Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the third most common cause of cancer-related death. One of the major problems faced by researchers and clinicians in this area is the lack of reliable disease biomarkers, which would allow for an earlier diagnosis, follow-up or prediction of treatment response, among others. In this regard, the “HCC circulome”, defined as the pool of circulating molecules in the bloodstream derived from the primary tumor, represents an appealing target, the so called liquid biopsy. Such molecules encompass circulating tumor proteins, circulating tumor cells (CTCs), extracellular vesicles (EVs), tumor-educated platelets (TEPs), and circulating tumor nucleic acids, namely circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA). In this article, we summarize recent findings highlighting the promising role of liquid biopsies as novel potential biomarkers in HCC, emphasizing on its clinical performance.

Viscoelastic tests in liver disease: where do we stand now?

A correct diagnosis of hepatocellular carcinoma (HCC) in cirrhotic patients with focal liver lesions is one of the most important issues nowadays. Probably one of the oldest debates in the hepatology community is whether to perform liver biopsy (LB) in all cirrhotic patients with focal liver lesions. We now face a time when oncology is moving towards personalized medicine. According to the current European Association for the study of Liver diseases HCC guidelines, LB has only a minor role in the management of HCC. However, the current recommendations were made more than five years ago. As time has passed, the development of high-throughput molecular technologies has helped reveal the main molecular mechanism involved in HCC development and progression. Several subtypes of HCC, with both molecular and histological characterization, have been described. Importantly, some of these subtypes have prognostic impact. In the context of personalized treatment, the role of LB will be carefully reconsidered. Until then, it is mandatory to know the various techniques of LB, their performances, complications and limitations. The balance of risk and benefit defines many of the decisions that we make as providers of medical care. In this review, we discuss not only the risks associated with LB, but also the benefits of biopsy in various clinical scenarios. Not long from now, the role of LB will be reconsidered. It is possible that we will go back in time and once again use biopsy for HCC diagnosis. Then again, we may move back to the future to try to improve the use of liquid biopsy in the follow-up of HCC patients after various treatment modalities.

Extracellular vesicles, comprising exosomes, microvesicles, and apoptotic bodies, represent an emerging field in disease diagnostics and prognosis. They can be isolated from peripheral blood of patients as well as from other body fluids and can therefore be considered a minimally invasive liquid biopsy screening tool. Especially their surface antigen composition can reveal information about disease backgrounds. For several liver diseases, including fatal hepatocellular and cholangiocellular carcinoma as well as other nonmalignant liver disorders such as nonalcoholic fatty liver disease, alcoholic hepatitis, or acute liver failure, it has been shown that extracellular vesicle (EV) surface profiling can be useful for disease diagnosis and prognosis. This review focuses on latest advances in these areas to improve liver disorder detection and management. Additionally, the authors will discuss possible therapeutic applications of EVs in liver diseases, which might be a potent treatment option in the future.

Aims: To report on the long-term impact of tumor and non-tumor related parameters on local recurrence, distant recurrence and survival in patients with naïve or recurrent type hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA).Methods: We performed 240 RFA sessions on 133 patients with 156 HCC nodules developed on a background of liver cirrhosis and analyzed the outcomes.Results: Contrast-enhanced ultrasound performed one month after RFA showed complete ablation in 119 out of 133 (89.65%) patients. With a median follow-up of 46 months, 3-, 5- and 7-year survival rates were 61.7%, 35.7%, and 22.6%, respectively. Previous ethanol injection and histological grade were significantly related to local tumor progression. Child-Pugh class, incomplete ablation, histological grade, previous ethanol injection, alpha-fetoprotein level before the treatment, and local recurrence were all significantly related to distant recurrence. Multivariate analysis demonstrated that age, Child-Pugh class, distant recurrence and multiple incomplete ablations were significantly related to survival.Conclusion: Radiofrequency ablation could be locally curative for HCC, resulting in a survival longer than 7 years. Previous ethanol injection and incomplete ablations were strongly associated with poor outcomes.