Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.

Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections are recorded annually, especially in poorly resourced places which have lax vaccination policies. Again, as HBV has no cure and chronic infection is lifelong, vaccines cannot help those already infected. Studies to thoroughly understand the HBV biology and pathogenesis are limited, leaving much yet to be understood about the genomic features and their role in establishing and maintaining infection. The current knowledge of the impact on disease progression and response to treatment, especially in hyperendemic regions, is inadequate. This calls for in-depth studies on viral biology, mainly for the purposes of coming up with better management strategies for infected people and more effective preventative measures for others. This information could also point us in the direction of a cure. Here, we discuss the progress made in understanding the genomic basis of viral activities leading to the complex interplay of the virus and the host, which determines the outcome of HBV infection as well as the impact of coinfections.

Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID\'s relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients\' heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.

Treatment of hepatic diseases presents a significant challenge due to their diverse nature. Ginsenosides, bioactive compounds derived from the root of Panax ginseng and widely used in traditional Chinese medicine, offer multifaceted protection to various organs in the body. Their versatile effects, including antioxidant, anti-inflammatory, anti-apoptotic and more, make them a promising approach for addressing hepatic disorders. This review explores the intricate molecular mechanisms and properties of ginsenosides in the prevention and treatment of liver ailments, from mild conditions to severe damage and liver fibrosis. Given the increasing prevalence of hepatic disorders, this article sheds light on the significant pharmaceutical potential of ginsenosides in the realm of hepatic disease management.

Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted via the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection via nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.

Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 (p = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 (p = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial for improving the therapeutic options and reducing the disease-related mortality.
OBJECTIVE: To investigate serum N-glycomics as diagnostic markers for HCC.
METHODS: We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N-glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers.
RESULTS: Of the 48 articles included, 11 evaluated the utility of N-glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha-fetoprotein (AFP), kininogen (Kin), α-1-antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post-translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics-based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92-0.97. However, these were based on single studies with limited sample sizes and should therefore be validated.
CONCLUSIONS: Alterations in serum N-glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible.

Hepatitis B virus and hepatitis C virus are the hepatitis subtypes that most commonly induce immune thrombocytopenia (ITP). Although the pathogenesis of viral hepatitis-associated ITP remains unclear, it may involve antibody cross-reactivity due to molecular mimicry, the formation of virus-platelet immune complexes, and T cell-mediated suppression of bone marrow hematopoiesis. Moreover, there is significant correlation between platelet count and the severity of viral hepatitis, the risk of progression to liver cirrhosis, and clinical prognosis. However, treatment of viral hepatitis-associated ITP is hindered by some antiviral drugs. In this review, we summarize research progress to date on the pathogenesis and treatment of viral hepatitis-related ITP, hoping to provide a reference for clinical diagnosis and treatment.

Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients\' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.

OBJECTIVE: Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels.
METHODS: PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups.
RESULTS: Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval).
CONCLUSIONS: Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.