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.