Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer diagnoses and deaths in the United States. This study serves as an update on secular trends in national HCC incidence rates while exploring potential geographic and racial/ethnic differences across all nine US census divisions. Methods: We analyzed HCC incidence data reported to the United States Cancer Statistics (USCS) database from 2001 to 2021 (excluding 2020 data, based on the Centers for Disease Control and Prevention's cautionary recommendations for COVID-19 pandemic data usage for trend analysis). We performed trend analyses of age-adjusted incidence rates in the US overall, by census divisions, and then stratified by race/ethnicity, using the National Cancer Institute's Joinpoint Regression Program. Results: Between 2001 and 2021, HCC incidence rates increased nationally, with an average annual percentage change (AAPC) of 2.51 (95% confidence interval (CI): 2.32-2.72); however, the rate decreased (annual percentage change (APC) -3.33 (95% CI: -4.78--1.96) in recent years from 2018 to 2021. Division 1 had the greatest decrease (APC -6.46 (95% CI: -9.62--3.96) from 2017 to 2021, while rates leveled in Division 6 (East South Central) and Division 7 (West South Central). HCC trends decreased substantially for non-Hispanic Black and Non-Hispanic Asian and Pacific Islander groups in almost all divisions in recent years, but trends were stable, decreased, or increased for other racial/ethnic populations. Conclusions: Despite declining national HCC incidence rates, these trends were not uniform across racial/ethnic groups or US census divisions. Race-specific interventions are needed to reduce disparities in HCC incidence in all US census divisions.

The genomic landscape of cancer cells is complex and heterogeneous, with aberrant DNA methylation being a common observation. Growing evidence indicates that oxidants produced from immune cells may interact with epigenetic processes, and this may represent a mechanism for the initiation of altered epigenetic patterns observed in both precancerous and cancerous cells. Around 20% of cancers are linked to chronic inflammatory conditions, yet the precise mechanisms connecting inflammation with cancer progression remain unclear. During chronic inflammation, immune cells release oxidants in response to stimuli, which, in high concentrations, can cause cytotoxic effects. Oxidants are known to damage DNA and proteins and disrupt normal signalling pathways, potentially initiating a sequence of events that drives carcinogenesis. While research on the impact of immune cell-derived oxidants on DNA methylation remains limited, this mechanism may represent a crucial link between chronic inflammation and cancer development. This review examines current evidence on inflammation-associated DNA methylation changes in cancers related to chronic inflammation.

Organoid culture has emerged as a forefront technology in the life sciences field. As "in vitro micro-organs", organoids can faithfully recapitulate the organogenesis process, and conserve the key structure, physiological function and pathological state of the original tissue or organ. Consequently, it is widely used in basic and clinical studies, becoming important preclinical models for studying diseases and developing therapies. Here, we introduced the definition and advantages of organoids and described the development and advances in hepatobiliary organoids research. We focus on applying hepatobiliary organoids in benign and malignant diseases of the liver and biliary tract, drug research, and regenerative medicine to provide valuable reference information for the application of hepatobiliary organoids. Despite advances in research and treatment, hepatobiliary diseases including carcinoma, viral hepatitis, fatty liver and bile duct defects have still been conundrums of the hepatobiliary field. It is necessary and crucial to study disease mechanisms, establish efficient and accurate research models and find effective treatment strategies. The organoid culture technology shed new light on solving these issues. However, the technology is not yet mature, and many hurdles still exist that need to be overcome. The combination with new technologies such as CRISPR-HOT, organ-on-a-chip may inject new vitality into future development.

Viral oncoproteins play crucial roles in transforming normal cells into cancer cells, representing a significant factor in the etiology of various cancers. Traditionally, identifying these oncoproteins is both time-consuming and costly. With advancements in computational biology, bioinformatics tools based on machine learning have emerged as effective methods for predicting biological activities. Here, for the first time, we propose an innovative approach that combines Generative Adversarial Networks (GANs) with supervised learning methods to enhance the accuracy and generalizability of viral oncoprotein prediction. Our methodology evaluated multiple machine learning models, including Random Forest, Multilayer Perceptron, Light Gradient Boosting Machine, eXtreme Gradient Boosting, and Support Vector Machine. In ten-fold cross-validation on our training dataset, the GAN-enhanced Random Forest model demonstrated superior performance metrics: 0.976 accuracy, 0.976 F1 score, 0.977 precision, 0.976 sensitivity, and 1.0 AUC. During independent testing, this model achieved 0.982 accuracy, 0.982 F1 score, 0.982 precision, 0.982 sensitivity, and 1.0 AUC. These results establish our new tool, VirOncoTarget, accessible via a web application. We anticipate that VirOncoTarget will be a valuable resource for researchers, enabling rapid and reliable viral oncoprotein prediction and advancing our understanding of their role in cancer biology.

Primary liver cancer is among the most common cancers globally. It is the sixth-most common malignancy encountered and the third-most common cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for about 90% of primary liver cancers. The majority of HCCs occur in patients with underlying cirrhosis, which results from chronic liver diseases such as fatty liver, hepatitis B and hepatitis C infections, and chronic alcohol use, which are the leading causes. The obesity pandemic has led to an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which leads to nonalcoholic steatohepatitis and could progress to cirrhosis. As HCC is among the most common cancers and occurs in the setting of chronic liver disease in most patients, screening the population at risk could help in early diagnosis and management, leading to improved survival. Screening for HCC is performed using biochemical marker testing such as α-fetoprotein (AFP) and cross-sectional imaging. It is critical to emphasize that HCC could potentially occur in patients without cirrhosis (non-cirrhotic HCC), which can account for almost 20% of all HCCs. The lack of cirrhosis can cause a delay in surveillance, which could potentially lead to diagnosis at a later stage, worsening the prognosis for such patients. In this article, we discuss the diagnosis of cirrhosis in at-risk populations with details on the different modalities available for screening HCC in patients with cirrhosis, emphasizing the role of abdominal ultrasounds, the primary imaging modality in HCC screening.

Accurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies.

To compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC.

We conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients' medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients' overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems.

Hepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit.

HKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases.

Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate β-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/β-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge. With the widespread use of the hepatitis B vaccine and antiviral therapy, the etiology of HCC is shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage HCC can be treated with potentially curative strategies such as surgical resection, liver transplantation, and radiofrequency ablation, improving long-term survival. However, most HCC patients, when diagnosed, are already in the intermediate or advanced stages. Molecular targeted therapy, followed by immune checkpoint inhibitor immunotherapy, has been a revolution in HCC systemic treatment. Systemic treatment of HCC especially for patients with compromised liver function is still a challenge due to a significant resistance to immune checkpoint blockade, tumor heterogeneity, lack of oncogenic addiction, and lack of effective predictive and therapeutic biomarkers.

Recently, metabolic associated steatotic liver disease (MASLD) became the leading cause of chronic liver disease worldwide and one of the most frequent causes of hepatocellular carcinoma (HCC). Nonetheless, in this epidemiological trend, viral hepatitis remains the major driver in hepatic carcinogenesis. Globally, hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma, with an overall attributable risk of approximately 40%, followed by hepatitis C virus (HCV), which accounts for 28-30% of cases, with significant geographic variations between the Eastern and Western world. Considering all the etiologies, HCC risk increases proportionally with the progression of liver disease, but the risk is consistently higher in patients with viral triggers. This evidence indicates that both direct (due to the oncogenic properties of the viruses) and indirect (through the mechanisms of chronic inflammation that lead to cirrhosis) mechanisms are involved, alongside the presence of co-factors contributing to liver damage (smoking, alcohol, and metabolic factors) that synergistically enhance the oncogenic process. The aim of this review is to analyze the oncogenic role of hepatitis viruses in the liver, evaluating epidemiological changes and direct and indirect viral mechanisms that lead to liver cancer.

Hepatocellular carcinoma (HCC), a common type of liver cancer, is increasing in incidence worldwide. An early diagnosis of hepatocellular carcinoma (HCC) is still challenging: Currently, few biomarkers are available to diagnose the early stage of HCC, therefore, additional prognostic biomarkers are required to identify potential risk factors. The present study analyzed gene expression levels of HCC tissue samples and the protein expression levels obtained from the GSE46408 HCC dataset using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The metabolically associated differentially expressed genes (DEGs), including DEGs involved in the glucose metabolism pathway, were selected for further analysis. Phosphoglycerate kinase 1 (PGK1), a glycolytic enzyme, was determined as a potential prognostic biomarker through Kaplan-Meier curve and clinical association variable analyses. This was also verified based on the expression levels of PGK1 in tumor tissue and protein expression levels in several liver cancer cell lines. PGK1 mRNA demonstrated a high level of expression in HCC tissue and was significantly associated with a poor prognosis, showing a negative association with survival time. In addition, as an independent risk factor, PGK1 may potentially be a valuable prognostic biomarker for patients with HCC. Furthermore, expression of PGK1 was associated with the early stages (stage I and T1) of HCC. Moreover, PGK1 mRNA expression levels demonstrated a positive association with progression of liver cancer. The results suggested that PGK1 mRNA may be involved in the degree of HCC malignancy and may be a future potential prognostic biomarker for HCC progression.

Background: Tenofovir and entecavir demonstrated substantial effectiveness in the reversion of fibrosis and reversed cirrhosis in patients with hepatitis B virus (HBV)-related cirrhosis. However, there has not been a definitive conclusion regarding the association between entecavir and tenofovir on the risk of cirrhosis-related complications. Therefore, this study aimed to investigate the comparative effectiveness between tenofovir and entecavir in HBV-related cirrhosis patients. Methods: This was a retrospective study using Taiwan's Health Insurance Research Database. We enrolled newly diagnosed HBV-related cirrhosis patients who initiated entecavir and tenofovir between 2011 and 2019. Treatment groups were determined by the initial HBV antiviral medication prescribed. The primary composite outcome was the development of hepatocellular carcinoma (HCC), death from any causes, and liver transplantation. The secondary outcomes included all the individual components of the primary outcome. The incidence rate was calculated for each outcome for both treatment groups using the Fine-Gray subdistribution hazard models. Propensity score adjustment was used to balance treatment groups. Results: A total of 7,316 propensity score-matched treatment-naïve patients and 3,524 propensity score-matched treatment-experienced patients were included. Within treatment-naïve patients, those receiving tenofovir showed significantly lower hazards of developing the composite outcome (HR, 0.79; p < 0.0001), hepatocellular carcinoma (HR, 0.86; p = 0.027), mortality (HR, 0.75; p < 0.0001), and liver transplantation (HR, 0.70; p = 0.0189) than those receiving entecavir. As for treatment-experienced patients, tenofovir was associated with a significantly lower risk of the composite outcome (HR, 0.82; p = 0.0033) and hepatocellular carcinoma (HR, 0.60; p < 0.0001), but it did not show a significantly different risk of all-cause mortality (HR, 0.93; p = 0.3374) or liver transplantation (HR, 1.17; p = 0.5112) compared to entecavir. Conclusion: Tenofovir presented a significantly lower incidence of cirrhosis-related complications than entecavir in patients with hepatitis B virus-related cirrhosis. However, no statistically significant difference in death and liver transplantation was seen in treatment-experienced patients.

The hepatitis B virus (HBV) continues to cause substantial health and economic burdens, and its target of elimination may not be reached in 2030 without further efforts in diagnostics, non-pharmaceutical prevention measures, vaccination, and treatment. Current therapeutic options in chronic HBV, based on interferons and/or nucleos(t)ide analogs, suppress the virus replication but do not eliminate the pathogen and suffer from several constraints. This paper reviews the progress on biotechnological approaches in functional and definitive HBV treatments, including gene-editing tools, i.e., zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9, as well as therapeutics based on RNA interference. The advantages and challenges of these approaches are also discussed. Although the safety and efficacy of gene-editing tools in HBV therapies are yet to be demonstrated, they show promise for the revitalization of a much-needed advance in the field and offer viral eradication. Particular hopes are related to CRISPR/Cas9; however, therapeutics employing this system are yet to enter the clinical testing phases. In contrast, a number of candidates based on RNA interference, intending to confer a functional cure, have already been introduced to human studies. However, larger and longer trials are required to assess their efficacy and safety. Considering that prevention is always superior to treatment, it is essential to pursue global efforts in HBV vaccination.

To analyze the hepatitis B virus (HBV) infection and mortality in Poland according to sociodemographic characteristics, trends over time, and the impact of the COVID-19 pandemic on hepatitis B epidemiology.

We examined HBV infection cases and deaths reported by national registries and used Joinpoint analysis to estimate time trends in the years 2005-2021. To assess the impact of the COVID-19 pandemic on HBV infection, we used monthly information and compared 2020-2022 with 2019.

The Joinpoint analysis showed that in Poland between 2005 and 2021, there were pronounced decreasing trends of acute HBV infection, and during the pandemic period, acute HBV infection dramatically decreased (annual percent change, APC2019-2021 for men -57.65%, and women -42.10%, both ptrend < 0.05). There was a fluctuation in trends for chronic HBV infection, shifting from positive to negative in both genders in 2016, and over the pandemic, there were decreasing trends (APC2019-2021 for men -26.94% and women -28.96%, both ptrend < 0.05). From March to July 2022, the value of the diagnosis rate of HBV infection was lower compared to the respective months in 2019, but from September to December 2022, the rate changes were positive. Mortality due to HBV infection decreased in both genders, mainly within the 2005-2019 period.

During the COVID-19 pandemic, a sharp decrease in HBV diagnosis rates in Poland, especially in acute cases, was observed. However, trends of hepatitis B infection require further monitoring. It is necessary to introduce a national screening program that also encompasses the population of migrants and improve the linkage to care.

The management of patients with chronic hepatitis B (CHB) is complex and spans multiple medical specialties. As a result of this complexity, patients with CHB often do not receive adequate monitoring including hepatocellular carcinoma (HCC) surveillance with abdominal ultrasonography. Previous studies have identified multiple factors associated with decreased HCC surveillance. We aimed to identify the impact of race and sex on HCC surveillance in patients with CHB.

We performed a single health system chart review between January 2018 and January 2022. Differences between sex and race were evaluated using the Chi-square test and Fisher's exact test, and continuous variables were analyzed using analysis of variance (ANOVA).

A total of 248 patient records between January 2018 and January 2022 were evaluated. In total 37% of females were adequately screened for HCC in any of the 6-month time frames compared to 26% of males. During the coronavirus disease 2019 (COVID-19) surge, surveillance rates were reduced in both men and women. During the first 6 months of the COVID-19 surge, there was a significant difference in screening between men and women (19% vs. 35%, P = 0.026). There was a decrease in HCC screening across all races during the COVID-19 surge; however, no significant difference when comparing races was found.

Men received less HCC surveillance compared to women. These differences were more pronounced during the COVID-19 pandemic surge. Obtaining appropriate surveillance is important and retrospective evaluations can help us determine the presence of health-related social needs so that progress can be made toward achieving health equity.

Viral gastroenteritis is the most common viral illness that affects the gastrointestinal (GI) tract, causing inflammation and irritation of the lining of the stomach and intestines. Common signs and symptoms associated with this condition include abdominal pain, diarrhea, and dehydration. The infections commonly involved in viral gastroenteritis are rotavirus, norovirus, and adenovirus, which spread through the fecal-oral and contact routes and cause non-bloody diarrhea. These infections can affect both immunocompetent and immunocompromised individuals. Since the pandemic in 2019, coronavirus gastroenteritis has increased in incidence and prevalence. Morbidity and mortality rates from viral gastroenteritis have declined significantly over the years due to early recognition, treatment with oral rehydration salts, and prompt vaccination. Improved sanitation measures have also played a key role in reducing the transmission of infection. In addition to viral hepatitis causing liver disease, herpes virus, and cytomegalovirus are responsible for ulcerative GI disease. They are associated with bloody diarrhea and commonly occur in im-munocompromised individuals. Hepatitis viruses, Epstein-Barr virus, herpesvirus 8, and human papillomavirus have been involved in benign and malignant diseases. This mini review aims to list different viruses affecting the GI tract. It will cover common symptoms aiding in diagnosis and various important aspects of each viral infection that can aid diagnosis and management. This will help primary care physicians and hospitalists diagnose and treat patients more easily.

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self-organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long-term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large-scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic infection and liver cancer has been clearly reported. The carcinogenic capacity of HBV has been reported for other solid tumors, but the largest number of studies focus on its possible lymphomagenic role. To update the correlation between HBV infection and the occurrence of lymphatic or hematologic malignancies, the most recent evidence from epidemiological and in vitro studies has been reported. In the context of hematological malignancies, the strongest epidemiological correlations are with the emergence of lymphomas, in particular non-Hodgkin's lymphoma (NHL) (HR 2.10 [95% CI 1.34-3.31], p=0.001) and, more specifically, all NHL B subtypes (HR 2.14 [95% CI 1.61-2.07], p<0.001). Questionable and unconfirmed associations are reported between HBV and NHL T subtypes (HR 1.11 [95% CI 0.88-1.40], p=0.40) and leukemia. The presence of HBV DNA in peripheral blood mononuclear cells has been reported by numerous studies, and its integration in the exonic regions of some genes is considered a possible source of carcinogenesis. Some in vitro studies have shown the ability of HBV to infect, albeit not productively, both lymphomonocytes and bone marrow stem cells, whose differentiation is halted by the virus. As demonstrated in animal models, HBV infection of blood cells and the persistence of HBV DNA in peripheral lymphomonocytes and bone marrow stem cells suggests that these cellular compartments may act as HBV reservoirs, allowing replication to resume later in the immunocompromised patients (such as liver transplant recipients) or in subjects discontinuing effective antiviral therapy. The pathogenetic mechanisms at the basis of HBV carcinogenic potential are not known, and more in-depth studies are needed, considering that a clear correlation between chronic HBV infection and hematological malignancies could benefit both antiviral drugs and vaccines.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.

Due to the complexity and heterogeneity of hepatocellular carcinoma, the existing clinical staging criterias are insufficient to accurately reflect the tumor microenvironment and predict the prognosis of HCC patients. Aggrephagy, as a type of selective autophagy, is associated with various phenotypes of malignant tumors.

This study aimed to identify and validate a prognostic model based on aggrephagy-related LncRNAs to assess the prognosis and immunotherapeutic response of HCC patients.

Based on the TCGA-LIHC cohort, aggrephagy-related LncRNAs were identified. Univariate Cox regression analysis and lasso and multivariate Cox regression were used to construct a risk-scoring system based on eight ARLs. CIBERSORT, ssGSEA, and other algorithms were used to evaluate and present the immune landscape of tumor microenvironment.

The high-risk group had a worse overall survival (OS) than the low-risk group. Patients in the high-risk group are more likely to benefit from immunotherapy because of their high infiltration level and high immune checkpoint expression.

The ARLs signature is a powerful predictor of prognosis for HCC patients, and the nomogram based on this model can help clinicians accurately determine the prognosis of HCC patients and screen for specific subgroups of patients who are more sensitive to immunotherapy and chemotherapy.

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by the environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas. FDA-approved drug library screen identified pitavastatin as an effective IL-33 inhibitor by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevented chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. IRF3-IL-33 axis was highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlated with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3 signaling pathway suppresses IL-33 expression and cancer-prone chronic inflammation. Statins present a safe and effective therapeutic strategy to prevent chronic inflammation and its cancer sequela.

To investigate the efficacy of precise hepatectomy in the treatment of patients with intermediate and advanced hepatocellular carcinoma and analyze the risk factors affecting prognosis.

Totally 104 patients with intermediate and advanced hepatocellular carcinoma from January 2018 to January 2019 were enrolled in this retrospective analysis. Of these, four patients lost to follow-up. Logistic regression was conducted to explore the odds ratio (OR) and 95% confidence interval (CI).

Compared with the control group, the precise hepatectomy decreased intraoperative blood loss (331.2928.91 to 203.29 ± 29.34 ml), operation time (198.29 ± 19.38 to 150.28 ± 18.27 min), perioperative blood transfusion volume (376.22 ± 25.93 to 228.29 ± 22.19 ml) (all P < 0.001). Logistic regression analysis of study group showed that hepatitis B infection (OR  = 1.746; 95% CI, 1.068-2.976), P  =  0.021, Child-Pugh classification (OR  =  2.319; 95% CI, 1.428-3.213), P < 0.001, Eastern Cooperative Oncology Group (ECOG) score (OR  =  2.287; 95% CI, 1.098-3.876; P  =  0.013) and Barcelona-Clinic Liver Cancer (BCLC) staging (OR = 2.029; 95% CI, 1.086-3.671; P = 0.022) were independent risk factors for prognosis of the precise hepatectomy.

Hepatitis B virus infection, Child-Pugh grade, ECOG score and BCLC staging grade were the independent risk factors affecting the prognosis of precise hepatectomy.

The incidence of liver cancer is continuously rising where hepatocellular carcinoma (HCC) remains the most common form of liver cancer accounting for approximately 80-90% of the cases. HCC is strongly prejudiced by the tumor microenvironment and being an inflammation-associated condition, the contribution of various immune mechanisms is critical in its development, progression, and metastasis. The tumor immune microenvironment is initially inflammatory which is subsequently replenished by the immunosuppressive cells contributing to tumor immune escape. Regardless of substantial advancement in systemic therapy, HCC has poor prognosis and outcomes attributed to the drug resistance, recurrence, and its metastatic behavior. Therefore, currently, new immunotherapeutic strategies are extensively targeted in preclinical and clinical settings in order to elicit robust HCC-specific immune responses and appear to be quite effective, extending current treatment alternatives. Understanding the complex interplay between the tumor and the immune cells and its microenvironment will provide new insights into designing novel immunotherapeutics to overcome existing treatment hurdles. In this review, we have provided a recent update on immunological mechanisms associated with HCC and discussed potential advancement in immunotherapies for HCC treatment.

HCC is a major health concern worldwide. PKC gamma, a member of the conventional PKC subclass, is involved in many cancer types, but the protein has received little attention in the context of single nucleotide polymorphisms and HCC. Therefore, the study aims to investigate the association of PKC gamma missense SNP with HCV-induced hepatocellular carcinoma.

The PKC gamma nsSNPs were retrieved from the ENSEMBL genome browser and the deleterious nsSNPs were filtered out through involvingPredictSNP2, CADD, DANN, FATHMM, FunSeq2 and GWAVA. Among the filtered nsSNPs, nsSNP rs1331262028 was identified to be the most pathogenic one. Through involving I-TASSER, ProjectHOPE, I-Mutant, MUpro, mCSM, SDM, DynaMut and MutPred, the influence of SNP rs1331262028 on protein structure, function and stability was estimated. A molecular Dynamic simulation was run to determine the conformational changes in mutant protein structure compared to wild. The blood samples were collected for genotyping analysis and for assessing ALT levels in the blood.

The study identified for the first time an SNP (rs1331262028) of PRKCG to strongly decrease protein stability and induce HCC. The RMSD, RMSF, and Rg values of mutant and wild types found were significantly different. Based on OR and RR values of 5.194 and 2.287, respectively, genotype analysis revealed a higher correlation between the SNP homozygous wild Typeform, AA, and the disease while patients with genotype AG have higher viral load.

Outcomes of the current study delineated PKC gamma SNP rs1331262028 as a genetic marker for HCV-induced HCC that could facilitate disease management after further validation.

The purpose of this study was to investigate the association of PNPLA3 single nucleotide polymorphisms (SNPs) (rs738409 C > G, rs3747207 G > A, rs4823173 G > A, and rs2896019 T > G) with hepatocellular carcinoma (HCC) susceptibility.

This case-control study included 484 HCC patients and 487 controls. Logistic regression analysis was performed to study the associations of PNPLA3 gene polymorphisms with HCC susceptibility, and odds ratios with their corresponding 95% confidence intervals were calculated to evaluate these correlations.

In the overall analysis, we found that the G allele (OR = 1.25, 95% CI = 1.04-1.50, p = 0.018, false discovery rate (FDR)-p = 0.035) and GG genotype (OR = 1.59, 95% CI = 1.06-2.39, p = 0.024, FDR-p = 0.048) of rs2896019 were significantly associated with increased HCC susceptibility. In stratified analysis, we found that all four SNPs were related to increased HCC susceptibility in subjects aged > 55 years. In haplotype analysis, the GAAG haplotype was significantly associated with increased HCC susceptibility (OR = 1.25, 95% CI = 1.03-1.53, p = 0.023, FDR-p = 0.046). Besides, we noticed that rs738409 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.007), and HCC patients with the GG genotype had a higher level of AFP.

Our study suggested that PNPLA3-rs2896019 was significantly associated with an increased susceptibility to HCC.

Transarterial chemoembolization (TACE) is one of the locoregional treatments for intermediate-stage hepatocellular carcinoma (HCC). Multidetector computed tomography (MDCT) is a widely used diagnostic tool for HCC. It can also evaluate tumor size, tumor number, and tumor invasion. This study aimed to determine the median survival time in intermediate-stage HCC patients who underwent TACE and to find out  prognostic factors influencing patients' survival time after TACE.

A computerized search of medical record database in Maharaj Nakorn ChiangMai Hospital from January 2016 to December 2019 revealed 187 intermediate-stage HCC patients who received TACE as the first-line treatment.

The median survival time of patients in this study was 9.9 months (95% CI: 8.3-11.6). The patients with aspartate aminotransferase-to-platelet ratio (APRI) less than 0.5 had a significantly better median survival time as compared with patients with APRI ratio more than 0.5; (13.2 months versus 9.9 months, p-value < 0.05). Univariate and multivariate Cox regression analysis demonstrated that tumor number > 7 and tumor size > 5 centimeters (cm) could be considered as independent parameters predicting poor overall survival time in the sufferers (HR 2.64 95%CI 1.68-4.15 and HR 2.38 95%CI 1.32-4.31, respectively).

Based on our findings, patients with intermediate-stage HCC who received TACE had a lower median survival time compared to previous studies. However, we identified APRI less than 0.5, tumor size less than 5 cm, and tumor number less than 7 as prognostic factors improving survival time in intermediate-stage HCC patients.

Hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and a leading cause of cancer-related death globally. HCC is associated with an indolent clinical presentation, resulting in frequent advanced stage diagnoses where surgical resection or transplant therapies are not an option and medical therapies are largely ineffective at improving survival. As such, there is a critical need to identify and enhance primary prevention strategies to mitigate HCC-related morbidity and mortality. Obesity is an independent risk factor for the onset and progression of HCC. Furthermore, obesity is a leading cause of nonalcoholic steatohepatitis (NASH), the fasting growing etiological factor of HCC. Herein, we review evolving clinical and mechanistic associations between obesity and hepatocarcinogenesis with an emphasis on the therapeutic efficacy of prevailing lifestyle/behavioral, medical, and surgical treatment strategies for weight reduction and NASH reversal.

The emergence of novel immunotherapies, such as immune-checkpoint inhibitors has changed the landscape of systemic cancer treatment. In hepatocellular carcinoma (HCC) patients, despite initial enthusiasm, the proportion of responders to immune-checkpoint inhibitors remains low. We provide a brief update of this rapidly evolving field, with specific focus on the development in the field of predictive factors and the immunomodulation induced by locoregional therapies.

Even if the immune contexture of HCC before the treatment remains the most promising predictive marker for response to immunotherapies, recent findings show that the cause of HCC may have also a key role. Specific inflammatory mechanisms induced by NASH may result in limited efficacy of immunotherapy compared with viral HCC. Other recent findings showed that percutaneous ablations are responsible for intratumoral immune changes and systemic immune system activation that may help to prevent recurrence when combined with immunotherapies. In case of multifocal HCC, transarterial therapies (TACE and SIRT) may help to turn a cold tumor type to a hot tumor type and could be associated with immune-checkpoint inhibitors to improve outcomes.

The future HCC management will focus on patient stratification for specific immunotherapies depending on the signature and cause of HCC and the best combined approaches in which locoregional therapies may play a pivotal role.