Subscribe

Radiation-based local-regional therapies for hepatocellular carcinoma (HCC) have gained wide acceptance due to promising rates of tumor response, survival, and safety profiles. After treatment, it is important to assess tumor response to determine further management, patient prognosis, and endpoint outcomes for clinical trials. To standardize imaging interpretation and reporting of HCC response to local-regional treatment, a few imaging-based response assessment systems were developed. Two of them have emerged as the most used: the Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Algorithm (LR-TRA) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST). While these systems have been validated for the assessment of response to ablative locoregional therapies, assessment of response to radiation-based therapies can be challenged by persistent or evolving imaging features and is still an area of active research. Following the advances in technology and a better understanding of tumor biology that allowed for the increased application of radiation-based local-regional therapies for the treatment of HCC, research is still needed to address the limitations of current imaging criteria for assessing tumor response to these novel techniques. In this review, we describe radiation-based liver-directed treatment options, examine imaging criteria for assessing treatment response, discuss practical limitations and gaps in knowledge when applying these response criteria, and address future directions that may help to improve accuracy and outcomes when assessing response to radiation-based HCC treatment. LESS      Full article

Artificial intelligence (AI) is an innovative discipline in medicine, impacting both hepatology and hepato-pancreato-biliary surgery, ensuring reliable outcomes because of its repeatable and efficient algorithms. A considerable number of studies about the efficiency of AI in the management of hepatocellular carcinoma (HCC) have been published. While its diagnostic role is well recognized, providing large amounts of quantitative radiological HCC features, its use in HCC treatment is still debated. Innovative use of AI may help to select the best approach for each patient as it is able to predict the outcomes after resection and/or other treatments. In this review, we assess the role of AI in selecting the best therapeutic option and predicting long-term risks after surgical or interventional treatments for HCC patients. Further studies are needed to consolidate AI applications. LESS      Full article

Human immunodeficiency virus (HIV) and hepatitis-B virus (HBV) infections are weighty public health challenges, especially in the African continent. The direct carcinogenic effect of HBV means that it remains a potent cause of early-onset hepatocellular carcinoma (HCC) in Sub-Saharan Africa (SSA), where it causes significant morbidity and mortality. The presence of HIV infection in HBV-infected patients poses a complicating factor, as coinfection has been shown to hasten the progression of liver disease to cirrhosis and HCC, and often resulting in early-age hepatocarcinogenesis with consequent late diagnosis and lower survival. In this review, we discuss this unique conundrum, the epidemiology of HIV-HBV coinfection in SSA, its effect on liver disease and development of HCC, as well as practices and barriers to HCC surveillance in this distinct population. We propose a way forward to curb this considerable health burden focusing on reduction of disease stigma, the need for easy-to-measure biomarkers, and implementation of large prospective studies in this population. LESS      Full article

Over the last decade, we have been facing a new aetiology responsible for the development of HCC - the non-alcoholic fatty liver disease (NAFLD). The prevalence of HCC development in this group is higher than that observed in the general population and in non-cirrhotic subjects with other causes of liver disease. Conventional ultrasound (US) is the first-line tool for HCC surveillance, but, in this population, it has a decreased diagnostic accuracy due to several particular features, including obesity and steatosis. Contrast-enhanced ultrasound (CEUS) appeared as a new branch of US due to its ability to depict the vascular architecture of all types of focal lesions (FLs). Nevertheless, CEUS has several limitations besides those inherited from US, which renders this method unreliable as the first-line HCC diagnostic tool and for HCC staging. Artificial intelligence eliminates operator limitations, which has led to an increased sensitivity and specificity of US. However, this approach is still in its early stages and more data are needed. Consequently, the purpose of the current study is to highlight the strengths and limits of US, along with its alternatives to HCC screening in NAFLD population. LESS      Full article

Nonalcoholic fatty liver disease (NAFLD) is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis (NASH), which may progress into cirrhosis and hepatocellular carcinoma (HCC). HCC represents the most common liver cancer, and it is a leading cause of death worldwide with an increasing trend for the future. Due to late diagnosis, non-responsiveness to systemic therapy, and high cancer heterogeneity, the treatment of this malignancy is challenging. To date, liver biopsy and ultrasound (US) are the gold standard procedures for HCC diagnosis and surveillance, although they are not suitable for mass screening. Therefore, it is impelling to find new, less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and recurrence. Common and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor onset. Furthermore, epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic conditions. The severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs (ctDNAs), microRNAs (miRNAs), and noncoding RNAs (ncRNAs), which are involved in several pathological processes that feature cancer, including cell growth, survival, and differentiation, thus representing appealing biomarkers for HCC. Therefore, this review discusses the current options for HCC surveillance, focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management. LESS      Full article

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder worldwide. It comprises a spectrum of conditions that range from steatosis to non-alcoholic steatohepatitis, with progression to cirrhosis and hepatocellular carcinoma. Currently, there is no FDA-approved pharmacological treatment for NAFLD. The pathogenesis of NAFLD involves genetic and environmental/host factors, including those that cause changes in intestinal microbiota and their metabolites. In this review, we discuss recent findings on the relationship(s) of microbiota signature with severity of NAFLD and the role(s) microbial metabolites in NAFLD progression. We discuss how metabolites may affect NAFLD progression and their potential to serve as biomarkers for NAFLD diagnosis or therapeutic targets for disease management. LESS      Full article

Hepatocellular carcinoma (HCC) is the fifth most widespread cancer responsible for one fourth of cancer-related deaths globally. Persistent infection with hepatitis B virus (HBV) remains the main cause of HCC summing up to 50% of its causative etiology. Our recent studies, supported by findings from others, uncovered that HBV and its close relative woodchuck hepatitis virus (WHV) integrate into hepatocyte genome almost immediately, hence in minutes after infection. Retrotransposons and genes with translocation potential were found to be frequent sites of HBV insertions, suggesting a mechanism of HBV DNA spread across liver genome from the earliest stages after virus invasion. Many other genes were identified as the sites of early hepadnavirus merges in human hepatocyte-like lines infected de novo with HBV and in natural woodchuck WHV infection model. It was uncovered that head-to-tail joins (HTJs) prevail among the earliest virus-host fusions, implying their formation via the non-homologous-end-joining (NHEJ) pathway. Overlapping homologous junctions resulting from the micro-homology-mediated-overlapping-joining (MHMOJ) were rarely detected. Formation of the initial HTJs coincided with strong induction of reactive oxygen species (ROS) and transient appearance of inducible nitric oxide (iNOS). This was accompanied by cell DNA damage and activation of the poly(ADP-ribose) polymerase 1 (PARP1)-mediated host DNA repair machinery, which may explain predominant HTJ format of the first virus-host fusions. Identification of initial integration sites and resulting alterations in hepatocyte phenotype may pave a way to discovery of reliable markers of HBV-triggered HCC, including HCC resulting from occult HBV infection. Our research strongly argues that HBV is an ultimate human carcinogen capable of initiation of a pro-oncogenic process immediately after first contact with a susceptible host. LESS      Full article

Mutations involving CTNNB1, the gene encoding beta-catenin, and other molecular alterations that affect the Wnt/beta-catenin signaling pathway are exceptionally common in hepatocellular carcinoma. Several of these alterations have also been associated with scarcity of immune cells in the tumor microenvironment and poor clinical response to immune checkpoint inhibitor therapy. In light of these associations, tumor biomarkers of beta-catenin status could have the potential to serve as clinical predictors of immunotherapy outcome. This editorial review article summarizes recent pre-clinical and clinical research pertaining to associations between beta-catenin activation and diminished anti-tumor immunity. Potential non-invasive biomarkers that may provide a window into this oncogenic mechanism of immune evasion are also presented and discussed. LESS      Full article

Liver disease accounts for approximately 2 million deaths per year worldwide with cirrhosis, viral hepatitis, and malignancy being the most common causes. Consequently, the regenerative capacity of the liver is a topic of extreme interest in the search for curative therapies to end-stage liver disease. Mesenchymal stem cells (MSCs) have emerged as a promising new therapy for hepatic regeneration. MSCs have multiple properties that make them an appropriate treatment option for liver disease including easy accessibility, targeted migration, immunomodulatory potential and antifibrotic/antioxidant effects. Additionally, MSCs have potential clinical applications in acellular therapy and tissue engineering. Liver regeneration with concurrent attenuation of liver injury makes MSCs a compelling therapeutic target in the setting of severe liver disease. This review outlines the mechanisms of MSC-driven liver regeneration and suggests potential clinical applications. LESS      Full article