Albumin, an interesting and functionally diverse protein, varies from 'native' to 'effective' (Review).

Human serum albumins (HSAs) are synthesized in the liver and are the most abundant proteins in plasma of healthy human. They play an important role in the pathophysiological processes of the liver and even the whole organism. Previous studies have mainly focused on the regulation of HSAs' expression. However, with the progress of research in recent years, it has been found that the content of circulating albumin cannot fully reflect the biological function of albumin itself. Given the aforementioned fact, the concept of serum 'effective albumin concentration' has been proposed. It refers to the content of albumin that is structurally and functionally intact. Alterations in the molecular structure and function of albumin have been reported in a variety of diseases, including liver disease. Moreover, these changes have been verified to affect the progression of oxidative stress­related diseases. However, the link between albumin structure and function has not been fully elaborated, and the mechanisms by which different forms of albumin affect disease also need to be further investigated. In this context, the present review mainly expounded the biological characteristics and functions of albumin, summarized the different types of post­translational modification of albumin, and discussed their functional changes and possible mechanisms in non­alcoholic fatty liver disease, alcoholic hepatitis, viral hepatitis and different stages of cirrhosis. This will help to improve understanding of the role of albumin in disease development and provide a more comprehensive physiological basis for it in disease treatment.

Phosphorylation of RGS16 at Tyr168 promote HBeAg-mediated macrophage activation by ERK pathway to accelerate liver injury.

Liver injury is closely associated with macrophage activation following HBV infection. Our previous study showed that only HBeAg, but not HBsAg and HBcAg, stably enhances inflammatory cytokine production in macrophages. And we also indicated that HBeAg could induce macrophage activation via TLR2 and thus aggravate the progression of liver fibrosis. However, the specific molecular mechanism of HBeAg in macrophage activation is not clear. We screened significantly overexpressed RGS16 from RNASeq results of HBeAg-stimulated macrophages and validated them with cellular assays, GSE83148 microarray dataset, and in clinical samples. Meanwhile, small interference, plasmid, and lentivirus transfection assays were used to establish cell models for knockdown and overexpression of RGS16, and q-PCR, ELISA, Transwell, and CCK-8 assays were used to analyze the role of RGS16 in HBeAg-induced macrophage activation. In addition, the upstream and downstream mechanisms of RGS16 in HBeAg-treated macrophage activation were explored using inhibitors, phostag gels, and RGS16 phosphorylation mutant plasmids. Finally, the effect of RGS16 on hepatic inflammation in murine tissues was evaluated by H&E staining, liver enzyme assay and immunofluorescence. RGS16 was significantly upregulated in HBeAg-induced macrophage activation, and its expression was enhanced with increasing HBeAg content and treatment time. Functional experiments showed that overexpression of RGS16 promoted the production of inflammatory factors TNF-α and IL-6 and boosted macrophage proliferation and migration, while knockdown of RGS16 exhibited the opposite effect. Mechanistically, we discovered that RGS16 is regulated by the TLR2/P38/STAT5 signaling pathway. Meanwhile, RGS16 enhanced ERK phosphorylation via its own Tyr168 phosphorylation to contribute to macrophage activation, thereby accelerating liver injury. Finally, in mice, overexpression of RGS16 markedly strengthened liver inflammation. HBeAg upregulates RGS16 expression through the TLR2-P38-STAT5 axis, and the upregulated expression of RGS16 enhances macrophage activation and accelerates liver injury by promoting ERK phosphorylation. In this process, phosphorylation of Tyr168 is necessary for RGS16 to function. KEY MESSAGES: RGS16 boosted HBeAg-induced macrophage inflammation, proliferation, and migration. Tyr168 phosphorylation of RGS16 affected by ERK promoted macrophage activation. HBeAg upregulated the expression of RGS16 through TLR2/P38/STAT5 signal pathway. RGS16 promoted liver injury by regulating macrophage functions in mouse model.

Race between virus and inflammasomes: inhibition or escape, intervention and therapy.

The inflammasome is a multiprotein complex that further regulates cell pyroptosis and inflammation by activating caspase-1. The assembly and activation of inflammasome are associated with a variety of diseases. Accumulative studies have shown that inflammasome is a key modulator of the host's defense response to viral infection. Indeed, it has been established that activation of inflammasome occurs during viral infection. At the same time, the host has evolved a variety of corresponding mechanisms to inhibit unnecessary inflammasome activation. Therefore, here, we review and summarize the latest research progress on the interaction between inflammosomes and viruses, highlight the assembly and activation of inflammosome in related cells after viral infection, as well as the corresponding molecular regulatory mechanisms, and elucidate the effects of this activation on virus immune escape and host innate and adaptive immune defenses. Finally, we also discuss the potential therapeutic strategies to prevent and/or ameliorate viral infection-related diseases via targeting inflammasomes and its products.

M1 macrophages may be effective adjuvants for promoting Th­17 differentiation in HBeAg positive hepatitis patients with ALT ≤2ULN.

Hepatitis B virus (HBV) infection can activate macrophages to accelerate liver disease progression, including inflammation and fibrosis. However, the exact mechanism remains undetermined. The present study assessed the effects of macrophage polarization and the related cytokines on Th­17 differentiation in HBeAg positive individuals with a HBV infection, and also evaluated the potential association of Th­17 cell frequency with the severity of liver injury. A cross­sectional study design was used to collect the clinical parameters, blood samples and liver tissue samples of patients with alanine transaminase £2x upper limit of normal and confirmed hepatitis B who underwent liver puncture in Qishan Hospital between January 2019­December 2021. Macrophage and Th­17 cell related factors were assayed using ELISA. The expression and quantification of cell surface antigen and intracellular markers in cells were assessed using flow cytometry. Pathological staining, including hematoxylin and eosin, reticular fiber staining and immunohistochemical staining were used to assess inflammation and fibrosis in the liver tissue. In the peripheral blood of patients with HBV infection, the number of CD14+ macrophages was significantly increased compared with the healthy control, especially in the hepatitis B e antigen (HBeAg) positive group. CD14+ macrophages were predominantly of the M1 type based on the assessment of the phenotype using flow cytometry and cytokine secretion. Furthermore, the percentage of M1 phenotype and related cytokines were positively correlated with Th­17 differentiation. IL­17A secreted by Th­17 was positively correlated with the degree of liver inflammation and fibrosis, as well as with the severity of liver disease, which indicated that the differentiation of Th­17 may be involved in the progression of liver disease. HBeAg may promote Th­17 differentiation and IL­17A production by M1 macrophages to accelerate the pathogenesis of liver inflammation and fibrosis in CHB patients.

FNDC3B protects steatosis and ferroptosis via the AMPK pathway in alcoholic fatty liver disease.

BACKGROUND: Alcoholic liver disease (ALD) is a leading cause of chronic liver disease worldwide with limited therapeutic options. The role of fibronectin type III domain-containing protein 3B (FNDC3B), an important regulator of metabolism, in ALD, and the underlying mechanism as well as its potential implication in ALD therapeutic strategies remain unknown. METHODS: Hepatocyte-specific FNDC3B knockdown or control C57BL/6 N mice received a Lieber-DeCarli diet for four weeks, followed by oral gavage (chronic-binge). Primary mouse hepatocytes and cell lines were used for in vitro studies. Liver injury, hepatic steatosis, and lipid peroxidation were assessed. RESULTS: In cultured cells and mouse livers, alcohol exposure increased FNDC3B expression. Hepatocyte-specific FNDC3B deletion aggravated alcohol-induced liver steatosis via AMP-activated protein kinase (AMPK) inhibition. In vitro, FNDC3B expression was negatively regulated by miR-192-5p. Furthermore, FNDC3B deletion significantly exacerbated ethanol-mediated lipid peroxidation. The RNA sequence assay revealed a connection between FNDC3B and ferroptosis, which was verified by the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Additionally, FNDC3B inhibition-mediated AMPK inactivation downregulated transferrin expression, which was associated with marked iron overload and ferroptosis. CONCLUSIONS: This study elucidated the critical role of FNDC3B in preventing hepatic steatosis and ferroptosis in response to chronic alcohol consumption. Our findings indicate that FNDC3B is a potential therapeutic target for ALD.

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.

Functions of regulators of G protein signaling 16 in immunity, inflammation, and other diseases.

Regulators of G protein signaling (RGS) act as guanosine triphosphatase activating proteins to accelerate guanosine triphosphate hydrolysis of the G protein α subunit, leading to the termination of the G protein-coupled receptor (GPCR) downstream signaling pathway. RGS16, which is expressed in a number of cells and tissues, belongs to one of the small B/R4 subfamilies of RGS proteins and consists of a conserved RGS structural domain with short, disordered amino- and carboxy-terminal extensions and an α-helix that classically binds and de-activates heterotrimeric G proteins. However, with the deepening of research, it has been revealed that RGS16 protein not only regulates the classical GPCR pathway, but also affects immune, inflammatory, tumor and metabolic processes through other signaling pathways including the mitogen-activated protein kinase, phosphoinositide 3-kinase/protein kinase B, Ras homolog family member A and stromal cell-derived factor 1/C-X-C motif chemokine receptor 4 pathways. Additionally, the RGS16 protein may be involved in the Hepatitis B Virus -induced inflammatory response. Therefore, given the continuous expansion of knowledge regarding its role and mechanism, the structure, characteristics, regulatory mechanisms and known functions of the small RGS proteinRGS16 are reviewed in this paper to prepare for diagnosis, treatment, and prognostic evaluation of different diseases such as inflammation, tumor, and metabolic disorders and to better study its function in other diseases.

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.

SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms.

As of April 1, 2022, over 468 million COVID-19 cases and over 6 million deaths have been confirmed globally. Unlike the common coronavirus, SARS-CoV-2 has highly contagious and attracted a high level of concern worldwide. Through the analysis of SARS-CoV-2 structural, non-structural, and accessory proteins, we can gain a deeper understanding of structure-function relationships, viral infection mechanisms, and viable strategies for antiviral therapy. Angiotensin-converting enzyme 2 (ACE2) is the first widely acknowledged SARS-CoV-2 receptor, but researches have shown that there are additional co-receptors that can facilitate the entry of SARS-CoV-2 to infect humans. We have performed an in-depth review of published papers, searching for co-receptors or other auxiliary membrane proteins that enhance viral infection, and analyzing pertinent pathogenic mechanisms. The genome, and especially the spike gene, undergoes mutations at an abnormally high frequency during virus replication and/or when it is transmitted from one individual to another. We summarized the main mutant strains currently circulating global, and elaborated the structural feature for increased infectivity and immune evasion of variants. Meanwhile, the principal purpose of the review is to update information on the COVID-19 outbreak. Many countries have novel findings on the early stage of the epidemic, and accruing evidence has rewritten the timeline of the outbreak, triggering new thinking about the origin and spread of COVID-19. It is anticipated that this can provide further insights for future research and global epidemic prevention and control.

Combined radiofrequency ablation or microwave ablation with transarterial chemoembolization can increase efficiency in intermediate-stage hepatocellular carcinoma without more complication: a systematic review and meta-analysis.

OBJECTIVES: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely used in combination with transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) in clinical practice. We aim to compare the efficacy and safety of TACE combined with RFA or MWA versus TACE monotherapy for intermediate-stage HCC. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The outcomes included overall survival (OS), progression-free survival (PFS), local tumor control (LTC) rate, and major complication. Subgroup analysis for different TACE combination therapies was performed. RESULTS: Ten studies with 1799 patients with intermediate-stage HCC were included. The pooled hazard ratio (HR) for OS was in favor of TACE combination therapy (HR, 0.50, 95% confidence interval [CI], 0.40-0.62). Specifically, the TACE combination therapy was associated with higher 1-, 3-, and 5-year OS rates. Regarding tumor progression, the TACE combination therapy showed significantly better PFS (HR, 0.47, 95% CI, 0.37-0.61) and higher 1-, 2- and 3-year PFS rates than TACE monotherapy. The pooled odds ratio (OR) for the LTC was also in favor of TACE combination therapy (OR, 0.36, 95% CI, 0.24-0.53). No significant difference was found between the two groups regarding the major complication rate (OR, 1.26, 95% CI, 0.74-2.16). These results were consistent across subgroups of TACE + RFA versus TACE and TACE + MWA versus TACE. CONCLUSION: TACE combined with RFA or MWA can provide significantly better OS, PFS and LTC than TACE monotherapy for patients with intermediate-stage HCC, without increasing the risk of major complications.

ATRA-mediated-crosstalk between stellate cells and Kupffer cells inhibits autophagy and promotes NLRP3 activation in acute liver injury.

The crosstalk between hepatic stellate cells (HSCs) and Kupffer cells (KCs) is involved in acute liver injury (ALI). Meanwhile, the change of lipid droplet in HSCs predicts the development of ALI. However, it is not clear whether all trans retinoic acid (ATRA), as one of the important products of lipid droplet metabolism from HSC, regulate the activation of KCs. Firstly, our results confirmed that ATRA release and IL-1ß production were significantly increased in a CCl4-induced model of ALI. In addition, we observed that ATRA could induce KCs to produce IL-1ß through retinoic acid receptor (RAR) in vitro. Further mechanism studies confirmed that RAR could promote priming of NLRP3 inflammasome through transcriptional activation. ATRA also blocked autophagic flow by activating the AKT/mTOR pathway, leading to an excessive accumulation of ROS, which further activated the NLRP3 inflammasome. Activated NLRP3 inflammasome caused pyroptosis of macrophages and explosive release of IL-1ß. In conclusion, we have uncovered a novel crosstalk pattern between HSCs and KCs, and ATRA-mediated-crosstalk between HSCs and KCs inhibits autophagy and promotes NLRP3 activation to aggravate acute liver injury.

N6-Methyladenosine Modification Participates in the Progression of Hepatitis B Virus-Related Liver Fibrosis by Regulating Immune Cell Infiltration.

Aim: N6-methyladenosine (m6A) modification has been demonstrated to play an important part in hepatitis B virus (HBV) infection and immune response. This study aims to further investigate whether m6A modification plays an important role in the progression of HBV-related liver fibrosis through the regulation of immune cell infiltration. Methods: In this study, 124 chronically HBV infected cases were obtained from the Gene Expression Omnibus database. In total, 489 m6A-and-stage related genes were selected to be associated with the m6A modification and the stage of liver fibrosis. Based on these genes, we identified two distinct gene clusters, gene clusterA and gene clusterB. The immune characteristics of the two clusters were comprehensively compared. The m6A-S score was constructed as quantification of individual m6A status. The correlations between m6A regulators and infiltrating immune cells were examined and compared in different pairs of groups with various m6A traits. Results: Biological functions, immune cell infiltration, and cytokines expression were compared between the two gene clusters proving that the gene clusterB was more immune active and had a more advanced liver fibrosis stage. The m6A-S score was associated with immune infiltration and the progression of liver fibrosis. Five different grouping conditions with different m6A traits were set up. According to the intersection of significant genes and cells, ALKBH5 interacting with macrophage and WTAP interacting with nature killer T cells may be key points in the progress of liver fibrosis. Conclusions: N6-methyladenosine modification is closely related to the immune cell infiltration and the fibrosis stage of chronic HBV-infected liver tissue. It provides us a better understanding of the progression of liver cirrhosis via evaluating the m6A modification pattern and immune infiltration characteristics.

CT-Based Radiomics Score Can Accurately Predict Esophageal Variceal Rebleeding in Cirrhotic Patients.

Purpose: This study aimed to develop a radiomics score (Rad-score) extracted from liver and spleen CT images in cirrhotic patients to predict the probability of esophageal variceal rebleeding. Methods: In total, 173 cirrhotic patients were enrolled in this retrospective study. A total of 2,264 radiomics features of the liver and spleen were extracted from CT images. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select features and generate the Rad-score. Then, the Rad-score was evaluated by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Kaplan-Meier analysis was used to assess the risk stratification ability of the Rad-score. Results: Rad-scoreLiver, Rad-scoreSpleen, and Rad-scoreLiver-Spleen were independent risk factors for EV rebleeding. The Rad-scoreLiver-Spleen, which consisted of ten features, showed good discriminative performance, with C-indexes of 0.853 [95% confidence interval (CI), 0.776-0.904] and 0.822 (95% CI, 0.749-0.875) in the training and validation cohorts, respectively. The calibration curve showed that the predicted probability of rebleeding was very close to the actual probability. DCA verified the usefulness of the Rad-scoreLiver-Spleen in clinical practice. The Rad-scoreLiver-Spleen showed good performance in stratifying patients into high-, intermediate- and low-risk groups in both the training and validation cohorts. The C-index of the Rad-scoreLiver-Spleen in the hepatitis B virus (HBV) cohort was higher than that in the non-HBV cohort. Conclusion: The radiomics score extracted from liver and spleen CT images can predict the risk of esophageal variceal rebleeding and stratify cirrhotic patients accordingly.

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.

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.

Liver resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND & AIMS: Liver resection (LR) and radiofrequency ablation (RFA) are commonly used for the treatment of recurrent hepatocellular carcinoma (HCC), but the optimal treatment modality remains unclear. We aimed to compare the efficacy and safety of LR vs RFA for recurrent HCC. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were major complications and hospital stay. RESULTS: Eighteen studies with 1991 patients with recurrent HCC were included. The pooled hazard ratio (HR) for OS demonstrated that LR had significantly better OS than RFA in recurrent HCC (HR, 0.81; 95% confidence interval [CI], 0.68-0.95). Specifically, LR was associated with higher 2-, 3- and 4-year OS rates compared with RFA. The pooled HR for DFS showed no significant difference between LR and RFA during the whole follow-up period (HR, 0.90; 95% CI, 0.76-1.07). However, LR was associated with significantly higher 2- to 5-year DFS rates compared to RFA. LR was also associated with more major complications (p < .001) and longer hospital stay (p < .001). Subgroup analyses demonstrated that LR and RFA had similar efficacy in patients with recurrent tumors less than 3 cm or patients presenting three or fewer recurrent nodules. CONCLUSION: LR could provide better long-term survival outcomes than RFA for recurrent HCC patients, while RFA has a higher safety profile. RFA can be a good alternative to LR for patients with small-sized recurrence or patients with a limited number of recurrent nodules. However, as tumor size increases, LR tends to be more efficacious.

A prediction model of major complications after radiofrequency ablation for recurrent hepatocellular carcinoma patients.

BACKGROUND: Postoperative major complications are potentially fatal to recurrent hepatocellular carcinoma (RHCC) patients. We aimed to construct a prediction model of major complications after RFA for RHCC patients. METHODS: We retrospectively reviewed the medical records of 407 RHCC patients who underwent RFA as second treatment. Patients were divided into two groups according to the date of RFA: training cohort (277 patients treated in 2010-2016) and validation cohort (130 patients treated in 2017-2019). 23 clinicopathological variables were recorded and analyzed. The logistic regression model was used to build a prediction model. RESULT: Major complications developed in 3.6 % of RHCC patients after RFA. In the multivariate analysis, tumor adjacent vessels (p = 0.004) and hepatitis C (p = 0.022) were associated with postoperative complications. The prediction model was described as follow: Risk score (major complication) = 5.180 + 3.391*tumor location+3.389*hepatic etiology, the Youden index was 0.642, the best cut-off value of the model was 8.57 (sensitivity, 78.57 %, specificity, 84.03 %). The area under the receiver operating characteristic curve of the predictive model was 0.85 (95 % CI, 0.82 to 0.88). The validation of the model demonstrated acceptable results, the sensitivity was 80.00 %, specificity was 98.40 %. CONCLUSIONS: This study developed a simple and reliable prediction model of postoperative major complications after RFA for RHCC patients.

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.