Tripartite motif protein 11 (TRIM11), an oncogene for human lung cancer via the DUSP6-mediated ERK1/2 signaling pathway.

Evidence suggests that Tripartite Motif Containing 11 (TRIM11) has pro-tumor activity in human non-small cell lung cancer (NSCLC). However, the roles and underlying mechanisms of TRIM11 in NSCLC have not yet been fully elucidated. In this work, human lung cancer cell lines (A549, H446, and H1975) were transfected with siRNA or lentiviruses to knockdown or overexpress TRIM11 and dual-specificity phosphatase 6 (DUSP6). The cell tumor response was assessed by determining the rate of proliferation, apoptosis, the uptake of 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG), and the secretion of lactic acid (LD). Dominant-negative (dn)-MEK1 was used to block the ERK1/2 pathway. The mechanism was investigated by assessing the protein levels of pyruvate kinase isozymes M2 (PKM2) and DUSP6, as well as the activation of ERK1/2 pathway. Our data confirmed the anti-cancer effect of siTRIM11 in human lung cancer by demonstrating inhibition of cancer cell proliferation, induction of apoptosis, prevention of 2-NBDG uptake, suppression of LD production, and prevention of lung cancer cell (A549) tumorigenicity in nude mice. The underlying mechanism involved the up-regulation of DUSP6 and the inhibition of ERK1/2 activity. Overexpression of TRIM11 induced tumorigenesis of NSCLC in vitro, and the activation of ERK1/2 was significantly reversed by DUSP6 overexpression or additional dn-MEK1 treatment. Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway. In conclusion, TRIM11 is an oncogene in NSCLC, likely through the DUSP6-mediated ERK1/2 signaling pathway.

A proposed modification for the Barcelona Clinic Liver Cancer staging system: Adding bile duct tumor thrombus status in patients with hepatocellular carcinoma.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is widely applied to stage hepatocellular carcinoma (HCC). However, it may be inaccurate when applied to East Asian HCC patients. In this study, a large Chinese HCC cohort was analyzed to evaluate possible modifications for the BCLC staging system. METHODS: Between January 1995 and December 2009, 622 HCC patients who underwent hepatectomy were enrolled. Prognostic risk factors were analyzed using univariate and multivariate analyses. The ability of the modified system to predict survival was evaluated by determining the area under the receiver operating characteristic curve. RESULTS: Patients without bile duct tumor thrombus (BDTT; 1-, 3- and 5-year overall survival, 80%, 60% and 48%, respectively) showed a substantial survival advantage over those with BDTT (1-, 3- and 5-year overall survival, 77%, 42% and 23%, respectively; χ2 = 6.280, P = 0.012). In BCLC stage 0-A patients, significant differences were identified between the BDTT group and the non-BDTT group, while no such differences were found in BCLC stage B patients. Based on this finding, BCLC stage 0-A BDTT patients were recategorized into stage B. The modified BCLC classification featured better performance in the prediction of overall survival than the original system (modified BCLC χ2 = 53.596, P < 0.001; original BCLC χ2 = 46.335, P < 0.001). The ability to predict mortality was also slightly higher using the modified BCLC system. CONCLUSIONS: Modification of the BCLC system to include BDTT status might further enhance its prognostic ability.

Splenectomy with Portoazygous Disconnection for Correction of Systemic Hemodynamic Disorders in Hepatic Cirrhosis Patients with Portal Hypertension: A Prospective Single-Center Cohort Study.

Objective: To investigate the effect of splenectomy for correction of systemic hemodynamic disorders in hepatic cirrhosis patients with portal hypertension. Methods: Hepatic cirrhosis patients with portal hypertension were enrolled from April 2015 to July 2018. Systemic hemodynamic parameters (heart rate, mean arterial pressure (MAP), cardiac output, and total peripheral vascular resistance (TPR)) were prospectively measured at baseline and 1 week, 1, 3, and 6 months, and 1, 2, and 3 years postoperatively. Paired analysis was conducted. Results: Sixty-nine patients were eligible, and 55 (79.7%) cases had a history of upper gastrointestinal bleeding. Child-Pugh classification was grade A in 41 (59.4%) cases, grade B in 26 (37.7%) cases, and grade C in 2 (2.9%) cases. The heart rate was significantly higher at 1 week postoperatively versus the baseline (P < 0.001). Meanwhile, the heart rate was significantly lower from 3 months to 2 years postoperatively versus the baseline (P < 0.05). The MAP was significantly higher at 6 months to 2 years postoperatively versus the baseline (P < 0.05). At 1 month postoperatively and 6 months to 2 years, the cardiac output was significantly lower versus the baseline (P < 0.05). At 1 month postoperatively and 6 months to 2 years, the TPR was significantly higher versus the baseline (P < 0.05). Conclusion: Splenectomy corrects systemic hemodynamic disorder in hepatic cirrhosis patients with portal hypertension, and the effect is rapid and durable.

Long-term consequences of stopping HBIG and/or nucleotide analogues in liver transplant recipients administered hepatitis B vaccination to prevent HBV reinfection.

BACKGROUND: The long-term administration of nucleotide analogues (NAs) and hepatitis B immune globulin (HBIG) comprises standard prophylaxis for patients with hepatitis B virus (HBV)-related liver diseases to prevent HBV reinfection after liver transplantation (LT). However, prolonging the prophylaxis strategy involves safety issues, such as the development of escape mutations and/or emerging resistant strains, and is also associated with high costs; further, it remains unclear how long prophylactic treatment should be continued. METHOD: Liver transplantation recipients responding to hepatitis B vaccination due to HBV-related liver diseases were retrospectively analysed after stopping HBIG and/or NAs, administered to prevent HBV reinfection, after long-term follow-up. The safety and effectiveness of the strategy were then evaluated for these responders. RESULT: Seventy-eight responders were enrolled. All responders discontinued HBIG, among which 36 stopped both HBIG and NAs. During follow-up, four recipients experienced HBV reinfection, which was associated with HBV escape mutations, after the withdrawal of both HBIG and NAs. No death or graft loss occurred in recipients during the follow-up period. CONCLUSION: A careful withdrawal of HBIG and/or NAs is feasible and safe for responders to hepatitis B vaccination receiving transplants for HBV-related liver diseases.

The Effect of Splenectomy on the Reversal of Cirrhosis: a Prospective Study.

BACKGROUND: Studies have demonstrated that liver fibrosis can be reversed by medication treatments. After splenectomy, cirrhosis patients have short-term changes in several serum markers for cirrhosis and liver stiffness. AIMS: To investigate the effect of splenectomy on the severity of cirrhosis. METHODS: A total of 62 patients with cirrhosis and portal hypertension receiving splenectomy from December 2014 to July 2017 were enrolled. The degree of cirrhosis was preoperatively and postoperatively evaluated by serum markers, including hyaluronan (HA), laminin, amino-terminal propeptide of type III procollagen (PIIINP), type IV collagen (C-IV), liver stiffness (FibroScan), and liver volume. RESULTS: HA levels significantly increased at 1 week and 1 month postoperation (both P < 0.05), whereas the levels of PIIINP and C-IV significantly decreased from 1 month to 12 months postoperation (all P < 0.05). In addition, elastography examination demonstrated that the FibroScan score significantly reduced from 1 month to 24 months postoperation as compared with the baseline level (all P < 0.05). CT scan showed that the liver volume significantly increased at 6 months postoperation (P < 0.05). Furthermore, the alteration trends of these serum markers and the FibroScan score were further confirmed by the multivariate linear regression. CONCLUSIONS: These observations suggested that splenectomy may result in long-term reversal of cirrhosis.

Usefulness of three-dimensional visualization technology in minimally invasive treatment for infected necrotizing pancreatitis.

AIM: To explore the value of three-dimensional (3D) visualization technology in the minimally invasive treatment for infected necrotizing pancreatitis (INP). METHODS: Clinical data of 18 patients with INP, who were admitted to the PLA General Hospital in 2017, were retrospectively analyzed. Two-dimensional images of computed tomography were converted into 3D images based on 3D visualization technology. The size, number, shape and position of lesions and their relationship with major abdominal vasculature were well displayed. Also, percutaneous catheter drainage (PCD) number and puncture paths were designed through virtual surgery (percutaneous nephroscopic necrosectomy) based on the principle of maximum removal of infected necrosis conveniently. RESULTS: Abdominal 3D visualization images of all the patients were well reconstructed, and the optimal PCD puncture paths were well designed. Infected necrosis was conveniently removed in abundance using a nephroscope during the following surgery, and the median operation time was 102 (102 ± 20.7) min. Only 1 patient underwent endoscopic necrosectomy because of residual necrosis. CONCLUSION: The 3D visualization technology could optimize the PCD puncture paths, improving the drainage effect in patients with INP. Moreover, it significantly increased the efficiency of necrosectomy through the rigid nephroscope. As a result, it decreased operation times and improved the prognosis.

A study on risk factors and diagnostic efficiency of posthepatectomy liver failure in the nonobstructive jaundice.

Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors.t test and χ test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes.Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

Postoperative inflammation as a possible cause of portal vein thrombosis after irreversible electroporation for locally advanced pancreatic cancer.

Portal vein thrombosis (PVT) is a rare but serious postoperative complication associated with irreversible electroporation (IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locally advanced pancreatic cancer. Drain removal and discharge of the patient from the hospital were scheduled on postoperative day (POD) 7; however, a magnetic resonance imaging scan revealed the presence of PVT. We suspected postoperative inflammation in the pancreas as the main cause of PVT. However, the patient did not undergo any medical treatment because she did not have any clinical symptoms, and she was discharged on POD 8.

A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma.

BACKGROUND: Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. METHODS: Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. RESULTS: All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. CONCLUSIONS: IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.

Knockdown of TRIM65 inhibits lung cancer cell proliferation, migration and invasion: A therapeutic target in human lung cancer.

Lung cancer is the most commonly diagnosed type of cancer worldwide. Although TRIM65 is an important protein involved in white matter lesion, the role of TRIM65 in human cancer remains less understood. Here, we reported that TRIM65 was significantly overexpressed in lung cancer tissues compared with adjacent normal lung tissues. Furthermore, TRIM65 expression was closely related to overall survival of patients with lung cancer. Knock down of TRIM65 in two lung cancer cell lines, SPC-A-1 and NCI-H358, resulted in a significant reduction in cell proliferation, migration, invasion and adhesion and a dramatic increase in G0-G1 phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TRIM65 expression inhibited NCI-H358 cell growth. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TRIM65 was positive related to cell cycle, metastasis up and RHOA-REG pathways, which was further validated by RT-PCR and Western blot in TRIM65 knockdown lung cancer cells and indicated a possible mechanism underlying its effects on lung cancer. In summary, our study suggests that TRIM65 may work as an oncogene and a new effective therapeutic target for lung cancer treatment.

[Clinicopathological characteristics and prognosis of solid pseudopapillary neoplasm of the pancreas: comparison between tumors ≤5 cm and larger tumors].

OBJECTIVE: To compare the clinicopathological characteristics and prognosis of patients with small (≤5 cm) solid pseudopapillary neoplasm of the pancreas (SPN) and those with large (>5 cm) SPNs. METHODS: We retrospectively analyzed the clinical characteristics, laboratory findings, radiological features, treatment and prognosis of 148 patients with histologically confirmed SPN between August, 2006 and December, 2014 and compared the data between patients with small SPNs (≤5 cm) and those with large SPNs (>5 cm). RESULTS: In the large SPN group, the female-to-male ratio was significantly higher than that in small SPN group (61/8 vs 56/23, P=0.009) and the patients were significantly younger in large SPN group (28.3±12.3 vs 33.0±11.4 years, P=0.016). Small SPNs (≤5 cm) typically presented as inhomogeneous solid or cystic tumors, while large SPNs (>5 cm) often appeared as homogeneous solid and cystic tumors, but they did not show any significant difference in aggressive behaviors (P=0.288). The 5-year disease-free survival of patients with small SPNs was 100%, and the 1-, 3-, and 5-year disease-free survival of patients with large SPNs was 98.6%, 94.9%, and 89.3%, respectively (P=0.030), showing no significant differences in the overall survival between the two groups. CONCLUSION: Small SPNs and large SPNs have different clinical characteristics. Even with complete resection, tumors larger than 5 cm are more likely to have tumor recurrence and metastasis, and close follow-up is recommended for these patients.

Risk factors of delayed gastric emptying following pancreaticoduodenectomy.

BACKGROUND: This study aims to explore the morbidity and risk factors of delayed gastric emptying (DGE) following pancreaticoduodenectomy. METHODS: Between 1 January 2013 and 31 December 2013, data from 196 consecutive patients who underwent pancreaticoduodenectomy in the Chinese PLA General Hospital were recorded retrospectively. A total of 17 factors were examined with univariate analysis, and multivariate logistic regression analysis was used to estimate relative risks. RESULTS: DGE occurred in 71 patients (36.2%). The incidence rates of grade A, grade B and grade C DGE were 22.4% (44/196), 6.1% (12/196) and 7.7% (15/196), respectively. There were three post-operative deaths for the entire series, with an overall mortality rate of 1.5%. Braun enteroenterostomy, clinically relevant post-operative pancreatic fistula (CR-POPF) and intra-abdominal collection correlated with DGE rates significantly in univariate analysis, whereas CR-POPF and intra-abdominal collection were independent risk factors in multivariate logistic regression analysis. Body mass index ≥25 kg/m(2) , CR-POPF and intra-abdominal collection correlated with clinically relevant DGE rates significantly and were independent risk factors in univariate analysis and multivariate regression. CONCLUSION: Only post-operative complications instead of operative methods were associated with DGE. Early diagnosis and timely treatment for pancreatic fistula and intra-abdominal collection were helpful to decrease morbidity and promote recovery of DGE.

The detection of (total and ccc) HBV DNA in liver transplant recipients with hepatitis B vaccine against HBV reinfection.

To investigate the levels of hepatitis B virus total DNA (HBV DNA) and covalently closed circular (ccc) DNA in liver transplant recipients who received hepatitis B vaccination, including responders and non-responders, following liver transplantation due to hepatitis B-related diseases and to investigate the efficacy of hepatitis B immune reconstitution against HBV reinfection. Twenty responders and 34 non-responders were enrolled in the present study. The levels of HBV total DNA and ccc DNA in peripheral blood mononuclear cells (PBMCs) and the liver and plasma were detected by real-time polymerase chain reaction (PCR). Fifty-three blood samples and 38 liver allograft tissues were acquired. For the responders, the mean serum titer for anti-HBs (antibodies against hepatitis B surface antigen) was 289 (46.64-1000) IU/ml. Also for the responders, HBV total DNA was detected in PBMCs for one recipient and in the liver for another recipient, but ccc DNA was not detected in either of those 2 recipients. For the non-responders, HBV total DNA was detected in PBMCS for 2 recipients, neither of whom had ccc DNA. Also for the non-responders, HBV total DNA was detected in the livers of 3 recipients, 2 of whom also had ccc DNA. All responders had discontinued hepatitis B immunoglobulin (HBIG), and 13 responders had discontinued antiviral agents. One responder experienced HBV recurrence during the follow-up period. For the majority of liver transplant recipients, no HBV total DNA or ccc DNA was detected in the blood or liver. The lack of HBV total DNA and ccc DNA both in PBMCs and the liver in liver transplant recipients who received hepatitis B vaccination to prevent HBV reinfection should be a prerequisite for the withdrawal of HBIG and/or antiviral agents.

Diagnosis and surgical treatment of esophageal gastrointestinal stromal tumors.

AIM: To retrospectively evaluate our experience with the diagnosis and surgical resection of esophageal gastrointestinal stromal tumors (GISTs). METHODS: Between January 2003 and August 2014, five esophageal GIST cases were admitted to our hospital. In this study, the hospital records, surgery outcomes, tumor recurrence and survival of these patients were retrospectively reviewed. RESULTS: The median age of the patients was 45.6 years (range: 12-62 years). Three patients presented with dysphagia, and one patient presented with chest discomfort. The remaining patient was asymptomatic. Four patients were diagnosed with esophageal GISTs by a preoperative endoscopic biopsy. Three patients underwent esophagectomy, and two patients underwent video-assisted thoracoscopic surgery. The mean operating time was 116 min (range: 95-148 min), and the mean blood loss was 176 mL (range: 30-300 mL). All tumors were completely resected. The mean length of postoperative hospital stay was 8.4 d (range: 6-12 d). All patients recovered and were discharged successfully. The median postoperative follow-up duration was 48 mo (range: 29-72 mo). One patient was diagnosed with recurrence, one patient was lost to follow-up, and three patients were asymptomatic and are currently being managed with close radiologic and clinical follow-up. CONCLUSION: Surgery is the standard, effective and successful treatment for esophageal GISTs. Long-term follow-up is required to monitor recurrence and metastasis.

Retrospective observation of therapeutic effects of adult auxiliary partial living donor liver transplantation on postpartum acute liver failure: a case report.

We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage III and coma. After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation. Emergency liver transplantation was recommended after multidisciplinary panel consultations. The donor, her mother, consented to donate her right liver. Auxiliary partial orthotopic living donor liver transplantion (APOLDLT) was performed. After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression. The combination of anti-hepatitis B virus (HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy. Both the patient and the donor recovered well without any complications. The patient was followed up regularly. Her liver function, clinical signs and symptoms improved significantly. Until now, the recipient has been living for more than 78 mo free of any complications. The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.

Galangin dampens mice lipopolysaccharide-induced acute lung injury.

Galangin, an active ingredient of Alpinia galangal, has been shown to possess anti-inflammatory and antioxidant activities. Inflammation and oxidative stress are known to play vital effect in the pathogenesis of acute lung injury (ALI). In this study, we determined whether galangin exerts lung protection in lipopolysaccharide (LPS)-induced ALI. Male BALB/c mice were randomized to receive galangin or vehicle intraperitoneal injection 3 h after LPS challenge. Samples were harvested 24 h post LPS administration. Galangin administration decreased biochemical parameters of oxidative stress and inflammation, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of galangin were associated with inhibition of nuclear factor (NF)-κB and upregulation of heme oxygenase (HO)-1. Galangin reduces LPS-induced ALI by inhibition of inflammation and oxidative stress.

Reestablishment of active immunity against HBV graft reinfection after liver transplantation for HBV-related end stage liver disease.

BACKGROUND: The aim of this study was to establish a hepatitis B virus (HBV) vaccination protocol among orthotopic liver transplantation (OLT) recipients under the coverage of a low-dose hepatitis B immunoglobulin (HBIG) combined with an antiviral agent prophylaxis protocol. METHOD: Two hundred OLT recipients were included in this study. The vaccine was injected at months 0, 1, 2, and 6. Low-dose HBIG combined with antiviral agent prophylaxis protocol was continued before reestablishment of active immunity against HBV in order to maintain a steady anti-HBs titer. RESULTS: Active immunity against HBV was reestablished in 50 patients, for an overall response rate of 25%. Of the 50 patients, 24 discontinued HBIG without any HBV graft reinfection during a follow-up period of 26.13 ± 7.05 months. 21 patients discontinued both HBIG and antiviral agents during a follow-up period of 39.86 ± 15.47 months, and 4 patients among them appeared to be HBsAg positive. There was no recipient death or graft loss because of HBV reinfection. CONCLUSIONS: Vaccination preventing HBV reinfection for OLT recipients is feasible. The strategy withdrawal of HBIG with induction of active immunity against hepatitis B is reasonable for long-term survivors of OLT; however, discontinuation nucleoside analogues should be cautious.

[The therapeutic mechanisms of sirolimus treatment for ischemic-type biliary lesions after liver transplantation].

OBJECTIVE: To investigate the pathogenesis of ischemic-type biliary lesions (ITBLs) in post-liver transplant patients and the possible therapeutic mechanisms of sirolimus. METHODS: The clinic data of 32 post-liver transplant patients with ITBLs from May 2004 to December 2010 was analyzed. There were including 25 male and 7 female patients with a median age of 46 years (ranging from 19 to 61 years). Patients were divided into those who received sirolimus (sirolimus group) and those who did not (control group). The expression of IL-2, FoxP3, and IL-10 in the portal area, liver function indexes, and bile duct injury score were assessed pre-ITBL, when ITBLs were identified, and after 6 months of sirolimus treatment. RESULTS: Compared with pre-ITBL optical density (OD) values, there was a significantly increase in IL-2 OD(0.138 ± 0.050 in control group and 0.141 ± 0.052 in sirolimus group), but not FoxP3 and IL-10 OD in both groups at the time ITBLs were diagnosed. After 6 months of treatment, the IL-2, FoxP3, and IL-10 OD values in the control group were not different from those when ITBLs were diagnosed. There was a significant reduction in post-therapy IL-2 OD(0.107 ± 0.043, t = 2.087, P = 0.044), and a significant elevation in FoxP3(0.213 ± 0.039) and IL-10 OD(0.187 ± 0.048) in sirolimus group as compared with those when ITBLs were diagnosed(t = -3.822 and -4.350, both P < 0.01). There was a significant increase in serum levels of ALT, AST, total bilirubin, γ-glutamyl transpeptidase and ALP at the time ITBLs were diagnosed compared with pre-ITBL levels in both groups. After 6 months of treatment, the above indexes had not changed in the control group, but significantly improved in the sirolimus group, and the bile duct injury score in the sirolimus group had significantly decreased(4.4 ± 2.4, Z = -2.568, P = 0.010). The 1-year and 3-year graft survival rates in the control group were 6/13 and 5/13, respectively, and 17/19 and 13/19, respectively, in the sirolimus group (χ(2) = 7.166, P = 0.007; χ(2) = 5.398, P = 0.020, respectively). CONCLUSIONS: Sirolimus can downregulate IL-2 expression and upregulate FoxP3 and IL-10 expression, thereby stimulating FoxP3+ Treg cells, suppressing immunopathological damage, and promoting epithelial repair in bile ducts.

Liver transplantation in acute-on-chronic liver failure patients with high model for end-stage liver disease (MELD) scores: a single center experience of 100 consecutive cases.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on risk factors and outcomes of LT for ACLF. METHODS: The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. RESULTS: One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. CONCLUSIONS: Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.