Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

Beta-Cell Tipe1 Orchestrates Insulin Secretion and Cell Proliferation by Promoting Gαs/cAMP Signaling via USP5.

Inadequate ß-cell mass and insulin secretion are essential for the development of type 2 diabetes (T2D). TNF-α-induced protein 8-like 1 (Tipe1) plays a crucial role in multiple diseases, however, a specific role in T2D pathogenesis remains largely unexplored. Herein, Tipe1 as a key regulator in T2D, contributing to the maintenance of ß cell homeostasis is identified. The results show that the ß-cell-specific knockout of Tipe1 (termed Ins2-Tipe1BKO) aggravated diabetic phenotypes in db/db mice or in mice with high-fat diet-induced diabetes. Notably, Tipe1 improves ß cell mass and function, a process that depends on Gαs, the α subunit of the G-stimulating protein. Mechanistically, Tipe1 inhibited the K48-linked ubiquitination degradation of Gαs by recruiting the deubiquitinase USP5. Consequently, Gαs or cAMP agonists almost completely restored the dysfunction of ß cells observed in Ins2-Tipe1BKO mice. The findings characterize Tipe1 as a regulator of ß cell function through the Gαs/cAMP pathway, suggesting that Tipe1 may emerge as a novel target for T2D intervention.

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.

Microwave ablation versus laparoscopic resection for hepatocellular carcinoma in patients with clinically significant portal hypertension: a propensity score-matched study of postoperative liver decompensation.

OBJECTIVES: The study of postoperative liver decompensation after microwave ablation (MWA) for hepatocellular carcinoma (HCC) in patients with clinically significant portal hypertension (CSPH) is still lacking. The purpose of the present study was to compare the postoperative liver decompensation after MWA and laparoscopic resection (LR) for HCC in patients with CSPH. METHODS: The present retrospective study enrolled 222 HCC patients with CSPH who underwent MWA (n = 67) or LR (n = 155). Postoperative liver decompensation, complications, postoperative hospital stays, and overall survival were analyzed. Factors associated with postoperative liver decompensation were identified. RESULTS: After propensity score matching, the postoperative liver decompensation rate was significantly lower in the MWA group than that in the LR group (15.5% versus 32.8%, p = 0.030). The multivariable regression analysis identified that type of treatment (MWA vs. LR, odds ratio [OR] 0.44; 95% confidence interval [CI], 0.21-0.91; p = 0.026) and Child-Pugh B (OR, 2.86; 95% CI, 1.24-6.61; p = 0.014) were independent predictors for postoperative liver decompensation. The rate of complications for patients in the MWA group was significantly lower than that in the LR group (p < 0.001). And MWA showed shorter postoperative hospital stays than LR (3 days vs. 6 days, p < 0.001). Overall survival rate between the two groups was not significantly different (p = 0.163). CONCLUSION: Compared with laparoscopic resection, microwave ablation has a lower rate of postoperative liver decompensation and might be a better option for HCC patients with CSPH. CLINICAL RELEVANCE STATEMENT: Microwave ablation exhibited a lower incidence of postoperative liver decompensation in comparison to laparoscopic resection, thereby conferring greater advantages to hepatocellular carcinoma patients with clinically significant portal hypertension. KEY POINTS: •Postoperative liver decompensation rate after microwave ablation was lower than that of laparoscopic resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. •Microwave ablation showed shorter postoperative hospital stays than laparoscopic resection. •Microwave ablation had fewer complications than laparoscopic resection.

Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease.

Purpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.

The impact of concomitant metabolic dysfunction-associated fatty liver disease on adverse outcomes in patients with hepatitis B cirrhosis: a propensity score matching study.

BACKGROUND AND AIMS: In cirrhotic patients, the clinical relevance of metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. We aimed to research the relationship between MAFLD and adverse clinical outcomes in patients with hepatitis B cirrhosis. METHODS: A total of 439 patients with hepatitis B cirrhosis were enrolled. Abdominal MRI and computed tomography were used to calculate liver fat content in order to evaluate steatosis. The Kaplan-Meier method was implemented to generate survival curves. The independent risk factors for prognosis were identified by multiple Cox regression. Propensity score matching (PSM) was used to reduce the influence of confounding factors. This study explored the relevance between MAFLD and mortality, first decompensation and further decompensation. RESULTS: In our study, most patients were decompensated cirrhosis (n = 332, 75.6%) and the ratio of decompensated cirrhosis patients in non-MAFLD to MAFLD group was 199 : 133. Compared to the non-MAFLD group, patients with MAFLD had worse liver function which mainly reflected that there were more Child-Pugh C patients and higher model for end-stage liver disease score in the MAFLD group. A total of 207 adverse clinical events occurred in the total cohort during a median follow-up of 47 months, including 45 deaths, 28 hepatocellular carcinoma, 23 first decompensation and 111 further decompensation. Cox multivariate analysis showed that MAFLD was an independent risk factor for death [hazard ratio (HR) 1.931; 95% confidence interval (CI) 1.019-3.660; P = 0.044 HR 2.645; 95% CI, 1.145-6.115; P = 0.023] and further decompensation (HR 1.859; 95% CI, 1.261-2.741; P = 0.002 HR 1.953; 95% CI, 1.195-3.192; P = 0.008) before and after PSM. In decompensated group with MAFLD, diabetes had a more significant effect on adverse prognosis than overweight or obesity and other metabolic risk factors. CONCLUSION: In patients with hepatitis B cirrhosis, concomitant MAFLD can predict a higher risk of further decompensation and death among decompensated individuals. According to patients among MAFLD, diabetes may be a major factor in the occurrence of adverse clinical events.

Four indices on Gd-EOB-DTPA-enhanced MRI can estimate liver functional reserve compared to ICG-R15: A systematic review and meta-analysis.

AIMS: To evaluate the value of four indices of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance as a potential imaging marker of liver functional reserve. METHODS: PubMed/Medline, Embase, Cochrane Library, and Web of Science were searched for studies concerning the relationship between Gd-EOB-DTPA-enhanced MRI and liver functional reserve estimated by ICG-R15, Pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated, Meanwhile, Sensitivity and subgroup analyses were performed along with Egger's test for the estimation of publication bias and potential heterogeneity. RESULTS: 14 publications with 1285 patients were included. The pooled r between relative liver enhancement (RLE), reduction rate of T1 relaxation time of the liver (rrT1), liver-to-spleen ratio (LSR), liver-to-muscle ratio (LMR), and ICG-R15 were -0.49 (95% CI, -0.56 to -0.41, p < 0.05), -0.47 (95% CI, -0.57 to -0.36, p < 0.05), -0.45 (95% CI, -0.55 to -0.34, p < 0.05), -0.50 (95% CI, -0.61 to -0.38, p < 0.05). moderate heterogeneity was observed between studies on rrT1, LSR, LMR, and ICG-R15 (p ≤ 0.05), but no significant heterogeneity was observed between RLE and ICG-R15. Further analysis shows that there was a notable heterogeneity between subgroup analysis of LSR and ICG-R15 stratified by years of publication, as well as rrT1 and LMR stratified by total patients and study design, the distribution funnel plots and the results of Egger's test showed no evidence of publication bias. CONCLUSIONS: RLE, LSR, LMR, and rrT1 all correlated significantly with ICG-R15-estimated hepatic functional reserve. The four indices represent a promising imaging biomarker in the prediction of liver functional reserve.

Endoscopic-Directed Trans-Gastric Retrograde Cholangiopancreatography in Patients With Roux-en-Y gastric Bypasses: A Meta-Analysis.

BACKGROUND AND AIM: Endoscopic ultrasound-directed trans-gastric retrograde cholangiopancreatography (EDGE) is a new procedure for treating pancreaticobiliary diseases in patients with Roux-en-Y gastric bypass (RYGB). The aim of this meta­analysis was to determine the overall outcomes and safety of EDGE. MATERIALS AND METHODS: We performed a computerized search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, through October 2022. The main outcome measures examined in the meta-analysis were technical and clinical success rates and overall adverse event (AE) rate, especially the lumen-apposing metal stent (LAMS) dislodgement rate. AE rates were assessed according to LAMS size (15 vs. 20 mm), number of stages (single vs. two) and access route (gastrogastric vs. jejuno-gastric). RESULTS: Fourteen trials with a total of 574 patients who had undergone 585 EDGE procedures were included in this study. The cumulative technical and clinical success and AE rates were 98%, 94%, and 14%, respectively. The commonest AE was LAMS dislodgement (rate 4%). The overall AE rate was lower in the 20-mm LAMS than in the 15-mm LAMS group (odds ratio [OR]=5.79; 95% confidence interval [CI]: 2.35 to 14.29). There were no significant differences in AE rate between number of stages (OR=1.36; 95% CI: 0.51 to 3.64) or differing access routes (OR=1.03; 95% CI 0.48 to 2.22). CONCLUSION: We here provide evidence that EDGE for endoscopic retrograde cholangiopancreatography yields good treatment outcomes in patients with RYGBs. The AE rate is significantly lower with 20-mm versus 15-mm LAMS; thus, the former is likely preferable.

Microwave ablation versus radiofrequency ablation as bridge therapy in potentially transplantable patients with single HCC ≤ 3 cm: A propensity score-matched study.

OBJECTIVES: The efficacy of microwave ablation (MWA) for hepatocellular carcinoma (HCC) as bridge therapy has been gradually confirmed. We aimed to compare the recurrence beyond the Milan criteria (RBM) rates in potentially transplantable patients with HCC receiving MWA or radiofrequency ablation (RFA) as bridge therapy. METHODS: In total, 307 potentially transplantable patients with single HCC ≤ 3 cm who initially received MWA (n = 82) or RFA (n = 225) were included. RBM, recurrence-free survival (RFS), and overall survival (OS) were compared between MWA and RFA groups by using propensity score matching (PSM). Competing risks Cox regression was used to identify predictors of RBM. RESULTS: After PSM, the 1-, 3-, and 5-year cumulative RBM rates were 6.8%, 18.3%, and 39.3% in the MWA group (n = 75), and 7.4%,18.5%, and 27.7% in the RFA group (n = 137), respectively, with no significant difference (p = 0.386). MWA and RFA were not the independent risk factors of RBM, and patients with higher alpha-fetoprotein, non-antiviral treatment, and higher MELD score were at greater risk of RBM. Neither corresponding RFS rates (66.7%, 39.2% and 21.4% vs. 70.8%, 47% and 34.7%, p = 0.310) nor OS rates (97.3%, 88.0%, and 75.4% vs. 97.8%, 85.1%, and 70.7%, p = 0.384) for 1-, 3- and 5-years were significantly different between the MWA and RFA groups. The MWA group showed more frequent major complications (21.4% vs. 7.1%, p = 0.004) and longer hospital stays (4 days vs. 2 days, p < 0.001) compared with the RFA group. CONCLUSION: MWA showed comparable RBM, RFS, and OS rates to RFA in potentially transplantable patients with single HCC ≤ 3 cm. Compared to RFA, MWA might provide the same effect as bridge therapy.

Microwave ablation versus surgical resection for subcapsular hepatocellular carcinoma: a propensity score-matched study of long-term therapeutic outcomes.

OBJECTIVES: The therapeutic efficacy of microwave ablation (MWA) for subcapsular hepatocellular carcinoma (HCC) has not been well characterized. We aimed to compare the long-term outcomes of MWA and surgical resection (SR) in patients with subcapsular HCC. METHODS: This retrospective study comprised 321 patients with subcapsular HCC meeting the Milan criteria who received MWA (n = 99) or SR (n = 222). Local tumor progression (LTP), overall survival (OS), and disease-free survival (DFS) were analyzed using propensity score matching (PSM) to compare the therapeutic efficacy. RESULTS: In the total cohort, there were no significant differences in 5-year LTP rates (14.0% vs. 8.9%, p = 0.12), OS rates (70.7% vs. 73.2%, p = 0.63), and DFS rates (38.3% vs. 41.2%, p = 0.22) between the MWA and SR groups. After PSM, the cumulative LTP rates at 1, 3, and 5 years were 9.7%, 14.0%, and 16.4% in the MWA group (n = 84) and 7.2%, 8.6%, and 10.6% in the SR group (n = 84), respectively, with no significant difference (p = 0.31). Neither corresponding OS rates (96.4%, 84.8%, and 73.0% vs. 95.2%, 85.5%, and 72.1%, p = 0.89) nor DFS rates (76.0%, 52.6%, and 38.1% vs. 76.2%, 44.7%, and 32.3%, p = 0.43) were significantly different between the MWA and SR groups. Whereas MWA obtained fewer complications for both cohorts (both p < 0.05). CONCLUSION: MWA showed comparable long-term therapeutic outcomes to SR, and it might be an alternative curative option for subcapsular HCC within the Milan criteria. KEY POINTS: • Microwave ablation showed comparable local tumor progression, overall survival, and disease-free survival to surgical resection for subcapsular hepatocellular carcinoma meeting the Milan criteria. • Microwave ablation obtained fewer complications and shorter postoperative hospital stay.

Comparison of patients with hepatitis B virus-associated hepatocellular carcinoma: Data from two hospitals from Turkey and China.

Aims: There are many studies on the incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), but very little is known about the HCC features in different populations. The study aimed to compare characteristics in two cohorts of patients with HBV-associated hepatocellular carcinoma, from Turkey and China. Methods: Data on patients with HBV-associated HCC diagnosed by imaging or liver biopsy were retrospectively collected from Shandong Provincial Hospital (n = 578) and Inonu University Hospital (n = 359) between January 2002 and December 2020, and the liver function and HCC characteristics were compared. Continuous variables were compared using Student's t-test or Mann-Whitney U test and categorical variables were compared using the χ2 test or Fisher's exact test. Results: The patients in the Turkish cohort had significantly worse Child-Pugh scores (Child-Pugh A: 38.3% vs. 87.9%; Child-Pugh B: 40.3% vs. 11.1%; Child-Pugh A: 24.1% vs. 1.0%; p < 0.001) and significantly higher levels of aspartate aminotransferase (66.5 vs. 36.0; p < 0.001), alanine aminotransferase (47.5 vs. 33.0; p < 0.001), total bilirubin (20.8 vs. 17.9; p < 0.001), and lower albumin levels (32.0 vs. 40.0; p < 0.001) than patients in Chinese cohort. The tumor characteristics showed the Barcelona Clinic Liver Cancer (BCLC) score (BCLC 1: 5.1% vs. 71.8%; BCLC 2: 48.7% vs. 24.4%; BCLC 3: 24.4% vs. 3.8%; BCLC 4: 21.8% vs. 0; all p < 0.001), maximum tumor diameter (5.0 vs. 3.5; p < 0.001), alpha-fetoprotein values (27.7 vs. 13.2; p < 0.001), and percentage of patients with portal vein tumor thrombus (33% vs. 6.1%; p < 0.001) were all significantly worse in the Turkish cohort compared with Chinese cohort. Conclusions: HBV-associated HCC from the Turkish cohort had worse liver function and more aggressive clinical characteristics than patients from the Chinese cohort.

A K-nearest Neighbor Model to Predict Early Recurrence of Hepatocellular Carcinoma After Resection.

Background and Aims: Patients with hepatocellular carcinoma (HCC) surgically resected are at risk of recurrence; however, the risk factors of recurrence remain poorly understood. This study intended to establish a novel machine learning model based on clinical data for predicting early recurrence of HCC after resection. Methods: A total of 220 HCC patients who underwent resection were enrolled. Classification machine learning models were developed to predict HCC recurrence. The standard deviation, recall, and precision of the model were used to assess the model's accuracy and identify efficiency of the model. Results: Recurrent HCC developed in 89 (40.45%) patients at a median time of 14 months from primary resection. In principal component analysis, tumor size, tumor grade differentiation, portal vein tumor thrombus, alpha-fetoprotein, protein induced by vitamin K absence or antagonist-II (PIVKA-II), aspartate aminotransferase, platelet count, white blood cell count, and HBsAg were positive prognostic factors of HCC recurrence and were included in the preoperative model. After comparing different machine learning methods, including logistic regression, decision tree, naïve Bayes, deep neural networks, and k-nearest neighbor (K-NN), we choose the K-NN model as the optimal prediction model. The accuracy, recall, precision of the K-NN model were 70.6%, 51.9%, 70.1%, respectively. The standard deviation was 0.020. Conclusions: The K-NN classification algorithm model performed better than the other classification models. Estimation of the recurrence rate of early HCC can help to allocate treatment, eventually achieving safe oncological outcomes.

Surgical resection versus radiofrequency ablation for early recurrent hepatocellular carcinoma.

BACKGROUND: Surgical resection (SR) and radiofrequency ablation (RFA) are reasonable treatment options for early recurrent hepatocellular carcinoma (rHCC), but it is still uncertain which treatment is better. The purpose of this study was to compare the therapeutic effects of SR and RFA on patients with early rHCC. METHODS: This study enrolled 168 patients with early rHCC who underwent SR or RFA. The 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: Before PSM, the 1-, 3-, 5-year OS (94.8%, 63.0%, 36.1% vs. 93.8%, 58.5%, 35.4%, P = 0.580) and PFS (50.7%, 22.7%, 12.0% vs. 68.8%, 30.3%, 15.9%, P = 0.224) were similar in RFA group and the SR group. After PSM, the 1-, 3-, 5-year OS (95.5%, 71.1%, 53.3% vs. 95.5%, 58.0%, 42.1%, P = 0.285) and PFS (50%, 36.4%, 27.3% vs. 68.2%, 25.6%, 12.8%, P = 0.999) were similar in the RFA group and the SR group. For patients with early recurrent tumors ≤3 cm, RFA and SR could achieve similar curative effects. However, SR was superior to RFA in terms PFS for patients with early recurrent tumors >3 cm, but the OS was similar. For all patients, RFA had significantly fewer complications and shorter hospitalization time compared with SR. CONCLUSION: SR achieves better tumor control compared with RFA for patients with early rHCC (>3 cm) after SR. RFA had significantly fewer complications and shorter hospitalization time compared with SR for all patients.

RECIST 1.1 versus mRECIST for assessment of tumour response to molecular targeted therapies and disease outcomes in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVES: Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to evaluate efficacy after molecular targeted therapies in hepatocellular carcinoma (HCC) patients is still controversial. A systemic review was performed to compare the objective response rate (ORR) and disease control rate (DCR) and a meta-analysis was conducted to compare the correlation between objective response and overall survival (OS). DESIGN: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: EMBASE, PubMed, Web of Science and Cochrane Library were searched through 31 December 2021. ELIGIBILITY CRITERIA: We included studies assessing the efficacy of molecular targeted therapy for HCC according to both RECIST 1.1 and mRECIST. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently. The consistency between RECIST 1.1 vs mRECIST is measured by the k coefficient. HRs with corresponding 95% CIs were used for meta-analysis. RESULTS: 23 studies comprising 2574 patients were included in systematic review. The ORR according to mRECIST is higher than RECIST1.1 (15.9% vs 7.8%, p<0.001). The DCR is similar (68.4% vs 67.2%, p=0.5). The agreement of tumour response is moderate for objective response (k=0.499) and perfect for progressive disease (k=0.901), calculated from 8 studies including 372 patients. OS was significantly longer in response group than non-response group according to mRECIST (HR 0.56, 95% CI 0.41 to 0.78, p=0.0004) calculated from 7 studies including 566 patients, however, the RECIST1.1 could not distinguish the OS well (HR 0.68, 95% CI 0.44 to 1.05, p=0.08). Subgroup analusis by type of treatment was conducted. CONCLUSIONS: mRECIST may be more accurate than RECIST 1.1 in assessing ORR after molecular targeted therapies in HCC patients and can better assess the prognosis. However, the performance of both criteria in assessing disease progression is identical. PROSPERO REGISTRATION NUMBER: CRD42020200895. ETHICS APPROVAL: Ethics approval is not required in this meta-analysis.

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.

Microwave ablation versus radiofrequency ablation for subcapsular hepatocellular carcinoma: a propensity score-matched study.

OBJECTIVES: Thermal ablation is now accepted as one of the curative treatments for patients with early-stage hepatocellular carcinoma (HCC), but the efficacy of this treatment for subcapsular HCC is not well characterized. Therefore, we aimed to compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) for patients with subcapsular HCC. METHODS: In total, 195 patients with subcapsular HCC who met the Milan criteria and underwent MWA or RFA were included. Local tumor progression (LTP), overall survival (OS), recurrence beyond the Milan criteria (RBM), and complications of these patients were compared. RESULTS: After propensity score matching, the 1-, 3-, and 5-year cumulative LTP rates were 6.7%, 9.6%, and 11.4% in the MWA group, and 13.4%, 24.6%, and 29.1% in the RFA group, respectively (p = 0.006). The cumulative rates of RBM were lower in patients treated with MWA than in those treated with RFA (4.4% versus 12% at 1 year; 14.5% versus 23.0% at 3 years; and 37.4% versus 53.9% at 5 years; p = 0.03). The OS rates at 1, 3, and 5 years were 97.1%, 85.9%, and 73.4% in the MWA group, and 95.6%, 80.4%, and 61.4% in the RFA group, respectively (p = 0.36). The rate of major complications showed no significant difference between the MWA group and the RFA group (17.4% vs. 11.6%, p = 0.33). CONCLUSION: Compared to RFA, MWA showed better tumor control for subcapsular HCC within the Milan criteria. There was no difference in the incidence of major complications between the two groups. KEY POINTS: •Compared to radiofrequency ablation, microwave ablation showed better local tumor control for patients with subcapsular hepatocellular carcinoma. •Microwave ablation showed similar major complication rates for patients with subcapsular hepatocellular carcinoma. •Microwave ablation may be preferred for patients with subcapsular hepatocellular carcinoma when they need to receive thermal ablation.

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.

The Combination of Shear Wave Elastography and Platelet Counts Can Effectively Predict High-Risk Varices in Patients with Hepatitis B-Related Cirrhosis.

BACKGROUND: Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. AIMS: To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. METHODS: Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. RESULTS: In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). CONCLUSIONS: The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.

Gadobenate dimeglumine-enhanced biliary imaging from the hepatobiliary phase can predict progression in patients with liver cirrhosis.

OBJECTIVES: To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced biliary imaging from the hepatobiliary phase in predicting hepatic decompensation and insufficiency for patients with cirrhosis. METHODS: This single-center retrospective study included 270 patients who underwent Gd-BOPTA-enhanced magnetic resonance imaging. The relative enhancement ratios of the biliary system (REB) and liver parenchyma (REL) in patients with normal liver function without underlying chronic liver disease and three groups of patients with Child-Pugh A, Child-Pugh B, and Child-Pugh C disease were measured. After a mean follow-up of 38.5 ± 22.5 months, prognostic factors were evaluated using the Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve analyses were performed to assess the capacity of the REB and REL to predict the development of hepatic decompensation and insufficiency. RESULTS: During the follow-up period, nine of 79 patients with Child-Pugh A disease developed hepatic decompensation. The REB was a significant predictive factor (hazard ratio (HR) = 0.40 (0.19-0.84); p = 0.016), but the REL showed no association with hepatic decompensation. Moreover, the areas under the ROC curves (AUCs) were 0.83 and 0.52 for the REB and REL, respectively. Thirty-eight of 207 patients with cirrhosis developed hepatic insufficiency. The REB was a significant predictive factor (HR = 0.24 (0.13-0.46); p < 0.0001), but the REL did not show statistically significant association with hepatic insufficiency. The AUCs were 0.82 and 0.57 for the REB and REL, respectively. CONCLUSIONS: Gd-BOPTA-enhanced biliary imaging from the hepatobiliary phase was valuable in predicting hepatic decompensation and insufficiency for cirrhotic patients. KEY POINTS: • Gd-BOPTA-enhanced biliary imaging was a significant predictive factor for hepatic decompensation in patients with cirrhosis. • Gd-BOPTA-enhanced biliary imaging was a significant predictive factor for hepatic insufficiency in patients with cirrhosis. • Gd-BOPTA-enhanced biliary imaging showed superior predictive values for adverse clinical outcomes compared to liver parenchymal imaging at the hepatobiliary phase.