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.

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.

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.

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.

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.

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.

Changes of platelet times neutrophil to lymphocyte ratio predict BCLC stage A hepatocellular carcinoma survival.

Platelet, neutrophil, and lymphocyte ratio (PNLR) has its own unique role in influencing postoperative recurrence for patients with hepatocellular carcinoma (HCC). Surgical stress can change systemic inflammatory response of patients. Thus the aim of this study was to identify the prognostic value of changes of platelet times neutrophil to lymphocyte ratio in hepatitis B related HCC within Barcelona clinical liver cancer (BCLC) stage A.Data of patients with HCC within BCLC stage A were reviewed. Pre-, intra- and postoperative variables were retrospectively and statistically analyzed. The postoperative variable was calculated based on the data obtained on the first postoperative month following liver resection.A total of 556 patients were included in present study. During the follow-up period, 257 patients experienced recurrence and 150 patients died. Multivariate analyses suggested multiple tumors (hazard ratio [HR] = 2.409; 95% confidence interval [CI] = 1.649-3.518; P < .001), microvascular invasion (MVI) (HR = 1.585; 95% CI = 1.219-2.061; P = .001), and increased postoperative PNLR (HR = 1.900; 95% CI = 1.468-2.457; P < .001) independently associated with postoperative recurrence, whereas MVI (HR = 1.834; 95% CI = 1.324-2.542; P < .001), postoperative neutrophil to lymphocyte ratio (NLR) (HR = 1.151; 95% CI = 1.025-1.294; P = .018) and increased postoperative PNLR (HR = 2.433; 95% CI = 1.667-3.550; P < .001) contributed to postoperative mortality. The 5-year recurrence-free survival and overall survival rates of patients with increased postoperative PNLR (N = 285) versus those with decreased postoperative PNLR (N = 271) were 36.8% versus 61.5% and 47.6% versus 76.4% respectively (P < .001).Changes of PNLR was a powerful prognostic indicator of poor outcomes in patients with HCC within BCLC stage A. PNLR should be monitored in our postoperative follow-up.

A new index predicts early allograft dysfunction following living donor liver transplantation: A propensity score analysis.

OBJECTIVE/AIM: The aim of this study was to identify a new index to predict early allograft dysfunction following living donor liver transplantation. METHODS: The study enrolled 260 adult living donor liver transplantation recipients. Postoperative laboratory variables were assessed for their association with the prevalence of early allograft dysfunction using the inverse probability of treatment weighting and propensity-score matching (n=93 pairs) analysis. RESULTS: Forty-seven recipients (18.1%) developed early allograft dysfunction. In multivariable analysis, the alanine aminotransferase and gamma-glutamyl transpeptidase levels on postoperative day 1 were independent predictors of early allograft dysfunction. The alanine aminotransferase to gamma-glutamyl transpeptidase ratio (AGR) was developed. All cases were divided into two groups (Group 1 [AGR≥8.47, n=103] and Group 2 [AGR<8.47, n=157]). AGR≥8.47 (OR 10.345, 95%CI 4.502-23.772, p<0.001), hepatorenal syndrome (OR 3.016, 95%CI 1.119-8.125, p=0.029), and graft to recipient weight ratio <0.8% (OR 2.155, 95%CI 1.004-4.624, p=0.049) were independent risk factors for early allograft dysfunction. The prevalence of early allograft dysfunction was higher in group 1 (after adjusting for inverse probability of treatment weighting [n=39; 37.9% vs n=8; 5.1%] and propensity-score matching [n=33; 35.5% vs n=2; 2.2%]) than that in group 2 (p<0.001). CONCLUSIONS: The postoperative AGR is a practical index for predicting early allograft dysfunction after living donor liver transplantation.

Transplantation versus hepatectomy for HCC beyond the Milan criteria: A propensity score analysis.

BACKGROUND: Increasing studies have suggested that surgical resection (SR) or liver transplantation (LT) could bring survival benefits for patients with hepacelluar carcinoma (HCC) beyond Milan criteria. This study compared the long-term survival of patients beyond the Milan criteria who received SR or LT. MATERIAL AND METHODS: A total of 461 HCC patients were retrospectively collected. Analysis was performed using propensity score matching (PSM), the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Prognosis was significantly better for the LT group than the SR group before (P < 0.001) and after PSM(p = 0.003). In subgroup analysis, for patients with lower AFP level, the 1-, 3-, and 5-year OS rates for the two groups were significantly different (86.7, 71.9, and 71.9% for group LT vs. 75.8, 48.1, and 10.7% for group SR, P = 0.003). For patients with smaller tumor size, the 1-, 3-, and 5-year OS rates were 78.3, 66.7, and 66.7% for group LT, and 83.8, 42.6, and 18.6% for group SR, p = 0.009). Transplantation was a favorable factor associated with prognosis before and after propensity score matching (HR 2.643). CONCLUSION: Our propensity model suggested that LT provided significantly better long-term survival than SR for HCC beyond Milan criteria before and after PSM.

MicroRNA-203 promotes liver regeneration after partial hepatectomy in cirrhotic rats.

BACKGROUND: Liver resection or partial hepatectomy (PH) is still the most commonly used therapeutic option for hepatocellular carcinoma (HCC) at present. However, the impaired regenerative ability induced by the accompanied liver cirrhosis is an important risk factor of posthepatectomy liver failure, and posthepatectomy liver failure is a feared complication that accounts for up to 75% of mortality after extensive liver resection. MicroRNA(miR)-203 is a tumor suppressor of HCC and may act as a positive intermediary in A20-enhanced interleukin (IL-6)/signal transducer and activator of transcription 3 (STAT3) pro-proliferative signals, which may promote liver regeneration after PH. However, its direct pro-proliferative effect on cirrhotic liver after hepatectomy is unknown. MATERIALS AND METHODS: Liver cirrhosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution in adult male Wistar rat. Rats with liver cirrhosis received portal vein injection of physiological saline, miR-203 lentivirus, or control empty lentivirus, and then 70% PH was performed under ether anesthesia 7 d later. Liver samples were harvested at 0, 24, 36, and 72 h after 70% PH. Hepatic expressions of cyclin D1 and Ki67 were checked to evaluate the liver regenerative ability. Hepatic expressions of IL-6, suppressor of cytokine signaling 3 (SOCS3), and phospho-STAT3 were also tested to clarify the mechanisms of miR-203 in liver regeneration. RESULTS: The regeneration of miR-203 overexpression cirrhotic liver after 70% PH was enhanced and peaked at 24 and 36 h after 70% PH. The cyclin D1-positive liver cells/high-power field (HPF) in miR-203 overexpression liver markedly increased at 24 and 36 h after 70% PH compared with 0-h samples. When comparing with the control groups, cyclin D1-positive liver cells/HPF in miR-203 overexpression liver were also significantly increased at 24 and 36 h after 70% PH. A similar result of the Ki67-positive liver cells/HPF was achieved at 36 h after 70% PH. The hepatic expression of IL-6 showed a rising tendency after 70% PH, and the levels of IL-6 are significantly higher in miR-203 overexpression livers. Hepatic expression of SOCS3 was negatively expressed with hepatic miR-203 expression level, and the reduced expression of SOCS3 facilitated the phosphorylation of STAT3. CONCLUSIONS: By targeting SOCS3 and then enhancing proliferating IL-6/STAT3 signaling pathway, hepatic overexpression of miR-203 can facilitate the initiation of liver regeneration and enhance the potency of liver regeneration after 70% PH in cirrhotic rat. Together with the tumor suppressive effect on HCC, miR-203 would be an ideal candidate for promoting liver regeneration in HCC patients undergoing liver resection without the risk of tumorigenesis or cancer recurrence.

miR-203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver.

Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR-203 adenovirus was administered to induce hepatic miR-203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR-203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non-tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR-203 overexpression further promoted the regeneration of the non-tumorous liver by upregulating Ki67 expression and enhancing IL-6/SOCS3/STAT3 pro-proliferative signals. Importantly, miR-203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR-203 overexpression reversed the epithelial-mesenchymal transition induced by hepatectomy through targeting IL-1ß, Snail1 and Twist1. In conclusion, our results suggested that miR-203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial-mesenchymal transition.

Alpha fetoprotein changes predict hepatocellular carcinoma survival beyond the Milan criteria after hepatectomy.

BACKGROUND: Assessing the outcomes of surgeries for hepatocellular carcinoma (HCC) patients who exceed the Milan criteria is necessary. Some studies have demonstrated that preoperative or postoperative alpha fetoprotein (AFP) can predict HCC patients' prognoses. METHODS: A total of 280 HCC patients who were positive for AFP and received curative resection were retrospectively analyzed. The patients were classified into three groups according to their preoperative and postoperative AFP levels (group A: normalized AFP; group B: AFP decreases >50%, but continued abnormality; and group C: AFP decreases <50%). Disease-free survival and overall survival rates were analyzed using the Kaplan-Meier method. The factors associated with AFP changes were evaluated by logistic regression. RESULTS: AFP dynamic changes were independently associated with disease-free survival and overall survival rates. Group A had better 3- and 5-y survivals than groups B or C (58.7% and 39.5% versus 31.3% and 14.9% versus 17.1% and 8.8%, P < 0.001). Preoperative AFP, tumor differentiation, tumor diameter, microvascular invasion, and satellite nodules remained significant risk factors that were associated with AFP changes. Furthermore, in group A, the disappearances of AFP within and beyond 8 wk resulted in similar overall survival rates (P > 0.05). Among those with HCC recurrence, the patients treated with resurgery or radiofrequency ablation achieved the best recurrence to death survivals. Those treated with transcatheter arterial chemoembolization achieved the next best survivals. CONCLUSIONS: AFP changes predicted the prognoses of patients with HCC beyond the predictions of the Milan criteria. Preoperative AFP (>400 ng/mL), tumor differentiation, tumor diameter, and satellite nodules were the risk factors related to AFP normalization. The regular follow-up and early detection of recurrent HCCs that are suitable for curative therapies, such as resurgery and radiofrequency ablation, might improve the prognoses. Other therapies, such as transcatheter arterial chemoembolization, might also be effective.

Liver resection versus liver resection plus TACE for patients with hepatocellular carcinoma beyond Milan criteria.

BACKGROUND: The recurrence of patients with hepatocellular carcinoma (HCC) beyond the Milan criteria after liver resection (LR) is common. This study aimed to clarify whether LR plus postoperative adjuvant transcatheter arterial chemoembolization (TACE) could improve the outcomes of patients with HCC beyond the Milan criteria after LR. METHODS: A total of 754 consecutive patients with HCC beyond the Milan criteria who received LR alone (n = 459) or LR + TACE (n = 295) were included. A propensity scoring matched model (PSM) was used to adjust for the baseline differences between the groups. RESULTS: The 1, 3, and 5-y recurrence-free survival (76.7%, 40.4%, and 30.8%, respectively, for the LR-alone group versus 78.3%, 50.5%, and 46.2%, respectively, for the LR + TACE group; P = 0.004) and overall survival (94.1%, 58.3%, and 36.3%, respectively, for the LR-alone group versus 95.3%, 71.3%, and 54.9%, respectively, for the LR + TACE group; P < 0.001) rates of patients who underwent LR alone were much lower than in the LR + TACE group. Multivariate Cox proportional hazards regression analysis showed that LR alone was an independent risk factor for postoperative recurrence and poor long-term survival. After one-to-one PSM, 284 patients who underwent LR alone and 284 patients who underwent LR + TACE were selected for further analyses. Similar results were observed in the PSM model. CONCLUSIONS: This study showed that LR + TACE may be beneficial for patients with HCC beyond the Milan criteria. Postoperative adjuvant TACE should be considered to patients with HCC beyond the Milan criteria.

Hepatic Resection Combined with Radiofrequency Ablation versus Hepatic Resection Alone for Multifocal Hepatocellular Carcinomas: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

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 hepatoeellular 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 transplantation versus surgical resection for HCC meeting the Milan criteria: A propensity score analysis.

The optimal treatment (liver transplantation [LT] vs surgical resection [SR]) for early-stage hepatocellular carcinoma (HCC) remains controversial.A total of 209 SR patients and 129 LT patients were identified at our institution. After eliminating 27 patients with Child-Pugh C, the data from 209 SR patients and 102 LT patients were analyzed using a propensity score matching (PSM) model. Forty-six pairs were generated. A subgroup analysis was conducted based on the alpha-fetoprotein (AFP) level or platelet count (PLT). A survival analysis was performed using the Kaplan-Meier method.Gender, satellite lesions, and the treatment method were predictors of HCC recurrence. The Ishak score and treatment methods were associated with long-term survival after surgery. Before PSM, LT patients had a better prognosis than those treated by SR. Among HCC patients with childhood A/B cirrhosis, after PSM, SR achieved similar overall survival outcomes compared with LT. LT and SR resulted in comparable long-term survival for patients with or without thrombocytopenia. Patients with an AFP ≥ 400 ng/mL might achieve more survival benefits from LT.Our propensity score model provided evidence that, compared with transplantation, surgical resection could result in comparable long-term survival for resectable early-stage HCC patients, except for the AFP ≥ 400 ng/mL HCC subgroup. Surgical resection might not be a contraindication for early-stage HCC patients with thrombocytopenia due to their similar prognosis after transplantation.

A simple prognostic score system predicts the prognosis of solitary large hepatocellular carcinoma following hepatectomy.

Solitary large hepatocellular carcinomas (SLHCC) form a heterogeneous group of patients with different survival probabilities. The aim of our study was to develop a simple prognostic index for identifying prognostic subgroups of SLHCC patients.A retrospective analysis of clinical data from 268 patients with operable SLHCC was conducted to investigate prognostic factors and to construct a score system based on risk factors. A Cox proportional hazard regression analysis was used to evaluate the variables associated with prognosis. Survival analyses were performed using Kaplan-Meier survival curves.Three variables remained in the final multivariate model: platelet to lymphocyte ratio (PLR), microvascular invasion (MVI), and tumor size with hazard ratios equal to 1.004 (95% confidence interval: 1.001-1.006), 1.092 (1.044-1.142), and 2.233 (1.125-2.233), respectively. A score of 1 was assigned to each risk factor. Patient scores were determined based on these risk factors; thus, the scores ranged between 0 and 3. Ultimately, three categories (0, 1-2, 3) were defined. Patients with scores of 3 had a 5-year survival rate of 25.4%, whereas patients with a score of 0 had a 5-year survival rate of 52.1%. The prognosis significantly worsened as the score increased. Similar results were found among cirrhotic and noncirrhotic patients.Our simple prognostic index successfully predicts SLHCC survival.