Search Results (1,211)

Alcohol-related hepatitis (AH) is a severe, life-threatening liver inflammation caused by chronic heavy drinking, with high short-term mortality despite abstinence and supportive care. The pathophysiology involves a compromised gut–liver axis, activation of Kupffer cells, stimulation of hepatic stellate cells, and progressive fibrosis. Increasing evidence suggests that microRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, play a role as modulators of these processes. Understanding dysregulated miRNAs in AH may provide insights into novel diagnostic and therapeutic interventions. Several miRNAs have been identified as critical regulators of AH pathogenesis. Upregulated miRNAs, including miRNA-217, miRNA-182, let-7b, miRNA-21, and miRNA-34a, promote inflammation through NF-κB activation, Toll-like receptor (TLR) signaling, cytokine production, and ductular reactions. Conversely, downregulated miRNAs such as miRNA-148a, miRNA-30e, and miRNA-483-3p are associated with impaired hepatocyte differentiation, dysregulated oxidative stress responses, and enhanced Mallory–Denk body formation. Considering that miRNAs are pivotal regulators of AH pathophysiology including immune activation, hepatocyte death, fibrosis, and metabolic dysregulation, their altered expression patterns not only illuminate key pathogenic pathways but also provide promising avenues for biomarker discovery and therapeutic targeting. This review aims to summarize the current literature regarding the miRNA profiles involved in alcohol-related hepatitis, their individual mechanistic roles in pathogenesis of AH, and their potential for biomarkers. Full article

Background: Fontan-associated liver disease (FALD) is a progressive condition resulting from chronic hepatic venous congestion following the Fontan procedure for univentricular heart defects. As survival improves in these patients, recognition and management of FALD have become increasingly important. Objective: To describe the pathophysiological mechanisms, imaging findings, and diagnostic approach to FALD, with a focus on the role of ultrasonography, including contrast-enhanced ultrasound (CEUS). Methods: This narrative review explores the evolution of FALD through a multidisciplinary lens, integrating cardiovascular and hepatic imaging data. Particular attention is paid to Doppler ultrasound and CEUS, both in early parenchymal changes and in the differential diagnosis of potential complications such as hepatic nodules. Results: FALD is characterized by progressive fibrosis due to long-standing passive congestion, resulting in a wide spectrum of imaging findings. B-mode ultrasound reveals hepatomegaly, heterogeneous parenchyma, and gallbladder wall thickening. Doppler studies show altered hepatic venous flow patterns, while CEUS provides dynamic vascular evaluation, highlighting areas of altered perfusion. In advanced stages, hypo-vascular areas in the late phase may simulate malignant lesions, emphasizing the need for careful interpretation. The role of liver biopsy, though limited by invasiveness, remains crucial in selected cases. Surveillance strategies are not standardized but require close multidisciplinary follow-up. Conclusions: FALD presents complex diagnostic challenges requiring integrated imaging and clinical assessment. CEUS emerges as a valuable, non-invasive tool in characterizing hepatic congestion and guiding management. Increased awareness and standardized protocols are essential for early detection and tailored care in this growing patient population. Full article

(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV infection. It is well-known that the early innate immune response of host cells plays an important role in the fight against virus infection. However, the interactions between HBV and the intrinsic innate immune system of hepatocytes are still not fully understood. The aim of this study was to confirm the interaction between HBV and hepatocytes, and to identify the interferon-stimulated genes (ISGs) regulated by HBx and their expression in association with HBV-associated HCC (HBV-HCC), so that we can refine our understanding of the interaction between HBV and ISGs and its potential influence on HBV-HCC. (2) Methods: We analyzed data concerning the stimulation of IFN-dependent genes in primary human hepatocytes (PHHs) transfected with pathogen DNA mimetics or infected with HBV in the GSE69590 database. Bioinformatic methods, such as GSEA, GO, and KEGG, were used to analyze the differentially expressed innate immunity genes and their related pathways to identify candidate intrinsic innate immune factors. qPCR on HepG2 and Huh7 cells, which highly express HBx, was used to detect relevant intrinsic innate immune factors. qPCR, RNAi, and Elisa methods were used to identify intrinsic innate immune factors in HBV-integrated HepG2.2.15 cells, and bioinformatics analysis was conducted on the HBV-infected tissues and cells in the GEO database. (3) Results: Inhibition of the JAK-STAT pathway enhanced HBV replication in HepG2 cells transfected with HBV plasmid and HepG2-NTCP cells infected with HBV. GSEA analysis of the GSE69590 data revealed significant changes in intrinsic innate immune pathways during HBV infection with PHH for 40 h. A total of 84 differentially expressed, candidate innate immunity genes were identified in GSE69590. Validation showed that TRIM22 and TRIM56 were down-regulated when HBx was expressed. Consistently, TRIM22 and TRIM56 were up-regulated following inhibition of HBx by transfection of HBx siRNA into HepG2.2.15 cells, and HBV pgRNA was up-regulated following down-regulated expression of TRIM22 and TRIM56 in HEK293 cells. Receiver operating characteristics (ROC) and overall survival (OS) analysis of 204 HBV-HCC patients showed that expression of TRIM22 was closely associated with HBV-HCC, and high expression of TRIM22 was associated with longer survival. (4) Conclusions: Innate immunity genes TRIM22 and TRIM56 are regulated by HBx, and higher expression of TRIM22 is closely related to longer survival of HBV-HCC patients. Full article

(1) Background: After HBV infection, viral transcripts and host RNA form a multi-layered interwoven regulatory network. However, a comprehensive map encompassing mRNA, miRNA, lncRNA, and circRNA is still lacking. This absence complicates the systematic explanation of the molecular mechanisms driving immune escape and metabolic reprogramming during the persistent infection stage. (2) Methods: In this study, we established a mouse model of chronic HBV infection and analyzed the differential expression of mRNA, miRNA, lncRNA, and circRNA through whole transcriptome sequencing (WTS). We constructed a competing endogenous RNA (ceRNA) network to systematically evaluate the overall impact of HBV on the host’s immune-metabolic pathways. (3) Results: RNA sequencing results indicated that HBV infection significantly up-regulated 194 mRNAs, 18 miRNAs, 184 lncRNAs, and 28 circRNAs, while down-regulating 42, 16, 122, and 31 corresponding transcripts, respectively. The differentially expressed genes were primarily enriched in pathways related to metabolism, immunity/inflammation, and signal transduction-ligand receptor interactions. Furthermore, the competitive endogenous RNA networks of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA constructed on this basis further identified miR-185-3p as a key core node. (4) Conclusions: In this study, based on whole transcriptome data, the gene expression profiles of rcccDNA/Ad-infected Alb-Cre transgenic mice (chronic HBV infection model) and normal Alb-Cre mice were systematically compared, and the core regulatory factor miR-185-3p of key differentially expressed genes was screened. The microRNA is expected to provide a new target for the precise treatment of chronic hepatitis B by targeted intervention of viral replication and high liver inflammation. Full article

Introduction and Objectives: Persistent hepatic inflammation serves as a key driver of fibrogenesis in chronic hepatitis B. Fibrosis is a complex molecular and cellular process. Podocalyxin is a type I transmembrane sialomucin, and physiological expression of podocalyxin has been identified in the liver. Pentraxin 3 plays a crucial role in humoral innate immune responses. Isthmin-1 has been associated with metabolic regulation and immune response modulation. We aimed to evaluate the immunoreactivities of podocalyxin, Isthmin-1, and pentraxin-3 in the liver tissue of patients with chronic hepatitis B. Materials and Methods: Power analysis was performed (effect size (f = 0.5), (α) = 0.05 and statistical power of 0.80). Sample size was calculated to be a total of 63 samples, with 21 samples per group. Individuals with negative hepatitis serology and normal liver histopathology, from whom liver tissue was obtained for any reason, were designated as the control group. Liver specimens of chronic hepatitis B were categorized into F0–F2 (no or mild fibrosis) and ≥F3 (advanced fibrosis). Immunohistochemical staining was performed to assess the expression and immunoreactivity of Podocalyxin, Isthmin-1, and Pentraxin-3. A histoscore was created based on the prevalence of staining immunoreactivity (0.1: <25%, 0.4: 26–50%, 0.6: 51–75%, 0.9: 76–100%) and intensity (0: none, +0.5: very low, +1: low, +2: moderate, +3: severe). Results: A statistically significant increase in Podocalyxin, Pentraxin-3, and Isthmin-1 immunoreactivities was found in fibrotic liver tissue compared to normal liver tissue and mild fibrotic groups (p < 0.05). Conclusions: We concluded that our findings suggest these proteins may have an additional role in the progression of liver fibrosis in chronic hepatitis B. Full article

Background: Serological screening for HBV is standard in hemodialysis, and vaccination is recommended for non-immune patients. Objective: To determine the cause of positive HBsAg detected shortly after vaccination. Methods: We conducted a retrospective study in a tertiary hemodialysis unit. Patients with HBsAg reactivity after receiving the adjuvanted HBV vaccine (Fendrix^®) were followed with serial serology until HBsAg clearance. Results: Forty-four patients were monitored; seven (15.9%) tested HBsAg-positive 1–7 days post-vaccination, with no evidence of acute hepatitis, prior HBV infection, transplantation, or chronic immunosuppression. Six cleared HBsAg on repeat testing; one remained positive until day 19, with HBsAg as the only marker. Conclusions: Vaccine-related transient HBsAg antigenemia can occur shortly after immunization. Recognizing this phenomenon and timing routine serology appropriately can prevent misinterpretation and unnecessary workups in CKD patients. Full article

Background/Objectives: Despite extensive research on hepatitis B virus (HBV), its post-transcriptional regulatory mechanisms remain incompletely characterized, particularly regarding epitranscriptomic modifications. This study aims to systematically profile the transcriptomic complexity and RNA modification landscape of HBV in hepatocellular carcinoma models. Methods: We transfected PLC/PRF/5 and Huh7 cells with the HBV 1.3-mer WT replicon plasmid, followed by qPCR measurement of viral load. Total nucleic acids extracted from transfected cells underwent nanopore direct RNA sequencing. The complete HBV transcriptome was then analyzed in two established hepatocellular carcinoma cell lines (PLC/PRF/5 and Huh7), with alternative splicing, polyadenylation, and RNA modifications identified through comprehensive bioinformatics analysis. Results: Our analysis revealed substantial transcriptomic diversity, identifying 34 distinct splice variants—including 14 previously unreported isoforms—with cell-type-specific expression patterns. Additionally, we detected 30 high-confidence RNA modification sites across HBV transcripts, with 93% (28 sites) conserved between both cellular environments. Notably, we observed significant intercellular heterogeneity in poly(A) tail length distributions. Conclusions: A comparison of the post-transcriptional processing modifications of HBV in PLC/PRF/5 and Huh7 cells reveals that the former may be better able to mimic the immune evasion mechanisms of chronic HBV infection. In contrast, the longer poly(A) tails present in Huh7 cells facilitate efficient replication, rendering these cells more amenable to the study of HBV transcription and replication mechanisms. These findings comprehensively elucidate the post-transcriptional regulatory mechanisms of hepatitis B virus in different hepatocellular carcinoma cell lines, establishing a critical benchmark for selecting appropriate experimental models in virology research. The identified transcriptomic features may provide new insights for developing antiviral strategies targeting the viral epigenome. Full article

Background/Objectives: The accurate evaluation of the fibrosis stage is critical for improving chronic hepatitis B (CHB) management and patient outcomes. This study aimed to compare the diagnostic accuracy of non-invasive fibrosis markers with liver biopsy for detecting significant, advanced fibrosis and cirrhosis. We further investigated the diagnostic performance of non-invasive markers according to HBeAg status to provide further insight into their clinical utility across patient subgroups. Methods: This single-center retrospective study included 536 treatment-naive patients with CHB who underwent liver biopsy. Patients were categorized into four groups according to the fibrosis stage: “no significant fibrosis” (F0–F2), “significant fibrosis” (F3–F6), “advanced fibrosis” (F4–F6), and “cirrhosis” (F5–F6). AAR, AAPRI, APRI, API, FIB-4, GPR, and S–index were compared among these groups. Results: In total, 536 treatment-naïve patients were analyzed (63.2% male; mean age 44.8 ± 12.9 years), of whom 25.4% were HBeAg-positive. API, FIB 4, GPR, and S-Index showed good performance (area under the curve [AUC] ≥ 0.8–0.9) in defining advanced fibrosis (≥F4), AAPRI, AAR, API, and APRI showed good performance ([AUC] < 0.700) in defining cirrhosis. The analysis showed that GPR had the highest AUC for ≥F3 (0.719) and ≥F4 (0.838), while FIB 4 had the highest AUC for cirrhosis (0.865). Conclusions: These findings highlight the value of non-invasive markers as inexpensive and easily applicable methods for clinicians in assessing the stage of liver fibrosis. The integration of these scores into the routine monitoring of chronic hepatitis B patients is expected to expand, enhancing clinical decision-making and reducing the necessity for liver biopsies. Full article

Background/Objectives: This study was conducted in an infectious disease clinic in southeastern Romania on a cohort of patients with chronic hepatitis C virus (HCV) infection. It aims to longitudinally evaluate biochemical parameters and the progression of liver fibrosis following treatment with direct-acting antivirals. Methods: One hundred eighty-one patients who experienced improvement in hepatic fibrosis 1–8 years after treatment (group A) were compared with eighty-six patients (except F0–F1) who had stable fibrosis or experienced worsening of hepatic fibrosis after antiviral treatment (group B). Results: The study demonstrated improvement and normalization of mean biochemical parameters in both groups, starting 4 weeks after initiation of therapy and remaining stable up to 5 years post-treatment. The only biochemical parameter that did not return to normal values was serum glucose, which showed elevated mean levels in both groups, with the highest values observed at 5 years post-treatment. Among all 267 patients, 181 (67.79%) showed improvement in hepatic fibrosis after DAA (direct-acting antivirals) therapy, 62 (23.22%) had stable fibrosis, and 24 (8.98%) experienced fibrosis worsening. Of those with improvement, 115 (63.53%) improved by one fibrosis stage, 49 (27.07%) by two stages, and 17 (9.39%) by three stages. Conclusions: This study highlights that more than half of Romanian HCV patients experienced regression of hepatic fibrosis and sustained normalization of most biochemical parameters up to 5 years after DAA treatment, confirming the long-term hepatic benefits of antiviral therapy. Full article

Background/Objectives: To investigate the role of hepatobiliary phase (HBP) signal intensity (SI) on Gadoxetic acid (GA)-enhanced liver magnetic resonance imaging (MRI) in improving the diagnostic accuracy of the histological grade of fibrosis in patients with chronic hepatitis B (CHB). Methods: This retrospective study enrolled patients with CHB who underwent biopsies from the highest and lowest intensity areas identified on HBP images obtained from GA-enhanced MRI. The patients were divided into two groups based on segmental SIs: Group 1 (maximum SI) and Group 2 (minimum SI). An ultrasound-guided tru-cut biopsy was performed in these two segments. Forty patients undergoing histopathological examination were included in the study. Group comparisons were examined using Chi-square and independent-sample t-tests, and receiver operating characteristic curve analysis (ROC) was performed to determine the cutoff values of the SI for modified histologic activity index (mHAI) and fibrosis grading. Results: There were no histopathological differences between the groups (p > 0.05), but significant inflammation and fibrosis were observed in hepatic segments with an SI value of <617 (p < 0.001). The ROC results showed that the predictive cutoff value of SI for mHAI and fibrosis grading were 606 (AUC: 0.83, 95% CI 0.737–0.921, p < 0.001) and 599 (AUC: 0.85, 95% CI 0.766–0.935, p < 0.001), respectively. Conclusions: In patients with CHB, performing a biopsy from the liver segment with the lowest SI on GA-enhanced MRI increases the diagnostic accuracy for assessing the histological severity of hepatic inflammation and fibrosis. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition globally, driven by strong genetic and environmental components. This review summarizes recent advances in understanding the genetic architecture of MASLD. Genome-wide association studies (GWAS) have identified several key risk variants, primarily in genes such as PNPLA3, TM6SF2, GCKR, and MBOAT7, which influence hepatic lipid metabolism and disease progression. By utilizing surrogate markers of MASLD, researchers have also identified numerous putative MASLD-associated genes, warranting further investigation through functional genomics approaches. Next-generation sequencing techniques have uncovered rare variants in genes like APOB and ABCB4, as well as protective variants in HSD17B13 and CIDEB. This review discusses the potential of polygenic risk scores for disease stratification and the development of genetically informed therapeutic strategies. Additionally, it explores the future of functional genomics approaches in discovering novel treatment strategies. While the evolving genetic landscape of MASLD provides promising insights for precision medicine approaches in diagnosis, prognosis, and treatment, significant translational gaps remain. Addressing these challenges will be critical for realizing the full potential of personalised approaches in clinical management. This review synthesizes these findings and discusses their implications for future research and clinical practice in MASLD. Full article

Chronic hepatitis B virus (HBV) infection is a major health problem that leads to approximately one million deaths every year worldwide. Mother-to-child transmission (MTCT) is the major cause of chronic HBV infection. HBV e antigen (HBeAg) is a secretory viral protein and modulates the immunological landscape of the newborn to promote HBV persistence. HBeAg actively reprograms innate and adaptive immunity. Mechanistically, HBeAg regulates macrophage polarization, suppresses dendritic cell and natural killer (NK) cell activities, impairs T cell and B cell functions, and promotes the expansion of myeloid-derived suppressor cells (MDSCs). These multifaceted effects contribute to immune tolerance and persistent HBV infection in the offspring of carrier mothers. Clinically, HBeAg status is a critical determinant for MTCT risk stratification and intervention, particularly in resource-limited settings. Despite advances in neonatal immunoprophylaxis and maternal antiviral therapy, residual transmission of HBV persists. Emerging approaches targeting HBeAg directly or restoring antiviral immunity offer promising avenues for breaking immune tolerance and achieving HBV elimination. This review summarizes current understanding of HBeAg-mediated immune modulation and highlights strategies that are being used to disrupt MTCT and treat HBV patients. Full article

Background: Obesity is a global epidemic and a complex chronic disease affecting more than one billion patients, leading to severe health issues like diabetes, heart disease, and cancer. While lifestyle changes are the first-line treatment, they are often insufficient. Current medications may cause severe side effects, including muscle loss and vision problems. Objectives: This systematic review aims to generalize and evaluate data from preclinical studies on the effect of flavonoid dihydroquercetin (DHQ) on weight loss in experimental animals compared with placebo-treated animals. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The protocol was registered in the PROSPERO database in August 2025 (CRD420251129793). Risk of bias (RoB) was assessed by using SYRCLE’s tool. Results: In total, eight studies included in the systematic review involved 175 animals (14 treatment groups and 9 control groups). Calculation of correlations between the reported effect on weight change and initial weight showed a strong association between these rates (R −0.9883). The intensity of DHQ effect depended on the condition: There were strong negative correlations between DHQ dose and the observed effect in diabetes mellitus (R −0.9056), hepatic lipid dysmetabolism (R −0.9339), and hepatic fibrosis (R −0.9025) in mice and rats’ data together. Conclusions: Intake of DHQ in the course of one month and three months resulted in a decrease in animals’ weight by 5.24% ± 1.95% and 18.29% ± 1.96% (p < 0.0001), respectively. Taken together, our results suggest the rationality for further research of DHQ as an anorexigenic agent, focusing on the stereochemistry of this flavonoid and its bioavailability optimization. Full article

Chronic hepatitis B virus (HBV) and Occult HBV infection (OBI) remain a health burden in sub-Saharan Africa. This study investigated HBV prevalence, circulating genotypes, and associated risk factors with HBV exposure among HIV-positive adults on antiretroviral therapy and pregnant women in southwestern Cameroon. A total of 233 HIV patients and 190 third-trimester pregnant women were screened for HBV DNA, viral load, serological markers (HBsAg, anti-HBc, and anti-HBs), and HBV genotypes were determined by partial sequencing of the S gene. HBV DNA was detected in 10% of HIV-positive patients and 4% of pregnant women, with an overall prevalence of 7%. OBI accounted for 9% and 3%, respectively. Anti-HBc seroprevalence was high (75% in HIV, 46% in pregnant women), while self-reported vaccination coverage was low (1% and 11%). Genotypes A, B, D, and E were identified, with genotype B reported for the first time in Cameroon. Immune escape mutations and the adefovir resistance mutation rtA181V were detected. Self-reported alcohol use was associated with HBV exposure in HIV patients (aOR = 2.08; p = 0.028) and inversely associated with tertiary education in pregnant women (aOR = 0.18; p = 0.038). This study highlights a significant burden of HBV and OBI among vulnerable populations in Cameroon. Full article

In this multicenter, retrospective study involving 62 patients, we investigated whether switching from entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) represents a superior treatment strategy for patients with chronic hepatitis B (CHB) experiencing low-level viremia (LLV). The study determined that TAF significantly improved both virological and biochemical outcomes. At 48 weeks, the complete virological response (CVR) rate was 77.8% for those who switched from ETV and 81.8% for those who switched from TDF, with Hepatitis B virus deoxyribonucleic acid (HBV DNA) negativity reaching 81% by month 12. Additionally, significant normalization of liver enzymes, albumin, and platelet counts was observed across the cohort. While the switch from TDF was associated with a significant increase in triglycerides and high-density lipoprotein (HDL) and a decrease in estimated glomerular filtration rate (eGFR), no such changes were detected in the ETV group. This evidence suggests that TAF provides robust virological control in LLV patients and is associated with favorable biochemical improvements. However, due to the study’s limitations, the strong assertion that TAF promotes the regression of liver fibrosis and reduces the risk of hepatocellular carcinoma (HCC) must be interpreted with caution. Full article