Chronic liver disease of various aetiologies with underlying cirrhosis is a serious cause of liver-related morbidity and mortality globally. The emerging role of non-invasive diagnostic/therapeutic tools in different stages of liver disease represents a challenge and an area of great interest for many researchers, which could differ in the clinical outcome of liver disease patients. Over a decade, several studies have evaluated the emerging role of circulating extracellular vesicles (EVs) as biomarkers and therapeutic targets in different liver diseases; They are small membrane-encapsulated particles that can act as potent vehicles via their cargos between different hepatic cell types and also between organs, because of their ability to transfer proteins, lipids, and nucleic acids to affect the recipient cells' related physiological functions. Hence, the issues related to the potential use of EVs as biomarkers in liver disease diagnosis, prognosis, and even to assess the response to treatment, have been handled in our review concluding that EVs have shown promising results as potential diagnostic tools and for further evaluation as therapeutic targets.

Liver transplantation (LT) represents a life-saving surgical procedure and is considered the current standard of care for the majority of patients having end-stage liver disease. As known, significant progress in organ preservation techniques, perioperative care, and strict immunosuppression protocols are associated with favorable patient/graft survival post-LT. Hence, proper evaluation of liver allograft-related complications among survivors has paid great attention, particularly the rejection sequel after LT. It is a seriously underestimated cause of allograft injury, which pushes researchers for understanding the exact pathogenesis of different types and proper time diagnosis for better management of such complications. However, it still represents a challenge because of the complexities related to diagnosis and histopathology. Hence, increasing clinical awareness with earlier diagnosis of post-LT rejection is essential through stimulating further studies. Therefore, our review will focus on the clinicopathological debates regarding liver allograft loss after transplantation.

Hepatocellular carcinoma is known to be a common primary liver malignancy and a serious leading cause of cancer-related mortality globally. Hence, ongoing recent advances in the genetic field regarding hepatocellular carcinoma paid researchers great attention to identifying various biomarkers to act as diagnostic and prognostic tools for the early detection of hepatocellular carcinoma and also developing targeted therapeutic agents that are indicated and available for advanced stages of hepatocellular carcinomas, however, their antitumor efficacy remains limited and under investigations. Therefore, our review summarized the genetic studies of liver cancer focusing on the somatic mutations, copy number variations, and epigenetic modifications that represent early alterations and oncodrivers in hepatocarcinogenesis, Moreover, the identification of genetic signatures and proteomic targets through hepatocellular carcinoma-related genome-wide screening, to show the ongoing clinical application of such analysis to facilitate diagnosis, prognosis and management of patients with hepatocellular carcinoma for a better outcome.