Purpose: This study aimed to investigate the efficacy of preoperative aspartate aminotransferase-to-platelet-ratio index (APRI) score to predict the risk of posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) after liver resection, and to compare the discriminatory performance of the APRI with the Child–Pugh score, model for end-stage liver disease (MELD) score, and albumin–bilirubin (ALBI) score. Patients and methods: A total of 1,044 consecutive patients with HCC who underwent liver resection were enrolled and studied. Univariate and multivariate analyses were performed to investigate risk factors associated with PHLF. Predictive discrimination of Child–Pugh, MELD, ALBI, and APRI scores for predicting PHLF were assessed according to area under the ROC curve. The cutoff value of the APRI score for predicting PHLF was determined by ROC analysis. APRI scores were stratified by dichotomy to analyze correlations with incidence and grade of PHLF. Results: PHLF occurred in 213 (20.4%) patients. Univariate and multivariate analyses revealed that Child–Pugh, MELD, ALBI, and APRI scores were significantly associated with PHLF. Area under the ROC analysis revealed that the APRI score for predicting PHLF was significantly more accurate than Child–Pugh, MELD, or ALBI scores. With an optimal cutoff value of 0.55, the sensitivity and specificity of the APRI score for predicting PHLF were 72.2% and 68.0%, respectively, and the incidence and grade of PHLF in patients with high risk (APRI score >0.55) was significantly higher than in the low-risk cohort (APRI score <0.55). Conclusion: The APRI score predicted PHLF in patients with HCC undergoing liver resection more accurately than Child–Pugh, MELD, or ALBI scores.

Misregulation of the p53-mdm2 loop function is a major mechanism to promote hepatocellular carcinoma (HCC). RBM38, a member of the RNA recognition motif (RRM) family of RNA binding proteins (RBPs), plays a fundamental role in the posttranscriptional control of gene expression and regulatory functions in human tumors. A novel RBM38-p53-mdm2 autoregulatory feedback loop has been demonstrated. However, its mechanistic role in HCC remains unclear. In the present study, we investigated the role and molecular mechanism of misregulation in the p53-mdm2 loop function by RBM38 in HCC. First we investigated the correlation of RBM38 activity and p53-mdm2 loop function in liver cancer cells and HCC tissues by western blot and quantitative RT-PCR. We then conducted functional assays to investigate the molecular roles of RBM38 in inhibiting liver cancer cells aggressiveness in vitro and suppressing tumorigenicity in vivo. We observed RBM38 protein expression was commonly silenced coupled with increased mdm2 and decreased wild type (wt) p53 in liver cancer cells and HCC tissues compared to the corresponding normal liver cells and adjacent liver tissues. RBM38 mRNA level was significantly lower in HCC than adjacent liver tissues, whereas mdm2 and wtp53 mRNA levels were similar between HCC and adjacent liver tissues. This implied that deactivation of RBM38 could disrupt the p53-mdm2 loop and promote HCC, even though p53 and mdm2 transcript amounts were stable. Then, we generated stable liver cancer cell lines with overexpressed RBM38 (RBM38-OE) and found that up-regulation of RBM38 could inhibit mdm2 and restore wtp53 expression. Luciferase assay shown that RBM38 destabilized the mdm2 transcript through binding to multiple AU-/U-rich elements in mdm2 3’-UTR. Furthermore, functional assays showed that ectopic expression of RBM38 could induce liver cancer cell apoptosis and senescence, inhibit proliferation and colony growth, and suppress migration and invasion in vitro. Lastly, RBM38 could suppress HCC tumorigenicity in vivo. Our findings suggested that RBM38 may be a core contributor in stabilizing the p53-mdm2 loop function to prevent HCC, and a potential novel target to provide a therapeutic strategy for HCC by inhibiting mdm2 and rescuing p53 from inactivation.

Purpose: Post-hepatectomy liver failure (PHLF) is a severe complication in hepatocellular carcinoma (HCC) patients who have undergone hepatectomy. This research aimed to investigate the combination of albumin–bilirubin (ALBI) score and aspartate aminotransferase-platelet ratio index (APRI) as a novel approach in predicting PHLF risk in hepatitis B virus (HBV)-related HCC patients. Patients and methods: HBV-related HCC patients who underwent hepatectomy from January 2006 to October 2013 were enrolled in this study. A novel model was constructed using a combination of ALBI and APRI scores to predict PHLF risk, and the prognostic value of the model was evaluated and compared with Child-Pugh (C-P) grade, ALBI score and APRI score. Results: A total of 1,055 HCC patients were retrospectively studied, which included 151 experienced PHLF. Univariable and multivariate analyses showed that the ALBI and APRI scores were independent predictors of PHLF. The area under the ROC curve (AUC) of the ALBI score, APRI score, and C-P grade was 0.717, 0.720, and 0.602, respectively, with AUC (ALBI) > AUC (C-P) (P AUC (C-P) (P AUC (ALBI) (P AUC (APRI) (P =0.047). Our results indicated that ALBI and APRI scores had higher discriminatory abilities than C-P grade in predicting the risk of PHLF, and the ALBI-APRI model could enhance the capability of predicting PHLF compared to ALBI or APRI alone. Conclusion: ALBI-APRI score is a novel and effective predictive model of PHLF for HBV-related HCC patients, and its accuracy in predicting the risk of PHLF is better than that of C-P, ALBI and APRI scores.

Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the barcelona clinical liver cancer treatment algorithms: A review and update Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the barcelona clinical liver cancer treatment algorithms: A review and update

Background: Systemic inflammatory response is a hallmark of cancer and plays a significant role in the development and progression of various malignant tumors. This research aimed to estimate the prognostic function of the C-reactive protein-albumin ratio (CAR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and compare it with other inflammation-based prognostic scores, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, systemic immune inflammation index, prognostic index, Glasgow prognostic score, and modified Glasgow prognostic score. Methods: Retrospective analysis was conducted on data from 1039 HCC cases who underwent curative liver resection. The prognostic performance of CAR was compared with other scores using the area under the time-dependent receiver operating characteristic (t-ROC) curve. Multivariable Cox regression analyses were performed to confirm independent predictors for disease-free survival (DFS) and overall survival (OS). Results: The area under the t-ROC curve for CAR in the evaluation of DFS and OS was significantly greater than that of other scores and alpha-fetoprotein (AFP). Patients were stratified based on the optimal cut-off value of CAR, and the data revealed that both DFS and OS were remarkably worse in the high-CAR set compared to the low-CAR set. Multivariable Cox analysis demonstrated that CAR was an independent prognostic parameters for assessing DFS and OS. Regardless of AFP levels, all patients were subsequently divided into significantly different subgroups of DFS and OS based on CAR risk stratification. Similar results were observed when applying CAR risk stratification to other scoring systems. CAR also showed good clinical applicability in patients with different clinical features. Conclusion: CAR is a more effective inflammation-based prognostic marker than other scores and AFP in predicting DFS as well as OS among patients with HCC after curative hepatectomy.

Background: To develop a nomogram for predicting the International Study Group of Liver Surgery (ISGLS) grade B/C posthepatectomy liver failure (PHLF) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. Methods: Patients initially treated with hepatectomy were included. Univariate regression analysis and stochastic forest algorithm were applied to extract the core indicators and reduce redundancy bias. The nomogram was then constructed by using multivariate logistic regression, and validated in internal and external cohorts, and a prospective clinical application. Results: There were 900, 300 and 387 participants in training, internal and external validation cohorts, with the morbidity of grade B/C PHLF were 13.5, 11.0 and 20.2%, respectively. The nomogram was generated by integrating preoperative total bilirubin, platelet count, prealbumin, aspartate aminotransferase, prothrombin time and standard future liver remnant volume, then achieved good prediction performance in training (AUC = 0.868, 95%CI = 0.836–0.900), internal validation (AUC = 0.868, 95%CI = 0.811–0.926) and external validation cohorts (AUC = 0.820, 95%CI = 0.756–0.861), with well-fitted calibration curves. Negative predictive values were significantly higher than positive predictive values in training cohort (97.6% vs. 33.0%), internal validation cohort (97.4% vs. 25.9%) and external validation cohort (94.3% vs. 41.1%), respectively. Patients who had a nomogram score < 169 or ≧169 were considered to have low or high risk of grade B/C PHLF. Prospective application of the nomogram accurately predicted grade B/C PHLF in clinical practise. Conclusions: The nomogram has a good performance in predicting ISGLS grade B/C PHLF in HBV-related HCC patients and determining appropriate candidates for hepatectomy.