CUL4B enhances the malignant phenotype of esophageal squamous cell carcinoma by suppressing TGFBR3 expression.

Cullin 4B (CUL4B), which acts as a scaffold protein in CUL4B-RING ubiquitin ligase complexes (CRL4B), is frequently overexpressed in cancer and represses tumor suppressors through epigenetic mechanisms. However, the expression and function of CUL4B in esophageal squamous cell carcinoma (ESCC) have not been well illustrated. In this study, we show that upregulation of CUL4B in ESCC cells enhances proliferation, invasion and cisplatin (CDDP)-resistance, while knockdown of CUL4B significantly represses the malignant activities. Mechanistically, we demonstrate that CUL4B promotes proliferation and migration of ESCC cells through inhibiting expression of transforming growth factor beta receptor III (TGFBR3). CRL4B complex binds to the promoter of TGFBR3, and represses its transcription by catalyzing monoubiquitination at H2AK119 and coordinating with PRC2 and HDAC complexes. Taken together, our findings establish a critical role for the CUL4B/TGFBR3 axis in the regulation of ESCC malignancy.

Establishment and validation of a diagnostic nomogram for significant histopathologic changes of hepatic injury in HBV-infected patients.

Background: Significant histopathologic changes of hepatic injury (SHCHI) play a decisive role in evaluating the condition and initiating antiviral in hepatitis B virus (HBV)-infected patients, especially those with normal or mildly elevated alanine transaminase levels. Considering that non-invasive methods were established through experience with chronic hepatitis C, the aim of this study was to establish and verify a nomogram based on hepatitis B for diagnosing SHCHI. Methods: Three hundred eighty-four patients who fulfilled requirements for participation were randomly assigned to training cohort (n=270) and validation cohort (n=114) according to 7:3. The selection criteria for clinical factors were based on the previous research papers. SHCHI was subgrouped as followed: grade ≥ G2 inflammation and/or stage ≥ S2 fibrosis. The predictive accuracy and discriminative ability of nomogram were determined by a concordance index (C-index), calibration curve and the area under the receiver-operating characteristic curve (AUROC). We also compared diagnostic value of nomogram with model for AST-to-PLT ratio index (APRI) score and model for Fibrosis-4 (FIB-4) score. Results: Two hundred and two patients (74.44%) and 87 patients (76.32%) were diagnosed as SHCHI, in the training and validation cohort. Logistic regression analysis illustrated that hepatitis B e antigen (HBeAg), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and prothrombin time (PT) all independently served as risk factors for SHCHI (P<0.05) and were thus utilized to create the nomogram. The nomogram had well-fitted calibration curves and attained excellent concordance indices of 0.80 and 0.75. The sensitivity of nomogram in the diagnosis of SHCHI was 79.7%, the specificity was 68.1%. The area under the curve {AUC; 0.80 [95% confidence interval (CI): 0.74-0.86]} for diagnosing SHCHI by the nomogram was greater in comparison to that of APRI [0.78 (95% CI: 0.71-0.84)], and FIB-4 [0.76 (95% CI: 0.69-0.82)]. Patients with nomogram scores less than 119 were considered to have a lower risk of SHCHI. Conclusions: The constructed nomogram is suitable to serve as a SHCHI screening tool in chronic HBV-infected patients. But the dependability of the nomogram will necessitate further confirmation in a prospective study and further external validation is needed.

Phosphogluconate dehydrogenase is a predictive biomarker for immunotherapy in hepatocellular carcinoma.

Background: Phosphogluconate dehydrogenase (PGD) is involved in the regulation of various tumors. However, its role in hepatocellular carcinoma (HCC) is poorly understood. This study tried to determine the prognostic efficacy of PGD and its value for immunotherapy in HCC. Methods: The data from the TCGA database was used to explore the predictive power of PGD expression and methylation on the overall survival (OS) of HCC through Cox regression and the Kaplan-Meier analysis. Then, we used the GEO and ICGC database to further verify the predictive power. Finally, the relationship between PGD and immune cells and the relationship between PGD and the efficacy of immunotherapy were explored through bioinformatics analysis in HCC. Results: PGD is highly expressed in HCC tissues, which is negatively regulated by PGD methylation. Low PGD expression and PGD hypermethylation predict better OS in HCC patients. Besides, a meta-analysis based on the TCGA, GSE14520, and ICGC databases further confirms that low PGD expression is closely related to favorable OS. Then, we find significant differences of immune cell infiltrations between high and low PGD expression groups. Expressions of immune checkpoints, most HLA members and tumor mutation burden (TMB) are higher in the high PGD expression group, which indicates beneficial efficacy of immunotherapy in this group. And the potential mechanisms of PGD are exhibited. Conclusion: PGD is an independent prognostic factor of HCC patients and plays an important role in immune cell infiltration and immunotherapy, which indicates that PGD can be used as a predictive biomarker for HCC immunotherapy.

The latest application progress of radiomics in prediction and diagnosis of liver diseases.

INTRODUCTION: Early detection and individualized treatment of patients with liver disease is the key to survival. Radiomics can extract high-throughput quantitative features by multimode imaging, which has good application prospects for the diagnosis, staging and prognosis of benign and malignant liver diseases. Therefore, this paper summarizes the current research status in the field of liver disease, in order to help these patients achieve personalized and precision medical care. AREAS COVERED: This paper uses several keywords on the PubMed database to search the references, and reviews the workflow of traditional radiomics, as well as the characteristics and influencing factors of different imaging modes. At the same time, the references on the application of imaging in different benign and malignant liver diseases were also summarized. EXPERT OPINION: For patients with liver disease, the traditional imaging evaluation can only provide limited information. Radiomics exploits the characteristics of high-throughput and high-dimensional extraction, enabling liver imaging capabilities far beyond the scope of traditional visual image analysis. Recent studies have demonstrated the prospect of this technology in personalized diagnosis and treatment decision in various fields of the liver. However, further clinical validation is needed in its application and practice.

Long noncoding RNA Ftx regulates the protein expression profile in HCT116 human colon cancer cells.

BACKGROUND: The long noncoding RNA (lncRNA) five prime to Xist (Ftx) is involved in distant metastasis in colorectal cancer (CRC). This study aimed to investigate Ftx alteration-induced proteomic changes in the highly metastatic CRC cell line HCT116. METHODS: Tandem mass tag (TMT)-based proteomics analysis was performed to detect the differential protein expression in Ftx-overexpressing and Ftx-silenced HCT116 cells. The differentially expressed proteins were classified and characterized by bioinformatics analyses, including gene ontology (GO) annotation, GO/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway/protein domain enrichment analyses, as well as hierarchical clustering. A total of 5471 proteins were quantified, and the proteins with |fold change|≥ 1.2 and p < 0.05 were identified as differentially expressed proteins in response to Ftx overexpression or silencing. RESULTS: The bioinformatics analyses revealed that the differentially expressed proteins were involved in a wide range of GO terms and KEGG signaling pathways and contained multiple protein domains. These terms, pathways, and protein domains were associated with tumorigenesis and metastasis in CRC. CONCLUSIONS: Our results indicate that the alteration of Ftx expression induces proteomic changes in highly metastatic HCT116 cells, suggesting that Ftx and its downstream molecules and signaling pathways could be potential diagnostic biomarkers and therapeutic targets for metastatic CRC.

EGFR/MET promotes hepatocellular carcinoma metastasis by stabilizing tumor cells and resisting to RTKs inhibitors in circulating tumor microemboli.

The receptor tyrosine kinases (RTKs) family is well-recognized as vital targets for the treatment of hepatocarcinoma cancer (HCC) clinically, whereas the survival benefit of target therapy sorafenib is not satisfactory for liver cancer patients due to metastasis. EGFR and MET are two molecules of the RTK family that were related to the survival time of liver cancer patients and resistance to targeted therapy in clinical reports. However, the mechanism and clinical therapeutic value of EGFR/MET in HCC metastasis are still not completely clarified. The study confirmed that EGFR/MET was highly expressed in HCC cells and tissues and the phosphorylation was stable after metastasis. The expression of EGFR/MET was up-regulated in circulating tumor microemboli (CTM) to accelerate IL-8 production and resistance to the lethal effect of leukocytes. Meanwhile, highly expressed EGFR/MET effectively regulated the Ras/MAPK pathway and stabilized suspended HCC cells by facilitating proliferation and inhibiting apoptosis. Moreover, EGFR/MET promoted phosphorylation of hetero-RTKs, which was dependent on high-energy phosphoric acid compounds rather than their direct interactions. In conclusion, highly expressed EGFR/MET could be used in CTM identification and suitable for preventing metastasis of HCC in clinical practice.

HBeAg mediates inflammatory functions of macrophages by TLR2 contributing to hepatic fibrosis.

BACKGROUND: We and others have confirmed activation of macrophages plays a critical role in liver injury and fibrogenesis during HBV infection. And we have also proved HBeAg can obviously induce the production of macrophage inflammatory cytokines compared with HBsAg and HBcAg. However, the receptor and functional domain of HBeAg in macrophage activation and its effects and mechanisms on hepatic fibrosis remain elusive. METHODS: The potentially direct binding receptors of HBeAg were screened and verified by Co-IP assay. Meanwhile, the function domain and accessible peptides of HBeAg for macrophage activation were analyzed by prediction of surface accessible peptide, construction, and synthesis of truncated fragments. Furthermore, effects and mechanisms of the activation of hepatic stellate cells induced by HBeAg-treated macrophages were investigated by Transwell, CCK-8, Gel contraction assay, Phospho Explorer antibody microarray, and Luminex assay. Finally, the effect of HBeAg in hepatic inflammation and fibrosis was evaluated in both human and murine tissues by immunohistochemistry, immunofluorescence, ELISA, and detection of liver enzymes. RESULTS: Herein, we verified TLR-2 was the direct binding receptor of HBeAg. Meanwhile, C-terminal peptide (122-143 aa.) of core domain in HBeAg was critical for macrophage activation. But arginine-rich domain of HBcAg hided this function, although HBcAg and HBeAg shared the same core domain. Furthermore, HBeAg promoted the proliferation, motility, and contraction of hepatic stellate cells (HSCs) in a macrophage-dependent manner, but not alone. PI3K-AKT-mTOR and p38 MAPK signaling pathway were responsible for motility phenotype of HSCs, while the Smad-dependent TGF-ß signaling pathway for proliferation and contraction of them. Additionally, multiple chemokines and cytokines, such as CCL2, CCL5, CXCL10, and TNF-α, might be key mediators of HSC activation. Consistently, HBeAg induced transient inflammation response and promoted early fibrogenesis via TLR-2 in mice. Finally, clinical investigations suggested that the level of HBeAg is associated with inflammation and fibrosis degrees in patients infected with HBV. CONCLUSIONS: HBeAg activated macrophages via the TLR-2/NF-κB signal pathway and further exacerbated hepatic fibrosis by facilitating motility, proliferation, and contraction of HSCs with the help of macrophages.

Derivation and validation of prognostic models for predicting survival outcomes in Acute-on-chronic liver failure patients.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with high bacterial infection (BI) and short-term mortality. However, many ACLF prognostic predictive modelsare complicated. The aim of this study is to develop prognostic models for ACLF patients to predict BI and mortality. We retrospective recruited 263 patients with ACLF from Shandong Provincial Hospital and Taizhou Enze Medical Center (Group) Enze Hospital. ACLF was defined according to the Asian Pacific Association for the Study of the Liver (APASL) criteria. Multivariable logistic regression was used to derive prediction models for occurring BI and 28-day mortality in ACLF patients. Ninety seven of 263 patients (37%) occurred BI and 41 of 155 (26%) died within 28 days of admission. C-reactive protein (CRP), glucose, and albumin were the independent predictors for occurring BI during the hospital stay. We also found that hepatic encephalopathy (HE), prothrombin time, activated partial thromboplastin time (APRI), and glucose were the independent predictors of 28-day mortality of ACLF patients. Using logistic regression model, we generated a new modified MELD model (M-MELD) by incorporating HE, APRI, and glucose. AUC of M-MELD model was 0.871, which were significantly higher than MELD score (AUC:0.734), MELD-Na score (AUC:0.742), and integrated MELD score (iMELD) (AUC:0.761). HE, MELD score, APRI, and blood glucose were independent risk factors for 28-day mortality of ACLF patients. The modified MELD model (M-MELD) by incorporating HE, APRI, and glucose has better discriminative performances compared with MELD in predicting 28-day mortality.

The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis.

About 250 million people worldwide are chronically infected with Hepatitis B virus (HBV), contributing to a large burden on public health. Despite the existence of vaccines and antiviral drugs to prevent infection and suppress viral replication respectively, chronic hepatitis B (CHB) cure remains a remote treatment goal. The viral persistence caused by HBV is account for the chronic infection which increases the risk for developing liver cirrhosis and hepatocellular carcinoma (HCC). HBV virion utilizes various strategies to escape surveillance of host immune system therefore enhancing its replication, while the precise mechanisms involved remain elusive. Accumulating evidence suggests that the proteins encoded by HBV (hepatitis B surface antigen, hepatitis B core antigen, hepatitis B envelope antigen, HBx and polymerase) play an important role in viral persistence and liver pathogenesis. This review summarizes the major findings in functions of HBV encoding proteins, illustrating how these proteins affect hepatocytes and the immune system, which may open new venues for CHB therapies.

Functional role of miR­155 in physiological and pathological processes of liver injury (Review).

There are several types of liver injury, including alcohol­induced liver injury, drug­induced liver injury, infectious liver injury, cirrhosis, liver ischemia/reperfusion injury and liver failure. In recent years, accumulated data have demonstrated that microRNAs (miRNAs/miRs) may be involved in the occurrence and development of a variety of systemic diseases, such as immune diseases, tumors and nervous system diseases. miR­155 is a key miRNA, which has been studied extensively and has been shown to target different genes. In the present review, the potential effects and mechanisms of miR­155 on the physiological and pathological processes of liver injury were reviewed from the perspective of cell stress, inflammation and activation of fibrosis. In addition, the potential benefits of miR­155 as a therapeutic target and predictor of liver injury were summarized.

Current directions, conceptions and viewpoints on 2019-nCoV (Review).

On December 31, 2019, the first case of a novel coronavirus infection was reported in Wuhan, China. The ongoing outbreak of the 2019 novel coronavirus (2019-nCoV) has caused immense global concern. According to the recommendations of the International Health Regulations Emergency Committee and the facts and cases that 215 other countries have also reported to date, the World Health Organization Director-General announced that the outbreak of 2019-nCoV constitutes a public health emergency of international concern and a severe threat to the human health worldwide. To date, the prevalence of the virus has continued in waves and is increasing globally. The present review briefly introduces the epidemiology of 2019-nCoV, as well as viral structural characteristics, and receptors and cells that may act after entering the body, laboratory examinations, imaging and pathological features, clinical manifestations, complications, treatment and management.

Microwave ablation versus radiofrequency ablation for perivascular hepatocellular carcinoma: a propensity score analysis.

BACKGROUND: To compare the efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) as first-line treatments for perivascular HCC. METHODS: This multicentre study enrolled 170 patients with perivascular HCC who underwent MWA or RFA. The ablation response, progression-free survival (PFS), overall survival (OS), and complications between the treatment groups for the total and propensity score-matched (PSM) cohorts were compared. RESULTS: The disease control rates for MWA and RFA were similar in total (94% vs. 91%, p = 0.492) and PSM (93% vs. 93%, p = 1.00) cohorts. The PFS rates at 1, 3, and 5 years were 71%, 55% and 52% in MWA group and 61%, 33% and 28% in RFA group (p = 0.017). The OS rates were comparable between two groups in total (p = 0.249) and PSM cohorts (p = 0.345). In subgroup analyses, the PFS of patients with periportal HCC (45 vs. 36 months, p = 0.048) and a single HCC nodule (51 vs. 42 months, p = 0.014) were significantly better in MWA group than RFA. Major complications were more frequent in the MWA group than in RFA (27% vs. 7%, p < 0.001). CONCLUSION: Compared with RFA, MWA provides better control of tumour progression especially in periportal HCC or single-nodule perivascular HCC patients.

[Retracted] Suppression of YAP by DDP disrupts colon tumor progression.

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that Fig. 6D contained images featuring overlapping data, which reportedly had been derived under different experimental conditions. Subsequently, further issues of data duplication were brought to light by another interested reader concerning the above article; first, certain of the images showing colony­forming assays in Fig. 4D were strikingly similar to images that had appeared in a previous publication by the same research group, and secondly, a couple of instances of data duplication were identified among the histopathological images presented within Fig. 7D. After having considered the various issues that have been brought to light with this paper, together with an appeal from the authors that a Corrigendum be published, the Editor of Oncology Reports has ruled that the article should be retracted from the publication on account of a lack of overall confidence in the presented data. Note that the authors were not in agreement that the number of errors reported and identified were sufficient to merit the retraction of the article. Additionally, the authors carefully checked the raw data and drew a conclusion that the final scientific conclusions were not affected. The Editor and the authors apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 2114­2126, 2018; DOI: 10.3892/or.2018.6297].

Four Autophagy-Related lncRNAs Predict the Prognosis of HCC through Coexpression and ceRNA Mechanism.

Abnormally expressed long noncoding RNAs (lncRNAs) have been reported to affect the occurrence and progression of hepatocellular carcinoma (HCC) by modulating the autophagy axis. However, none of studies has explored the clinical significance of these autophagy-related lncRNAs in HCC comprehensively. In this study, the RNA-seq, miRNA-seq, and clinical data of normal and HCC patients from the TCGA database and autophagy genes from the Human Autophagy Database were extracted. Subsequently, we screened out 78 differentially expressed autophagy-related lncRNAs, and four prognostic-related lncRNAs (LUCAT1, AC099850.3, ZFPM2-AS1, and AC009005.1) were eventually used to develop the prognostic model. This signature could be regarded as an independent prognostic signature for HCC patients and has the highest prediction efficiency than other clinicopathological factors for the 1-, 3-, and 5-year survival (AUC = 0.764, 0.738, and 0.717, respectively). Additionally, regardless of whether the clinical information is complete for HCC patients, the autophagy-related lncRNA model shows a good predictive power for the overall survival. Importantly, the coexpression network of 4 lncRNAs and 11 autophagy-related genes was constructed. Moreover, based on the bioinformatic analyses, our results found that LUCAT1 and ZFPM2-AS1 may affect the autophagic activity in HCC through the hsa-miR-495-3p/DLC1 and hsa-miR-515-5p/DAPK2 axis, respectively. In conclusion, we establish an effective prognostic model for HCC patients and shed new light on the autophagy-related regulatory mechanisms of the identified lncRNAs.

Seven immune-related genes prognostic power and correlation with tumor-infiltrating immune cells in hepatocellular carcinoma.

BACKGROUND: Given poor prognosis and the lack of efficient therapy for advanced hepatocellular carcinoma, immunotherapy has emerged as an increasingly important role. However, there were few reports on the correlation between immune-related genes and HCC. The purpose of this study is to construct a novel immune-related gene-based prognostic signature for HCC and to explore the potential mechanisms. METHODS: We organized expression data of 374 HCC samples and 50 nontumor samples from TCGA database. A robust signature was constructed by Cox regression analysis based on the immune-related genes, which were filtered by differential genes analysis and Cox regression analysis. Then, the correlation analysis between the signature and clinical characteristics was conducted. And the signature was validated in ICGC database. Furthermore, the relationships between immune cell infiltration and the signature were explored by bioinformatics analysis. RESULTS: Seven genes-based model (Risk score = BIRC5 * 0.0238 + FOS * 0.0055 + DKK1 * 0.0085 + FGF13 * 0.3432 + IL11 * 0.0135 + IL17D * 0.0878 + SPP1 * 0.0003) was constructed eventually and it was proved to be an independent prognostic factor for HCC patients. The signature-calculated risk scores were shown to be positively correlated with the infiltration of these five immune cells, including macrophages, neutrophils, CD8+T, dendritic, and B cells. And the results suggested that high amplication of BIRC5, FGF13, IL11, IL17D, and SPP1 were more likely correlated with immune cell infiltration. Finally, PPI network, TFs-based regulatory network and gene enrichment plots were performed to show potential molecular mechanisms. CONCLUSION: We construct a robust immune-related gene-based prognostic signature with seven genes and explore potential mechanisms about it, which may contribute to the immunotherapy research for HCC.

Negative feedback loop of ERK/CREB/miR-212-3p inhibits HBeAg-induced macrophage activation.

The activation of liver macrophages is closely related to liver injury after HBV infection. Our previous results demonstrated that HBeAg played a key role in inducing macrophage activation. As we all know, miRNAs are involved in the regulation of multiple immune cell functions. Meanwhile, we have shown that miR-155 positively regulates HBeAg-induced macrophage activation and accelerates liver injury. Subsequently, based on our previous miRNA sequencing results, we further evaluated the role of miR-212-3p called 'neurimmiR' in HBeAg-induced macrophages in this study. First, miR-212-3p expression was significantly elevated in HBeAg-treated macrophages. Meanwhile, we found up-regulation of miR-212-3p significantly decreased the production of cytokines, whereas knockdown of miR-212-3p held the opposite effect by gains and losses of function. Mechanically, although MAPK signal pathway, including ERK, JNK and p38, was activated in HBeAg-induced macrophages, only ERK promoted the expression of miR-212-3p via transcription factor CREB, which was able to bind to the promoter of miR-212-3p verified by ChIP assay. Moreover, we further indicated that up-regulated miR-212-3p inhibited HBeAg-induced inflammatory cytokine production through targeting MAPK1. In conclusion, miR-212-3p was augmented in HBeAg-stimulated macrophages via ERK/CREB signal pathway and the elevated miR-212-3p suppressed inflammatory cytokine production induced by HBeAg through targeting MAPK1.

Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study.

BACKGROUND: Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process. AIM: To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes. METHODS: SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows-wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs. RESULTS: Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S). CONCLUSION: The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.

Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤ 5 cm) after initial curative resection.

OBJECTIVES: Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection, but the management of recurrent HCC remains unclear. To compare the efficacy and safety of radiofrequency ablation (RFA) and repeat resection as the first-line treatment in recurrent HCC. METHODS: This multicenter retrospective study analyzed 290 patients who underwent RFA (n = 199) or repeat resection (n = 91) between January 2006 and December 2016 for locally recurrent HCC (≤ 5 cm) following primary resection. We compared the overall survival (OS), progression-free survival (PFS), and complications between the two treatment groups for the total cohort and the propensity score matched (PSM) cohort. RESULTS: The 1-, 3-, and 5-year OS (90.7%, 69.04%, 55.6% vs. 87.7%, 62.9%, 38.1%, p = 0.11) and PFS (56.5%, 27.9%, 14.6% vs. 50.2%, 21.9%, 19.2%, p = 0.80) were similar in the RFA group and the repeat resection group. However, RFA was superior to repeat resection in complication rate and hospital stay (p ≤ 0.001). We observed similar findings in the PSM cohort of 48 pairs of patients and when OS and PFS were measured from the time of the primary resection. The OS of the RFA group was significantly better than repeat resection group among those with 2 or 3 recurrent tumor nodules in both the total cohort (p = 0.009) and the PSM cohort (p = 0.018). CONCLUSION: RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. RFA is more efficient and safer than repeat resection in patients with 2 or 3 recurrent tumor nodules. KEY POINTS: • Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection. • RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. • RFA may be preferred for those with 2 or 3 recurrent HCC nodules.