Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization.

BACKGROUND: Polydatin, a glucoside of resveratrol, has been shown to have protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. METHODS: After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. RESULTS: Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1ß, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. CONCLUSIONS: Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.

MiR-942-3p Promotes the Proliferation and Invasion of Hepatocellular Carcinoma Cells by Targeting MBL2.

MicroRNAs (miRNAs), a subgroup of small noncoding RNAs, play critical roles in tumor growth and metastasis. Accumulating evidence shows that the dysregulation of miRNAs is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism by which miR-942-3p contributes to HCC remains undocumented. The association between miR-942-3p expression and the clinicopathological characteristics in HCC patients was analyzed by The Cancer Genome Atlas data set. The targets of miR-942-3p were identified by bioinformatic analysis and dual luciferase report assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays were performed to assess the functional role of miR-942-3p in HCC cells. Consequently, we found that miR-942-3p expression level was elevated in HCC tissues and cell lines as compared with the normal tissues and was associated with the pathological stage and tumor node metastasis (TNM) stage, acting as an independent prognostic factor of poor survival in patients with HCC. Ectopic expression of miR-942-3p enhanced the proliferation and invasive potential of HCC cells, but inhibition of miR-942-3p expression had the opposite effects. Mannose-binding lectin 2 (MBL2) was further identified as a direct target of miR-942-3p and possessed a negative correlation with miR-942-3p expression and unfavorable survival in patients with HCC. Restoration of MBL2 inhibited the progression of HCC cells and attenuated the tumor-promoting effects induced by miR-942-3p. In conclusion, miR-942-3p may act as an oncogenic factor in HCC cells by targeting MBL2 and provide a potential marker for patients with HCC.

Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial.

OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.

Long-term exposure to PM2.5 lowers influenza virus resistance via down-regulating pulmonary macrophage Kdm6a and mediates histones modification in IL-6 and IFN-ß promoter regions.

Atmospheric particulates, especially PM2.5, not only damage the respiratory system, but also play important roles in pulmonary immunity. China is influenced by atmospheric diffusion conditions, industrial manufacturers, and heating and discharging. PM2.5 levels in the air rise substantially in the winter, which is also a period of flu high-incidence. Although an epidemiological link exists between PM2.5 and flu, we do not understand how long-term PM2.5 inhalation affects pulmonary immunity and the influenza virus response. Our study has prepared an in vivo PM2.5 mouse pharyngeal wall drop-in model and has found that PM2.5 exposure leads to mouse inflammatory injuries and furthers influenza A infection. Our results suggest that short-term exposure to PM2.5 significantly enhances the survival rate of influenza A-contaminated mice, while long-term PM2.5 inhalation lowers the capacity of pulmonary macrophages to secrete IL-6 and IFN-ß. A disorder in the pulmonary innate defense system results in increased death rates following influenza infection. On a macromolecular level, this mechamism involves Kdm6a down-regulation after long-term exposure to PM 2.5 and a resultant increase in H3K4 and H3K9 methylation in IL-6 and IFN-ß promoter regions. In summary, PM2.5 causes injuries of lung tissue cells and downregulates immune defense mechanisms in the lung.

Excessive intraoperative blood loss independently predicts recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Several studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear. METHODS: A total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan-Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis. RESULTS: The median follow-up was 28 months (range, 1-131 months). Kaplan-Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60-3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64-3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L. CONCLUSIONS: Excessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.

A quantitative assessment model of T-cell immune function for predicting risks of infection and rejection during the early stage after liver transplantation.

Although more and more clinical studies indicated that ImmuKnow assay could efficiently assess the immune status of recipients, it still has the challenge to predict the occurrence of clinical adverse events. This study aimed to establish a quantitative assessment model, which could more efficiently predict immune function of T lymphocytes after liver transplantation based on three indexes: CD4+ T lymphocyte count (C), CD4+/CD8+ ratio (R), and ImmuKnow adenosine triphosphate (ATP) value (A). We selected 194 recipients and measured the A, C, and R index every week, then obtained the Fisher linear discriminant functions by SPSS 16.0. Next, we divided the recipients into three groups: infection, stable, and rejection groups according to clinical status. After calculating, the discriminant function, 0.012A + 0.019C + 1.322R (simplified into T = 2A + 3C + 200R), was selected to represent the T-cell-mediated immune function. Based on the model, the optimal cutoff T values for infection and rejection were 1415 (sensitivity = 80%, specificity = 79.9%,AUC = 92.3%) and 1939.5 (sensitivity = 93.9%, specificity = 77.6%, AUC = 88.6%), relatively (p < 0.001). In conclusion, this model may be a more feasible way to evaluate the cellular immune function status in liver transplantation recipients.

Postreperfusion syndrome during orthotopic liver transplantation: a single-center experience.

BACKGROUND: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China. METHODS: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0. RESULTS: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%). CONCLUSION: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

The relationship between adenosine triphosphate within CD4(+) T lymphocytes and acute rejection after liver transplantation.

BACKGROUND: There have been increasing interests in the relationship between CD4(+) T lymphocytes and acute rejection (AR) in transplantation. In this study, we explore the role of CD4(+) T lymphocytes after liver transplantation. METHODS: From February to October 2009, 87 patients underwent liver transplantation. They were divided into the AR group and non-acute rejection (NAR) group, with 56 healthy individuals in the control group. Blood specimens were collected preoperatively and at one, two, and four wk postoperatively for all groups and also on the day when AR occurred and one wk after intravenous glucocorticoid therapy for the AR group. Adenosine triphosphate (ATP) levels were measured using the ImmuKnow™ test kits for immune cell functions. RESULTS: After transplantation, the ATP levels within CD4(+) T lymphocytes were significantly elevated in the two groups when compared with the preoperative levels. It peaked in the AR group and was significantly higher than that of the NAR group (p < 0.05). By ROC curve analysis, the obvious elevation of the ATP value one wk after transplantation had better sensitivity and specificity in diagnosing the AR. The ATP sensitivity rate for early AR was 85.7% and specificity rate 80.9% when the cutoff value was 407 µg/L. The ATP value collected on the day of AR occurrence has apparently positive correlation with the rejection acting index (RAI) (p < 0.01). After the intravenous glucocorticoid therapy, all the ARs were reversed and the ATP value declined significantly compared with the control group and that on the day when AR occurred (p < 0.01). CONCLUSIONS: During the early postoperative period (especially at first week after liver transplantation), the elevation of ATP levels within CD4(+) T lymphocytes has good sensitivity and specificity in diagnosing the AR at early stage. And the degree of AR has positive relationship with ATP value. After the intravenous glucocorticoid therapy, the obvious declination of AR might be used in evaluating the effectiveness of anti-rejection treatment.

Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation.

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 °C University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 °C UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent. CONCLUSION: The cadaveric venous allograft preserved in 4 °C UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.

Aged-related Function Disorder of Liver is Reversed after Exposing to Young Milieu via Conversion of Hepatocyte Ploidy.

Previous study showed that senescent hepatocytes from aged liver could be rejuvenated after repopulated in the young recipient liver. The proliferative capacity of hepatocytes was restored with the senescence reversal. However, it is unknown whether metabolic and homeostatic function of aged liver, as well as age-dependent liver steatosis could be rejuvenated or alleviated. Here, we found that senescent hepatocytes from aged liver were rejuvenated after exposing to young blood. An autonomous proliferation of senescent hepatocytes which resulting in ploidy reversal might be the underlying mechanism of senescent reversal. After performing 2/3 partial hepatectomy (2/3PHx) in young blood exposed old liver, delayed DNA synthesis of senescent hepatocytes was rescued and the number of BrdU positive hepatocytes was restored from 4.39±2.30% to 17.85±3.21%, similarly to that in the young mice at 36 hours post 2/3PHx. Moreover, Cyclin A2 and Cyclin E1 overexpression of hepatocytes in aged liver facilitating the G1/S phase transition was contributed to enhance liver regeneration. Furthermore, lipid droplet spread widely in the elderly human liver and old mouse liver, but this aged-associated liver steatosis was alleviated as senescence reversal. Collectively, our study provides new thoughts for effectively preventing age-related liver diseases.

Inhibition of SIRT1 Limits Self-Renewal and Oncogenesis by Inducing Senescence of Liver Cancer Stem Cells.

PURPOSE: Cancer stem cells (CSCs) have been considered involving in tumorigenesis, local recurrence, and therapeutic drug resistance of hepatocellular carcinoma (HCC). To investigate novel and effective methods for targeting hepatic CSCs is crucial for a permanent cure of liver cancer. METHODS: The expression level of SIRT1 was detected in CSCs of HCC tissues and cancer cell lines. Expression of CSC markers, the self-renewal and tumorigenic ability of liver CSCs were analyzed with SIRT1 inhibition. Cellular senescence-related markers were used to detect CSCs senescence after inhibition of SIRT1. RESULTS: SIRT1 was highly expressed in CSCs of HCC cell lines and human HCC tissues. In vitro study revealed that decreasing of SIRT1 level significantly downregulated the stemness-associated genes of liver CSCs and reduced the CSC stemness properties. Also, downregulated SIRT1 suppressed liver CSCs proliferation by decreasing their self-renewal abilities. Furthermore, CSCs with decreased SIRT1 expression showed limited tumorigenicity and formed smaller HCC tumor in vivo. And SIRT1 decreased CSCs became more susceptible to chemotherapeutic drugs. Mechanistically, SIRT1 decreased CSCs became senescence through the activation of p53-p21 and p16 pathway. The data further indicated that the tumor formed from SIRT1-knockdown CSCs exhibited higher senescence-associated ß-galactosidase (SA-ß-Gal) activity but lower proliferative capacity. CONCLUSION: Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment.

A single-center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. METHODS: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. RESULTS: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor-node-metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre-operative alpha-fetoprotein (AFP) level were independent risk factors affecting the overall survival and post-operative recurrence-free survival rates of patients with HCC. Pathological staging and pre-operative local treatment of HCC had no obvious correlation with the post-operative recurrence-free survival rate. CONCLUSION: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre-operative AFP level are closely related to the recurrence of HCC following LT.

[Effects of astilbin on maturation and immunologic function of mouse bone marrow-derived dendritic cells].

OBJECTIVE: To explore the effects of astilbin on the maturation and immunologic function of mouse bone marrow-derived dendritic cells (DCs). METHODS: Mouse bone marrow cells were cultured with recombinant mouse granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) for 5 days to get immature DCs (imDCs), then the imDCs was cultured in the presence of 1 microg/mL lipopolysaccharide (LPS) or LPS (1 microg/mL) plus astilbin (25, 50, 100 microg/mL) for 48 h. Then, the cells were harvested, and the apoptosis, immunophenotypes and antigen phagocytosis capability of imDCs in LPS, and low-, medium- and high-dose astilbin groups were analyzed by flow cytometry. Contents of p40 subunit of interleukin-12 (IL-12p40) in the supernatants were detected with enzyme-linked immunosorbent assay (ELISA). The stimulatory activity of the harvested cells on allogeneic T cells in mixed lymphocyte reactions (MLR) was tested by incorporation of 3H-thymidine, and the contents of IL-2, IL-4, IL-10 and interferon-gamma (INF-gamma) in the supernatants of MLR were examined by ELISA. RESULTS: At the concentrations of 25 to 100 microg/mL, astilbin exhibited no toxicity on co-cultured DCs. Compared with the lipopolysaccharide, low-, medium- and high-dose astilbin could decrease the expression levels of major histocompatibility complex-Ia (MHC-Ia), CD40, CD80 and CD86 molecules in DCs. DCs in the low-, medium- and high-dose astilbin groups exhibited weaker capabilities for antigen phagocytosis and less contents of IL-12p40 in the supernatants than in the LPS group. Furthermore, low-, medium- and high-dose astilbin showed weak activities in stimulating the proliferation of allogeneic T cells as compared with the LPS (P<0.05). Compared with the LPS, low-, medium- and high-dose astilbin could decrease IL-2 and INF-mu secretion from T cells in MLR but had no effect on IL-10 secretion. CONCLUSION: Astilbin can inhibit maturation of mouse bone marrow-derived DCs with dose-dependent effect and exert negative effects on immunologic function of the DCs.

Tailored classification of portal vein thrombosis for liver transplantation: Focus on strategies for portal vein inflow reconstruction.

Portal vein thrombosis (PVT) is currently not considered a contraindication for liver transplantation (LT), but diffuse or complicated PVT remains a major surgical challenge. Here, we review the prevalence, natural course and current grading systems of PVT and propose a tailored classification of PVT in the setting of LT. PVT in liver transplant recipients is classified into three types, corresponding to three portal reconstruction strategies: Anatomical, physiological and non-physiological. Type I PVT can be removed via low dissection of the portal vein (PV) or thrombectomy; porto-portal anastomosis is then performed with or without an interposed vascular graft. Physiological reconstruction used for type II PVT includes vascular interposition between mesenteric veins and PV, collateral-PV and splenic vein-PV anastomosis. Non-physiological reconstruction used for type III PVT includes cavoportal hemitransposition, renoportal anastomosis, portal vein arterialization and multivisceral transplantation. All portal reconstruction techniques were reviewed. This tailored classification system stratifies PVT patients by surgical complexity, risk of postoperative complications and long-term survival. We advocate using the tailored classification for PVT grading before LT, which will urge transplant surgeons to make a better preoperative planning and pay more attention to all potential strategies for portal reconstruction. Further verification in a large-sample cohort study is needed.

Bruton's Tyrosine Kinase Inhibitor Attenuates Warm Hepatic Ischemia/Reperfusion Injury via Modulation of the NLR Family Pyrin Domain Containing 3 Inflammasome.

The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a widely studied inflammasome that plays a critical role in inflammatory responses. Many triggers, including microbial pathogens (ie, bacteria and viruses) and other signals (ie, reactive oxygen species, adenosine triphosphate, urate, silicon, and asbestos), can stimulate the NLRP3 inflammasome. Liver ischemia/reperfusion (I/R) injury is a common pathologic process during liver surgery and shock and can induce severe liver damage. Although its pathogenesis is still unclear, oxidative stress and overproduction of the inflammatory response are likely to contribute to I/R injury. The NLRP3 inflammasome is activated during the I/R process, resulting in further recruitment and activation of caspase-1. Activated caspase-1 cleaves the pro-forms of interleukin-1ß and interleukin-18 and results in their maturation, triggering a proinflammatory cytokine cascade and causing liver damage. Bruton's tyrosine kinase is a critical molecule involved in diverse cellular pathways, such as proliferation, apoptosis, inflammation, and angiogenesis. Intrahepatic Bruton's tyrosine kinase is mainly expressed on Kupffer cells and sinusoidal endothelial cells, and the inflammasome is activated in Kupffer cells. Our study found that inhibition of Bruton's tyrosine kinase effectively attenuated liver I/R injury by suppressing activation of the NLRP3 inflammasome in Kupffer cells.

Prediction of survival after liver transplantation for chronic severe hepatitis B based on preoperative prognostic scores: a single center's experience in China.

BACKGROUND: The aim of this study was to estimate the utility of a preoperative model of end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score in predicting the prognosis after othotopic liver transplantation (OLT) for chronic severe hepatitis B (CSHB) and explore the prognostic factors. METHODS: The outcome of 137 patients who underwent OLT using donors after cardiac death (DCDs) for CSHB in our center was reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method; the log-rank test was used for univariate analysis; and the Cox proportional hazards regression model was used for prognostic factors screening. RESULTS: The overall mortality rate was 33.6% (46/137); and 1-month, 6-month, 1-year, and 5-year patient survival rates were 75.8, 72.0, 71.0, and 60.1%, respectively. Most patients (33/46) died during the first month after OLT. The area under the curve values generated by the receiver operating characteristics curves were 0.82 [95% confidence interval (CI) 0.72-0.92] and 0.68 (95% CI 0.58-0.79), respectively (P < 0.01), for the MELD and CTP models in predicting 1-month mortality after OLT. Patients with a preoperative MELD score <33.8 or a CTP score <12.5 had significantly better prognosis than those with higher scores (P < 0.05). Other mortality predictors include hepatic encephalopathy, preoperative infection, serum creatinine > or = 1.5 mg/dl. CONCLUSIONS: The MELD score was more efficient than the CTP score for evaluating the short-term prognosis in patients with CSHB undergoing OLT using DCDs, which should be taken into consideration during graft allocation.

Liver transplant recipients with portal vein thrombosis: a single center retrospective study.

BACKGROUND: Portal vein thrombosis (PVT) used to be a contraindication for liver transplantation (LT). This obstacle has been delt with following the improvement of LT-related techniques and therapeutic approaches to thrombosis. But the effect of PVT on LT outcomes is still controversial. We reviewed retrospectively the outcome of LT patients with PVT as well as risk factors and surgical management according to PVT grades. METHODS: A total of 465 adult LTs were performed from December 2002 through December 2006. Operative findings and the result of preoperative ultrasonography and imaging were reviewed for PVT grading (Yerdel grading). Comparison of risk factors, variables associated with perioperative period and prognosis between recipients with and without PVT is based on the grades. RESULTS: In the 465 LTs, 42 were operatively confirmed to have PVT (9.0%) (19 recipients with grade 1, 14 with grade 2, 7 with grade 3, and 2 with grade 4). Increased age and treatment of portal hypertension were associated with PVT. Grade 1 or 2 PVT was treated by direct anastomosis or single thrombectomy. In grade 3 PVT patients, the donor PV was directly anastomosed to the dilated branch of the recipient portal venous system or to the distal open superior mesenteric vein through an interposition vein graft if needed. Grade 4 PVT was managed by our modified cavoportal hemitransposition technique. The comparison between PVT patients and controls showed no significant difference in operative duration and blood transfusion (P>0.05). The flow rate of the PV was lower in the PVT patients (48.881+/-12.788 cm/s) than in the controls (57.172+/-21.715 cm/s, P<0.05). The PVT patients had such postoperative complications as renal failure and PV rethrombosis (P<0.05). The 1-year survival rates in PVT and non-PVT patients were 78.6% and 76.4% respectively (P>0.05); the 3-year survival rates were 58.8% and 56.4% respectively (P>0.05). CONCLUSIONS: PVT is not contraindicated for LT if it is graded. PVT recipients may have post-transplantation complications like renal failure and PV rethrombosis, and operative difficulty and patient survival are similar to those in recipients without PVT. Development of therapeutic approaches and accumulation of experience in dealing with PVT further improve the outcomes of LT in PVT recipients.

[Protective effects of astilbin on renal ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effects of astilbin on renal ischemia-reperfusion (IR) injury in rats. METHODS: Twenty-four male SD rats, two months old, were randomly allocated into three groups: sham-operated group (n=8), untreated group (n=8) and astilbin group (n=8). Rats in the untreated group and the astilbin group underwent temporary renal artery occlusion to induce IR injury. The rats in the astilbin group were intraperitoneally injected with 12 mg/mL astilbin at a dose of 30 mg/kg from 3 day before IR injury until to be sacrificed once per day, and rats in the untreated group were injected with equal volume of normal saline at the same time. After 6-hour reperfusion, blood urea nitrogen (BUN) and serum creatinine (SCr) and histological changes of the renal tissues were detected to evaluate renal injury. Expressions of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein in the renal tissues and the serum contents of interleukin-6 (IL-6) and IL-1beta were also measured with semi-quantitative reverse transcription-polymerase chain reaction, Western blotting or enzyme-linked immunosorbent assay. RESULTS: Compared with the untreated group, BUN and SCr levels were significantly decreased in the astilbin group after 6-hour reperfusion (P<0.01), and similar results were also found in histological examination. The expressions of MCP-1 mRNA and protein in renal tissues in the astilbin group were lower than those in the untreated group. The serum contents of IL-6 and IL-1beta were decreased in the astilbin group as compared with the untreated group (P<0.01). CONCLUSION: Astilbin can ameliorate kidney IR injury in rats by inhibiting the production of chemokine MCP-1 and cytokines IL-6 and IL-1beta.

Report of 8 cases of liver retransplantation.

BACKGROUND: Retransplantation of the liver is required for several complications of primary grafting, such as primary allograft non-function, hepatic artery thrombosis, biliary problems, or chronic ductopenic rejection. Surgeons usually take regrafting as the only pathway to treat those patients who are considered to have a poor outcome after the first operation. Whether the retransplantation is early or late, further attempts at rescue with a second or more grafts are associated with higher mortality and morbidity. However, retransplantation plays a role in improving survival of the patients. Therefore, it is necessary to summarize the experiences in liver retransplantation, as well as the factors influencing operative effects. METHOD: The clinical data of 8 patients who received liver retransplantation in our center were analyzed retrospectively. RESULTS: Complications of the biliary tract occurred in 5 of the 8 patients, chronic rejection in 2, and embolism in the hepatic artery in 1. Infections occurred in 7 patients before engraftment. Patient 1 had developed renal failure before the surgery, and he died of severe infection and multi-organ failure after transplantation. Patient 4 had a massive hemorrhage during the operation and also died of multi-organ failure after transplantation. Patient 7 developed intracranial hemorrhage and abdominal infection and died soon after transplantation. The other 5 patients recovered and discharged from the hospital. CONCLUSIONS: Liver retransplantation is the only measure that can be taken to save the lives of patients whose liver allograft fails to function. It is very important that the indications and time of retransplantation are carefully selected. Factors leading to harmful effects on retransplantation include the preoperative condition of the recipient, a difficult and prolonged operation, massive hemorrhage during the operation, and severe complications after the surgery.