Background: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that excludes them from potentially curative surgical treatment. Lenvatinib is associated with a high objective response rate (ORR) (40.6%) in advanced HCC, indicating the potential for tumor downstaging and conversion to surgical intervention. We report the case of a patient with recurrent, advanced HCC who achieved a partial response and downstaging following third-line treatment with lenvatinib but missed the opportunity for conversion hepatectomy. Case Presentation: A male Chinese patient aged 42 years presented with an obstructive liver lesion, revealed by CT imaging to be a single tumor in segments V and VIII of the liver, without macrovascular invasion. The patient had chronic hepatitis B infection, Barcelona Clinic Liver Cancer (BCLC) Stage A, normal liver function (Child-Pugh Score 5 and Grade A) and AFP level 4.45 ng/mL. The patient underwent a successful hepatectomy but experienced recurrence 14 months later. The recurrent tumor was detected at an early stage and the patient underwent successful radiofrequency ablation and transarterial chemoembolization. After a further 11 months, the patient experienced a second relapse characterized by multiple disseminated metastases in the left and right lobes of the liver and possible macrovascular invasion, equal to BCLC Stage B/C. The patient received lenvatinib and achieved a partial response with complete disappearance of a number of lesions, recovering to BCLC Stage A and becoming eligible for liver transplantation. However, the patient refused surgery and after 4 months experienced progressive disease. Conclusion: Our case suggests that radical treatment, such as conversion hepatectomy or liver transplantation, should be undertaken quickly following downstaging and within the expected PFS time associated with lenvatinib. However, further studies are required to provide additional evidence for this treatment strategy.

Hepatocellular carcinoma (HCC) is the predominant pathological type of liver cancer. Several therapeutic treatments, including sorafenib and regorafenib, have only modestly improved survival in patients with HCC. The aim of this study was to investigate the expression profiles and the regulation of competitive endogenous RNAs (ceRNAs) of the sorafenib-related target genes in HCC. Based on clinical information and expression profiles of HCC clinical samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, shared differentially expressed genes (DEGs) were analyzed and identified. Sorafenib-associated DEGs (SADs) were obtained by intersecting the DEGs with the sorafenib target genes from SuperTarget database. The expression patterns of SADs were verified in the Oncomine database. The biological functions of the SADs were annotated by gene set enrichment analysis (GSEA). In addition, a ceRNA network associated with SADs was constructed. Long non-coding RNAs (lncRNAs) in network that were significantly associated with overall survival were identified as prognosis of patients by Cox regression analysis. Finally, the expression levels of prognostic genes in HCC tissues and cell lines were verified using qRT-PCR. Gene expression differential analysis yielded a total of 146 common DEGs were obtained, including 21 upregulated and 125 downregulated DEGs. Among them, ten SADs were detected to be differentially expressed between tumor and normal tissues, including AXL, CYP2C19, CYP2C8, CYP2C9, CYP3A4, FGFR2, GMNN, PDGFRA, and TTK. GSEA analysis grouped them into three categories by function. The first category (CYP2C19, CYP2C8, CYP2C9 and CYP3A4) and second category (GMNN, TTK and EGER2) had the opposite roles in the enriched terms and pathways, while the third class (AXL and PDGFRA) has enrichment terms and pathways that intersect with those of the first and second categories. A ceRNA network associated with SADs was also constructed including 49 lncRNAs, 14 miRNAs, and 8 mRNAs. Three of these lncRNAs, SNHG7, GAS5 and HCP5, were found upregulated in HCC tissues and to be independent predictors in HCC patients. Significant correlations were found in expression between the prognostic lncRNAs and SADs. Ten SADs were systematically identified using expression data from HCC and normal tissues from TCGA and GEO datasets. GSEA analysis provided us with insight into the function of SADs. In the future, we will continue to explore the mechanisms of coordinated regulation of SADs-related prognostic lncRNAs and SADs at the ceRNA axis level and their potential functions in the development of HCC.

Objective: The incidence of metabolic syndrome (MS) increases after liver transplantation. This study was performed to evaluate the impact of MS on patients’ quality of life after liver transplantation. Methods: We collected the medical records of 152 patients during their post-liver transplantation outpatient follow-up. Quality of life was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey. Data on the patients’ general condition as well as MS-related indicators were assessed in all patients. Based on the MS diagnostic criteria proposed by the International Diabetes Federation in 2005, the patients were divided into two groups: those with and without MS. We then analyzed the factors influencing MS and their impact on the patients’ quality of life. Results: After liver transplantation, age and underlying liver disease were significantly associated with MS and diabetes, and sex and body mass index were associated with central obesity. Central obesity affected the patients’ general health (GH) score and health transition (HT) score, and hypertension affected their GH score and physical component score (PCS). Conclusions: After liver transplantation, central obesity had a negative impact on patients’ GH score and HT score, and hypertension affected their GH score and PCS.

Overexpression of apoptosis-stimulating protein 2 of p53 (ASPP2) induces apoptotic cell death in hepatoma cells (e.g. HepG2 cells) by enhancing the transactivation activity of p53, but long-term ASPP2 overexpression fails to induce more apoptosis since activation of the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway impairs the pro-apoptotic role of ASPP2. In this study, in recombinant adenovirus-ASPP2-infected HepG2 cells, ASPP2 overexpression induces amphiregulin expression in a p53-dependent manner. Although amphiregulin initially contributes to ASPP2-induced apoptosis, it eventually impairs the pro-apoptotic function of ASPP2 by activating the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway, leading to apoptosis resistance. Moreover, blocking soluble amphiregulin with a neutralizing antibody also significantly increased apoptotic cell death of HepG2 cells due to treatment with methyl methanesulfonate, cisplatin, or a recombinant p53 adenovirus, suggesting that the function of amphiregulin involved in inhibiting apoptosis may be a common mechanism by which hepatoma cells escape from stimulus-induced apoptosis. Thus, our data elucidate an apoptosis-evasion mechanism in hepatocellular carcinoma and have potential implications for hepatocellular carcinoma therapy.

Nowadays, primary liver cancer is still a major threat to human health. Anoikis is a particular form of programed cell death that has an inhibitory effect on neoplasm metastasis. Although several prognostic models based on anoikis‐related genes for Hepatocellular carcinoma (HCC) have been established, signatures associated with anoikis‐related lncRNAs have not been identified. To fill this blank space, the authors built up a prognostic signature and appraised its value in guiding immunotherapy. Eleven prognostic anoikis‐related lncRNAs were identified through Least Absolute Shrinkage and Selection Operator Cox analysis. The accuracy of the risk signature in predicting prognosis was verified by K–M survival analysis and Receiver operating characteristic analysis. We further discovered that the high‐risk group was often enriched in signal pathways related to cell growth and death and immune response; in addition, in the low‐risk group, cells often undergo metabolic changes through gene set enrichment analysis. Finally, we realised that HCC patients in the high‐risk group were upregulated in immune‐checkpoint molecules and tend to have a higher tumour mutation burden level which indicated a higher sensitivity to immunotherapy. All in all, the anoikis‐related lncRNAs risk signature showed excellent ability in predicting prognosis and may guide the application of immunotherapy in future clinical practice.

Background: The size and function of the future liver remnant (FLR) is an essential consideration for both eligibility for treatment and postoperative prognosis when planning surgical hepatectomy. Over time, a variety of preoperative FLR augmentation techniques have been investigated, from the earliest portal vein embolization (PVE) to the more recent Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) procedures. Despite numerous publications on this topic, no bibliometric analysis has yet been conducted.Methods: Web of Science Core Collection (WoSCC) database was searched to identify studies related to preoperative FLR augmentation techniques published from 1997 to 2022. The analysis was performed using the CiteSpace [version 6.1.R6 (64-bit)] and VOSviewer [version 1.6.19].Results: A total of 973 academic studies were published by 4431 authors from 920 institutions in 51 countries/regions. The University of Zurich was the most published institution while Japan was the most productive country. Eduardo de Santibanes had the most published articles, and Masato Nagino was the most frequently co-cited author. The most frequently published journal was HPB, and the most cited journal was Ann Surg, with 8088 citations. The main aspects of preoperative FLR augmentation technique is to enhance surgical technology, expand clinical indications, prevent and treat postoperative complications, ensure long-term survival, and evaluate the growth rate of FLR. Recently, hot keywords in this field include ALPPS, LVD, and Hepatobiliary Scintigraphy.Conclusion: This bibliometric analysis provides a comprehensive overview of preoperative FLR augmentation techniques, offering valuable insights and ideas for scholars in this field.