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Anticoagulation with warfarin might result in the resolution of more advanced PVT effectively and safely in patients with liver cirrhosis. In addition, we did not demonstrate the benefit of anticoagulation for the decompensation or death.

Background and AimA large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma (HCC) and the results were controversial. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC.MethodsMEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Library were searched from January 1990 to October 2013 and these databases were searched for appropriate studies combining TACE and sorafenib in treatment of HCC. Two authors independently reviewed the databases and extracted the data and disagreements were resolved by discussion. Effective value and safety were analyzed. Effective value included disease control rate (DCR), time to progression (TTP) and overall survival (OS).Results17 studies were included in the study. In the 10 noncomparative studies, DCR ranged from 18.4 to 91.2%. Median TTP ranged from 7.1 to 9.0 months, and median OS ranged from 12 to 27 months. In the 7 comparative studies, the hazard ratio (HR) for TTP was found to be 0.76 (95% CI 0.66–0.89; P<0.001) with low heterogeneity among studies (P = 0.243; I2 = 25.5%). However, the HR for OS was found to be 0.81 (95% CI 0.65–1.01; P = 0.061) with low heterogeneity among studies (P = 0.259; I2 = 25.4%). The common toxicities included fatigue, diarrhea, nausea, hand foot skin reaction (HFSR), hematological events, hepatotoxicity, alopecia, hepatotoxicity, hypertension and rash/desquamation. AEs are generally manageable with dose reductions.ConclusionsCombination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS. Further well-designed randomized controlled studies are needed to confirm the efficacy of combination therapy.

Adjunctive variceal embolization during TIPS procedures might be beneficial in the prevention of variceal rebleeding. However, given the heterogeneity of type of stents, embolic agents, type of varices, and indications of variceal embolization among studies, additional well-designed randomized, controlled trials with larger sample size and use of covered stents should be warranted to confirm these findings.

Background and AimsThe 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.MethodsAll 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.ResultsOverall, 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.ConclusionsPost-operative TACE, rather than pre-operative TACE, may be considered as an adjunctive treatment option for HCC treated with hepatic resection.

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.

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 ¼ 0.9) but weak between mRECIST and RECIST (k ¼ 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.

BackgroundTransarterial chemoembolization (TACE) is the recommended treatment for hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) B-stage, whereas sorafenib is an orally administered small molecule target drug for BCLC C-stage. This updated systemic review and meta-analysis focuses on identifying the efficacy of the combination of TACE with sorafenib, which remains controversial despite years of exploration.MethodsPubMed, EMBASE, Scopus and the Cochrane Library were systematically reviewed to search for studies published from January 1990 to May 2017. Studies focusing on the efficacy of combination therapy for unresectable HCC were eligible. The hazard ratio (HR) with 95% confidence intervals (95% CIs) for time to progression (TTP), overall survival (OS), disease control rate (DCR) and aetiology were collected. The data were then analysed through fixed/random effects meta-analysis models with STATA 13.0. The incidence and severity of treatment-related adverse events (AEs) were also evaluated.ResultsTwenty-seven studies were included. Thirteen non-comparative studies reported median OS (ranging from 18.5 to 20.4 months), median TTP (ranging from 7 to 13.9 months) and DCR (ranging from 18.4 to 95%). Fourteen comparative studies provided median OS (ranging from 7.0 to 29.7 months) and median TTP (ranging from 2.6 to 10.2 months). Five comparative studies provided DCR (ranging from 32 to 97.2%). Forest plots showed that combination therapy significantly improved TTP (HR = 0.66, 95% CI 0.50–0.81, P = 0.002) rather than OS (HR = 0.63, 95% CI 0.55–0.71, P = 0.058), compared to TACE alone. DCR increased significantly in the combination therapy group (OR = 2.93, 95% CI 1.59–5.41, P = 0.005). Additional forest plots were drawn and no significant differences were observed with regard to survival outcome among various aetiologies. Forest plots for separate analysis of regions showed the HR for TTP was 0.62 (95% CI 0.45–0.79, P = 0.002) in the Asian countries group, and 0.82 (95% CI 0.59–1.05, P = 0.504)) in western countries. The HR for OS was 0.61 (95% CI 0.48–0.75, P = 0.050) in the Asian countries group and was 0.88 (95% CI 0.56–1.20, P = 0.845) in western countries. These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region. The most common AEs included fatigue, hand-foot skin reaction, diarrhoea and hypertension.ConclusionsCombination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR. More well-designed studies are needed to investigate its superiority for OS.Electronic supplementary materialThe online version of this article (10.1186/s12876-018-0849-0) contains supplementary material, which is available to authorized users.