Search Results (428)

Aflatoxins (AFs), harmful secondary metabolites produced by the genus Aspergillus, particularly Aspergillus flavus and Aspergillus parasiticus, are one of the best-known potent mycotoxins, posing a significant risk to public health. The primary type, especially aflatoxin B₁ (AFB₁), is a potent carcinogen associated with liver cancer, immunosuppression, and other health problems. Environmental factors such as high temperatures, humidity, and inadequate storage conditions promote the formation of aflatoxin in staple foods such as maize, peanuts, and rice. Immunocompromised individuals, including those with HIV/AIDS, hepatitis, cancer, or diabetes, are at increased risk due to their reduced detoxification capacity and weakened immune defenses. Chronic exposure to AF in these populations exacerbates liver damage, infection rates, and disease progression, particularly in developing countries and moderate-income populations where food safety regulations are inadequate and reliance on contaminated staple foods is widespread. Biomarkers such as aflatoxin-albumin complexes, urinary aflatoxin M₁, and aflatoxin (AF) DNA adducts provide valuable insights but remain underutilized in resource-limited settings. Despite the globally recognized health risk posed by AF, research focused on monitoring human exposure remains limited, particularly among immunocompromised individuals. This dynamic emphasizes the need for targeted studies and interventions to address the particular risks faced by immunocompromised individuals. This review provides an up-to-date overview of AF exposure in immunocompromised populations, including individuals with cancer, hepatitis, diabetes, malnutrition, pregnant women, and the elderly. It also highlights exposure pathways, biomarkers, and biomonitoring strategies, while emphasizing the need for targeted interventions, advanced diagnostics, and policy frameworks to mitigate health risks in these vulnerable groups. Addressing these gaps is crucial to reducing the health burden and developing public health strategies in high-risk regions. Full article

Liver cirrhosis represents the end-stage of chronic hepatic injury, arising from a diverse range of etiologies including viral hepatitis, alcohol abuse and non-alcoholic fatty liver disease. A key driver of cirrhosis is hepatic fibrogenesis, a multifaceted process involving hepatic stellate cell activation, inflammatory signaling and extracellular matrix accumulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as pivotal regulators in this context, modulating gene expression networks that govern inflammation, fibrosis and hepatocarcinogenesis. This review synthesizes current evidence on the role of miRNAs in liver cirrhosis, emphasizing specific miRNAs such as miR-21, miR-122, miR-125, miR-146 and miR-155. These miRNAs influence pathways involving TGF-β, NF-κB and PI3K/Akt signaling, contributing to either fibrogenic progression or its suppression. The unique expression profiles and stability of miRNAs in biological fluids position them as promising non-invasive biomarkers for cirrhosis diagnosis and monitoring. Moreover, therapeutic modulation of miRNA activity through mimics or inhibitors holds future potential, though delivery and safety challenges remain. Advancing our understanding of miRNA-mediated regulation in cirrhosis could transform current diagnostic and therapeutic strategies, enabling more precise and personalized liver disease management. Full article

Hepatitis D virus (HDV) infection remains a major cause of severe liver disease among hepatitis B virus (HBV)-infected patients, contributing to accelerated progression to cirrhosis and hepatocellular carcinoma. Pegylated interferon-α remains the first-line therapy for chronic HDV infection in most cases. However, despite its approval for HBV and hepatitis C virus (HCV) infections, its use in HDV is largely driven by a lack of other options and is constrained by its limited efficacy, suboptimal durability of response, and a substantial side effect profile. Meanwhile, bulevirtide, an entry inhibitor, became the first agent to be approved for use in chronic HDV infections by the European Medicines Agency (EMA), and several other therapies are currently being investigated as well. In this review, we provide updates on recent advancements in HDV treatment and novel therapies. Full article

Background: Early diagnosis of hepatocellular carcinoma (HCC) and monitoring of therapeutic results remain clinical challenges. Methods: In a prospective study, we evaluated the diagnostic capabilities of the serum level of glypican-3 in 70 patients with chronic advanced compensated liver disease: 40 cases with confirmed HCC and 30 cases with chronic viral hepatitis with bridging fibrosis or cirrhosis as a control group. The glypican-3 concentration was analyzed in the context of the disease characteristics. Results: The mean level of glypican-3 in HCC patients was 50.84 ± 75.98 ng/mL, significantly higher compared to the control group of 5.69 ± 10.43 ng/mL. A progressive increase in alpha-fetoprotein in accordance with the stage of neoplastic disease was observed, but this tendency was not assessed for glypican-3. Two cut-off levels can be suggested for glypican-3: 2.5 ng/mL to exclude HCC with an optimal sensitivity of 85%, and 33.7 ng/mL for confirmation of HCC, with a specificity of 96.7%. The diagnostic accuracy of serum glypican-3 was 80.0% for HCC, 82.1% for alpha-fetoprotein, and 87.4% for both tumor markers. Conclusions: This pilot study suggests a complementary role of glypican-3 with alpha-fetoprotein and better diagnostic performance when combining tumor biomarkers. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and its progression increases the risk of liver-related and overall mortality. This exploratory research evaluated the potential impact of a 3-month intervention involving dietary counseling and liraglutide therapy on liver fibrosis and related metabolic markers in patients with MASLD and obesity without diabetes. Methods: In this prospective, single-arm exploratory intervention, 28 adult patients with MASLD and obesity received structured dietary counseling and daily subcutaneous liraglutide for 12 weeks. Liver fibrosis was assessed using non-invasive indices (FIB-4, APRI, BARD, ELF) and transient elastography performed with the FibroScan^® device (Echosens, Paris, France). Results: After 3 months, a significant reduction in liver stiffness (−7.14%, p < 0.05) and ELF score (from 6.71 to 6.63; −1.2%, p < 0.05) was observed. APRI (p = 0.06) and FIB-4 (p = 0.09) showed trends toward improvement, while the BARD score and AST/ALT ratio remained unchanged. Conclusions: Short-term liraglutide therapy combined with lifestyle modification may improve early-stage liver fibrosis in patients with MASLD and obesity, as indicated by reductions in liver stiffness and ELF score. These preliminary findings highlight the potential of advanced non-invasive fibrosis markers in monitoring treatment response. However, as an exploratory study, results should be interpreted with caution, and larger, long-term trials are needed to confirm these observations and evaluate efficacy in patients with more advanced fibrosis stages. Full article

Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. Methods: We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as TP53, CTNNB1, TERT, IDH1/2, and FGFR2. In parallel, we evaluated studies addressing the gut–liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host–microbe interactions influence tumorigenesis and therapeutic response. Results: HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. Conclusions: The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut–liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA. Full article

There are currently no approved therapeutic treatments targeting metabolic dysfunction-associated steatotic liver disease (MASLD). Albumin, a liver-produced plasma protein with anti-inflammatory and antioxidant properties, is reduced in advanced liver disease. Considering the role of chronic obesity-induced inflammation in MASLD pathogenesis, we investigated whether albumin administration could prevent disease progression to metabolic dysfunction-associated steatohepatitis (MASH). MASLD was induced in mice using a high-fat and high-cholesterol (PC) treatment for 8 weeks, followed by treatment with bovine serum albumin (BSA; 0.8 mg/kg) every three days for another 8 weeks. This regimen prevented time-dependent weight gain, regardless of diet, with 57% and 27% reductions in mice fed a standard chow (Std Chow) or PC diet, respectively. Further, supplementation reduced nuclear factor kappa B (NF-κB) activation by 2.8-fold (p = 0.0328) in PC-fed mice, consistent with albumin’s known anti-inflammatory properties. Unexpectedly, albumin also reduced hepatic neutral lipid accumulation and circulating non-esterified fatty acids. While PC-fed mice did not exhibit full progression to MASH, albumin treatment significantly increased hepatic matrix metalloproteinase-2 expression, suggesting the inhibition of early fibrotic signalling. While further studies are needed to elucidate the underlying mechanisms, these findings offer new insight into the potential of albumin, either alone or in combination with other therapies, to reduce hepatic steatosis in MASLD. Full article

Background and Aims: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently associated with fatigue and mild cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays key roles in neuroplasticity, immune regulation, and metabolism. This study aimed to evaluate plasma BDNF levels in early-stage PBC and examine their clinical and biochemical associations. Methods: In this observational study, plasma BDNF, IL-6, and IL-18 concentrations were measured by ELISA in 45 patients with early-stage PBC and 31 age- and sex-matched healthy controls (mean age 60.5 years; 96% women). All participants underwent liver elastography using point shear wave elastography (ElastPQ), Doppler ultrasound, laboratory testing, and assessment of cognitive function (PHES) and fatigue severity (MFIS). Non-invasive fibrosis scores (APRI, FIB-4) were calculated. Results: Median plasma BDNF concentrations were significantly higher in PBC patients than in controls [median: 21.04 ng/mL (IQR: 10.68–38.07) vs. 5.80 ng/mL (IQR: 4.58–7.54); p < 0.0001]. In PBC patients, higher BDNF levels correlated inversely with liver stiffness measured by ElastPQ (R = −0.39, p = 0.0258), spleen dimensions, splenic vein flow volume (R = −0.49, p = 0.0018), suggesting an association with milder liver fibrosis and early hemodynamic alterations. A trend toward association between BDNF and IL-6 levels was observed in multivariate analysis. No significant associations were found between BDNF concentrations and markers of hepatocellular injury, cognitive performance, or fatigue severity. Conclusions: Plasma BDNF concentrations are elevated in early-stage PBC and inversely correlate with liver fibrosis severity. No significant associations were found with hepatocellular injury, cognitive function, or fatigue. These findings suggest that BDNF may play a protective role against hepatic fibrogenesis, or alternatively, that BDNF concentrations may decline with advancing liver disease. Further studies are needed to clarify its significance in PBC. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently become the leading cause of chronic liver disease and can progress to hepatocellular carcinoma (HCC) through multiple pathogenic mechanisms. Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor activated by proteases such as trypsin, tryptase or coagulation factors VII and Xa. Recent studies have shown that PAR2 expression is increased in the liver of patients with MASLD or liver fibrosis. Its activation is linked to metabolic dysfunction through several pathways, including SREBP1c activation, AMPK inhibition and Akt-induced insulin resistance. Inhibition of PAR2 has been effective in reducing MASLD progression in different animal models. Notably, PAR2 blockade has also been effective in more advanced stages of the disease by dampening chronic inflammation and fibrogenesis through the inhibition of hepatic stellate cell activation and of TGF-β and SerpinB3 production. PAR2 also plays a role in cancer development, promoting tumour proliferation, angiogenesis and expression of immune checkpoint inhibitors (like PD-L1, CD47 and CD24). Due to its multifaceted involvement in liver disease, PAR2 is emerging as a key therapeutic target in this clinical context. This review aims to summarise current knowledge on PAR2′s role in MASLD and its potential as a therapeutic target. Full article

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and remains one of the leading causes of cancer-related mortality. Its incidence continues to rise worldwide, and it is currently the fastest-growing cancer by incidence in the United States. HCC most often arises in the context of chronic liver disease, particularly cirrhosis. While chronic viral hepatitis (hepatitis B and C) has traditionally been the primary etiologic factor, recent advances in antiviral therapies and prevention strategies have shifted the epidemiological landscape. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease are increasingly prominent risk factors, especially in Western populations. This shift underscores the need for targeted risk factor modification, improved early detection, and enhanced surveillance protocols. The management of HCC necessitates a multidisciplinary approach, incorporating locoregional therapies, surgical resection, liver transplantation, and systemic therapies for advanced-stage disease. Recent advances in systemic treatments, including immune checkpoint inhibitors and combination therapies, have transformed the therapeutic landscape. Despite these developments, significant challenges persist in optimizing treatment, identifying predictive biomarkers, and personalizing therapy. Ongoing research is focused on refining molecular classifications and advancing precision medicine strategies to improve outcomes. This review provides a comprehensive overview of the etiology, surveillance strategies, diagnostic approaches, molecular features, and current treatment modalities for HCC. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with metabolic-dysfunction-associated steatohepatitis (MASH) and alcohol-related liver disease (ALD) emerging as major etiologies. This review explores the epidemiological trends, pathogenesis, and clinical management of HCC arising from MASH and ALD, highlighting both the shared and distinct mechanisms. MASH-HCC is driven by metabolic dysregulation, including obesity, insulin resistance, and lipotoxicity, with genetic polymorphisms such as PNPLA3 and TM6SF2 playing critical roles in disease progression. ALD-HCC, in contrast, is propelled by the toxic byproducts of ethanol metabolism, including acetaldehyde and reactive oxygen species, which induce chronic inflammation, and fibrosis. Both conditions also involve immune dysregulation, gut dysbiosis, and increased intestinal permeability, contributing to hepatic carcinogenesis. The review emphasizes that, while there is consensus regarding the screening of HCC in cirrhosis patients, there is lack of consensus on screening strategies for non-cirrhotic MASH patients who are also at risk for HCC. This underscores the importance of the early detection of cirrhosis using advanced diagnostic tools such as transient elastography and fibrosis scores. Current therapeutic approaches, ranging from surgical resection, liver transplantation, and locoregional therapies to systemic therapies like immune checkpoint inhibitors, are discussed, with an emphasis on the need for personalized treatment strategies. Finally, the review highlights future research priorities, including the development of novel biomarkers, exploration of the gut–liver axis, and deeper investigation of the interplay between genetic predisposition and environmental factors. By synthesizing these insights, the review aims to inform multidisciplinary approaches to reduce the global burden of MASH- and ALD-related HCC and improve patient outcomes. Full article

Introduction: The clinical implementation of noninvasive tests for liver fibrosis assessment has attracted increasing attention, particularly for diagnosing advanced fibrosis (≥F3). This observational study aimed to evaluate the stratification accuracy of nine direct and seven indirect biomarkers across four etiologies: chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver cirrhosis (ALC), and nonalcoholic liver cirrhosis (NALC). Materials and Methods: Our study was conducted on 116 participants, including 96 with chronic liver disease (16 CHB, 15 CHC, 49 ALC, and 16 NALC) and 20 healthy controls. The values of direct (aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum albumin, platelet count, international normalized ratio, gamma-glutamyl transpeptidase, CD5 antigen-like, and transforming growth factor-beta 1) and indirect non-serological biomarkers (De Ritis ratio, albumin–bilirubin score, gamma-glutamyl transpeptidase-to-platelet ratio, aspartate aminotransferase-to-platelet-ratio index, fibrosis-4 index, INR-to-platelet ratio, and fibrosis quotient) were analyzed for their discriminative power in fibrosis stratification. Results: Statistical analyses revealed a significant correlation (0.05 level; two-tailed), and AUC 95% CI ranged within 0.50–1.00 between the direct and indirect biomarker values across all etiologies. Among the evaluated biomarkers, the recorded AUC was 0.998 in CHB for APRI, 0.981 in CHC for FIB-4, and 1.000 in ALC and NALC for APRI and AST, respectively, while CD5L consistently achieved an AUC of 1.000 across all etiologies. Conclusions: These findings suggest that applying a multifactorial approach in liver pathology may improve diagnosis accuracy compared to the use of individual biomarkers and can provide data that may inform the development of clinically applicable mathematical models. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), the leading chronic liver condition globally, constitutes a major etiological contributor to hepatocellular carcinoma (HCC). Its transition from steatosis to non-alcoholic steatohepatitis (NASH) involves progressive fibrosis, ultimately predisposing to HCC. The pathogenesis involves multifactorial interactions among genetic susceptibility, environmental triggers, and obesity-associated metabolic dysregulation. Crucially, the gut–liver axis serves as a pivotal regulatory mechanism in MASLD development. Current therapeutic strategies prioritize lifestyle interventions for metabolic syndrome management, while pharmacological options remain limited, underscoring the need for new therapies. Emerging evidence highlights phenolic acids—bioactive phytochemicals from medicinal plants—as multi-target agents against MASLD. These compounds demonstrate therapeutic efficacy via antioxidative modulation of stress, anti-inflammatory activity, and gut–liver axis regulation. This review synthesizes recent advances in natural phenolic acids for MASLD intervention, emphasizing their potential as preventive and therapeutic candidates. Their multimodal mechanisms may inform innovative drug development paradigms targeting MASLD pathogenesis. Full article

Background: Hepatitis E virus (HEV) infection poses a significant health risk across diverse demographic groups, particularly among pregnant women, immunocompromised individuals, patients with chronic liver disease, and the elderly. The global epidemiology of HEV reveals distinct patterns of prevalence, transmission, and disease severity among these populations, necessitating targeted vaccination strategies. The licensing of the Hecolin (HEV 239) vaccine offers promise, but gaps in clinical trial data and varying immune responses in high-risk groups challenge its widespread applicability. Scope: This review synthesizes data on HEV’s epidemiology, discusses the susceptibility of vulnerable populations, evaluates the efficacy and safety of HEV 239, and highlights the urgent need for clinical research tailored to these groups. Key findings underscore the complexity of vaccine response influenced by immunological, physiological, and environmental factors. Additionally, potential advancements in vaccine technology, including the development of broad-spectrum vaccines and innovative delivery systems, are discussed as future directions. Strategies: Addressing regulatory, economic, and logistical barriers remains crucial for effective HEV vaccination programs. A multidisciplinary approach integrating public health policy, rigorous clinical evaluations, and collaborative frameworks is essential to ensure equitable access to HEV vaccination, ultimately improving health outcomes on a global scale. Full article