Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker.

BACKGROUND: Integrator complex subunit 6 (INTS6) was found to play a tumour suppressing role in certain types of solid tumours. In this study, we wanted to determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu, European Journal of Cancer, 51:S94, 2015). METHODS: First, we used a microarray analysis to explore the mRNA expression levels in HCC and paired normal liver tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of 50 HCC tissues and adjacent normal liver tissues; third, we used Western blot analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver tissues; fourth, we used immunohistochemistry to determine the INTS6 expression levels in 70 archived paraffin-embedded HCC samples. Finally, we investigated the suppressive function of INTS6 in the Wnt pathway. RESULTS: Herein, according to the microarray data analysis, the expression levels of INTS6 were dramatically down-regulated in HCC tissues vs. those in normal liver tissues (p<0.05). qRT-PCR and Western blot analyses showed that the INTS6 mRNA and protein expression was significantly down-regulated in tumour tissues compared to the adjacent normal liver tissues (p<0.05). Immunohistochemical assays revealed that decreased INTS6 expression was present in 62.9% (44/70) of HCC patients. Correlation analyses showed that INTS6 expression was significantly correlated with serum alpha-fetoprotein levels (AFP, p =0.004), pathology grade (p =0.005), and tumour recurrence (p =0.04). Kaplan-Meier analysis revealed that patients with low INTS6 expression levels had shorter overall and disease-free survival rates than patients with high INTS6 expression levels (p =0.001 and p =0.001). Multivariate regression analysis indicated that INTS6 was an independent predictor of overall survival and disease-free survival rates. Mechanistically, INTS6 increased WIF-1 expression and then inhibited the Wnt/ß-catenin signalling pathway. CONCLUSION: The results of our study show that down-regulated INTS6 expression is associated with a poorer prognosis in HCC patients. This newly identified INTS6/WIF-1 axis indicates the molecular mechanism of HCC and may represent a therapeutic target in HCC patients.

Pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) as a novel plasma-based biomarker for hepatocellular carcinoma screening.

In this study, we aimed to determine whether the pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) in plasma could be used as a novel approach to screen for and detect hepatocellular carcinoma (HCC). We explored the clinical role of INTS6P1: First, the expression level of INTS6P1 was measured in a cohort of 33 HCC tissue samples and adjacent normal liver tissue, next, the INTS6P1 expression was detected in the culture medium and tumor cells in a cellular experiment, and last, the diagnostic performance of INTS6P1 was examined in an independent cohort of 100 people. The expression level of INTS6P1 was remarkably downregulated in the HCC tissues compared with that in the normal liver tissues (p = 0.0066). In plasma, the INTS6P1 levels were significantly decreased in HCC patients compared with non-HCC patients (p < 0.01). Additionally, we inferred that INTS6P1 might be a prospective biomarker for screening HCC patients in which the serum-AFP levels were lower than 20 ng/ml by the area under the curve-receiver operating characteristic (AUC-ROC) analysis (p < 0.05). Pseudogene INTS6P1 could be used as a novel HCC plasma-based biomarker and might improve the accuracy of HCC screening.

Short-term administration of steroids does not affect postoperative complications following liver resection: Evidence from a meta-analysis of randomized controlled trials.

AIM: Although perioperative short-term administration of steroids can attenuate surgical stress response following liver resection, there is no consensus concerning the effect on postoperative complications. This study aims to use meta-analysis to quantitatively investigate the effect of perioperative short-term administration of steroids on postoperative complications following liver resection. METHODS: A systematic published work search was performed to detect randomized controlled trials (RCT) assessing the effect of perioperative short-term administration of steroids on outcomes following liver resection. Parameters of surgical stress, hospital stay and postoperative complications were analyzed. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan version 5 and meta-analyses were performed using a random-effects model. RESULTS: Five RCT published between 2001 and 2011 containing a total of 379 patients were eligible for final analysis. Serum total bilirubin, interleukin-6 and C-reactive protein were significantly lower in the steroid than in the control group on postoperative day 1 (P = 0.02, 0.004 and 0.02, respectively). There was no difference in duration of hospital stay between the steroid and control group (P = 0.37). The analysis of end-points including infective complications (odds ratio [OR], 0.95), wound complications (OR, 0.67), bile leakage (OR, 0.58) and overall complications (OR, 0.50) revealed no difference between steroid administration and no treatment. There was no postoperative death or adverse effect attributable to steroid treatment in all patients. CONCLUSION: On currently available evidence, short-term administration of steroids does not increase incidence of complications in patients undergoing liver resection.

Retinoic acid receptor-related receptor alpha (RORalpha) is a prognostic marker for hepatocellular carcinoma.

Retinoic acid receptor-related receptor alpha (RORalpha) has been proven to play a tumor suppressive role in certain types of solid tumors. However, the clinical characteristic of RORalpha has not been reported by far. This study investigated the expression of RORalpha in hepatocellular carcinoma (HCC) and evaluated its relationship with clinical parameters and prognosis in HCC patients. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to detect RORalpha expression levels in 20 paired HCC and corresponding adjacent non-cancerous tissues. Immunohistochemistry was performed on 100 archived paraffin-embedded HCC samples. Statistical analyses evaluated the correlations between RORalpha expression and clinicopathological features. qRT-PCR showed that RORalpha mRNA expression was significantly down-regulated in tumors compared to the adjacent non-cancerous tissues, and Western blots found that RORalpha protein expression was also reduced in tumor tissues. Immunohistochemical assays revealed that decreased RORalpha expression was present in 65 % of HCC patients. Correlation analyses showed that RORalpha expression was significantly correlated with serum alpha fetoprotein (AFP, p = 0.005), pathology grade (p < 0.001), tumor recurrence (p = 0.008), and vascular invasion (p < 0.001). Kaplan-Meier analysis revealed that patients with low RORalpha expression levels had a shorter overall and disease-free survival than patients with high expression (p < 0.001 and p = 0.002, respectively). Multivariate regression analysis indicated that RORalpha was an independent predictor for overall survival and disease-free survival. In conclusion, the results of our study showed that down-regulated RORalpha expression was associated with poorer prognosis in HCC patients. RORalpha may be a new potential prognostic marker for HCC patients.

A technique of recipient portal venoplasty and cuff insertion for portal revascularization in orthotopic rat liver transplantation.

BACKGROUND: In addition to suprahepatic vena cava anastomosis in two-cuff rat liver transplantation, recipient portal vein revascularization is one of the most difficult procedures that must be performed, especially for beginners. MATERIALS AND METHODS: A total of 43 cases of liver transplantation were performed. Rats in Group 1 and Group 2 were subjected to transplant procedures that used the conventional and portal venoplasty techniques, respectively. The portal vein anastomosis duration, anhepatic phase length, portal vein surgical complications, and 1 wk post-transplant survival rates were recorded for each group. RESULTS: The portal revascularization duration was statistically significantly less for Group 2 versus Group 1 (1.50 ± 0.61 min and 4.32 ± 0.67 min, respectively, P < 0.05). The anhepatic phase length of Groups 1 and 2 were 21.79 ± 1.27 min and 18.55 ± 1.47 min, respectively (P < 0.05). No significant differences between the groups were observed in relation to either portal vein surgery complications or 1-week survival rates. CONCLUSIONS: The recipient portal venoplasty and cuff insertion technique is a safe and fast alternative surgical option for portal revascularization in two-cuff rat liver transplantations performed by a single trainee.

Clinical study on prevention of HBV re-infection by entecavir after liver transplantation.

PURPOSE: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re-infection after liver transplantation (LT). METHODS: A retrospective matched case-control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. RESULTS: Two hundred and fifty-two patients were enrolled. The average duration of follow-up was 38.5 and 41.2 months (LAM and ETV groups) (p>0.05). Duration of pre-operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p>0.05). The HBV DNA level decreased from 3.89×10(6) to 5.31×10(5) copies/mL before LT in the LAM group, and decreased from 8.74×10(6) to 5.49×10(4) copies/mL in the ETV group (p<0.05). Eighteen patients in LAM group developed HBV re-infection and 0 in ETV group. CONCLUSION: ETV is superior to LAM for preventing HBV re-infection following LT.

[Preoperative neutrophil-lymphocyte ratio as a prognostic predictor after liver transplantation for hepatocellular carcinoma].

OBJECTIVE: To analyze the negative impact of preoperative neutrophil-lymphocyte ratio (NLR) on the tumor recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation. METHODS: The clinical data of HBV (hepatitis B virus)-associated HCC patients undergoing liver transplantation were retrospectively analyzed. Their clinical and pathological risk factors for tumor-free survival were evaluated by univariate analysis. The analysis of Cox multiple regression was performed to determine the parameters of predicting the HCC recurrence. NLR ≥ 2.5 was considered to be elevated. RESULTS: A total of 76 patients were identified. Among them, 37 had an elevated NLR. The 1, 3 and 5-year tumor-free survival rates were 69.2%, 52.7% and 50.9% respectively. The disease-free survival for patients with high NLR was significantly worse than that for those with normal NLR (1, 3, and 5 year survivals at 56.3%, 37.6% and 37.6% vs 81.1%, 66.9% and 63.3% respectively; P = 0.011). Univariate analysis of factors revealed that tumor size > 5 cm, tumor number > 3, vascular invasion, serum α-fetoprotein level ≥ 400 µg/L and NLR ≥ 2.5 were preoperative predictors of disease-free survival. Cox regression analysis showed that the presence of vascular invasion, tumor number > 3 and NLR ≥ 2.5 were independent prognostic factors of worse disease-free survival. CONCLUSION: An elevated NLR significantly increases the risk for tumor recurrence in HCC patients undergoing liver transplantation.

[Clinical analysis between "early" versus "late" liver retransplantation].

OBJECTIVE: To compare early and late orthotopic liver retransplantation (re-OLT) for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 36 re-OLTs from January 2004 to July 2009 were analyzed retrospectively, consisting of the first group with 17 cases of early re-OLT and the second group with 19 cases of late re-OLT. The average ages were (45 ± 13) years and (48 ± 10) years, and the time intervals were (49 ± 54) days and (514 ± 342) days in early re-OLT group and late re-OLT group, respectively. RESULTS: Biliary tract complications were the main indications for early re-OLT and late re-OLT. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration and perioperative mortality except the MELD score. Outcome was fatal for 8 patients in early re-OLT and 10 patients in late re-OLT. Three deaths were due to severe sepsis-related disease, 3 deaths due to multiple organ failure in early re-OLT and 4 deaths due to severe sepsis-related disease, 3 deaths due to recurrence of HCC in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 52.9% and 41.2%, respectively, for patients in early re-OLT, and 63.2% and 52.6%, respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups (P > 0.05). CONCLUSIONS: The similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, experienced surgical procedures and effective perioperative anti-infection strategy contribute to the improvement of the overall survival rate of the patients after re-OLT.

Contrast-enhanced ultrasound for the evaluation of hepatic artery stenosis after liver transplantation: potential role in changing the clinical algorithm.

Hepatic artery stenosis (HAS) is a common complication in liver transplant patients. Conventional angiography remains the gold standard for diagnosis. Recently, contrast-enhanced ultrasound (CEUS) has begun providing real-time angiographic-like images of vessels and allowing the accurate diagnosis of arterial diseases such as hepatic artery thrombosis. The purpose of this study was to evaluate the efficacy of CEUS in depicting HAS after liver transplantation. Forty-seven liver transplant recipients underwent CEUS examinations with the intravenous injection of microbubble contrast agents. The reference standard was conventional angiography for 15 patients and computed tomographic angiography for 32 patients. The presence, degree, location, and type of HAS were evaluated. For the detection of HAS by CEUS, the following was found: an accuracy of 91.5% (43/47), a sensitivity of 92.3% (36/39), a specificity of 87.5% (7/8), a positive predictive value of 97.3% (36/37), and a negative predictive value of 70% (7/10). CEUS corrected false-positive findings on color Doppler ultrasound in 7 of 47 cases (14.9%). The accuracy of CEUS in identifying the location and type of HAS was 92.3% (36/39) and 84.6% (33/39), respectively. CEUS is a useful noninvasive technique for the detection of HAS in liver transplant patients because it provides comprehensive information, including the presence, location, degree, and type. A positive CEUS finding suggests angiography as the next step rather than a computed tomography scan and may thereby alter the clinical imaging algorithm.

[Risk factors predicting late mortality after liver transplantation for benign end-stage liver disease].

OBJECTIVES: To find out the risk factors predicting long-term survival, and to explore the measures for further improving the survival outcome of whom underwent liver transplantation (LT) for benign end-stage liver disease. METHODS: The common causes of late death after LT and risk factors were retrospectively analyzed in 221 consecutive patients, who underwent LT from October 2003 to June 2007 and survived more than one year. Twenty-six potential risk factors were assessed by the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step down Cox proportional hazard regression analysis to screen the independent risk factors influencing the recipient's long-term survival. RESULTS: There were 28 recipients died one year later after LT during the follow-up period. The major causes of late mortality were related to infectious complications 5.0% (11/221), biliary complications 3.6% (8/221) and HBV recurrence/reinfection 1.4% (3/221). After Cox proportional hazard regression analysis, 5 covariables finally retained in the formula were: age (RR = 2.325, P = 0.009), ABO blood group (RR = 2.206, P = 0.015), cold ischemia time (RR = 3.001, P = 0.000), post-infection region (RR = 1.665, P = 0.007) and biliary complications (RR = 2.655, P = 0.004). CONCLUSION: Age (≥ 60 years), ABO blood group (incompatible), cold ischemia time (> 12 h), infectious complications (lung infection) and biliary complications (diffuse biliary stricture) significantly impact patient's survival time.

Evaluation of the microcirculatory disturbance of biliary ischemia after liver transplantation with contrast-enhanced ultrasound: preliminary experience.

The aim of this study was to determine the efficacy of contrast-enhanced ultrasound for depicting the perfusion of hilar bile ducts in ischemic-type biliary lesions after orthotopic liver transplantation. Thirteen transplant recipients with ischemic-type biliary lesions and 12 patients without ischemic-type biliary lesions underwent ultrasound examinations after the injection of 1.5 mL of an intravenous contrast agent. The enhancement of the hilar bile duct wall in the arterial, portal venous, and late phases was qualitatively graded as higher, equal, lower, or none with respect to that of the adjacent liver parenchyma. No or low contrast enhancement was seen in 10 of 13 patients (76.90%) with biliary ischemia, whereas increased contrast enhancement with respect to the normal liver parenchyma was found in all 12 patients without biliary ischemia. The difference in the enhancement patterns between the 2 groups was significant (P = 0.0001). In conclusion, contrast-enhanced ultrasound is a new imaging modality to depict perfusion of the hilar bile duct. No or low contrast enhancement of the bile duct wall in the arterial phase may reflect the microcirculatory disturbance of biliary ischemia and may contribute to its early diagnosis.

[Immunization with dendritic cells infected with mTERT adenovirus vector effectively elicits immunity against mouse H22 hepatoma in vivo].

OBJECTIVE: To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding mTERT on induction of mTERT antigen specific immunity against H22 hepatoma in vivo. METHODS: Forty Bal B/c mice were subcutaneously immunized with Ad-mTERT infected DC. Cytotoxicity of mTERT specific CTL was determined by 51Cr release assay. IL-2 and IFN-gamma were tested by ELISA. IFN-gamma ELISPOT assays were performed for measuring antigen specific IFN-gamma production by T cells. Tumor size and survival of the immunized mice were recorded and evaluated whether preexisting hepatoma metastases could be supressed after immunization with mTERT-expressing DCs. RESULTS: The lytic activity of CTL, IL-2 (871.25 pg/ml), IFN-gamma (169.15 ng/ml) and IFN-gamma secreting cells (378/10(6) spleen cells) elicited by the Ad-mTERT infected DCs were much stronger and higher than that by Ad-GFP group (131.6 pg/ml, 15.4 ng/ml, 36/10(6) spleen cells, P<0.05), DC group (71.3 pg/ml, 10.5 ng/ml, 21/10(6) spleen cells, P<0.05), PBS group (65.8 pg/ml, 7.4 ng/ml, 18/10(6) spleen cells, P<0.05). In prophylaxis and treatment experiment the Ad-mTERT/DCs immunized mice lived significantly longer than other groups, demonstrating that primary DCs were genetically modified to express the mTERT antigen and could suppress the tumor growth. CONCLUSION: Adenovirus vector mediated mTERT infected DCs can effectively induce mTERT antigen specific antitumor activity, and can induce protective and therapeutic antitumor immunity.

[Significance of lipopolysaccharides, toll-like receptor and inducible nitric oxide synthase in hepatopulmonary syndrome].

OBJECTIVE: To investigate the role of lipopolysaccharides (LPS), toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS) in the development of hepatopulmonary syndrome (HPS). METHODS: Seventy-one patients were divided into 3 groups: end-stage liver disease with HPS (HPS group, n = 31), end-stage liver disease without HPS (non-HPS group, n = 30) and healthy volunteers (n = 10). Blood was collected at pre-OLT and Days 3, 7, 14, 21 and 28 post-OLT to detect the plasma LPS level, TLR2mRNA and iNOSmRNA in peripheral blood monocytes. RESULTS: The LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were 4.31 +/- 3.267 ng/L, 336,594.10 +/- 366,901.14 and 63,982.24 +/- 74,127.47 copies/microg RNA respectively; 1.62 +/- 1.34 ng/L, 336,321.53 +/- 222,317.17 and 44,169.9 +/- 24,993.00 copies/microg RNA respectively in non-HPS group and 0.94 +/- .69 ng/L, 10,338.28 +/- 3,814.64 and 19,168.49 +/- 2,417.35 copies/microg RNA in normal control group. LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were higher than those in non-HPS group without significance (P > 0.05), but significantly higher than those in control group (P < 0.05). The TLR2mRNA decreased in all end-stage liver disease patients at post-OLT with the improvement of liver function and oxygenation. CONCLUSION: The dysfunction of intestinal barrier and intestinal endotoxemia may be the important mechanisms of HPS through the elevation of LPS level and the expressions of TLR2mRNA and iNOSmRNA.

[Multimodality interventional treatments for biliary complications after orthotopic liver transplantation: a preliminary study].

OBJECTIVE: To describe the technique, efficacy, and safety of multimodality interventional treatments for biliary complications after orthotopic liver transplantation (OLT). The core of multimodality interventional treatments is percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to May 2008, seventy-two patients with biliary complications afte OLT were closed in our study. On the basis of the cholangiographic appearance, patients were classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and anastomotic biliary fistulae (n = 6). All patients were treated in our hospital, including PTBD only in 6 patients, PTBD combined with balloon dilation in 50 patients, balloon dilation and plastic stent implantation in 10 patients, balloon dilation and metallic stent implantation in 6 patients. Their data were analyzed retrospectively, including serum hemobilirubin, cholangiographic appearance and complications. RESULTS: PTBD were successful in all cases. The clinical symptoms improved or eliminated were observed in 66 cases, the effective rate was 91.7% (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients underwent second PTBD for the obstruction of biliary stents, and 38 patients maintained drainage tube for long-term. In 66 patients with biliary obstruction, the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76 micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate of biliary tract infection was 14.3% and 43.8% respectively with the tip of drainage tube placed in biliary duct and in duodenum. There was a significantly statistical difference between these two items (chi(2) = 4.886, P = 0.027). CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is a effective therapeutic modality for biliary complications after OLT, which can improve patients' clinical symptoms, elevate patients' quality of life. The tip of drainage tube being placed in biliary duct can decrease the rate of biliary tract infection significantly.

[Risk factors predicting the prognosis of orthotopic liver transplantation in hepatopulmonary syndrome].

OBJECTIVE: To observe the effect of orthotopic liver transplantation (OLT) on hepatopulmonary syndrome (HPS) and investigate risk factors predicting the prognosis of OLT. METHODS: Twenty-six cases of HPS and 30 cases of non-HPS were analyzed treated from April 2004 to January 2006. Survival rates after OLT were compared and risk factors predicting the prognosis of OLT in HPS were researched by univariant and COX analysis. RESULTS: The 28 days survival rate in HPS after OLT was 76.9% (20/26), half a year survival rate and one year survival rate were both 61.5% (16/26). Whereas the one year survival rate of patients without HPS was 100%(P < 0.05). By univariant analysis, shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs, PaO2 and PaO2/FiO2 in room air before operation were relative to the prognosis of peri-operative period and half a year outcome after OLT in HPS (P < 0.05). Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs (OR = 1.182, P = 0.001), and mechanical ventilation time (OR = 1.003, P = 0.053) after OLT were independent risk factors predicting the prognosis of OLT in HPS by COX analysis. Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs > or = 28.4%, or PaO2 < or = 56 mm Hg (1 mm Hg = 0.133 kPa) before OLT predicted the poor outcome of OLT in HPS. The sensitivity were 83.3% and 85.0% respectively, and the specificity were 95.0% and 83.3% respectively. CONCLUSIONS: OLT is an effective treatment for HPS.Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs before OLT and mechanical ventilation time after OLT were independent risk factors for the prognosis of OLT in HPS.

[Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B].

OBJECTIVES: To study the practical use of the serum sodium incorporated model for end-stage liver disease (MELD-Na) on clinic and to assess its validity by the concordance-statistic in predicting the prognosis of the patients with chronic severe hepatitis B. METHODS: Adult patients with a diagnosis of chronic severe hepatitis B between January 2007 and December 2007 in a single center were analyzed. The serum sodium, MELD, MELD-Na, and Delta MELD-Na (Delta MELD=MELD score at 14 days after medical treatment-MELD score at admission) scores of 426 patients with chronic severe hepatitis B were calculated. The 3-month mortality in patients was measured, and the validity of the models was determined by means of the concordance-statistic. RESULTS: The area under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 month were 0.718, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group <25, 25-30, >30-35, >35- <40 and > or = 40 were 2.0%, 5.4%, 35.4%, 53.8% and 86.9% respectively. There was a significant difference of 3-month mortality between the five groups (P<0.05). The 3-month mortality of Delta MELD-Na> 0 group was 65.9%, and the Delta MELD-Na < or = 0 group was 15.8%. There was a significant difference of 3-month mortality between the two groups (P<0.05). CONCLUSIONS: MELD-Na score is a valid model to predict 3-month mortality in patients with chronic severe hepatitis B. Delta MELD-Na is clinically useful parameters for predicting the therapeutic effect of chronic severe hepatitis B.

Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B.

BACKGROUND: Serum sodium predicts prognosis in chronic severe hepatitis B and may improve the prognostic accuracy of the model for end-stage liver disease (MELD) score, but the available information is limited. The present study was undertaken to study the clinical use of the serum sodium incorporated MELD (MELD-Na) and assess its validity by the concordance (c)-statistics in predicting the prognosis of the patient with chronic severe hepatitis B. METHODS: A total of 426 adult patients with a diagnosis of chronic severe hepatitis B between January 1, 2007, and December 31, 2007 at a single center were studied. The scores of serum sodium, MELD, MELD-Na, and DeltaMELD-Na (DeltaMELD-Na = MELD-Na at 14 days after medical treatment -MELD-Na score on admission) of the patients with chronic severe hepatitis B were calculated. The 3-month mortality in the patients was measured, and the validity of the models was determined by means of the concordance (c) statistics. RESULTS: The average MELD, MELD-Na scores of survival group were 25.70 +/- 5.08 and 26.60 +/- 6.90, and those of dead group were 35.60 +/- 6.78 and 42.80 +/- 9.57 on admission. There was a significant difference in MELD and MELD-Na between the survival and dead groups (P < 0.01). The average DeltaMELD-Na score of the survival group was -0.97 +/- 3.51, and that of the dead group was 3.45 +/- 2.38 at 2 weeks after the treatment. There was a significant difference in DeltaMELD-Na between the survival and dead groups (P < 0.01). The areas under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 months were 0.742, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group < 25, 25-30, 31-34, 35-40 and > 40 were 2.0%, 5.4%, 35.4%, 53.8 % and 86.9%, respectively. There was a significant difference in the 3-month mortality between the five groups (P < 0.05). The 3-month mortality of the DeltaMELD-Na > 0 group was 65.9%, and that of the DeltaMELD-Na = 0 group was 15.8%; there was a significant difference in the 3-month mortality between the two groups (P < 0.05). CONCLUSIONS: MELD-Na score is a valid model to predict the 3-month mortality in patients with chronic severe hepatitis B. DeltaMELD-Na is a clinically useful parameter for predicting the therapeutic effect of chronic severe hepatitis B.

Early liver retransplantation versus late liver retransplantation: analysis of a single-center experience.

BACKGROUND: Orthotopic liver retransplantation (re-OLT) is the only effective therapy for irreversible failure of a liver graft. Early and late graft failure gives way to two different clinical conditions that should be discussed separately. This study was designed to compare early and late re-OLT for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 31 re-OLTs at our center from January 2004 to February 2007 were analyzed retrospectively, consisting of the first group with 14 cases of early re-OLT and the second group with 17 cases of late re-OLT. RESULTS: Biliary tract complications were the main indications for early re-OLT (57.1%) and late re-OLT (52.9%). Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration, and perioperative mortality; except for the model of end-stage liver disease (MELD) score. Outcome was fatal for 7 patients in early re-OLT and 9 patients in late re-OLT. Two deaths were due to multiple organ failure with 3 deaths due to severe sepsis-related disease in early re-OLT, and 4 deaths were due to severe sepsis-related disease with 3 deaths due to recurrence of hepatocellular carcinoma (HCC) in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 55.2% and 36.9%, respectively, for patients in early re-OLT, and 65.1% and 52% respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups. CONCLUSIONS: Similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, adequate preoperative preparation, experienced surgical procedures, and effective perioperative anti-infection strategy contribute to the improvement of overall survival rates of patients after re-OLT.

[Long-term survival after liver transplantation for benign end-stage liver disease in adults].

OBJECTIVE: To evaluate the long-term survival rates of the adults with benign end-stage liver disease (BELD) after liver transplantation (LT) and the causes of death. METHODS: The common causes of late death (after more than 1 year) after LT were retrospectively analyzed in 203 consecutive patients with BELD who underwent LT from Oct. 2003 to May.2006. RESULTS: The 1, 2 and 3-year survival rates were 88.7%, 85.5%, and 81.2% respectively. The 2-year and 3-year survival rates of the patients with HBV-related liver disease were 88.4% and 84.5% respectively, not significantly different from those of patients with non-HBV-related liver disease (75.6% and 64.0% respectively, P = 0.144). 165 recipients survived for more than 1 year and 21 recipients died during the period between 12 and 48 months after LT with a mean of (22.7 +/- 6.6) months. The common causes of late death included related to infectious complications (4.8%, 8/165), biliary tract complications (3.6%, 6/165), HBV re-infection (1.8%, 3/165), chronic rejection (1.2%, 2/165), renal functional lesion (0.6%, 1/165), and hepatic arterial complication (0.6%1/165). CONCLUSION: Satisfactory long-term survival can be achieved in most adult recipients with BELD after LT and the major causes that influence the long-term survival are infectious complications, biliary tract complications, and HBV re-infection. Prevention of these complications, rational use of immunosuppressant, and regular follow-up are essential to improve long-term survival.