Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed increasingly, and in one half of diagnosed patients, recurrence will develop. Thus, it is urgent to identify recurrence-related markers. We investigated the effectiveness of CpG methylation in predicting recurrence for patients with E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four independent centers were sorted by three phases. In the discovery phase, 66 tumor samples were analyzed using the Illumina Methylation 450k Beadchip. Two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to select significant CpGs. In the training phase, penalized Cox regression was used to further narrow CpGs into 140 samples. In the validation phase, candidate CpGs were validated using an internal cohort (n = 141) and two external cohorts (n = 191 and n =104). Results After combining the 46 CpGs selected by the Least Absolute Shrinkage and Selector Operation and the Support Vector Machine-Recursive Feature Elimination algorithms, three CpGs corresponding to SCAN domain containing 3, Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1, and peptidase inhibitor 3 were highlighted as candidate predictors in the training phase. On the basis of the three CpGs, a methylation signature for E-HCC (MSEH) was developed to classify patients into high- and low-risk recurrence groups in the training cohort ( P < .001). The performance of MSEH was validated in the internal cohort ( P < .001) and in the two external cohorts ( P < .001; P = .002). Furthermore, a nomogram comprising MSEH, tumor differentiation, cirrhosis, hepatitis B virus surface antigen, and antivirus therapy was generated to predict the 5-year recurrence-free survival in the training cohort, and it performed well in the three validation cohorts (concordance index: 0.725, 0.697, and 0.693, respectively). Conclusion MSEH, a three-CpG-based signature, is useful in predicting recurrence for patients with E-HCC.

The high incidence of recurrence and the poor prognosis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive markers of HCC invasion and prognosis. In this study, we evaluated the expression pattern of two members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40 normal hepatic tissue specimens, 149 HCC specimens and their adjacent non-tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37.6% (56/149) and 49.0% (73/149) of the HCC specimens, respectively, but were rarely detected in adjacent non-tumourous tissues and were never detected in normal hepatic tissue specimens. Nevertheless, only high expression of MSI2 correlated with poor prognosis. In addition, MSI2 up-regulation correlated with clinicopathological parameters representative of highly invasive HCC. Further study indicated that MSI2 might enhance invasion of HCC by inducing epithelial–mesenchymal transition (EMT). Knockdown of MSI2 significantly decreased the invasion of HCC cells and changed the expression pattern of EMT markers. Moreover, immunohistochemistry assays of 149 HCC tissue specimens further confirmed this correlation. Taken together, the results of our study demonstrated that MSI2 correlates with EMT and has the potential to be a new predictive biomarker of HCC prognosis and invasion to help guide diagnosis and treatment of post-operative HCC patients.

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma (HCC) have resulted in improved response rates. This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection, a 'conversion therapy' strategy. However, conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed. Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review: Many research centers in China have accumulated significant experience implementing HCC conversion therapy. Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC; however, there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields. In order to summarize and learn from past experience and review current challenges, the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma (2021 Edition) was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice. Sixteen consensus statements on the implementation of conversion therapy for HCC were developed. The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

Sorafenib is the most recommended first‐line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC‐mediated metastasis relies on vascular pattern, but not on migration and invasion of cancer cells. In this study, we aimed to explore whether vascular pattern could predict sorafenib benefit. Two cohorts of patients were recruited from four academic hospitals. The survival benefit of sorafenib treatment for patients with or without the VETC pattern (VETC+/VETC–) was investigated. Kaplan‐Meier analyses revealed that sorafenib treatment significantly reduced death risk and prolonged overall survival (OS; in cohort 1/2, P = 0.004/0.005; hazard ratio [HR] = 0.567/0.408) and postrecurrence survival (PRS; in cohort 1/2, P = 0.001/0.002; HR = 0.506/0.384) in VETC+ patients. However, sorafenib therapy was not beneficial for VETC‐ patients (OS in cohort 1/2, P = 0.204/0.549; HR = 0.761/1.221; PRS in cohort 1/2, P = 0.121/0.644; HR = 0.728/1.161). Univariate and multivariate analyses confirmed that sorafenib treatment significantly improved OS/PRS in VETC+, but not VETC–, patients. Further mechanistic investigations showed that VETC+ and VETC– HCCs displayed similar levels of light chain 3 (LC3) and phosphorylated extracellular signal‐regulated kinase (ERK) in tumor tissues (pERK) or endothelial cells (EC‐pERK), and greater sorafenib benefit was consistently observed in VETC+ HCC patients than VETC– irrespective of levels of pERK/EC‐pERK/LC3, suggesting that the different sorafenib benefit between VETC+ and VETC– HCCs may not result from activation of Raf/mitogen‐activated protein kinase kinase (MEK)/ERK and vascular endothelial growth factor (VEGF)A/VEGF receptor 2 (VEGFR2)/ERK signaling or induction of autophagy. Conclusion: Sorafenib is effective in prolonging the survival of VETC+, but not VETC–, patients. VETC pattern may act as a predictor of sorafenib benefit for HCC.

Objective: The present study aimed to investigate the effectiveness of parenteral nutritional support with ω-3 PUFAs–based lipid emulsions in patients after liver resection. Methods: A total of 119 patients were randomly assigned to the immunonutrition (IM) group (n = 59) and control group (n = 60). The IM group was continuously given Omegaven® 10% 100 mL/day rather than regular nutrition for five days postoperatively. Venous blood samples were obtained from all subjects before surgery and D1, D3 and D7 after surgery. Results: No significant difference was found in baseline characteristics of the two groups. On D1 after surgery, no statistically significant differences were observed in the blood sample tests between the two groups. On D3 after surgery, the levels of white blood cell count (WBC), alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (TBil) were dramatically decreased in the IM group (t = 3.065, p = 0.003; t = 2.149, p = 0.034; t = 5.313, p= 0.001; and t = 2.419, p = 0.017, respectively). Furthermore, on D7 after surgery, not only could a significant decrease be observed in the IM group concerning the levels of WBC, ALT and TBil (t = 3.025, p = 0.003; t = 2.094, p = 0.038; and t = 2.046, p = 0.043, respectively), but it was also seen in the level of Δprothrombintime (PT) (t = 2.450, p = 0.016). An increase in the level of prealbumin (Pre-Alb) in the IM group was observed on D7 after surgery (t = 2.237, p = 0.027). The frequency of total complications in the IM group were significantly lower than in the control group (χ2 = 4.225, p = 0.040 and χ2 = 3.174, p = 0.075). The trend favored the IM group in reducing the total infective complications rate (χ2 = 3.174, p = 0.075). A significant decrease in the duration of the hospital stay after surgery was also observed in the IM group (t = 2.012, p = 0.047).Conclusion: ω-3 PUFAs–based lipid emulsions for treatment of patients after hepatectomy are safe and effective in controlling inflammation, protecting liver function, and consequently reducing the rate of total complications and the duration of the hospital stay.