This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy.

This randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3 months, while Group 2 (Zinc group, n = 25) received 50 mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration. Baseline and 3-month post-intervention assessments included evaluating serum levels of hyaluronic acid, transforming growth factor beta-1, and fibronectin. Furthermore, indices of liver fibrosis, such as the Fibrosis Index based on the 4 factors (FIB-4) and the Aspartate Transaminase-to-Platelet-Ratio Index (APRI), were calculated during these assessments.

At baseline, the two studied groups had no statistical difference in demographic and laboratory data. After treatment, serum zinc levels significantly increased in the zinc-treated group compared to the control group. Additionally, serum fibronectin and hyaluronic acid levels were significantly reduced in group 2 (zinc group) compared to group 1 (control group). Moreover, zinc group showed lower APRI scores than the control group after a 3-month follow-up period, but there was non-significant difference in FIB-4 scores between the two groups after treatment. Furthermore, total bilirubin levels were reduced after zinc therapy for 3 months.

Administering zinc sulfate could potentially serve as a safe and efficient therapeutic strategy for the management of hepatic fibrosis in individuals with chronic hepatitis C virus.

ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

Accurate and reliable diagnosis and monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) and expanding antifibrotic therapeutic options targeting reversibility of early-stage cirrhosis. This highlights the need to develop more refined and effective noninvasive techniques for the dynamic assessment of fibrogenesis and fibrolysis.

We conducted a literature review on PubMed, from 1 December 1970, to 1 November 2024, to evaluate and compare available blood-based and imaging-based noninvasive tools for hepatic fibrosis diagnosis and monitoring. Simple scores such as FIB-4 and NAFLD fibrosis score are suitable for excluding significant or advanced fibrosis, while tertiary centers should adopt complex scores and liver stiffness measurement as part of a secondary diagnostic and more comprehensive evaluation. Moreover, the advent of multiomics for high-resolution molecular profiling, and integration of artificial intelligence for noninvasive diagnostics holds promise for revolutionizing fibrosis monitoring and treatment through novel biomarker discovery and predictive omics-based algorithms.

The increased shift toward noninvasive diagnostics for liver fibrosis needs to align with personalized medicine, enabling more effective, tailored management strategies for patients with liver disease in the future.

Extracellular vesicles (EVs) are bilayer vesicles released by cells in the microenvironment of the liver including parenchymal and non-parenchymal cells. They are the third important mechanism in the communications between cells, besides the secretion of cytokines and chemokines and the direct cell-to-cell contact. The aim of this review is to discuss the important role of EVs in viral liver disease, as there is increasing evidence that the transportation of viral proteins, all types of RNA, and viral particles including complete virions is implicated in the pathogenesis of both viral cirrhosis and viral-related hepatocellular carcinoma. The biogenesis of EVs is discussed and their role in the pathogenesis of viral liver diseases is presented. Their use as diagnostic and prognostic biomarkers is also analyzed. Most importantly, the significance of possible novel treatment strategies for liver fibrosis and hepatocellular carcinoma is presented, although available data are based on experimental evidence and clinical trials have not been reported.

In the present issue of the World Journal of Hepatology, Ferrassi et al examine the problem of liver fibrosis staging in chronic hepatitis C. They identify novel biomarkers in an effort to predict accurate fibrosis staging with the aid of the metabolome of Hepatitis C patients. Overall I think Ferrassi et al took a different approach in identifying fibrosis biomarkers, by looking at the patients' metabolome. Their biomarkers clearly separate patients from controls. They can also separate out, patients with minimal fibrosis (F0-F1 stage) and patients with cirrhosis (F4 stage). Obviously, if these biomarkers were to be widely used, tests for all the important metabolites would need to be readily available for use in hospitals or outpatient setting and that may prove difficult and above all, costly. Nevertheless, this step could eventually lead to a metabolomic approach for novel biomarkers of Fibrosis. Obviously, it would need to be validated, but could represent a step towards the Holy Grail of Hepatology.

Viruses have evolved sophisticated mechanisms to manipulate host cell processes and utilize intracellular organelles to facilitate their replication. These complex interactions between viruses and cellular organelles allow them to hijack the cellular machinery and impair homeostasis. Moreover, viral infection alters the cell membrane's structure and composition and induces vesicle formation to facilitate intracellular trafficking of viral components. However, the research focus has predominantly been on the immune response elicited by viruses, often overlooking the significant alterations that viruses induce in cellular organelles. Gaining a deeper understanding of these virus-induced cellular changes is crucial for elucidating the full life cycle of viruses and developing potent antiviral therapies. Exploring virus-induced cellular changes could substantially improve our understanding of viral infection mechanisms.

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response. The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.