Correlation between the expressions of circular RNAs in peripheral venous blood and clinicopathological features in hepatocellular carcinoma.

BACKGROUND: Recent studies have reported that circular RNAs (circRNAs) are involved in the development of hepatocellular carcinoma (HCC). This study evaluated the expression of preoperative peripheral venous blood circRNAs in HCC patients and their predictive ability for microvascular invasion (MVI). METHODS: Seven circRNAs (circMTO1, circ-10720, circZKSCAN1, cSMARCA5, circHIPK3, circSETD3 and ciRS-7) were screened from the literature as circRNAs with reported biological functions in HCC. The expression levels of seven circRNAs in preoperative blood samples and HCC tissues were detected by quantitative reverse transcription polymerase chain reaction. The correlations between the circRNA expressions in blood and the clinicopathological factors of HCC patients were analyzed. The risk factors of MVI were analyzed by univariate and multivariate logistic regression. The functional role of circSETD3 in cell migration and invasion was evaluated by wound healing and Transwell assays in vitro. RESULTS: The expressions of all seven circRNAs were measured in peripheral venous blood samples. The venous expression levels of circHIPK3 and circMTO1 were significantly associated with gender, while circ-10720 and circMTO1 levels were significantly correlated with gross vascular invasion. Furthermore, circMTO1 and cSMARCA5 levels were significantly associated with alpha-fetoprotein level and ciRS-7 was significantly associated with satellite nodules. Importantly, low venous circSETD3 expression was significantly associated with prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) level, MVI, gross vascular invasion, and liver capsule. Furthermore, venous circSETD3 expression had predictive ability for MVI. Knockdown of circSETD3 promoted cell invasion and metastasis in vitro. CONCLUSIONS: CircRNAs were stably present in peripheral venous blood and associated with multiple clinicopathological characteristics of HCC patients. Venous circSETD3 was an independent risk factor of MVI and shows ability to predict MVI in HCC patients before surgery.

Circadian Rhythms Have Effects on Surgical Outcomes of Liver Transplantation for Patients With Hepatocellular Carcinoma: A Retrospective Analysis of 147 Cases in a Single Center.

AIM: To investigate the impact of circadian rhythms on the outcomes of liver transplantation on patients suffering from hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed data of patients who underwent liver transplantation from 2012 to 2017 in our center. Based on the begin time of transplantation, these patients were separated into 2 groups: day group and night group. The intraoperative and postoperative clinical variables were analyzed to find out the impact of the circadian rhythms. Multivariate analysis was performed to examine strength associations between the begin time of operation and surgical outcomes. RESULTS: A total of 147 patients were included in this study: 102 patients in the day group and 45 patients in the night group. Compared with the day group, patients in the night group had higher incidence of intraoperative massive hemorrhage (11.1% vs 2.0%, P = .048), more intraoperative blood loss (2168.00 ± 2324.20 mL vs 1405.88 ± 1037.69 mL, P = .040), and more requirement of red blood cells (RBC) suspension (8.59 ± 7.11 u vs 6.37 ± 5.78 u, P = .048). In addition, total operation time in the night group was longer than that in the day group (8.90 ± 1.65 hours vs 8.26 ± 1.69 hours, P = .034), as well as the cold ischemia time (9.35 ± 5.03 hours vs 7.21 ± 3.93 hours, P = .014). Furthermore, the night group had higher incidence of other intraoperative complications (13.3% vs 2.9%, P = .038), postoperative abdominal infection (20.0% vs 6.9%, P = .038), and more hospital cost (37,357.96 ± 6779.96 dollars vs 33,551.75 ± 11,683.38 dollars, P = .045). Moreover, patients in the night group needed longer time to restore hepatic function to normal (21.77 ± 10.91 days vs 17.54 ± 10.80 days, P = .033). Multivariate analysis showed that begin time of operation was the independent risk factor of longer operation time, more blood loss during operation, higher incidence of massive hemorrhage and other intraoperative complications, longer time for restoration of hepatic function to normal, higher incidence of abdominal infection at the early stage after transplantation, and more hospital cost (all P value ≤ .05). CONCLUSION: Liver transplantation performed at night was associated with higher incidence of intraoperative and early postoperative complications, as well as higher hospital cost. And these worsened outcomes all could be explained by the influence that circadian rhythms had on patients or medical workers.

Preoperative albumin-bilirubin grade plus platelet-to-lymphocyte ratio predict the outcomes of patients with BCLC stage A hepatocellular carcinoma after liver resection.

There is little information regarding the predictive ability of albumin-bilirubin grades (ALBI) plus platelet-to-lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) following liver resection. In this study, we aimed to evaluate the prognostic power of the ALBI-PLR score in patients with hepatitis B virus-related (HBV-related) HCC within Barcelona Clinic Liver Cancer (BCLC) stage A after liver resection.Around 475 patients were included in this study. Patients with preoperative ALBI grades 1, 2, or 3 were allocated a score of 0, 1, or 2, respectively. Patients with preoperative PLR >150 or ≤150 were allocated a score of 0 or 1, respectively. The ALBI-PLR score was the summary of the ALBI and PLR scores.During the follow-up period, 256 patients experienced recurrence, and 150 patients died. Multivariate analysis revealed tumor size, multiple tumors, positive HBV-DNA load, cirrhosis, and ALBI-PLR score as being independently associated with postoperative recurrence, whereas tumor size, high preoperative α-fetoprotein level, and ALBI-PLR score were independent risk factors for postoperative mortality. HCC patients with high ALBI-PLR score had poor recurrence-free and overall survival.The preoperative ALBI-PLR score is a surrogate marker for predicting HBV-related HCC patient's prognosis after liver resection. A high ALBI-PLR score is associated with a high incidence of postoperative recurrence and mortality.

Comparison of Transarterial Chemoembolization Combined with Radiofrequency Ablation Therapy versus Surgical Resection for Early Hepatocellular Carcinoma.

Both radiofrequency ablation (RFA) and surgical resection (SR) are radical treatment recommended for early hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is a palliative treatment for intermediate HCC, and TACE+RFA combined therapy is considered superior to TACE or RFA alone for management of early HCC. This systematic review compared the efficacy and safety of TACE+RFA combined therapy with SR for early HCC. Web of Science, PubMed, EMBASE, and the Cochrane Library were searched for literatures related with our topic. The primary endpoint was overall survival (OS), and the secondary endpoint was the recurrence-free survival (RFS) rate; safety was measured by the rate of major complications. The effect sizes of OS, RFS, and local progression rates were expressed by odds ratio (OR), while the effect size of complications was presented using relative risk. TACE+RFA combined therapy and SR had a similar 1-year OS rate [OR: 1.84; 95% confidence interval (CI): 0.82, 4.14; P > 0.05], 3-year OS rate (OR: 0.84; 95% CI: 0.43, 1.67; P > 0.05), 1-year RFS rate (OR: 0.77; 95% CI: 0.53, 1.11; P > 0.05), and 3-year RFS rate (OR: 0.88; 95% CI: 0.48, 1.42; P > 0.05) for early HCC. However, the 5-year OS rate (OR: 0.54; 95% CI: 0.40, 0.73; P < 0.05) and 5-year RFS rate (OR: 0.49; 95% CI: 0.27, 0.90; P < 0.05) were lower in patients with TACE+RFA than in those with SR. SR is associated with better long-term survival outcomes and a lower recurrence rate than TACE+RFA for patients with early HCC and is the optimal choice for patients with early HCC.

A novel combined systemic inflammation-based score can predict survival of intermediate-to-advanced hepatocellular carcinoma patients undergoing transarterial chemoembolization.

BACKGROUND: There is currently limited information regarding the prognostic ability of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) for hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of the dNLR-PNI in patients with intermediate-to-advanced HCC after transarterial chemoembolization (TACE). METHODS: A total of 761 HCC patients were enrolled in the study. The dNLR-PNI was retrospectively calculated in these patients, as follows: patients with both an elevated dNLR and a decreased PNI, as determined using the cutoffs obtained from receiver operating characteristic curve analysis, were allocated a score of 2, while patients showing one or neither of these alterations were allocated a score of 1 or 0, respectively. RESULTS: During the follow-up period, 562 patients died. Multivariate analysis suggested that elevated total bilirubin, Barcelona Clinic Liver Cancer C stage, repeated TACE, and dNLR-PNI were independently associated with unsatisfactory overall survival. The median survival times of patients with a dNLR-PNI of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 22.5-39.5), 16.0 (95% CI 12.2-19.7) and 6.0 (95% CI 4.8-7.2) months, respectively (P < 0.001). CONCLUSIONS: The dNLR-PNI can predict the survival outcomes of intermediate-to-advanced HCC patients undergoing TACE, and should be further evaluated as a prognostic marker for who are to undergo TACE treatment.

The choose of different surgical therapies of hepatic alveolar echinococcosis: A single-center retrospective case-control study.

The aim of this study was to evaluate different surgical therapies for hepatic alveolar echinococcosis in different clinical stages.We analyze the clinical data of 115 patients who received surgical treatment in West China Hospital from January 2004 to June 2016. Among these patients, 77 cases underwent radical hepatic resection (group A, n = 77); 17 cases underwent palliative resection (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21) with 12 cases of orthotopic liver transplantation and 9 cases of liver autotransplantation.The postoperative complication rate of radical hepatic resection group was 13.0% (10/77), which is statistically significant (P < .05) than the rate of palliative resection group 29.4% (5/17) or liver transplantation group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall median survival rate of radical resection was 72/77, higher than the rate of palliative group (12/17) or transplantation group (17/21), which was also statistically significant (P < .01).In our study, we believe in that all stages of hepatic alveolar echinococcosis should take active surgical interventions, and radical hepatic resection should be considered as the first-choice treatment for early stage of alveolar echinococcosis, while palliative surgery is still helpful to relieve symptoms and improve the life quality for advanced patients. Liver transplantation might also be an alternative option for the late-stage hepatic alveolar echinococcosis.

Postoperative Albumin-Bilirubin Grade Change Predicts the Prognosis of Patients with Hepatitis B-Related Hepatocellular Carcinoma Within the Milan Criteria.

OBJECTIVE: Albumin-bilirubin (ALBI) grade has been validated as a simple, evidence-based, and objective prognostic tool for patients with hepatocellular carcinoma (HCC). However, minimal information is available concerning postoperative ALBI grade changes in HCC. This study aimed to investigate the prognostic value of postoperative ALBI grade changes in patients with hepatitis B virus (HBV)-related HCC within the Milan criteria after liver resection. METHODS: Patients with HBV-related HCC within the Milan criteria who underwent liver resection between 2010 and 2016 at West China Hospital were reviewed (N = 258). A change in ALBI grade was defined as first postoperative month ALBI grade-preoperative ALBI grade. If the value was >0, postoperative worsening of ALBI grade was considered; otherwise, stable ALBI grade was considered. Cox proportional hazard regression analyses were used to determine the factors that influence recurrence and survival. RESULTS: During the follow-up, 130 patients experienced recurrence and 47 patients died. Multivariate analyses revealed that postoperative worsening of ALBI grade (HR 1.541, 95% CI 1.025-2.318, P = 0.038), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P = 0.004), and multiple tumors (HR 1.676, 95% CI 1.075-2.615, P = 0.023) were associated with postoperative recurrence, whereas MVI (HR 2.737, 95% CI 1.475-5.080, P = 0.001), postoperative worsening of ALBI grade (HR 2.268, 95% CI 1.227-4.189, P = 0.009), high alpha-fetoprotein level (HR 2.055, 95% CI 1.136-3.716, P = 0.017), and transfusion (HR 2.597, 95% CI 1.395-4.834, P = 0.003) negatively influenced long-term survival. Patients with postoperative worsening of ALBI grade exhibited increased incidence of recurrence and worse long-term survival. CONCLUSION: Postoperative worsening of ALBI grade was associated with increased recurrence and poorer overall survival for patients with HBV-related HCC within the Milan criteria. We should pay attention to liver function changes in HCC patients after liver resection.

Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China.

BACKGROUND: Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive (HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of mainland China. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal. AIM: To evaluate the safety of using hepatitis B virus (HBV) core antibody-positive donors for liver transplantation in Chinese patients. METHODS: We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study. RESULTS: In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative (HBcAb-) liver grafts. The 1-, 3- and 5-year survival rates in patients and grafts between the two groups were similar (patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3- and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcAb+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive (HBsAg+) and HBsAg negative (HBsAg-) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg- patients with HBcAb+ liver grafts (13.23%), in which HBV naive recipients suffered most (31.82%), although this difference did not affect patient and graft survival (P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody (anti-HBs) titer (more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks. CONCLUSION: HBcAb+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.

Hepatic resection combined with radiofrequency ablation versus hepatic resection alone for multifocal hepatocellular carcinomas: A meta-analysis.

This meta-analysis aimed to comprehensively assess the efficacy and safety of hepatic resection combined with radiofrequency ablation versus hepatic resection (HR) alone for the treatment of multifocal hepatocellular carcinomas (HCC). A literature search was conducted from the database including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and China Biology Medicine (CBM) disc. The primary outcomes included the 1-, 3-, 5-year overall survival (OS) and disease-free survival (DFS) rate. The secondary outcomes contained the intraoperative parameters and postoperative adverse events (AEs). These parameters were all analyzed by RevMan 5.3 software. After carefully screening relevant studies, four retrospective studies of high quality involving 466 patients (197 in the combined group and 269 in the HR group) were included in this study. The pooled results showed that the 1-, 3-, 5-year OS rate in the combined group were comparable with those in the HR group (OR=0.77, 0.96, 0.88; P=0.33, 0.88, 0.70, respectively). Similarly, there was no significant difference in 1-, 3-, 5-year DFS rate between the combined group and the HR alone group (OR=0.57, 0.83, 0.72; P=0.17, 0.37, 0.32, respectively). And the intraoperative parameters and postoperative AEs were also comparable between the above two cohorts. However, two included studies reported that tumor often recurred in the ablation site in the combined group. The present meta-analysis indicated that the HR combined with RFA could reach a long-term survival outcome similar to curative HR for multifocal HCC patients. And this therapy may be a promising alternative for these patients with marginal liver function or complicated tumor distribution. Furthermore, high quality randomized controlled trials (RCTs) are imperative to verify this conclusion.

Liver resection versus transplantation for multiple hepatocellular carcinoma: a propensity score analysis.

The aim of this study was to compare the outcomes of patients with multiple hepatocellular carcinoma (HCCs) after liver resection (LR) versus liver transplantation (LT). Patients who had multiple HCCs without macrovascular invasion and who underwent LT or LR between 2007 and 2013 were reviewed. A propensity score matching model was used to adjust baseline differences between the two groups. A total of 204 patients were selected for the current study, including 137 LR patients and 67 LT patients. During follow-up, 100 patients experienced recurrence, and 78 patients died. The 5-year recurrence-free survival rate was 71.1% for the LT group and 31.1% for the LR group (P<0.001). The 5-year overall survival rate was 73.4% for the LT group and 39.8% for the LR group (P<0.001). Moreover, the LT group had better recurrence-free survival and overall survival rates than the LR group regardless of whether the patients met or exceeded the Milan criteria. The multivariate analysis showed that microvascular invasion and LR were independent risk factors for postoperative recurrence, whereas only LR was associated with an increased incidence of mortality. After applying one-to-one propensity score matching, similar results were observed in the propensity score matching model. Our study suggested that LT provided a better prognosis for patients with multiple HCCs than LR regardless of whether the patients met the Milan criteria.