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BACKGROUND & AIMS: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. METHODS: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. RESULTS: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). CONCLUSIONS: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. IMPACT AND IMPLICATIONS: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with 10-40% of cases involving portal vein tumor thrombosis (PVTT), leading to poor outcomes and a short survival. The effectiveness of PVTT treatment in patients with HCC is still controversial. Methods: This prospective dual-center study cohort comprised 60 patients with HCC and PVTT who underwent PVR-EPRFA-ST using a novel intravascular radiofrequency system followed by vascular stent placement across the PVTT stenosed segment under fluoroscopy guidance. Results: PVR-EPRFA-ST was technically and clinically successful in 54/60 (90%) and 37/54 (68.5%) patients, respectively. The mean tumor size, PVTT length, post-ablation luminal diameter, and median duration of the recanalized PV patency were 8.6 ± 3.4 cm, 4.1 ± 2.1 cm, 10.3 ± 1.8 mm, and 13.4 months. Higher technical and clinical success rates were associated with a longer survival (177 ± 17.3 days, HR: 0.3, 95%CI 0.12-0.71, p = 0.04; and 233 ± 18.3 days, HR: 0.14, 0.07-0.27, p < 0.001). A shorter survival was associated with Child-Pugh C (HR: 2.7, p = 0.04), multiple tumors (HR: 1.81, p = 0.03), and PVTT length (HR: 1.16, p = 0.04). Conclusions: PVR-EPRFA-ST was feasible and effective for the treatment of selected patients with PVTT, especially in patients with Child-Pugh A/B, single tumors, or a shorter PVTT length.

BackgroundAlthough alcohol abstinence may be an effective intervention for alcohol-associated cirrhosis, its association with prognosis has not been systematically assessed or quantified.AimsTo determine the prevalence of alcohol abstinence, factors associated with alcohol abstinence and the impact of abstinence on morbidity and overall survival in people with alcohol-associated cirrhosis.MethodsWe searched Medline and Embase from inception to 15 April 2023 for prospective and retrospective cohort studies describing alcohol abstinence in people with known alcohol-associated cirrhosis. Meta-analysis of proportions for pooled estimates was performed. The method of inverse variance, employing a random-effects model, was used to pool the hazard ratio (HR) comparing outcomes of abstinent against non-abstinent individuals with alcohol-associated cirrhosis.ResultsWe included 19 studies involving 18,833 people with alcohol-associated cirrhosis. The prevalence of alcohol abstinence was 53.8% (CI: 44.6%-62.7%). Over a mean follow-up duration of 48.6 months, individuals who continued to consume alcohol had significantly lower overall survival compared to those who were abstinent (HR: 0.611, 95% CI: 0.506-0.738). These findings remained consistent in sensitivity/subgroup analysis for the presence of decompensation, study design and studies that assessed abstinence throughout follow-up. Alcohol abstinence was associated with a significantly lower risk of hepatic decompensation (HR: 0.612, 95% CI: 0.473-0.792).ConclusionsAlcohol abstinence is associated with substantial improvement in overall survival in alcohol-associated cirrhosis. However, only half of the individuals with known alcohol-associated cirrhosis are abstinent.

As the Editor-in-Chief of World Journal of Gastroenterology, every week prior to a new issues online publication, I perform a careful review of all encompassed articles, including the title, clinical and/or research importance, originality, novelty, and ratings by the peer reviewers. Based on this review, I select the papers of choice and suggest pertinent changes (e.g., in the title) to the Company Editors responsible for publication. This process, while time-consuming, is very important for assuring the quality of publications and highlighting important articles that Readers may revisit.

Sorafenib, FDA-approved therapy for patients with advanced hepatocellular carcinoma (HCC), leads to limited improvement in overall survival. However, it may indirectly impact the expansion and activity of natural killer (NK) cells. While NK cell-based immunotherapies generally exhibit favorable safety profiles, their effectiveness in controlling solid tumor growth is constrained, primarily due to the absence of antigen specificity and suboptimal expansion and persistence within the tumor microenvironment. In this study, we postulated that enhancing NK cell functionality via cytokine activation could bolster their viability and cytotoxic capabilities, leading to an improved therapeutic response when combined with sorafenib. Memory-like (ML)-NK cells were generated through the supplementation of optimal concentrations of interleukin (IL)-12 and IL-18 cytokines. Following a single day of treatment, cytotoxicity against rat and human HCC cells was evaluated via flow cytometry analysis. A rat HCC model was developed in 30 animals via subcapsular implantation and assigned to control, NK, sorafenib, ML-NK, and combination groups. Sorafenib was administered orally, and NK cells were delivered via the intrahepatic artery. Tumor growth was measured one week after treatment evaluation. Therapeutic efficacy during in-vitro and in-vivo analysis was investigated through a one-way ANOVA test, followed by pairwise two-tailed Student t-tests, considering P < 0.05 statistically significant. The in-vitro experiment results demonstrated that sorafenib and conventional NK cell therapies induced more substantial cell death than the control group (P < 0.01). ML NK cells significantly improved cell death compared to conventional NK cell immunotherapy. Furthermore, sorafenib in combination with ML-NK cells significantly decreased the viability of HCC cells (P < 0.05) compared to sorafenib plus conventional NK cell combination therapy. In vivo experiments have shown that sorafenib and ML-NK cell immunotherapy reduced the growth rate of HCC tumors compared to conventional NK immunotherapy and control groups. Notably, a combination of sorafenib and ML-NK cell immunochemotherapy resulted in the most significant suppression of tumor growth when compared to other therapies. In conclusion, our experimental findings demonstrate that the concurrent administration of sorafenib and ML-NK immunotherapy enhances cytotoxicity against HCC by optimizing the therapeutic response through cytokine activation, resulting in a significant decrease in tumor growth.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) incidence is increasing and correlated with metabolic dysfunction-associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease), even in patients without advanced liver fibrosis who are more likely to be diagnosed with advanced disease stages and shorter survival time, and less likely to receive a liver transplant. Machine learning (ML) tools can characterize large datasets and help develop predictive models that can calculate individual HCC risk and guide selective screening and risk mitigation strategies. METHODS: Tableau and KNIME Analytics were used for descriptive analytics and ML tasks. ML models were developed using standard laboratory and clinical parameters. Sci-kit learn algorithms were used for model development. Data from University of California (UC), Davis, were used to develop and train a pilot predictive model, which was subsequently validated in an independent dataset from UC San Francisco. MASLD and HCC patients were identified by International Classification of Diseases-9/10 codes. RESULTS: Of the patients diagnosed with MASLD (n = 1561 training; n = 686 validation), HCC developed in 14% (n = 227) of the UC Davis training cohort and 25% (n = 176) of the UC San Francisco validation cohort. Liver fibrosis determined by the noninvasive Fibrosis-4 score was the strongest single predictor for HCC in the model. Using the validation cohort, the model predicted HCC development at 92.06% accuracy with an area under the curve of 0.97, F1-score of 0.84, 98.34% specificity, and 74.41% sensitivity. CONCLUSION: ML models can aid physicians in providing early HCC risk assessment in patients with MASLD. Further validation will translate to cost-effective, personalized care of at-risk patients.

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.

Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.

BackgroundHepatocellular carcinoma (HCC) is a common liver malignancy with limited treatment options. Previous studies expressed the potential synergy of sorafenib and NK cell immunotherapy as a promising approach against HCC. MRI is commonly used to assess response of HCC to therapy. However, traditional MRI-based metrics for treatment efficacy are inadequate for capturing complex changes in the tumor microenvironment, especially with immunotherapy. In this study, we investigated potent MRI radiomics analysis to non-invasively assess early responses to combined sorafenib and NK cell therapy in a HCC rat model, aiming to predict multiple treatment outcomes and optimize HCC treatment evaluations.MethodsSprague Dawley (SD) rats underwent tumor implantation with the N1-S1 cell line. Tumor progression and treatment efficacy were assessed using MRI following NK cell immunotherapy and sorafenib administration. Radiomics features were extracted, processed, and selected from both T1w and T2w MRI images. The quantitative models were developed to predict treatment outcomes and their performances were evaluated with area under the receiver operating characteristic (AUROC) curve. Additionally, multivariable linear regression models were constructed to determine the correlation between MRI radiomics and histology, aiming for a noninvasive evaluation of tumor biomarkers. These models were evaluated using root-mean-squared-error (RMSE) and the Spearman correlation coefficient.ResultsA total of 743 radiomics features were extracted from T1w and T2w MRI data separately. Subsequently, a feature selection process was conducted to identify a subset of five features for modeling. For therapeutic prediction, four classification models were developed. Support vector machine (SVM) model, utilizing combined T1w + T2w MRI data, achieved 96% accuracy and an AUROC of 1.00 in differentiating the control and treatment groups. For multi-class treatment outcome prediction, Linear regression model attained 85% accuracy and an AUC of 0.93. Histological analysis showed that combination therapy of NK cell and sorafenib had the lowest tumor cell viability and the highest NK cell activity. Correlation analyses between MRI features and histological biomarkers indicated robust relationships (r = 0.94).ConclusionsOur study underscored the significant potential of texture-based MRI imaging features in the early assessment of multiple HCC treatment outcomes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, and classifying the developmental stages of HCC can help with early prognosis and treatment. This study aimed to investigate diagnostic and prognostic molecular signatures underlying the progression of HCC, including tumor initiation and growth, and to classify its developmental stages based on gene expression levels. We integrated data from two cancer systems, including 78 patients with Edmondson-Steiner (ES) grade and 417 patients with TNM stage cancer. Functional profiling was performed using identified signatures. Using a multinomial logistic regression model (MLR), we classified controls, early-stage HCC, and advanced-stage HCC. The model was validated in three independent cohorts comprising 45 patients (neoplastic stage), 394 patients (ES grade), and 466 patients (TNM stage). Multivariate Cox regression was employed for HCC prognosis prediction. We identified 35 genes with gradual upregulation or downregulation in both ES grade and TNM stage patients during HCC progression. These genes are involved in cell division, chromosome segregation, and mitotic cytokinesis, promoting tumor cell proliferation through the mitotic cell cycle. The MLR model accurately differentiated controls, early-stage HCC, and advanced-stage HCC across multiple cancer systems, which was further validated in various independent cohorts. Survival analysis revealed a subset of five genes from TNM stage (HR: 3.27, p < 0.0001) and three genes from ES grade (HR: 7.56, p < 0.0001) that showed significant association with HCC prognosis. The identified molecular signature not only initiates tumorigenesis but also promotes HCC development. It has the potential to improve clinical diagnosis, prognosis, and therapeutic interventions for HCC. This study enhances our understanding of HCC progression and provides valuable insights for precision medicine approaches. • 35 genes gradually regulate in HCC progression in both cancer stage and grade. • These molecular signatures enhance cell proliferation via impact on the mitotic cycle. • Using MLR model, 10 genes accurately classify HCC stages across cancer systems. • Statistically significant subsets of genes emerge as prognostic markers for HCC. [ABSTRACT FROM AUTHOR]

Summary: Background: Optimal glycaemic control has well‐established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver‐related outcomes. Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver‐related mortality. Methods: In a population‐based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3‐year lead‐in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver‐related mortality. Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow‐up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver‐related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61–0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29–1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54–0.80), sex (SHR 0.68–0.69), BMI <25 or ≥25 kg/m2 (SHR 0.63–0.75), smoking (SHR 0.61–0.72), hepatic steatosis (SHR 0.67–0.68) and aspirin/statin/metformin use (SHR 0.67–0.75). A lower risk of liver‐related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61–0.80). Conclusions: Glycaemic control is an independent risk factor for HCC and liver‐related mortality, and should be incorporated into oncoprotective strategies in the general DM population. [ABSTRACT FROM AUTHOR]

Summary: Aim: This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases. Methods: In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023. Results: Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non‐conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non‐conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non‐conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively). Conclusions: Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: The prognostic impact of previous‐HBV‐infection (pHBV) in non‐HBV‐related hepatocellular carcinoma (non‐HBV‐related‐HCC) and the prevalence, characteristics and significance of recently developed high‐sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. Methods: We retrospectively screened patients with newly diagnosed non‐HBV‐related‐HCC (standard HBsAg‐test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non‐HBV‐related‐HCC. Results: A total of 401 non‐HBV‐related‐HCC patients were included (288 with pHBV/113 without pHBV). In non‐HBV‐related‐HCC, pHBV did not affect overall survival (OS). Among non‐HBV‐related‐HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non‐HBV‐related‐HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non‐HBV‐related‐HCC patients with non‐B‐non‐C aetiology and advanced HCC. Conclusions: In non‐HBV‐related‐HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis. [ABSTRACT FROM AUTHOR]

ABSTRACT The year 2024 is the year of new clinical practice and management guidelines for chronic hepatitis B virus (HBV) infection. World Health Organization (WHO) published the updated HBV guidelines in March 2024. In contrast, two key international societies for liver diseases, including the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL), are currently in the process of updating their clinical practice guidelines for HBV. In 2022, China published their HBV guidelines, regarded as one of the most uncompromising ones as the threshold to start antiviral treatment is set at detectable HBV DNA above 10–20 IU/mL. In this chapter, the latest developments in the HBV guidelines with a specific focus on the Chinese & WHO guidelines are discussed. Specifically, the pros and cons of lowering treatment thresholds and the benefits of treating more people to avoid the complications of chronic hepatitis B, specifically HCC, are reviewed. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the primary forms of liver cancer and is currently the sixth most prevalent malignancy worldwide. In addition to surgical interventions, effective drug treatment is essential for treating HCC. With an increasing number of therapeutic drugs for liver cancer undergoing clinical studies, the therapeutic strategies for advanced HCC are more diverse than ever, leading to improved prospects for HCC patients. Molecular targeted drugs and immunotherapies have become crucial treatment options for HCC. Treatment programs include single-agent molecular-targeted drugs, immunotherapies, combinations of immunotherapies with molecular-targeted drugs, and dual immune checkpoint inhibitors. However, further exploration is necessary to determine the optimal pharmacological treatment regimens, and the development of new effective drugs is urgently needed. This review provides an overview of the current globally approved drugs for liver cancer, as well as the latest advances in ongoing clinical research and drug therapies. Additionally, the review offers an outlook and discussion on the prospects for the development of drug therapy approaches for HCC. [ABSTRACT FROM AUTHOR]

Background and aims: Compared with tyrosine kinase inhibitor (TKI) monotherapy, TKI combined with PD1 can improve the therapeutic effect of liver cancer and has been widely used in clinical practice. However, there is a lack of effective biomarkers to identify patients who would benefit more from this combination therapy. Therefore, this study aimed to evaluate whether baseline lymphocyte counts can identify patients with liver cancer who would benefit from targeted immune combination therapy. Methods: Data from patients with hepatocellular carcinoma (HCC) who received TKIs or TKIs in combination with PD1 between June 2018 and June 2020 were retrospectively collected. The patients were divided into high and low groups based on the median absolute count of peripheral lymphocytes before systemic therapy and differences in overall survival (OS) and progression-free survival (PFS) between TKI and TKI+PD1 were compared between the two groups. Results: In total, 72 patients were included in this study, with a median follow-up of 1.5 years. Both PFS and OS in the TKI+PD1 group showed a good prognostic trend (p = 0.058 and p = 0.077, respectively). Subgroup analyses based on peripheral blood lymphocyte counts showed that the combination regimen had a significant PFS and OS advantage only in patients with high peripheral blood lymphocyte counts (p = 0.036 and p = 0.031, respectively), but not in patients with low absolute peripheral blood lymphocyte counts (p = 0.819 and p = 0.913, respectively). Conclusions: Peripheral blood lymphocyte count is a simple and effective biomarker that can be used to identify patients with liver cancer who will benefit more from TKI+PD-1 combination therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma is considered the most common cause of hepatic focal lesions in Egypt. TACE is still the recommended treatment approach for patients in the intermediate stage. In the current research, we evaluated the safety and efficacy of percutaneous radiofrequency ablation (RFA) for a selected category in the intermediate stage (BCLC stage B). Methods: This prospective study was conducted in the Department of Gastroenterology, Hepatology, Faculty of Medicine, Beni-Suef University between September 2022, and March 2024. In addition to AFP, Pelviabdominal ultrasound and computerized tomography (CT) were used for HCC diagnosis. According to the Child–Pugh score plus Milan and up-to-7 criteria, we used Modified Bolondi's Subclassification (Kinki Criteria), to sub-classifies the BCLC B stage into B1/B2/B3 subcategories. Radiofrequency ablation was done in the interventional ultrasound unit. Treatment efficacy was assessed 6 months after tumor ablation. Results: One hundred twenty participants were enrolled in our research trial, 72 (60%) were within the intermediate stage, and 48 (40%) had early-stage HCC. Most of our patients were males, 78 (65%). All the early-stage-HCC patients were Child–Pugh Score A (n = 48), while the intermediate-stage (BCLC B) group was classified in both Child–Pugh Score A (n = 59) and B (n = 16). Within the intermediate group (BCLC-stage B), All enrolled cases fell within category "B1" within the Kinki Criteria. Logistic regression analysis illustrated that the pre-treatment level of Platelet count and post-treatment level of AFP shows a statistically significant prediction effect on treatment response rate with p-value (0.028 and 0.007 respectively). Conclusion: percutaneous radiofrequency ablation is considered an effective treatment option for the B1 subcategory according to Kinki Criteria for intermediate-stage HCC (BCLC-B1) but long-term follow-up is recommended. [ABSTRACT FROM AUTHOR]

Background: Assay of Transposase Accessible Chromatin Sequencing (ATAC-seq) is a high-throughput sequencing technique that detects open chromatin regions across the genome. These regions are critical in facilitating transcription factor binding and subsequent gene expression. Herein, we utilized ATAC-seq to identify key molecular targets regulating the development and progression of hepatocellular carcinoma (HCC) and elucidate the underlying mechanisms. Methods: We first compared chromatin accessibility profiles between HCC and normal tissues. Subsequently, RNA-seq data was employed to identify differentially expressed genes (DEGs). Integrating ATAC-seq and RNA-seq data allowed the identification of transcription factors and their putative target genes associated with differentially accessible regions (DARs). Finally, functional experiments were conducted to investigate the effects of the identified regulatory factors and corresponding targets on HCC cell proliferation and migration. Results: Enrichment analysis of DARs between HCC and adjacent normal tissues revealed distinct signaling pathways and regulatory factors. Upregulated DARs in HCC were enriched in genes related to the MAPK and FoxO signaling pathways and associated with transcription factor families like ETS and AP-1. Conversely, downregulated DARs were associated with the TGF-β, cAMP, and p53 signaling pathways and the CTCF family. Integration of the datasets revealed a positive correlation between specific DARs and DEGs. Notably, PRPF3 emerged as a gene associated with DARs in HCC, and functional assays demonstrated its ability to promote HCC cell proliferation and migration. To the best of our knowledge, this is the first report highlighting the oncogenic role of PRPF3 in HCC. Furthermore, ZNF93 expression positively correlated with PRPF3, and ChIP-seq data indicated its potential role as a transcription factor regulating PRPF3 by binding to its promoter region. Conclusion: This study provides a comprehensive analysis of the epigenetic landscape in HCC, encompassing both chromatin accessibility and the transcriptome. Our findings reveal that ZNF93 promotes the proliferation and motility of HCC cells through transcriptional regulation of a novel oncogene, PRPF3. [ABSTRACT FROM AUTHOR]

Background: DNA methylation biomarkers are one of the most promising tools for the diagnosis and differentiation of adenocarcinomas of the liver, which are among the most common malignancies worldwide. Their differentiation is important because of the different prognoses and treatment options. This study aimed to validate previously identified DNA methylation biomarkers that successfully differentiate between liver adenocarcinomas, including the two most common primary liver cancers, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), as well as two common metastatic liver cancers, colorectal liver metastases (CRLM) and pancreatic ductal adenocarcinoma liver metastases (PCLM), and translate them to the methylation-sensitive high-resolution melting (MS-HRM) and digital PCR (dPCR) platforms. Methods: Our study included a cohort of 149 formalin-fixed, paraffin-embedded tissue samples, including 19 CRLMs, 10 PCLMs, 15 HCCs, 15 CCAs, 15 colorectal adenocarcinomas (CRCs), 15 pancreatic ductal adenocarcinomas (PDACs) and their paired normal tissue samples. The methylation status of the samples was experimentally determined by MS-HRM and methylation-specific dPCR. Previously determined methylation threshold were adjusted according to dPCR data and applied to the same DNA methylation array datasets (provided by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)) used to originally identify the biomarkers for the included cancer types and additional CRLM projects. The sensitivities, specificities and diagnostic accuracies of the panels for individual cancer types were calculated. Results: In the dPCR experiment, the DNA methylation panels identified HCC, CCA, CRC, PDAC, CRLM and PCLM with sensitivities of 100%, 66.7%, 100%, 86.7%, 94.7% and 80%, respectively. The panels differentiate between HCC, CCA, CRLM, PCLM and healthy liver tissue with specificities of 100%, 100%, 97.1% and 94.9% and with diagnostic accuracies of 100%, 94%, 97% and 93%, respectively. Reevaluation of the same bioinformatic data with new additional CRLM projects demonstrated that the lower dPCR methylation threshold still effectively differentiates between the included cancer types. The bioinformatic data achieved sensitivities for HCC, CCA, CRC, PDAC, CRLM and PCLM of 88%, 64%, 97.4%, 75.5%, 80% and 84.6%, respectively. Specificities between HCC, CCA, CRLM, PCLM and healthy liver tissue were 98%, 93%, 86.6% and 98.2% and the diagnostic accuracies were 94%, 91%, 86% and 98%, respectively. Moreover, we confirmed that the methylation of the investigated promoters is preserved from primary CRC and PDAC to their liver metastases. Conclusions: The cancer-specific methylation biomarker panels exhibit high sensitivities, specificities and diagnostic accuracies and enable differentiation between primary and metastatic adenocarcinomas of the liver using methylation-specific dPCR. High concordance was achieved between MS-HRM, dPCR and bioinformatic data, demonstrating the successful translation of bioinformatically identified methylation biomarkers from the Illumina Infinium HumanMethylation450 BeadChip (HM450) and lllumina MethylationEPIC BeadChip (EPIC) platforms to the simpler MS-HRM and dPCR platforms. [ABSTRACT FROM AUTHOR]

Background: A combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and immune checkpoint inhibitors (ICIs) yields a high tumor response rate and survival benefit in unresectable hepatocellular carcinoma (uHCC). However, the selection criteria for different ICIs remain unclear. This study aims to compare the efficacy and safety of PD-1/PD-L1 antibodies combined with HAIC and lenvatinib. Methods: This retrospective study included 184 patients with uHCC treated with HAIC+lenvatinib+PD-1/PD-L1 antibody from June 2019 to January 2022. We utilized propensity score matching (PSM) to select and match 60 patients treated with HAIC + durvalumab + lenvatinib (HDL) against 60 patients treated with HAIC + PD-1 antibodies + lenvatinib (HPL) to compare the efficacy and safety profiles of these two groups. Results: After PSM, the baseline characteristics were well-balanced between the HDL and HPL groups. The overall survival (p = 0.293) and progression-free survival (p = 0.146) showed no significant difference. The objective response rate (ORR) was higher in the HDL group compared to the HPL group according to modified RECIST (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040), respectively. The incidence of grade 3 or 4 adverse events (AEs) was 10.0% and 18.3% (p = 0.191) in the HDL and HPL groups, respectively. Conclusions: PD-L1 antibody appears to be a preferable companion in the combination therapy of HAIC + ICIs + lenvatinib compared to PD-1 antibody, showing higher ORR and relatively lower incidence of severe AEs. Further prospective studies involving a larger patient population are warranted. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a prevalent form of liver cancer that poses significant challenges regarding morbidity and mortality rates. In the context of HCC, immune cells play a vital role, especially concerning the presentation of antigens. This review explores the intricate interactions among immune cells within HCC, focusing on their functions in antigen presentation and the modulation of T-cell responses. We begin by summarizing the strategies that HCC uses to escape immune recognition, emphasizing the delicate equilibrium between immune surveillance and evasion. Next, we investigate the specific functions of various types of immune cells, including dendritic cells, natural killer (NK) cells, and CD8+ T cells, in the process of antigen presentation. We also examine the impact of immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the pathways involving programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1), on antigen presentation, while taking into account the clinical significance of checkpoint inhibitors. The review further emphasizes the importance of immune-based therapies, including cancer vaccines and CAR-T cell therapy, in improving antigen presentation. In conclusion, we encapsulate the latest advancements in research, propose future avenues for exploration, and stress the importance of innovative technologies and customized treatment strategies. By thoroughly analyzing the interactions of immune cells throughout the antigen presentation process in HCC, this review provides an up-to-date perspective on the field, setting the stage for new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a global health concern with high prevalence and mortality. A marine alkaloid, AP‐427, has been reported to show potential for HCC treatment. However, its use is limited by low solubility and high toxicity. We aimed to investigate the preformulation parameters and develop AP‐427 liposomes to improve its clinical suitability. A stability‐indicating HPLC assay was established, and the physicochemical properties of AP‐427 were analyzed. Afterward, AP‐427 liposomes were prepared and characterized, and their cytotoxicity was evaluated. AP‐427 had a low solubility at physiological pH, a LogD of 2.56 ± 0.03, and a basic pKa of 3.24 ± 0.12. An entrapment efficiency of 52.71 ± 3.2% was achieved after optimization. The resulting AP‐427 liposomes were 147.2 ± 3.4 nm and stable up to three months when stored in a pellet form at 4°C. The crystallization of AP‐427 in liposomes became less ordered, and AP‐427 liposomes exhibited a controlled release fitted in Korsmeyer–Peppas model, indicating the release was driven by diffusion. Furthermore, AP‐427 liposomes showed a 3.6 times reduced cytotoxicity against HepG2 cells compared with free AP‐427, potentially enhancing its antitumor efficacy. In conclusion, the precise preformulation parameters advanced the AP‐427 liposomal formulation development, which showed potential for HCC treatment. Practical Applications: The aaptamine derivative AP‐427 has shown cytotoxic effects against hepatocellular carcinoma. However, the low solubility and high toxicity limit its clinical application. The present study aims to prepare liposomal formulation to solve the current problems. Results obtained from this study shed light on challenges related to drug solubility and have paved the way for the development of an effective AP‐427 liposomal formulation with promising application in hepatocellular carcinoma therapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the feasibility and efficacy of near-infrared fluorescence-guided laparoscopic anatomical hepatectomy (LAH) using a novel indocyanine green (ICG)-human serum albumin complex (HSA) in patients with hepatocellular carcinoma. Methods: Clinical data of hepatocellular carcinoma patients who underwent ICG-HSA fluorescence-guided LAH at our center from January 2024 to April 2024 were prospectively collected and analyzed. Ultraviolet absorption spectroscopy was used to test the absorption and stability of ICG-HSA complex solutions under different conditions. After determining the optimal ratio, the complex was administered intravenously during surgery to perform negative staining via Glissonean pedicle isolation. LAH was performed along the fluorescence-demarcated boundaries. Results: Thirty-one patients were included (24 men; mean age, 54.61 ± 13.54 years). The median maximum tumor diameter was 2.80 (interquartile range [IQR], 2.00–4.00) cm. S8 segmentectomy (22.6%) and right posterior segmentectomy (19.4%) were the most common resections performed. Successful fluorescence negative staining was achieved in all patients using ICG and HSA at a 1:6 molar ratio at room temperature. Mean operation time was 297.58 ± 85.53 min, Median intraoperative blood loss was 100.0 mL (IQR, 50.0–200.0). The median surgical margin distance was 0.90 cm (IQR, 0.40–1.50). The postoperative complication rate was 45.2% (35.5% Clavien–Dindo grade I and 9.7% grade II). The median length of hospital stay was 5.0 days (IQR, 4.0–5.0). Conclusion: ICG-HSA-assisted LAH is safe and feasible. Compared with free ICG, the novel ICG-HSA complex exhibits better optical properties and in vivo stability, which can improve the accuracy of intraoperative liver segment localization and optimize the anatomical dissection plane. It has the potential to become an ideal fluorescent imaging agent for anatomical hepatectomy. [ABSTRACT FROM AUTHOR]

Background: Liver resection and percutaneous thermal ablation (PTA) are considered curative option for hepatocellular carcinoma (HCC). This study aims to compare short- and long-term outcomes between open liver resection (OLR), laparoscopic liver resection (LLR), and PTA in elderly patients with single HCC and to define a liver map for therapeutic strategy according to HCC location and size. Methods: A multicenter retrospective study was conducted in 10 European Hospital Center, including 239 consecutive liver resection (OLR and LLR) and PTA in elderly patients ≥ 70 years old with single HCC ≤ 30 mm. Perioperative data and long-term oncological outcomes were collected and compared between groups before and after propensity score matching. Results: A total of 239 patients were enrolled, distributed as follows: 61 in the ORL group, 88 in the LLR group, and 90 in the PTA group. The hospital stay was longer in OLR and LLR groups compared to the PTA group (6, 5 and 3 days, respectively, p < 0.05). Morbidity was lower in the PTA group compared to the OLR group (11 vs. 26%, respectively, p < 0.05). Overall survival (OS) at 5 years was significantly higher in the OLR and LLR groups compared to the PTA group (82, 81, and 34%, respectively, p < 0.001). Disease-free survival (DFS) at 5 years was also significantly higher in the ORL and LLR groups compared to the PTA group (66, 50 and 20%, respectively, p < 0.001). These results were also confirmed after a propensity score matching analysis between surgery group (OLR and LLR) and the PTA group. PTA was the most used treatment for subcapsular and deep HCC not in contact with vascular structures compared to OLR and LLR. Conclusion: PTA in elderly patients ensures a shorter hospital stay and lower morbidity but worst survival compared to liver resection. [ABSTRACT FROM AUTHOR]

Background: The impact of metabolic dysfunction-associated fatty liver disease (MAFLD) on laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to compare the outcomes of LLR for MAFLD-HCC and Non-MAFLD-HCC. Methods: Patients with HCC who received LLR between October 2017 and July 2021 were enrolled. Inverse probability of treatment weighting (IPTW) was used to generate adjusted comparisons. Both short- and long-term outcomes were evaluated accordingly. Results: A total of 887 patients were enrolled, with 140 in MAFLD group and 747 in Non-MAFLD group. After IPTW adjustment, baseline factors were well matched. The MAFLD group was associated with more blood loss (210 vs 150 ml, p = 0.022), but with similar postoperative hospital stays and complication rates. The 1- and 3-year overall survival rates were 97.4% and 92.5% in MAFLD group, and 97.5% and 88.3% in Non-MAFLD group, respectively (p = 0.14). The 1- and 3-year disease-free survival rates were 84.8% and 62.9% in MAFLD group, and 80.2% and 58.8% in Non-MAFLD group, respectively (p = 0.31). Conclusions: LLR for MAFLD-HCC was associated with more blood loss but with comparable postoperative recovery and long-term survival compared with Non-MAFLD-HCC patients. LLR is feasible and safe for HCC patients with MAFLD background. [ABSTRACT FROM AUTHOR]

Background: There is still poor evidence about the safety and feasibility of laparoscopic liver resection (LLR) for huge (> 10 cm) hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long-term outcomes of LLR versus open liver resection (OLR) for patients with huge HCC from real-life data from consecutive patients. Methods: Data regarding all consecutive patients undergoing liver resection for huge HCC were retrospectively collected from a Korean referral HPB center. Primary outcomes were the postoperative results, while secondary outcomes were the oncologic survivals. Results: Sixty-three patients were included in the study: 46 undergoing OLR and 17 LLR. Regarding postoperative outcomes, there were no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications, and R1 resection rates. After a median follow-up of 48.4 (95% CI 8.9–86.8) months, there were no statistically significant differences in 3 years OS (59.3 ± 8.7 months vs. 85.2 ± 9.8 months) and 5 years OS (31.1 ± 9 months vs. 73.1 ± 14.1 months), after OLR and LLR, respectively (p = 0.10). Similarly, there was not a statistically significant difference in both 3 years DFS (23.5% ± 8.1 months vs. 51.6 ± months) and 5 years DFS (15.7 ± 7.1 months vs. 38.7 ± 15.3 months), respectively (p = 0.13), despite a potential clinically significant difference. Conclusion: LLR for huge HCC may be safe and effective in selected cases. Further studies with larger sample size and more appropriate design are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiation therapy for hepatocellular carcinoma necessitates the implantation of gold fiducial markers in the liver, resulting in artifacts on computed tomography (CT) scans, which affect radiomic feature values. Purpose: This report aims to assess the effect of these artifacts on radiomic features and how removing CT slices affects radiomic features extracted from 3D regions of interest (ROI). Methods: First, the range variation in 38 tumor contours unaffected by artifacts was assessed after sequentially and randomly removing 25%, 50%, 75% of slices. Subsequently, the agreement of feature values before and after removing ROI slices containing artifacts from 186 patients' CT scans was assessed with Lin's concordance correlation coefficient (CCC) and a Wilcoxon signed‐rank test. Results: In artifact‐free tumor volumes, at least 71% of features remain robust with up to 50% of slices removed, while 56% remains robust with up to 75% of slices removed. When comparing contours before and after removing slices containing artifacts, around a third of features in the tumor contour and surrounding area remain robust (CCC > 0.9), compared to 44% in the healthy liver. Concerning the tumor, 13% (Gray Level Size Zone Matrix) to 61% (first order) of the features remain robust (CCC > 0.9). Over 90% of features differ significantly as assessed by Wilcoxon signed‐rank test, however. Conclusions: This study demonstrates that removing slices containing artifacts is a feasible solution for the CT fiducial problem in this patient population and provides insight into which features are affected. [ABSTRACT FROM AUTHOR]

The nervous system significantly participates in maintaining homeostasis, and modulating repair and regeneration processes in the liver. Moreover, the nervous system also plays an important role in the processes associated with the development and progression of liver disease, and can either potentiate or inhibit these processes. The aim of this review is to describe the mechanisms and pathways through which the nervous system influences the development and progression of liver diseases, such as alcohol‐associated liver disease, nonalcoholic fatty liver disease, cholestatic liver disease, hepatitis, cirrhosis, and hepatocellular carcinoma. Possible therapeutic implications based on modulation of signals transduction between the nervous system and the liver are also discussed. [ABSTRACT FROM AUTHOR]

Aim: Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long‐term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real‐world setting. Methods: A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression. Results: In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05). Conclusions: These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long‐term outcomes of patients with CHB in the Japanese population. [ABSTRACT FROM AUTHOR]

Aim: Autotaxin (ATX) is a newly identified liver fibrosis biomarker; however, its clinical usefulness remains unclear. Therefore, we analyzed the changes in patients with chronic hepatitis B virus infection treated with nucleos(t)ide analogs (NAs) to evaluate its usefulness. We also investigated the predictors of hepatocellular carcinoma development, including ATX, in patients with chronic hepatitis B based on their clinical characteristics. Methods: This retrospective study included 179 patients with hepatitis B virus infection treated with NAs for >2 years. First, we measured the ATX levels before and up to 10 years after initiating entecavir (therapy for 88 patients whose serial ATX levels could be measured before and during entecavir therapy. Subsequently, for 179 patients whose ATX levels could be measured at the commencement of NAs, we examined the factors involved in developing hepatocellular carcinoma, including ATX. Results: The ATX levels showed a gradual and significant decrease during the observation period of up to 10 years. Multivariable analysis showed that a baseline ATX/upper limits of normal ratio ≥1.214, age, and alkaline phosphatase levels were independent risk factors for hepatocellular carcinoma development. The combination of age and ATX/upper limits of normal ratio was used to stratify the high‐risk groups for liver carcinogenesis. Conclusions: A decrease in ATX levels up to 10 years after the commencement of therapy suggested that ATX is a helpful biomarker in evaluating fibrosis in patients undergoing long‐term NA therapy. Furthermore, this study showed that combining age and the baseline ATX/upper limits of normal ratio may help identify high‐risk carcinogenesis groups. [ABSTRACT FROM AUTHOR]

Background and aim: MicroRNAs (miRs) are now a well-known subject in various tumor genesis and are studied as early diagnostic biomarker. Many arrays of miRs were incorporated in the pathogenesis of HCV-related hepatocellular carcinomas (HCV-HCC). In this respect, we aimed to evaluate the diagnostic role of circulating miR-21, miR-122, and miR-222 in Egyptian patients with HCV-HCC. Patient and methods: Between June 2018 and April 2019, a cross-sectional comparative study was designed to evaluate the circulating miR-21, miR-122, and miR-222 by quantitative Real-Time PCR. For analytical purposes, patients were categorized into three groups: chronic HCV group (CHC-group, n = 22), HCV-related liver cirrhosis (LC-group, n = 22), and HCV-related hepatocellular carcinoma (HCV-HCC-group, n = 54). Results: Serum levels of miR-21 and miR-222 increased with the progressive course from CHC to LC and HCC; p <.001. Serum levels of miR-122 in HCC patients were significantly lower than non-HCC patients (CHC and LC patients, n = 44); p <.001. However, the differences in levels of serum miR-122 between CHC and LC were not statistically significant; P = 0.8. ROC curve analysis showed that the sensitivity and specificity of miR-21 were 61.1% and 95.5%, miR-222 were 71.7% and 93.2%, and miR-122 were 98.2% and 100%. The positive predictive value for miRNA-21, miRNA-122, and miRNA-222 were 13.4%, 93.3%, and 10.5% respectively. The Negative predictive value for miRNA-21, miRNA-122, and miRNA-222 were 94.3%, 97.8%, and 92.7% respectively. Conclusion: MiR-21 and miR-222 could be potential markers for advanced liver damage, while miR-122 had the best diagnostic accuracy and could be a promising marker for detection of HCC. [ABSTRACT FROM AUTHOR]

Ribosomal proteins (RPs) are essential components of ribosomes, playing a role not only in ribosome biosynthesis, but also in various extra-ribosomal functions, some of which are implicated in the development of different types of tumors. As universally acknowledged, hepatocellular carcinoma (HCC) has been garnering global attention due to its complex pathogenesis and challenging treatments. In this review, we analyze the biological characteristics of RPs and emphasize their essential roles in HCC. In addition to regulating related signaling pathways such as the p53 pathway, RPs also act in proliferation and metastasis by influencing cell cycle, apoptosis, angiogenesis, and epithelial-to-mesenchymal transition in HCC. RPs are expected to unfold new possibilities for precise diagnosis and individualized treatment of HCC. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Adiponectin, a key adipokine, shows promise as a non‐invasive biomarker for liver cirrhosis by reflecting inflammation and metabolic changes, but conflicting findings highlight the need for a systematic review and meta‐analysis to clarify its role. Our study aimed to evaluate adiponectin levels across various stages of liver cirrhosis, compare them with other chronic liver diseases (CLD) and hepatocellular carcinoma (HCC), and assess its potential as a diagnostic and prognostic biomarker.Our systematic search was conducted on September 2023 using PubMed, EMBASE and Scopus, searching for observational studies evaluating serum and plasma adiponectin levels in liver cirrhosis. Inclusion and exclusion criteria were applied, and study quality was assessed using the Newcastle‐Ottawa Scale. To evaluate the overall effect size, we utilized a random‐effects model along with a mean difference (MD) analysis. The principal summary outcome was the MD in adiponectin levels.We included 16 articles involving 2617 subjects in our qualitative and quantitative synthesis. We found significantly higher adiponectin levels in liver cirrhosis patients (8.181 [95% CI 3.676, 12.686]), especially in Child‐Pugh B individuals (13.294 [95% CI 4.955, 21.634]), compared to controls. Child‐Pugh A patients did not show significant differences compared to controls. In addition, adiponectin levels were significantly elevated in primary biliary cholangitis (PBC) patients compared to controls (8.669 [95% CI .291, 17.047]), as well as in liver cirrhosis compared to other CLD patients (4.805 [95% CI 1.247, 8.363]), including non‐alcoholic fatty liver disease (NAFLD) (8.532 [95% CI 3.422, 13.641]), but not viral hepatitis. No significant MD was observed between liver cirrhosis and HCC patients.Adiponectin levels are significantly elevated in liver cirrhosis, especially in advanced stages, potentially serving as a biomarker for advanced cirrhosis. Adiponectin also differentiates cirrhosis from other CLD, including NAFLD. However, its role in distinguishing cirrhosis from viral hepatitis and HCC is limited. [ABSTRACT FROM AUTHOR]

Objective: Transcatheter Arterial Chemoembolization (TACE) is the first choice for the treatment of advanced-stage hepatocellular carcinoma (HCC). However, TACE suffers from a lack of specificity and rapid drug release. Herein, a targeted redox-responsive peptide (TRRP) was synthesized and used as a carrier of doxorubicin (DOX) to enhance the efficacy of TACE through tumor cells targeting and controlled drug release. Methods: TRRP has a high loading capacity of DOX and a sensitive drug release behavior at high glutathione (GSH) concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models. Results: TRRP has a high loading capacity of DOX and a sensitive drug release behavior at GSH concentration. Moreover, TRRP could bind to the transferrin receptor on the surface of tumor cells, which enhanced the efficacy of TACE and reduced side effects of TACE. TACE with TRRP@DOX dispersed in lipiodol shows an enhanced therapeutic outcome compared to the treatment with DOX + lipiodol emulsion in orthotopic rat HCC models. Conclusions: This study demonstrated that TRRP was a promising therapeutic agent for enhancing TACE therapy for HCC treatment. [ABSTRACT FROM AUTHOR]

Purpose: This review aims to provide a comprehensive summary of DECT techniques, acquisition workflows, and post-processing methods. By doing so, we aim to elucidate the advantages and disadvantages of DECT compared to conventional single-energy CT imaging. Methods: A systematic search was conducted on MEDLINE/EMBASE for DECT studies in liver imaging published between 1980 and 2024. Information regarding study design and endpoints, patient characteristics, DECT technical parameters, radiation dose, iodinated contrast agent (ICA) administration and postprocessing methods were extracted. Technical parameters, including DECT phase, field of view, pitch, collimation, rotation time, arterial phase timing (from injection), and venous timing (from injection) from the included studies were reported, along with formal narrative synthesis of main DECT applications for liver imaging. Results: Out of the initially identified 234 articles, 153 met the inclusion criteria. Extensive variability in acquisition parameters was observed, except for tube voltage (80/140 kVp combination reported in 50% of articles) and ICA administration (1.5 mL/kg at 3–4 mL/s, reported in 91% of articles). Radiation dose information was provided in only 40% of articles (range: 6–80 mGy), and virtual non-contrast imaging (VNC) emerged as a common strategy to reduce the radiation dose. The primary application of DECT post-processed images was in detecting focal liver lesions (47% of articles), with predominance of study focusing on hepatocellular carcinoma (HCC) (27%). Furthermore, a significant proportion of the articles (16%) focused on enhancing DECT protocols, while 15% explored metastasis detection. Conclusion: Our review recommends using 80/140 kVp tube voltage with 1.5 mL/kg ICA at 3–4 mL/s flow rate. Post-processing should include low keV-VMI for enhanced lesion detection, IMs for tumor iodine content evaluation, and VNC for dose reduction. However, heterogeneous literature hinders protocol standardization. [ABSTRACT FROM AUTHOR]

Purpose: To provide detailed reports on radiation doses during transarterial chemoembolization (TACE) in the cone-beam computed tomography (CBCT) era and to identify the associated factors. Methods: This retrospective study included 385 consecutive patients who underwent initial conventional TACE for hepatocellular carcinoma (HCC) between January 2016 and December 2017. In most cases, CBCT was performed at the common hepatic artery or celiac axis to confirm the location of the tumor and the three-dimensional hepatic artery anatomy. Superselective TACE was performed for all technically feasible cases. Information on total dose area product (DAP), total cumulative air kerma (CAK), fluoroscopy time, and DAP and CAK of each digital subtraction angiography (DSA) and CBCT scan was recorded. Multiple linear regression analysis was performed to identify the factors associated with increased DAP during TACE. Results: The mean values of total DAP and CAK were 165.2 ± 81.2 (Gy·cm²) and 837.1 ± 571.0 (mGy), respectively. The mean fluoroscopy time was 19.1 ± 10.3 min. The mean DAP caused by fluoroscopy, DSA, and CBCT was 51.8 ± 43.9, 28.0 ± 24.1, and 83.9 ± 42.1 Gy·cm², respectively. Male sex, a high body mass index, largest tumor size > 3 cm, presence of aberrant right and left hepatic arteries, and superselective TACE were identified as independent predictors of increased total DAP during TACE. Conclusion: We were able to provide detailed reports on radiation doses during TACE and associated factors. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency, characteristics and clinical significance of incidental pelvic findings reported on abdominopelvic CT performed for hepatocellular carcinoma (HCC) surveillance in at-risk patients. Material and methods: This two-center retrospective study received institutional review board approval with a waiver of informed consent. The radiologic reports of the CT exams performed 1/1/2010–2/28/2023 for HCC surveillance were reviewed. Exams were obtained with intravenous contrast material and included hepatic arterial and portal venous phases of the abdomen; images of the pelvis were acquired during the portal venous phase. Reported imaging findings and imaging-related recommendations either by the radiologists or the corresponding caregiver, if present, were retrospectively tabulated. The patient's medical records were reviewed to determine if there were any recommendations that were considered clinically important and culminated in any further interventions or treatments. Results: 259 adults (1st center: mean age, 60 ± 11 years, 49% male and 2nd center: 56.26 ± 6.2 years, 48% male) at risk for HCC underwent 327 abdominopelvic CT exams for HCC surveillance at two centers. A total of 622 pelvic findings (mean, 2.2/ exam) were reported, including 131 bladder, 120 alimentary tract, 133 vascular, 51 gynecologic, 37 prostate, 33 lymph node, 27 inguinal, 44 peritoneal, and 46 skeletal. 52 of 622 reported findings (8.3%) were associated with actionable recommendations. 24 of the 52 actionable recommendations/clinical suggestions were implemented as follows: five complimentary imaging, ten additional laboratory tests, and nine non-imaging recommendations. Of note, only eight applied recommendations culminated in a clinical outcome, which included four urinary tract infection treatments. Conclusion: Pelvic CT findings were associated with a clinical benefit to the patient in 1.3% of exams. These results suggest that pelvic imaging should be omitted from CT-based HCC surveillance. Clinical relevance: Without compromising valuable information, patients undergoing HCC surveillance-CT may not require additional pelvic coverage. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the enhancement patterns in the hepatobiliary phase (HBP) and pathological features of nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) patients. Methods: In this single-institution retrospective study, 27 consecutive cirrhosis patients with 29 histologically confirmed NIN-HCCs who underwent preoperative examination via Gd-EOB-DTPA-enhanced MRI were enrolled from January 2016 to September 2023. Two blinded radiologists assessed the imaging features of both the inner and outer nodules in NIN-HCCs to reach a consensus on the Liver Imaging Reporting & Data System (LI-RADS) categories of the lesions. Based on the different enhancement patterns of the inner and outer nodules in the HBP, NIN-HCCs were classified into different groups and further divided into different types. Imaging features and LI-RADS categories were subsequently compared among the groups. Pathological findings for NIN-HCCs were also evaluated. Results: Among 29 NIN-HCCs, all inner nodules showed hypervascularity, with a maximum diameter of 13.2 ± 5.5 mm; 51.7% (15/29) showed "wash-in with washout" enhancement; and 48.3% (14/29) showed "wash-in without washout" enhancement. All outer nodules showed hypovascularity, with a maximum diameter of 25.6 ± 7.3 mm, and 51.9% (14/29) showed a washout appearance on PVP. Among all the lesions, the maximum diameter was 27.5 ± 6.8 mm; 12 (41.4%) lesions were LR-4, and 17 (58.6%) lesions were LR-5. NIN-HCCs were classified into hypointense (62.1%, 18/29) and isointense (37.9%, 11/29) groups based on the signal intensity of the outer nodules in the HBP. In the hypointense group, 2 (6.9%) of the inner nodules were hypointense (type A), 11 (37.9%) were isointense (type B), and 5 (17.2%) were hyperintense (type C) compared to the background hypointense outer nodules. In the isointense group, 9 (31.0%) of the inner nodules were hypointense (type D), 2 (6.9%) were isointense (type E), and no (0%) was hyperintense (type F) compared to the background isointense outer nodules. There were no significant differences in the diameter, dynamic enhancement patterns of the inner or outer nodules, or LI-RADS scores of the lesions between the hypointense group and the isointense group (all P > 0.05). Histologically, the inner nodules of NIN-HCCs were mainly composed of moderately differentiated HCC (75.9% 22/29), whereas the outer nodules consisted of either well-differentiated HCC or high-grade dysplastic nodules (HGDNs). Conclusions: NIN-HCCs exhibit specific MRI findings closely associated with their pathological features. The spectrum of HBP enhancement patterns provides valuable insights into the underlying cell biological mechanisms of these lesions. NIN-HCC subtypes may be used as a morphologic marker in the early stage of multistep hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. Material and methods: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. Results: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). Conclusion: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. Clinical relevance statement: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. Key Points: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC). Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors. Results: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = −0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = −0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02). Conclusions: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment. Clinical relevance statement: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy. Key Points: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment. [ABSTRACT FROM AUTHOR]

Gut dysbiosis has been implicated in the pathogenesis of hepatocellular carcinoma (HCC) arising from diverse etiological factors. Microbe-associated molecular patterns (MAMPs), microbial metabolites, and fungi are capable of modulating the metabolic pathways and immune composition of the HCC microenvironment. The gut microbiome holds potential as a novel tool for early diagnosis and evaluation of the outcome response, especially to immune checkpoint inhibitors (ICIs). Targeted manipulation of the gut microbiome through diets, antibiotics, probiotics, fecal microbiota transplantation (FMT), and nano-delivery systems may augment therapeutic efficacy in the management of HCC. The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC. [ABSTRACT FROM AUTHOR]

• H3K36me3, H3K4me3, H3K79me2, and H3K9ac co-regulate gene expression in HCC. • Key histone modifications in five key regions co-regulate gene expression. • CBX2 , CEBPZOS , LDHA , and UMPS are key target genes associated with prognosis. • Key target genes are associated with immune microenvironment and drug sensitivity. Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. Studies have shown that histone modification plays an important regulatory role in the occurrence and development of HCC. However, the specific regulatory effects of histone modifications on gene expression in HCC are still unclear. This study focuses on HepG2 cell lines and hepatocyte cell lines. First, the distribution of histone modification signals in the two cell lines was calculated and analyzed. Then, using the random forest algorithm, we analyzed the effects of different histone modifications and their modified regions on gene expression in the two cell lines, four key histone modifications (H3K36me3, H3K4me3, H3K79me2, and H3K9ac) and five key regions that co-regulate gene expression were obtained. Subsequently, target genes regulated by key histone modifications in key regions were screened. Combined with clinical data, Cox regression analysis and Kaplan-Meier survival analysis were performed on the target genes, and four key target genes (CBX2 , CEBPZOS , LDHA , and UMPS) related to prognosis were identified. Finally, through immune infiltration analysis and drug sensitivity analysis of key target genes, the potential role of key target genes in HCC was confirmed. Our results provide a theoretical basis for exploring the occurrence of HCC and propose potential biomarkers associated with histone modifications, which may be potential drug targets for the clinical treatment of HCC. [ABSTRACT FROM AUTHOR]

Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival. In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0–1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival. At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7–2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p<0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3–32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3–not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable–not evaluable] vs 28·3 months [12·8–43·8]; hazard ratio 0·26 [0·10–0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable–not evaluable] vs 32·8 months [15·0–50·5]; 0·19 [0·05–0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival. The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials. None. [ABSTRACT FROM AUTHOR]

Background: Recent genome-wide association studies (GWASs) in liver diseases have generated some polygenic risk scores (PRSs), but their predictive effectiveness on hepatocellular carcinoma (HCC) risk assessment remains unclear. Methods: Here, we constructed a novel combined polygenic risk score and evaluated its increment to the well-established risk model. We used 15 HCC-associated genetic loci from two PRSs and FinnGen GWAS data to calculate a PRS-combined score and to fit the related PRS model in the UK Biobank cohort (N = 436,162). The PRS-combined score was further assessed for risk stratification for HCC integrating with the recommended clinical risk scores. Results: The PRS-combined model achieved a better AUC (0.657) than that of PRS-HFC (0.637) and PRS-cirrhosis (0.645). The top 20% of the PRS-combined distribution had a 3.25 increased risk of HCC vs. the middle decile (45–55%). At the population level, the addition of PRS-combined to the CLivD score significantly increased the C-statistic (from 0.716 to 0.746) and provided a remarkable improvement in reclassification (NRI = 0.088) at the 10-year risk threshold of 0.2%. In clinic, additional assessment of PRS-combined would reclassify 34,647 intermediate-risk participants as high genetic risk, corresponding to an increase of 63.92% (62/97) of the HCC events classified at high risk using the Fibrosis-4 alone. Conclusions: The PRS may enhance HCC risk prediction effectiveness in the general population and refine risk stratification of the conventional clinical indicator. [ABSTRACT FROM AUTHOR]

Background and Aims: It has been described that recompensation can improve prognosis in patients with cirrhosis. However, recompensation after transjugular intrahepatic portosystemic shunt (TIPS) has not been studied. We evaluated the impact of recompensation after TIPS on the risk of hepatocellular carcinoma (HCC) and death, and we compared it with compensated cirrhosis patients. Methods: An observational study of consecutive patients with cirrhosis undergoing TIPS between 2008 and 2022 was performed. Baveno VII definition of recompensation was used including patients with or without diuretics/Hepatic encephalopathy prophylaxis. A prospective cohort of consecutive compensated cirrhosis patients was used for comparison. Results: Overall, 208 patients with cirrhosis were included, 92 compensated and 116 decompensated who underwent TIPS. After 1 year, 24% achieved recompensation. Liver function (MELD 12 ± 5 vs. 15 ± 6; p =.049), LDL‐cholesterol (97 mg/dL vs. 76 mg/dL, p =.018), white cell count (7.96 × 109/dL vs. 6.24 × 109/dL, p =.039) and platelets (129 × 109/dL vs. 101 × 109/dL, p =.039) were associated with recompensation. Recompensation was associated with a reduction in the risk of HCC (p =.020). Multivariable analysis showed that this risk was significantly higher in non‐recompensated patients (p =.003) but no differences were observed in recompensated compared with compensated patients (p =.816). Similarly, decompensated patients presented lower survival rates (p =.011), while no differences were observed between recompensated and compensated patients (p =.677). Conclusions: Recompensation after TIPS has a clear impact on the incidence of HCC and death, with a similar prognosis than patients with compensated cirrhosis. Liver function is associated with recompensation, suggesting the importance of considering early TIPS in patients with indication. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) presents a significant global health burden, with varying survival rates across regions. The presence of pulmonary metastases (PM) in HCC predicts a poorer prognosis, yet the global understanding of the progression and management is limited. This study aims to systematically review the burden of PM in HCC, document current treatment approaches, and evaluate treatment effectiveness through meta-analysis. A comprehensive literature search was conducted across multiple databases. Articles were screened, and data extraction was performed independently by two reviewers. Statistical analyses were conducted to synthesise data and assess treatment outcomes. A total of 82 articles were included, comprising a population of 3241 participants with documented PM. Our analysis revealed a linear relationship between the HCC population size and the occurrence of PM (p < 0.005). Surgical intervention demonstrated the lowest hazard ratio (0.128) and significantly improved survival rates compared to other treatment modalities. However, data quality limitations underscore the need for further research to delineate patient subsets benefitting from surgical intervention for PM. Our findings advocate for continued investigation into PM management strategies, notably the role of surgical resection alongside systemic therapies, to improve outcomes in HCC patients with PM. [ABSTRACT FROM AUTHOR]

We sought to assess the impact of various perioperative factors on the risk of severe complications and post-surgical mortality using a novel maching learning technique. Data on patients undergoing resection for HCC were obtained from an international, multi-institutional database between 2000 and 2020. Gradient boosted trees were utilized to construct predictive models. Among 962 patients who underwent HCC resection, the incidence of severe postoperative complications was 12.7% (n = 122); in-hospital mortality was 2.9% (n = 28). Models that exclusively used preoperative data achieved AUC values of 0.89 (95%CI 0.85 to 0.92) and 0.90 (95%CI 0.84 to 0.96) to predict severe complications and mortality, respectively. Models that combined preoperative and postoperative data achieved AUC values of 0.93 (95%CI 0.91 to 0.96) and 0.92 (95%CI 0.86 to 0.97) for severe morbidity and mortality, respectively. The SHAP algorithm demonstrated that the factor most strongly predictive of severe morbidity and mortality was postoperative day 1 and 3 albumin-bilirubin (ALBI) scores. Incorporation of perioperative data including ALBI scores using ML techniques can help risk-stratify patients undergoing resection of HCC. [ABSTRACT FROM AUTHOR]

Repeat open hepatectomy (ROH) for recurrent liver tumors is the preferred approach especially after initial open hepatectomy (OH). The aim of this study is to assess feasibility and safety of repeat laparoscopic hepatectomy (RLH) after initial OH in 2 high volume hepato-biliary hospitals. Patients were retrieved from prospective data bases from 2012 to 2020. The patients were divided into two groups according to the approach used for repeat hepatectomy, ROH and RLH groups. Sixty-seven patients matched the criteria, 20 in RLH and 47 in ROH. Diagnoses were hepatocellular carcinoma in 52.3%, intrahepatic cholangiocarcinoma in 7.7% and colorectal liver metastases in 40%. Median operative time and blood loss were lower in RLH (199 vs 260 min, and 100 vs 400 ml respectively), as well as overall postoperative complications (20% vs 49%). There were 2 conversions (10%) due to adhesions and one died of postoperative pancreatitis in RLH. Median hospital stay was lower in RLH (5 vs 9 days). RLH is a feasible, safe technique and a realistic option to be considered in selected patients after previous OH. Early conversion should be considered when adhesions are more severe than expected. [ABSTRACT FROM AUTHOR]