Hongyu Li

Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis of observational studies

BACKGROUND & AIMS Systematic review and meta-analysis were performed to evaluate the safety and efficacy of anticoagulation for the treatment of portal vein thrombosis (PVT) in cirrhotic patients. METHODS The PubMed, EMBASE, Cochrane Library, and ScienceDirect databases were searched. The rates of bleeding complications and portal vein recanalization in patients who received anticoagulant therapy were pooled. The odds ratio (OR) with 95% confidence interval (CI) was calculated to express the difference in the rate of portal vein recanalization between anticoagulation and non-anticoagulation groups. All meta-analyses were conducted by using a random-effects model. RESULTS Sixteen of 960 initially identified papers were included. Two studies reported a low incidence of major anticoagulation-related complications (4% [2/55] and 3% [1/33]), but no lethal complications occurred. The rate of anticoagulation-related bleeding ranged from 0% to 18% with a pooled rate of 3.3% (95% CI=1.1%-6.7%). The heterogeneity was not significant in the meta-analysis. The total rate of portal vein recanalization ranged from 37% to 93% with a pooled rate of 66.6% (95% CI=54.7%-77.6%). The rate of complete portal vein recanalization ranged from 0% to 75% with a pooled rate of 41.5% (95% CI=29.2%-54.5%). However, the heterogeneity was significant in the 2 meta-analyses. The rate of complete portal vein recanalization was significantly higher in anticoagulation group than in non-anticoagulation group (OR=4.16, 95% CI=1.88-9.20, P=0.0004). The heterogeneity was not significant in the meta-analysis. CONCLUSION Anticoagulation could achieve a relatively high rate of portal vein recanalization in cirrhotic patients with PVT. Given that only a small number of non-randomized comparative studies are reported, randomized controlled trials are warranted to confirm the risk-to-benefit of anticoagulation in such patients, especially anticoagulation-related bleeding.

Serum Liver Fibrosis Markers for Predicting the Presence of Gastroesophageal Varices in Liver Cirrhosis: A Retrospective Cross-Sectional Study.

Background and Aims. A retrospective cross-sectional study was conducted to evaluate the role of hyaluronic acid (HA), laminin (LN), amino-terminal propeptide of type III procollagen (PIIINP), and collagen IV (CIV) in predicting the presence of gastroesophageal varices (GEVs) in patients with liver cirrhosis. Methods. We enrolled 118 patients with liver cirrhosis who underwent the tests for the four serum liver fibrosis markers and upper gastrointestinal endoscopy at the same admissions. The predictive values of the four serum liver fibrosis markers were evaluated by the areas under the receiving operator characteristics curves (AUROCs) with 95% confidence intervals (CIs). Results. The prevalence of GEVs was 88% (104/118). The AUROCs for HA, LN, PIIINP, and CIV levels in predicting the presence of GEVs were 0.553 (95% CI: 0.458 to 0.644, P = 0.5668), 0.490 (95% CI: 0.397 to 0.584, P = 0.9065), 0.622 (95% CI: 0.528 to 0.710, P = 0.1099), and 0.560 (95% CI: 0.466 to 0.652, P = 0.4909). The PIIINP level at a cut-off value of 31.25 had a sensitivity of 73.1% and a specificity of 57.1%. Conclusions. The present study did not recommend HA, LN, PIIINP, and CIV levels to evaluate the presence of GEVs in liver cirrhosis.

Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma: A systematic review and meta-analysis of observational studies

Background and aims Neutrophil to lymphocyte ratio (NLR) is an inflammatory-based marker. A systematic review and meta-analysis was performed to explore the prognostic role of NLR in patients with hepatocellular carcinoma (HCC). Results Overall, 598 papers were identified, of which 90 papers including 20,475 HCC patients were finally included. Low baseline NLR was significantly associated with better overall survival (HR = 1.80, 95% CI: 1.59–2.04, p < 0.00001) and recurrence-free or disease-free survival (HR = 2.23, 95% CI: 1.80–2.76, p < 0.00001). Low post- treatment NLR was significantly associated with better overall survival (HR = 1.90, 95% CI: 1.22–2.94, p = 0.004). Decreased NLR was significantly associated with overall survival (HR = 2.23, 95%CI: 1.83–2.72, p < 0.00001) and recurrence-free or disease-free survival (HR = 2.23, 95% CI: 1.83–2.72, p < 0.00001). The findings from most of subgroup meta-analyses were consistent with those from the overall meta-analyses. Materials and Methods All relevant literatures were identified via PubMed, EMBASE, and Cochrane library databases. Hazard ratio (HR) with 95% confidence interval (95%CI) was calculated. Subgroup meta-analyses were performed according to the treatment options, NLR cut-off value ranges, and regions. Conclusions NLR should be a major prognostic factor for HCC patients. NLR might be further incorporated into the prognostic model of HCC.

Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis

Background and Aims The prognosis of hepatocellular carcinoma (HCC) treated with hepatic resection may be improved by the adjunctive use of transarterial chemoembolization (TACE). This study aimed to systematically compare the outcomes between hepatic resection with and without TACE groups. Methods All relevant randomized controlled trials (RCTs) and non-RCTs were searched by the PubMed, EMBASE, and Cochrane Library databases. Overall survival (OS) and disease-free survival (DFS) were two major outcomes. Meta-analyses were performed according to the timing of TACE (pre- or post-operative TACE). Subgroup analyses were also performed. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated. Results Overall, 55 papers were included (14 RCTs and 41 non-RCTs). Overall meta-analyses demonstrated that OS and DFS were statistically similar between hepatic resection with and without pre-operative TACE groups (HR = 1.01, 95%CI = 0.87–1.19, P = 0.87; HR = 0.91, 95%CI = 0.82–1.01, P = 0.07). Subgroup analyses of RCTs or non-RCTs showed that OS and DFS remained statistically similar between hepatic resection with and without pre-operative TACE groups. Subgroup analysis of incomplete or no tumor necrosis showed that OS was worse in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group. By contrast, subgroup analysis of complete tumor necrosis showed that DFS was better in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group. Overall meta-analyses demonstrated that OS and DFS were better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group (HR = 0.85, 95%CI = 0.72–1.00, P = 0.06; HR = 0.83, 95%CI = 0.73–0.94, P = 0.004). Subgroup analyses of RCTs, vascular invasion, or large HCC showed that OS and DFS remained better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group. By contrast, subgroup analyses of non-RCTs, no vascular invasion, or small HCC showed that OS and DFS were statistically similar between the two groups. Conclusions Post-operative TACE, rather than pre-operative TACE, may be considered as an adjunctive treatment option for HCC treated with hepatic resection.

Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study

Background Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. Material/Methods All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. Results A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506–0.6 and 0.539–0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601–0.664 and 0.596–0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627–0.69 and 0.607–0.692, respectively. Conclusions APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis.

Management of hepatocellular carcinoma: an overview of major findings from meta-analyses

This paper aims to systematically review the major findings from meta-analyses comparing different treatment options for hepatocellular carcinoma (HCC). A total of 153 relevant papers were searched via the PubMed, EMBASE, and Cochrane library databases. They were classified according to the mainstay treatment modalities (i.e., liver transplantation, surgical resection, radiofrequency ablation, transarterial embolization or chemoembolization, sorafenib, and others). The primary outcome data, such as overall survival, diseases-free survival or recurrence-free survival, progression-free survival, and safety, were summarized. The recommendations and uncertainties regarding the treatment of HCC were also proposed.

Diabetes is associated with an increased risk of in-hospital mortality in liver cirrhosis with acute upper gastrointestinal bleeding.

1 Yilmaz B, Aydin H, Can G, Sentürk Z, Üstüner B, Yilmaz H, et al. The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in inactive hepatitis B carriers. Eur J Gastroenterol Hepatol 2014; 26:1325–1328. 2 Yayla C, Canpolat U, Akyel A, Gayretl Yayla K, Akboğa MK, Eyiol A, et al. Association of neutrophil–lymphocyte ratio with impaired aortic elasticity in newly diagnosed and never-treated hypertensive patients. Blood Press Monit 2015. [Epub ahead of print]. 3 Buyukkaya E, Karakas MF, Karakas E, Akçay AB, Tanboga IH, Kurt M, Sen N. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost 2014; 20:159–163. 4 Tsai JC, Sheu SH, Chiu HC, Chung FM, Chang DM, Chen MP, et al. Association of peripheral total and differential leukocyte counts with metabolic syndrome and risk of ischemic cardiovascular diseases in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2007; 23:111–118. 5 Shim WS, Kim HJ, Kang ES, Ahn CW, Lim SK, Lee HC, Cha BS. The association of total and differential white blood cell count with metabolic syndrome in type 2 diabetic patients. Diabetes Res Clin Pract 2006; 73:284–291. 6 European Association for the study of the liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009; 50:227–242.

Role of D-dimer in the Development of Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis

Background and Aims: A meta-analysis was performed to explore the role of the D-dimer in the development of portal vein thrombosis (PVT) in liver cirrhosis. Methods: All papers were searched via PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang, and VIP databases. A standardized mean difference (SMD) with 95% confidence interval (CI) was pooled. Results: Overall, 284 studies were initially identified, of which 21 were included. Cirrhotic patients with PVT had a significantly higher D-dimer concentration than those without PVT (pooled SMD = 1.249, 95%CI = 0.740–1.758). After the portal hypertension-related surgery, cirrhotic patients with PVT had a similar preoperative D-dimer concentration to those without PVT (pooled SMD = 0.820, 95%CI = −0.122–0.286), but a higher postoperative value of D-dimer concentration than those without PVT (pooled SMD = 2.505, 95%CI = 0.975–4.036). Notably, the D-dimer concentration at the 1st postoperative day was similar between cirrhotic patients with and without PVT (pooled SMD = 0.137, 95%CI = −0.827–1.101), but that at the 7th post-operative day was higher in cirrhotic patients with PVT than in those without PVT (pooled SMD = 1.224, 95%CI = 0.277–2.171). Conclusion: D-dimer might be regarded as a diagnostic marker for PVT in liver cirrhosis. In addition, postoperative D-dimer testing is worthwhile for the diagnosis of PVT after portal hypertension-related surgery.

Epidemiology, Risk Factors, and In-Hospital Mortality of Venous Thromboembolism in Liver Cirrhosis: A Single-Center Retrospective Observational Study

Background Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be increased in liver cirrhosis. We conducted a single-center study to explore the epidemiology, risk factors, and in-hospital mortality of VTE in Chinese patients with liver cirrhosis. Material/Methods All patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and December 2013 were retrospectively included. Results Of 2006 patients with liver cirrhosis included, 9 patients were diagnosed with or developed VTE during hospitalization, including 5 patients with a previous history of DVT, 1 patient with either a previous history of DVT or new onset of PE, and 3 patients with new onset of VTE (PE, n=1; DVT, n=2). Risk factors for VTE included a significantly higher proportion of hypertension and significantly higher red blood cells, hemoglobin, alanine aminotransferase, aspartate aminotransferase, prothrombin time (PT), international normalized ratio (INR), D-dimer, and Child-Pugh scores. The in-hospital mortality was significantly higher in patients with VTE than those without VTE (33.3% [3/9] versus 3.4% [67/1997], P<0.001). Conclusions VTE was observed in 0.4% of patients with liver cirrhosis during hospitalization and it significantly increased the in-hospital mortality. Elevated PT/INR aggravated the risk of VTE.

Comparison of cytotoxic T lymphocyte responses against pancreatic cancer induced by dendritic cells transfected with total tumor RNA and fusion hybrided with tumor cell

Pancreatic cancer (PC) is a deadly human malignancy. Dendritic cell (DC)-based immunotherapy with whole tumor antigens demonstrates potential efficiency in cancer treatment. Tumor RNA and tumor fusion hybrid cells are sources of whole tumor antigens for preparing DC tumor vaccines. However, the efficacy of these sources in eliciting immune responses against PC has not yet to be directly compared. In the present study, patient-derived PC cells and DCs were fused (DC–tumor hybrids) and primary cultured PC cell-derived total RNA was electroporated into autologous DCs (DC–tumor RNA). The antitumor immune responses induced by DC–tumor hybrids and DC–tumor RNA were compared directly. The results showed that both RNA and hybrid methodologies could induce tumor-specific cytotoxic T lymphocyte (CTL) responses, but pulsing DCs with total tumor RNA could induce a higher frequency of activated CTLs and T-helper cells than fusing DCs with autologous tumor cells. In addition, DC–tumor RNA triggered stronger autologous tumor cell lysis than DC–tumor hybrids. It could be concluded that DCs pulsed with whole tumor RNA are superior to those fused with tumor cells in priming anti-PC CTL responses. Electroporation with total tumor RNA may be more suitable for DC-based PC vaccination.