Hepatitis C viral infections present a significant global health challenge, carrying substantial economic implications. These infections manifest in various clinical forms, including acute and chronic hepatitis, liver cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC emerge as the primary contributors to mortality in hepatitis virus-induced liver diseases. To alleviate the public health impact of this disease, it is imperative to enhance the diagnosis and treatment rates among hepatitis C virus-infected individuals. The advent of direct-acting antivirals (DAAs), especially pan-genotypic regimens such as a combination of sofosbuvir and velpatasvir, has shown remarkable progress in achieving hepatitis C cure. However, potential obstacles, such as drug adverse effects and resistance-associated substitutions (RASs), warrant attention. Managing chronic hepatitis C (CHC) requires tailored treatment plans, vigilant monitoring, and judicious re-treatment strategies.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and its death rate is rising faster than that of any other cancer, while we still lack effective treatments. The increasing incidence of liver cancer in western countries is closely associated with the growing prevalence of metabolic dysfunction-associated steatohepatitis (MASH) linked to metabolic diseases. While the contribution of lipids in the progression of MASH pathogenesis and its progression to HCC is well recognized, the specific contribution of cholesterol is subject to controversy. The liver plays a central role in cholesterol metabolism, where the majority of its biosynthesis, storage, excretion, recycling, and conversion into bile acids occur. Moreover, cholesterol is implicated in numerous hepatocyte cellular processes, encompassing endoplasmic reticulum function, formation of lipid microdomains in the plasma membrane, metabolism of lipoproteins, and mitochondrial function and performance. Therefore, it is not surprising that cholesterol plays key roles in initiation, promotion, and survival of HCC cells and there are several lines of evidence pointing to that cancer cells are subverting cholesterol metabolism to foster their proliferation and survival through various mechanisms. This narrative review provides a concise overview of the physiological and pathological roles of cholesterol in the transition from healthy hepatocytes to HCC, in the context of MASH. Gaining further understanding of how hepatic cancer cells disrupt cholesterol homeostasis and how these perturbations impact cancer progression will facilitate the identification of novel and more effective cancer treatment strategies in this complex and devastating disease.

Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

The most common type of liver cancer is hepatocellular carcinoma (HCC) causes a lower survival rate even after systemic treatment. Previous studies have shown evidence that various molecular and epigenetic mechanisms are involved in the transition of HCC from normal liver cells. Epigenetics plays an important role in maintaining genomic stability in normal liver cells. Apart from the mutation of genes, epigenetic factors are involved in HCC progression. miRNA tends to be a major epigenetic factor involved in regulating major cell cycle pathways. miRNA regulates the HCC progression by inhibiting the major apoptotic pathways and favors angiogenesis and tumor microenvironment. Apart from regulating major pathways, miRNA appears to regulate tight junction integrity. Tight junction proteins appear to be strong barrier proteins involved in cell adhesion and integrity. Disturbance in cell adhesion and integrity leads to the major dysregulation of cell cycle resulting in cancer progression. Moreover, dysregulation of tight junction integrity was observed in the pathogenesis of HCC. The regulation of tight junction proteins via miRNA were studied in various diseases. Here, we discussed the regulation of tight junction proteins via miRNA in HCC progression. This review may focus on the significance of miRNA in cellular function and its role in regulating tight junction proteins that impact in HCC progression which opens a new approach to develop a new diagnostic marker for an early detection of HCC and novel therapeutic approach against HCC.

It is generally accepted that eradication of Helicobacter pylori (H. pylori) infection may reduce the risk of the development of gastric cancer. Recommendations for global generalized tests and treat all individuals detected positive for H. pylori infection are currently proposed. However, the bacterium is commensal and harmless for the vast majority of the infected population. Moreover, eradication may have detrimental consequences in several groups of patients. In the present review, the current epidemiological data and recommendations for eradication in connection with the possible beneficial effects of the colonization with H. pylori in diseases such as asthma and allergies or chronic gastro-intestinal disorders such as inflammatory bowel disease and Barrett’ esophagus are presented the problems with increasing antibiotic resistance were also examined. Specific groups of patients where eradication of H. pylori may be necessary and endoscopic surveillance is advised were identified. Finally, based on the paradox of high H. pylori prevalence and low gastric risk as reported for areas of Africa, Asia, South America, and Greece, alternatives that may replace the widespread eradication of H. pylori with equal if not better results and more prudent use of the available financial resources are proposed. Mediterranean diets and alcohol and smoking reduction are among the well documented alternatives.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies.

This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude hepatocellular carcinoma (HCC). It turns out to be a case of portal vein thrombosis and hepatic pseudo-infarction. It is better to postpone the therapeutic intervention, whether surgical or chemotherapeutic, in cases not confirmed to be HCC for at least 3 months to avoid misdiagnosis of hepatic pseudo-infarction.

The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The reasons for this organ-specific metastatic process have been investigated for decades. This review first provides an overview of recent breakthroughs in this field, introducing intercellular communication between circulating tumor cells and the heterogeneous cell populations of the liver, and modifications to the extracellular matrix (ECM). Subsequently, to improve the understanding of the molecular mechanisms involved in the metastasis of colorectal cancer to the liver, the second leading cause of cancer-related mortality, the recent literature on this question was analyzed. Among the various parameters involved, the mechanisms behind the activation of hepatic stellate cells, proteins inducing ECM remodeling, specific genomic features of liver metastases, metabolic rewiring, and characteristics of stromal-enriched microenvironments were discussed. To provide more insights into the molecular determinants of liver metastatic colonization, important findings reported on a set of mitochondrial proteins were addressed, the relative abundance of which changed in the liver during the progression stage of an aggressive experimental model of peritoneal malignant mesothelioma in immunocompetent rats. Based on previous studies cross-comparing the liver proteomes from curcumin-treated tumor-bearing rats/untreated tumor-bearing rats/normal rats, data from the literature were reviewed for 25 mitochondrial proteins of interest. Their role in lipid metabolism, heme biosynthesis, the electron transport chain, small molecule transport, mitochondrial dynamics, the tricarboxylic acid cycle, and protection against oxidative stress were analyzed in the context of both cancer and non-malignant liver diseases.