Hepatocellular carcinoma (HCC) is the fourth leading global cause of tumor-related mortality. HCC has a high prevalence in patients with chronic liver diseases, and it mostly results from cirrhosis caused by infection with blood-borne viruses. Despite the implementation of various diagnostic and prevention strategies, the rates of new HCC cases and mortality are increasing globally due to the aging and growth of the world population as well as their increased exposure to dominant risk factors like alcohol, hepatitis B and C, and clinical correlates of metabolic syndrome. Modeling studies indicate that sanitation practices, implementation of vaccination programs against hepatitis B, and expanded recognition and treatment of patients with chronic hepatitis B and C could greatly contribute to the eradication of viral hepatitis B and C. While the availability of generic antiviral drugs could partially overcome the bottleneck represented by the lack of resources in low and middle-income countries, where viral hepatitis is the leading cause of liver cancer, the enthusiasm for the prevention of liver cancer through antiviral therapy is mitigated by the risk of cancer in many patients who are treated late in the hepatitis course. The present work aimed to review in detail the various types, epidemiology, and carcinogenesis mechanisms of viral infections that are associated with a significantly increased risk for the development of HCC.

Worldwide, hepatocellular carcinoma (HCC) is a frequent complication of liver diseases and remains a major cause of cancer-related mortality. In addition, the prevalence of nonalcoholic steatohepatitis (NASH) as prerequisite of hepatocarcinogenesis, even in the absence of cirrhosis, is rising rapidly. The early detection of HCC has been crucial in improving the survival outcomes of those patients. However, in the mostly obese NASH population, diagnostic sensitivity of ultrasound-based HCC screening approaches is limited. On the other hand, biomarkers for HCC show promising potential to improve early detection, providing reproducible, investigator-independent results that can be used either alone or integrated with other biomarkers for scoring models. In the past, validation has been limited due to a lack of prospective longitudinal cohort studies. At present, large-scale retrospective phase-III- biomarker- development gives hope for the availability of biomarker-based screening approaches in the near future. This review focuses on the potential impact of biomarkers on surveillance strategies, potentially allowing for earlier HCC diagnosis.

Liver transplantation (LT) provides an excellent option for the long-term survival of patients with unresectable hepatocellular carcinoma (HCC) based on the Milan criteria. Despite careful selection of patients, HCC may still recur after LT, which represents the most important negative predictor of post-transplant survival. The growing demand for LT in HCC has led to the expansion of patient selection criteria, with a resultant increase in the risk of post-transplant HCC recurrence. Numerous tumor and host factors predict HCC recurrence. The morphological, histological, and serological characteristics of tumors in predicting HCC recurrence have been extensively studied. Furthermore, the type and duration of anticancer response before LT has also been considered a surrogate marker of tumor aggressiveness and is associated with the risk of recurrence. The demographic and clinical characteristics of recipients, as well as the type and duration of exposure to immunosuppressive therapy, represent the main host-related risk factors. Many studies have attempted to describe predictive models for the risk of HCC recurrence, considering evaluable parameters both before and after LT. Although many models have been proposed, relatively few have been externally validated on different patient populations. This paper aims to comprehensively summarize the available data on the predictive factors of HCC recurrence after LT, and to examine and discuss those that have been externally validated.

Portal vein thrombosis (PVT) is a common complication after splenectomy, causing a possible negative impact on the prognosis of patients with liver cirrhosis. However, the risk factors of PVT are not completely clear. Many factors are related to the occurrence of postoperative PVT, such as hemodynamic changes, splenomegaly, splenectomy, coagulation and anticoagulation disorder, liver cirrhosis, platelet count, D-dimer level, infection, inflammation, and other factors.Hemodynamic changes are mainly caused by thicker portal and splenic vein diameters, larger spleen, slower portal vein blood flow rate, lower portal vein pressure before and after surgery, etc. It is timely detection and advanced prevention that really matter in reducing PVT incidence and improving patient prognosis. We systematically reviewed the researches on the risk factors and therapies of PVTto provide useful information on a comprehensive understanding for researchers.

Aim: β-catenin activation is known to promote liver regeneration and play a role in the pathogenesis of liver cancer. Recently, we detected intranuclear inclusions (NI) in hepatocellular carcinoma (HCC) containing degenerated cell organelles and lysosomal proteins and delimited by a completely closed nuclear membrane. The presence of NI was positively associated with patient survival. The aim of the current study was to investigate a possible association between proteins of the Wnt/β-catenin pathway with NI morphology and survival.

Methods: We examined NI in 72 paraffin-embedded specimens of HCC. Immunohistochemistry (IHC) and immunofluorescence (IF) were performed to investigate the content and shape of NI. β-catenin gene (CTNNB1 ) mutations were analyzed by next generation sequencing.

Results: We detected the accumulation of β-catenin and glutamine synthetase (a target gene of β-catenin) proteins within NI. Further, we found immunopositivity for the lysine demethylase KDM2A in NI. KDM2A is known to be involved in β-catenin degradation. We detected significant associations between the presence of β-catenin and autophagy-associated proteins in NI. Double-IF revealed co-localization of β-catenin and p62 in the same NI. Kaplan-Meier survival analysis showed that the presence of NI containing KDM2A protein accumulations displayed a significant benefit in overall survival.

Conclusion: We detected accumulations of β-catenin and proteins associated with the Wnt/β-catenin pathway partly together with autophagy-associated proteins in the same inclusion. Our finding that KDM2A immunopositivity within NIs was associated with favorable clinical outcomes and suggests a biological significance of NI.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Epidemiological studies have not only shed light on the prevalence and incidence of the disease but have also unmasked important environmental risk factors, including the role of diabetes and dyslipidemia in disease pathogenesis. Genetic association studies have identified single nucleotide polymorphisms implicated in NAFLD-HCC, many of which are part of lipid metabolism pathways. Through these clinical studies and subsequently, translational and basic research, the role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in HCC prevention and treatment. In this review, we summarize the recent epidemiological studies describing the burden of NAFLD-HCC in different patient populations and countries. We discuss the genetic and environmental risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin. We also summarize what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of surveillance in NAFLD-HCC patients.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high mortality rate. Heterogeneity is the main biological characteristic of HCC, which manifests through the different biological behaviors of each phenotype and ultimately, affects patient prognosis and treatment efficacy. Various aggressive biological behaviors are considered to be associated with the poor prognosis of HCC patients including poor differentiation, microvascular invasion, intracellular fat accumulation, invasive growth, bile duct invasion or tumor thrombosis, and tumor spread and metastasis, and have been reported as prognostic biomarkers. In addition, HCC results from multifactor synergistic damage, and various factors related to genetics, molecular pathology and immunohistochemistry such as β-catenin, Ki67, cytokeratin-19, and epithelial cell adhesion molecule have an impact on HCC differentiation and prognosis. This article is an overview of the biological behaviors that lead to poor prognosis of HCC, and the roles of morphological and quantitative noninvasive imaging biomarkers in the evaluation and prediction of these behaviors. Some common biomarkers related to genetics, molecular pathology and immunohistochemistry are also briefly summarized. It is hoped that this review will provide clinicians and radiologists with an update on the development of liver imaging, and provide directions for the combination of radiology, genetics, molecular pathology and histopathology to better predict the prognosis of HCC patients.