysm of the common hepatic artery and a left accessory hepatic artery arising from a second aneurysm of the left gastric artery (Michels type V). A complex reconstruction was created to transplant the liver. Multiple arterial anastomosis was made and the hepatic inflow of the transplanted liver restored. Although the procedure increased the risk of hepatic artery thrombosis, one more organ supposed to be discarded was saved.