Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells.

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16- NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16- and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

Prevalence of prothrombotic factors in patients with Budd-Chiari syndrome or non-cirrhotic nonmalignant portal vein thrombosis: A hospital-based observational study.

BACKGROUND AND AIM: Comprehensive investigations on the prothrombotic factors of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and non-cirrhotic nonmalignant portal vein thrombosis (PVT), in Eastern patients are scarce. METHODS: Between March 2012 and July 2017, 812 consecutive patients, including 418 BCS and 394 non-cirrhotic nonmalignant PVT patients, were admitted to Xijing Hospital (a Chinese tertiary academic hospital) and screened for prothrombotic factors. Odds ratios (ORs), 95% confidence intervals (CIs), and P-trends were calculated by using conditional logistic regression. RESULTS: The prevalence of myeloproliferative neoplasms (MPNs) was only 6.3% among BCS patients but 28.3% among PVT patients. Notably, the presence of MPNs was associated with a higher risk of hepatic vein-type BCS (OR 9.9, 95% CI 3.6-26.7, P-trend < 0.001) and extensive thrombosis in PVT (OR 4.1, 95% CI 1.9-8.9, P-trend < 0.001). Calreticulin mutations existed in 2.7% of SVT patients. Furthermore, the prevalence of antiphospholipid antibody syndrome and protein C, protein S, or antithrombin deficiency in BCS patients was 7.3% and 22.5%, respectively, similar to that in patients with PVT (7.4% and 25.7%). In addition, factor V Leiden mutation, prothrombin G20210A mutation, and paroxysmal nocturnal hemoglobinuria were identified in < 1% of both BCS and PVT patients. CONCLUSION: There is a significant positive association between MPNs and hepatic vein-type BCS or non-cirrhotic nonmalignant PVT with extensive thrombosis. Additionally, calreticulin mutations should be tested in JAK2V617F -negative SVT patients in China. However, screening for factor V Leiden mutation, prothrombin G20210A mutation, and paroxysmal nocturnal hemoglobinuria may be unnecessary.

Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial.

BACKGROUND: The survival benefit of early placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with cirrhosis and acute variceal bleeding is controversial. We aimed to assess whether early TIPS improves survival in patients with advanced cirrhosis and acute variceal bleeding. METHODS: We did an investigator-initiated, open-label, randomised controlled trial at an academic hospital in China. Consecutive patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomly assigned (2:1) to receive either early TIPS (done within 72 h after initial endoscopy [early TIPS group]) or standard treatment (vasoactive drugs continued to day 5, followed by propranolol plus endoscopic band ligation for the prevention of rebleeding, with TIPS as rescue therapy when needed [control group]). Randomisation was done by web-based randomisation system using a Pocock and Simon's minimisation method with Child-Pugh class (B vs C) and presence or absence of active bleeding as adjustment factors. The primary outcome was transplantation-free survival, analysed in the intention-to-treat population, excluding individuals subsequently found to be ineligible for enrolment. This study is registered with ClinicalTrials.gov, number NCT01370161, and is completed. FINDINGS: From June 26, 2011, to Sept 30, 2017, 373 patients were screened and 132 patients were randomly assigned to the early TIPS group (n=86) or to the control group (n=46). After exclusion of three individuals subsequently found to be ineligible for enrolment (two patients in the early TIPS group with non-cirrhotic portal hypertension or hepatocellular carcinoma, and one patient in the control group due to non-cirrhotic portal hypertension), 84 patients in the early TIPS group and 45 patients in the control group were included in the intention-to-treat population. 15 (18%) patients in the early TIPS group and 15 (33%) in the control group died; two (2%) patients in the early TIPS group and one (2%) in the control group underwent liver transplantation. Transplantation-free survival was higher in the early TIPS group than in the control group (hazard ratio 0·50, 95% CI 0·25-0·98; p=0·04). Transplantation-free survival at 6 weeks was 99% (95% CI 97-100) in the early TIPS group compared with 84% (75-96; absolute risk difference 15% [95% CI 5-48]; p=0·02) and at 1 year was 86% (79-94) in the early TIPS group versus 73% (62-88) in the control group (absolute risk difference 13% [95% CI 2-28]; p=0·046). There were no significant differences between the two groups in the incidence of hepatic hydrothorax (two [2%] of 84 patients in the early TIPS group vs one [2%] of 45 in the control group; p=0·96), spontaneous bacterial peritonitis (one [1%] vs three [7%]; p=0·12), hepatic encephalopathy (29 [35%] vs 16 [36%]; p=1·00), hepatorenal syndrome (four [5%] vs six [13%]; p=0·10), and hepatocellular carcinoma (four [5%] vs one [2%]; p=0·68). There was no significant difference in the number of patients who experienced other serious adverse events (ten [12%] vs 11 [24%]; p=0·07) or non-serious adverse events (21 [25%] vs 19 [42%]; p=0·05) between groups. INTERPRETATION: Early TIPS with covered stents improved transplantation-free survival in selected patients with advanced cirrhosis and acute variceal bleeding and should therefore be preferred to the current standard of care. FUNDING: National Natural Science Foundation of China, National Key Technology R&D Program, Optimized Overall Project of Shaanxi Province, Boost Program of Xijing Hospital.

TIPSS for variceal bleeding in patients with idiopathic non-cirrhotic portal hypertension: comparison with patients who have cirrhosis.

BACKGROUND: In patients with idiopathic non-cirrhotic portal hypertension (INCPH), the usual recommended strategy for management of variceal bleeding is the same as that in cirrhosis. However, this policy has been challenged by the different natural history between INCPH and cirrhosis. AIM: To compare outcomes after transjugular intrahepatic portosystemic shunt (TIPSS) between INCPH and cirrhotic patients admitted for variceal bleeding. METHODS: Between March 2001 and September 2015, 76 consecutive patients with biopsy-proven INCPH undergoing TIPSS for variceal bleeding in a tertiary-care centre were included. 76 patients with cirrhotic portal hypertension receiving TIPSS for variceal bleeding, and matched for age, sex, Child-Pugh class, stent type and index year of TIPSS creation served as controls. RESULTS: Patients with INCPH, compared to those with cirrhosis, had significantly lower mortality (11% vs 36% at 5 years, adjusted HR, 0.37; 95% CI 0.15-0.87, P = 0.022), overt hepatic encephalopathy (16% vs 33% at 5 years, adjusted HR, 0.35; 95% CI 0.16-0.75, P = 0.007) and hepatic impairment, despite similar rates of further bleeding (33% vs 32% at 5 years, adjusted HR, 0.72; 95% CI 0.36-1.44, P = 0.358), and shunt dysfunction (35% vs 36% at 5 years, adjusted HR, 0.84; 95% CI 0.41-1.72, P = 0.627). These findings were consistent across different relevant subgroups. CONCLUSIONS: Patients with INCPH treated with TIPSS for variceal bleeding had similar progression of portal hypertension (further bleeding and shunt dysfunction) but fewer complications of liver disease (overt hepatic encephalopathy and hepatic insufficiency) and lower mortality rate compared with cirrhotic patients with comparable liver function.

Hand-foot-skin reaction of grade ≥ 2 within sixty days as the optimal clinical marker best help predict survival in sorafenib therapy for HCC.

Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43-0.67, P < 0.001) and likelihood of progression by 26% (adjusted HR 0.74, 95%CI 0.58-0.96, P = 0.020) compared with non-responders. Notably, 2HFSR60 remained an effective discriminator among most subgroups and had superior predictive ability to previous definitions, even according to the landmark analysis. Conclusions Our study demonstrated that 2HFSR60, with the best discriminatory ability compared to currently available definitions of sorafenib-related adverse events, could be the optimal clinical marker to identify sorafenib responders with decreased risk of death by half.

Percutaneous Transhepatic Biliary Stent Implantation for Obstructive Jaundice of Perihilar Cholangiocarcinoma: A Prospective Study on Predictors of Stent Patency and Survival in 92 Patients.

PURPOSE: To evaluate prognostic factors for stent patency and survival in patients with perihilar cholangiocarcinoma (pCCA) who underwent percutaneous biliary stent placement. MATERIALS AND METHODS: This prospective study followed 92 consecutive patients with pCCA who underwent metal stent placement between January 2013 and July 2014. Of the total number of patients, 11 had ascites, and 36 had biliary obstruction for > 1 month at the time of stent placement. Cumulative patency and survival rates were assessed with Kaplan-Meier curves, and independent predictors were calculated with Cox regression. A new formula was developed to predict patient survival. RESULTS: Tumor size was significantly associated with stent patency (hazard ratio = 2.425; 95% confidence interval, 1.134-5.168). Independent predictors of survival included lymph node metastasis, intrahepatic mass lesion, cancer antigen 19-9 (CA19-9), ascites, and duration of jaundice. A new equation was developed to assess risk: R = 7 × (duration of biliary obstruction-0 if < 30 d, 1 if > 30 d) + 7 × (CA19-9-0 if < 500, 1 if > 500) + 7 × (ascites-0 if none present, 1 if ascites present) + 10 × (lymph node metastasis-0 if no metastasis, 1 if metastasis present) + 9 (intrahepatic mass lesion-0 if absent, 1 if present). Among patients who developed stent occlusion, patients who underwent recanalization of the occluded stent had longer survival compared with patients who did not undergo recanalization (109 d vs 29 d, P = .001). CONCLUSIONS: Prognostic factors for survival after percutaneous stent placement in patients with pCCA were tumor stage, duration of jaundice, CA19-9, and ascites. Tumor size affected stent patency. Prognosis for patients with reintervention after occlusion of the stent improved.

The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization.

This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2-66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24-3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15-2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy.

Transjugular Intrahepatic Portosystemic Shunt for Extrahepatic Portal Venous Obstruction in Children.

OBJECTIVES: To evaluate the feasibility and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for extrahepatic portal venous obstruction with recurrent variceal bleeding in children. METHODS: From November 2005 to December 2013, 28 consecutive paediatric patients with extrahepatic portal venous obstruction treated with TIPS for recurrent variceal bleeding refractory to medical/endoscopic therapy and/or surgical treatment in a tertiary-care centre were followed until last clinical evaluation or death. The median follow-up time was 36.0 months (range 4.0-106.0 months). RESULTS: Seventeen boys and 11 girls of ages 7.1 to 17.9 years (median 12.3 years) weighing 19.0 to 62.0 kg (median 33.5 kg) were treated. TIPS was successfully placed in 17 of 28 (60.7%) patients via a transjugular approach alone (n = 4), a combined transjugular/transhepatic approach (n = 9), or a combined transjugular/transsplenic approach (n = 4). Shunt dysfunction occurred in 6 of 17 (35.3%) patients. The cumulative 1- and 3-year free-from-variceal-rebleeding rates in TIPS success group were higher than those in TIPS failure group (75.0% and 67.5% vs 45.5% and 18.2%, respectively, P = 0.0075). Compared with the TIPS failure group, the improvements in the height-for-age z scores were greater in the TIPS success group (P = 0.017). Procedure-related complication occurred in 1 patient (3.6%), and no episode of post-TIPS hepatic encephalopathy occurred in any patient. Except 1 patient in the TIPS success group died at 115 postoperative days, all patients were alive. CONCLUSIONS: TIPS is feasible and effective in children with extrahepatic portal venous obstruction and recurrent variceal bleeding. TIPS could represent a less-invasive alternative to traditional surgical portosystemic shunting or a valuable treatment option if surgery and endoscopic treatment failed.

Percutaneous transhepatic biliary metal stent for malignant hilar obstruction: results and predictive factors for efficacy in 159 patients from a single center.

AIM: To investigate and compare the efficacy and safety of percutaneous transhepatic biliary stenting (PTBS) using a one- or two-stage procedure and determine the predictive factors for the efficacious treatment of malignant hilar obstruction (MHO). METHODS: 159 consecutive patients with MHO who underwent PTBS were enrolled between January 2010 and June 2013. Patients were classified into one- or two-stage groups. Independent predictors of therapeutic success were evaluated using a logistic regression model. RESULTS: 108 patients were treated with one-stage PTBS and 51 patients were treated with two-stage PTBS. The stents were technically successful in all patients. Successful drainage was achieved in 114 patients (71.4 %). A total of 42 early major complications were observed. Re-interventions were attempted in 23 patients during follow-up. The cumulative primary patency rates at 3, 6, and 12 months were 88, 71, and 48 %, respectively. Stent placement using a one- or two-stage procedure did not significantly affect therapeutic success, early major complications, median stent patency, or survival. A stent placed across the duodenal papilla was an independent predictor of therapeutic success (odds ratio = 0.262, 95 % confidence interval [0.107-0.642]). Patients with stents across papilla had a lower rate of cholangitis compared with patients who had a stent above papilla (7.1 vs. 20.3 %, respectively, p = 0.03). CONCLUSIONS: The majority of patients with MHO who underwent one-stage PTBS showed similar efficacy and safety outcomes compared with those who underwent two-stage PTBS. Stent placement across the duodenal papilla was associated with a higher therapeutic success rate.

Thrombotic risk factors in Chinese nonmalignant and noncirrhotic patients with portal vein thrombosis: an observational study with a systematic review of the literature.

BACKGROUND: Until now, no data on the routine screening for thrombotic risk factors in Chinese nonmalignant and noncirrhotic patients with portal vein thrombosis (PVT) have been reported. METHODS: A total of 141 nonmalignant and noncirrhotic patients with PVT who underwent screening tests for thrombotic risk factors between September 2009 and August 2012 were included in this study. RESULTS: The JAK2 V617F mutation was found in 35 of the 141 patients tested. Neither the JAK2 exon 12 mutation nor the MPL W515 L/K mutation was found in any of the 50 patients tested. Overt myeloproliferative neoplasms (MPNs) were diagnosed in 13 patients (polycythemia vera, n=1; essential thrombocythemia, n=9; idiopathic myelofibrosis, n=3). Latent MPNs were considered in 23 patients with the JAK2 V617F mutation but without any significant abnormalities, as determined through regular blood tests. Anticardiolipin IgG antibodies were positive in none of the 136 patients tested. Paroxysmal nocturnal hemoglobinuria was not found in any of the 141 patients tested. Neither the factor V G1691A mutation nor the factor II G20210A mutation was found in any of the 72 patients tested. The C677T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) was found in 29 of the 38 patients tested. Hyperhomocysteinemia was detected in eight of the 39 patients tested. CONCLUSION: MPNs are an important thrombotic risk factor in Chinese patients with PVT. However, the extreme rarity of paroxysmal nocturnal hemoglobinuria, anticardiolipin IgG antibodies, and factor V G1691A and factor II G20210A mutations has precluded any support for the implementation of routine screening for these thrombotic factors in such patients. Additional case-control studies should confirm the role of the MTHFR C677T mutation and hyperhomocysteinemia in the pathogenesis of PVT.

Transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis: prognostic factors in a single-center study of 188 patients.

Transarterial chemoembolization (TACE) could achieve a better survival benefit than conservative treatment for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). In this retrospective study, all HCC patients with Child-Pugh score <7 and PVTT who were consecutively admitted to our center between January 2006 and June 2012 and underwent TACE were enrolled. The efficacy and safety of TACE were analyzed. Prognostic factors were determined by Cox regression analysis. Of the 188 patients included, 89% had hepatitis B virus infection, 100% were at Barcelona Clinic Liver Cancer stage C, and 81% (n = 152) and 19% (n = 36) were at Child-Pugh classes A and B, respectively. The incidence of procedure-related complications was 88%. No procedure-related death was found. The median overall survival was 6.1 months. Type of PVTT (hazard ratio [HR] = 2.806), number of tumor lesions (HR = 2.288), Child-Pugh class (HR = 2.981), and presence of metastasis (HR = 1.909) were the independent predictors of survival. In conclusion, TACE could be selectively used for the treatment of advanced HCC with PVTT. But a high rate of postoperative adverse events should not be undermined in spite of no procedure-related death. Preoperative type of PVTT, number of tumor lesions, Child-Pugh class, and metastasis could predict the prognosis of these patients.

EASL- and mRECIST-evaluated responses to combination therapy of sorafenib with transarterial chemoembolization predict survival in patients with hepatocellular carcinoma.

PURPOSE: Published studies have not investigated the suitability of Response Evaluation Criteria in Solid Tumors (RECIST), European Association for the Study of the Liver (EASL) criteria, and modified RECIST (mRECIST) for assessing the response of patients with hepatocellular carcinoma to treatment with sorafenib combined with transarterial chemoembolization. Here, we aimed to define the earliest time at which the response to combination therapy could be accurately assessed and validate the prognostic value of these criteria at this early posttherapy time point. EXPERIMENTAL DESIGN: A total of 114 consecutive patients with hepatocellular carcinoma receiving combination therapy were retrospectively enrolled. The therapy response at different time points was assessed using RECIST, EASL, and mRECIST. Cox regression analysis and Kaplan-Meier curves were used to assess overall survival (OS) in the responders and nonresponders. RESULTS: At the third follow-up (median, 94 days; range, 89-102 days) after therapy, the response rates obtained using EASL (50.6%) and mRECIST (51.6%) were greater than that obtained using RECIST (16.5%). The agreement was strong between the mRECIST and EASL results (k = 0.9) but weak between mRECIST and RECIST (k = 0.3). The EASL and mRECIST responses significantly correlated with survival. Risk reductions of 52% and 50% were observed for EASL and mRECIST responders, respectively, compared with nonresponders. However, no significant association between the treatment response and survival was observed using RECIST. CONCLUSIONS: The earliest time to evaluate the response to combination therapy is 3 months (median, 94 days) after therapy. EASL and mRECIST responses are independent predictors for OS at this early time point.

Transjugular intrahepatic portosystemic shunt for symptomatic portal hypertension in hepatocellular carcinoma with portal vein tumor thrombosis.

AIM: Transjugular intrahepatic portosystemic shunt (TIPS) represents a major advance in the treatment of complications of portal hypertension. However, this procedure is contraindicated in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). This study aims to evaluate the safety and efficacy of TIPS in these patients with portal hypertension and determine the predictors of survival after TIPS creation. METHODS: Between 2005 and 2011, 58 consecutive HCC patients with symptomatic portal hypertension and concomitant PVTT underwent TIPS placement. Procedure-related complications, treatment efficacy of portal hypertension complications and survival were evaluated. RESULTS: After TIPS, no patient experienced major procedure-related complications such as hemorrhage or contrast extravasation. Portosystemic pressure gradient was decreased by 14 mmHg on average. Refractory ascites was partially or completely resolved in 19 of 20 patients. Hydrothorax was decreased in all of eight patients. Acute variceal bleeding was successfully controlled in all of five patients. Severe diarrhea was controlled successfully in all of nine patients. During the follow-up period (mean, 78.5 days; range, 11-1713), 56 patients died and two patients remained alive. The median survival period after TIPS was 77 days. Multivariate Cox regression analysis showed that ascites (P = 0.026), white blood cell (P = 0.007) and degree of PVTT (P < 0.001) were independent predictors for survival. CONCLUSION: TIPS may be effective for the palliative treatment of portal hypertension in HCC patients with PVTT. Major procedure-related complications were rarely observed. Ascites, white blood cell and degree of PVTT were independently associated with survival.

Prognostic factors in non-malignant and non-cirrhotic patients with portal cavernoma: an 8-year retrospective single-center study.

AIM: To evaluate the outcome of non-malignant and non-cirrhotic patients with portal cavernoma and to determine the predictors for survival. METHODS: Between July 2002 and June 2010, we retrospectively enrolled all consecutive patients admitted to our department with a diagnosis of portal cavernoma without abdominal malignancy or liver cirrhosis. The primary endpoint of this observational study was death and cause of death. Independent predictors of survival were identified using the Cox regression model. RESULTS: A total of 64 patients were enrolled in the study. During a mean follow-up period of 18 ± 2.41 mo, 7 patients died. Causes of death were pulmonary embolism (n = 1), acute leukemia (n = 1), massive esophageal variceal hemorrhage (n = 1), progressive liver failure (n = 2), severe systemic infection secondary to multiple liver abscesses (n = 1) and accident (n = 1). The cumulative 6-, 12- and 36-mo survival rates were 94.9%, 86% and 86%, respectively. Multivariate Cox regression analysis demonstrated that the presence of ascites (HR = 10.729, 95%CI: 1.209-95.183, P = 0.033) and elevated white blood cell count (HR = 1.072, 95%CI: 1.014-1.133, P = 0.015) were independent prognostic factors of non-malignant and non-cirrhotic patients with portal cavernoma. The cumulative 6-, 12- and 36-mo survival rates were significantly different between patients with and without ascites (90%, 61.5% and 61.5% vs 97.3%, 97.3% and 97.3%, respectively, P = 0.0008). CONCLUSION: The presence of ascites and elevated white blood cell count were significantly associated with poor prognosis in non-malignant and non-cirrhotic patients with portal cavernoma.

Transjugular intrahepatic portosystemic shunt for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: study protocol for a randomised controlled trial.

INTRODUCTION: Portal vein thrombosis (PVT) increases the risk of variceal rebleeding in liver cirrhosis. However, the strategy for preventing variceal rebleeding in cirrhotic patients with PVT has not been explored. This study aims to evaluate whether the transjugular intrahepatic portosystemic shunt (TIPS) or conventional therapy is preferable for the prevention of variceal rebleeding in liver cirrhosis patients with PVT. METHODS AND ANALYSIS: This is a randomised controlled trial comparing the safety and efficacy of TIPS versus conventional therapy (ie, endoscopic therapy combined with non-selective ß-blockers and anticoagulants) for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. A total of 50 cirrhotic patients with PVT (thrombus >50% of portal vein lumen occupancy) and a history of variceal bleeding will be stratified according to the Child-Pugh class and degree of PVT, and randomised into the TIPS and conventional therapy groups. The primary objective was to compare the incidence of variceal rebleeding between the two groups. The secondary objectives were to compare the overall mortality, variceal rebleeding-related mortality, portal vein recanalisation and complications between the two groups, and to observe the progression of PVT in patients without portal vein recanalisation. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Xijing hospital (No. 20110224-5), and was registered at ClinicalTrials.gov (NCT01326949). All participants give written informed consent. The first patient was recruited into our study on 4 June 2011. A total of 29 patients were recruited through 5 March 2013 (14 and 15 patients assigned to the TIPS and conventional therapy groups, respectively). If TIPS is superior to conventional therapy for the prevention of variceal rebleeding in cirrhotic patients with PVT, TIPS might be recommended as the first-line therapy in such patients. But a small sample size potentially limits the generalisation of our conclusions. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 29 March 2011. The trial registration number is NCT01326949. TRIAL STATUS: The first patient was recruited into our study on 4 June 2011. A total of 29 patients were recruited through 5 March 2013 (14 and 15 patients assigned to the TIPS and conventional therapy groups, respectively).

Prevalence of paroxysmal nocturnal hemoglobinuria in Chinese patients with Budd-Chiari syndrome or portal vein thrombosis.

BACKGROUND AND AIM: Routine screening for paroxysmal nocturnal hemoglobinuria (PNH) in patients with Budd-Chiari syndrome (BCS) or portal vein thrombosis (PVT) has been recommended in Western countries. However, little is known about whether the routine screening test should be necessary in Chinese patients with BCS or PVT. We conducted a prospective observational study to examine the prevalence of PNH in these patients. METHODS: Patients with primary BCS or non-malignant PVT who were consecutively admitted to our department or regularly followed up between September 2009 and December 2011 were eligible for the study and detected the expression of CD55 and CD59 on erythrocytes and granulocytes. The CD55 or CD59 deficiency was considered as the proportion of erythrocytes or granulocytes with normal expression of CD55 or CD59 was less than 90%. PNH was diagnosed by both CD55 and CD59 deficient clone at flow cytometry of peripheral blood cells. RESULTS: CD55 and/or CD59 deficiencies were found in 1.6% (2/127) of patients with primary BCS, 1.0% (1/100) of non-malignant and non-cirrhotic patients with PVT, and 4.7% (4/85) of cirrhotic patients with PVT. Only one patient had both CD55 and CD59 deficiencies on granulocytes. But he had been diagnosed with PNH before BCS. CONCLUSIONS: Paroxysmal nocturnal hemoglobinuria was very rare in Chinese patients with BCS or PVT, suggesting that routine screening for PNH should not be indiscriminately performed in such patients.

Studies on immunoregulatory and anti-tumor activities of a polysaccharide from Salvia miltiorrhiza Bunge.

In this study, we purified and characterized a polysaccharide (SMP-W1) from Salvia miltiorrhiza and investigated its anticancer and immunoregulatory potential in vitro and in vivo. The monosaccharide composition, protein content, uronic acid content, total carbohydrate content, viscosity and molecular weight of SMP-W1 were analyzed. In vitro, SMP-W1 had an antiproliferative effect on hepatocellular carcinoma H22 cells, especially at the high concentration of 400 µg/ml. Simultaneously the polysaccharide SMP-W1 significantly inhibited tumor growth and increased serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in rats, as well as the secretion of TNF-α. In addition, the body weight, spleen index and thymus index in tumor-bearing mice were significantly improved by SMP-W1 treatment. Taken together, these results indicated that SMP-W1 possessed strong in vivo and in vitro anti-tumor activity and improves the immune response in tumor-bearing mice. Therefore, it could be developed as an anti-tumor agent with immunomodulatory activity.

CT features of non-malignant portal vein thrombosis: a pictorial review.

Portal vein thrombosis (PVT) is a rare clinical entity in general population, but a relatively frequent entity in liver cirrhosis. Severe PVT-related complications are potentially lethal, such as ischemic intestinal infarction and complications of portal hypertension. Additionally, occlusive PVT can not only increase the incidence of variceal rebleeding, but also significantly decrease the cirrhotic patients' survival. Based on the clinical significance of PVT, early diagnosis is very critical to allow for rapid establishment of appropriate treatment and improvement of prognosis. Dynamic CT scan is an important diagnostic modality of PVT. The objective of this pictorial review is to illustrate various CT features of non-malignant portal vein thrombosis and its associated abnormalities. Evolution of portal vein thrombosis, such as stage, degree, and extension of thrombus, can be evaluated according to CT demonstrations, which is helpful to timely adopt appropriate treatment modality. Other associated CT findings include the dilation of collateral veins around the obstructed portion of portal vein and the hepatic perfusion and morphology abnormalities.

Transjugular intrahepatic portosystemic shunt may be superior to conservative therapy for variceal rebleeding in cirrhotic patients with non-tumoral portal vein thrombosis: a hypothesis.

The presence of occlusive portal vein thrombosis (PVT) greatly changes the natural history of liver cirrhosis, because it not only significantly increases the incidence of variceal rebleeding but also negatively influences the survival. However, due to the absence of strong evidence, no standard treatment algorithm for the secondary prophylaxis of variceal bleeding in cirrhotic patients with non-tumoral PVT has been established. Previous randomized controlled trials have demonstrated that transjugular intrahepatic portosystemic shunt (TIPS) can significantly decrease the incidence of variceal rebleeding in cirrhotic patients without PVT, compared with conservative therapy (i.e., endoscopic plus pharmacological therapy). Further, several large cohort studies have confirmed that TIPS can effectively prevent variceal rebleeding in cirrhotic patients with non-tumoral PVT. On the other hand, TIPS can facilitate recanalizing the thrombosed portal vein by endovascular manipulations, even in the presence of cavernous transformation of the portal vein (CTPV). More importantly, successful TIPS insertions can maintain the persistent portal vein patency, and avoid thrombus extension into the portal venous system. By comparison, anticoagulation therapy can achieve portal vein recanalization only in patients with partial PVT, but not in those with occlusive PVT or CTPV, and the use of anticoagulants may aggravate the risk of variceal bleeding in cirrhotic patients with a history of variceal bleeding. Collectively, we hypothesize that TIPS may be superior to conservative therapy for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. Randomized controlled trials should be conducted to evaluate the survival benefit of TIPS in these patients.