Search Results (161)

Background: Although immune complex formation is widely acknowledged as the etiological agent for the development of systemic lupus erythematosus, polyarteritis nodosa, reactive arthritis, etc., its roles in chronic hepatitis are less understood. This study aims to compare the immunohistochemistry profile of immune complex deposition in patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH). Methods: Immunohistochemistry of C4d, a widely used marker for complement deposition was employed on liver biopsies from 72 and 15 patients with CHB and AIH, respectively. Statistical analysis was performed to analyze its prevalence and its association with a range of clinical and histological parameters. Results: Among the 15 AIH biopsies examined, C4d deposition was observed in 11 cases (73.3%), the majority of which showed a periportal staining pattern (10/11). In CHB, 61 (84.7%) of 72 cases tested positive for C4d, which did not differ significantly with that of AIH. While the periportal pattern was predominantly observed in CHB cases, positive staining in central veins, sinusoids, and hepatic parenchyma were also documented. In particular, C4d deposition is significantly associated with elevated serum ALT and liver inflammation in CHB. Of note, in specimens with a patchy parenchymal C4d staining pattern, a spatially correlated HBsAg IHC signal was observed in adjacent sections from the same tissue. Conclusions: These data suggest an involvement of immune complex-mediated immunopathy in autoimmune hepatitis and HBV-induced hepatitis. The positive intrahepatic C4d signal was associated with heightened liver inflammation. The colocalization of the C4d signal on hepatocytes with HBsAg strongly suggests a causal relationship between viral activity and complement deposition. These observations align with our recent evidence implicating the contribution of capsid–antibody complexes in the pathogenesis of CHB. Full article

Background. To meet the WHO’s viral hepatitis elimination goal by 2030, the Minister of Health (Italy) introduced free HCV screening among people born between 1969 and 1989 and those at greater risk (people in the care of the addiction services and detained). Aims. To estimate the following: (i) the prevalence of HCV in hospitalized patients born before 1969 not included in the free HCV screening, (ii) the prevalence of transaminase values outside the range, and (iii) the HBV prevalence in a subgroup of patients. Methods. Anti-HCV antibodies and transaminase values were prospectively evaluated in patients born before 1969 and admitted to the Santa Maria alle Scotte Hospital in Siena. The first screening (October 2021–July 2022) was conducted in the Internal Medicine Division (cohort 0), and the second one (May 2024–October 2024) in Internal Medicine, Gastroenterology, and Geriatric Units (cohorts 1–3), including clinical features and HBV markers in a subgroup of patients. Results. Overall, 774 subjects underwent HCV screening. In the first screening period, 1.4% (8/567) of patients were anti-HCV+, of whom 0.7% were HCV RNA+ (4/567). In the second, 3.9% of patients (8/207) were anti-HCV+ and 0.9% were viremic (2/207). Overall, HCV prevalence was 0.8%. Of 96 patients in the gastroenterology cohort, 8 patients were at risk for occult HBV infection (8.3%). Conclusions. Our study demonstrates a chronic HCV infection prevalence of 0.8% in hospitalised patients born before 1969 and a prevalence of 8.3% of people at risk for occult HBV infection in a subgroup of patients residing in South-Eastern Tuscany, confirming that an opportunistic screening can identify the unrecognized people affected by viral hepatitis. Full article

Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)—an accurate marker of neutrophil extracellular traps (NETs)—were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients. Full article

Infections with the Hepatitis B (HBV) and Hepatitis C (HCV) viruses share some transmission routes, which is why coinfection with these viruses becomes common, especially in endemic areas. This study evaluated the immunological response profile, viral load, and liver damage in groups monoinfected with HBV or HCV and in those co-infected with HBV/HCV. The groups were composed of 22 patients monoinfected by HCV, 22 patients monoinfected by HBV, and 34 co-infected by HBV/HCV, according to serological markers and molecular biology tests. The study was carried out from December 2017 to October 2019. Virus detection employed enzyme immunoassay, Enzyme-Linked Immunosorbent Assay (ELISA), and real-time PCR, while liver function and fibrosis were assessed using biochemical tests and Fibroscan. To research the immunological profile, cytokines were quantified using the BIO-Plex Pro Human Cytokine. Comparing the groups, both mono- and co-infected patients exhibited a Th1 immune response profile. HCV monoinfection notably showed significantly elevated serum levels of INF-γ (p < 0.01) and TNF-α (p < 0.01). The viral load was significantly higher in the HCV monoinfected group when compared to the other groups. Regarding liver damage, patients with a high level of fibrosis (F4) presented significant levels of cytokines INF-γ (p < 0.001), IL-17 (p < 0.0001), and TNF-α (p < 0.0001). Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. Immunosuppressive therapy administration increases the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation. This study aimed to investigate the hepatitis screening rate, serological status, and protective antibody levels among the Taiwanese IBD population. This single-center retrospective study included patients with IBD from January 2016 to December 2024. Hepatitis serological markers were analyzed. Patients were categorized into active HBV infection (HBsAg-positive), resolved HBV infection (HBsAg-negative and anti-HBc-positive), and non-HBV-infected groups, with prevalences of 7.5%, 32.5%, and 0.9%, respectively. This study included 347 patients with IBD (UC: 68.3%; CD: 31.7%), with a mean age of 47.1 ± 16.4 years. Patients born after 1984 demonstrated a significantly reduced HBsAg positivity (0.9% vs. 11.0%; p < 0.05) and resolved HBV infection (52.2% vs. 1.0%; p < 0.05). However, among non-HBV-infected individuals, only 42.0% had protective anti-HBs levels (≥10 mIU/mL), despite vaccination program initiation. In this study, we found an overall HBsAg positivity rate of 7.5% and an anti-HCV seropositivity rate of 0.9% in our IBD population. Taiwan’s HBV vaccination program has effectively reduced the HBV prevalence. However, a significant proportion of vaccinated individuals lack sufficient protective antibody levels, thereby requiring continued HBV screening and booster vaccinations. Full article

Background/Objectives: Alcohol-related liver disease (ARLD) is a major cause of chronic liver disease, yet its clinical profile in Albania, a region with high HBV prevalence and rising alcohol consumption, remains poorly characterized. This study evaluates the clinical markers of advanced ARLD as noninvasive fibrosis indicators, acknowledging limitations in observational data and the need for validation in diverse populations. Methods: In this cross-sectional study, 200 patients with ARLD were classified as having mild or advanced disease based on clinical, biochemical, and imaging criteria. Associations between socioeconomic factors, nutritional status, and fibrosis markers with advanced ARLD were assessed using multivariate logistic regression, adjusted for age, sex, smoking status, and duration of alcohol use. Results: Lower Prognostic Nutritional Index (PNI) score was significantly associated with advanced ARLD (OR 0.95, 95% CI 0.91–0.99; p = 0.014), suggesting a potential role of nutritional status in disease progression. Higher APRI and FIB-4 scores were associated with an increased risk of advanced ARLD (APRI: OR 1.27, 95% CI 0.71–2.26; FIB-4: OR 1.10, 95% CI 0.81–1.51), though these associations did not reach statistical significance. Conclusions: This study provides a first clinical assessment of ARLD in Albania, highlighting the potential role of nutritional and fibrosis markers in risk stratification. While the study design limits definitive conclusions, our findings underscore the need for larger prospective studies to validate these associations and further investigate the influence of metabolic and socioeconomic factors on ARLD progression in Albania. Full article

This study aimed to assess the prevalence of HDV (hepatitis delta virus), HCV (hepatitis C virus), and HIV (human immunodeficiency virus) coinfections among HBsAg-positive patients and to determine the severity of liver fibrosis and biochemical markers. Furthermore, the study sought to evaluate the noninvasive fibrosis scores (APRI and FIB4) in predicting the severity of liver disease in patients with hepatitis B. A retrospective analysis of 1434 patients with chronic HBV admitted between January 2020 and December 2024 was conducted at Sincan Tertiary Hospital. The positivity rates of the following antibodies were the focus of the study: anti-HDV, anti-HCV, and anti-HIV. In addition to these, the levels of HIV-RNA, HCV-RNA and HBV-DNA, as well as several biochemical markers (ALT, AST, INR, albumin, bilirubin and platelet count) were also evaluated. The APRI and FIB-4 scores were calculated. Of the 1434 patients, 49 (3.4%) tested positive for anti-HDV, 784 were screened for anti-HCV, and 749 were screened for anti-HIV. The positivity rates were 3.4% (27/784) and 3.4% (26/749), respectively. According to ROC analysis, the FIB-4 score had a statistically significant effect on predicting anti-HDV negativity (AUC = 0.59, p = 0.031). However, the APRI score was not a significant predictor for anti-HDV positivity (AUC = 0.53, p > 0.05). APRI and FIB-4 scores did not have a statistically significant discriminatory power in predicting anti-HCV and anti-HIV positivity (p > 0.05). The cut-off value for the FIB-4 score in predicting anti-HDV positivity was 1.72, with a sensitivity of 61.4% and a specificity of 42.9% (p = 0.031). Among the HCV/RNA-positive patients (n = 5), all were male, and two also had positive anti-HBe results with undetectable HBV/DNA levels. One HIV/RNA-positive patient, a foreign national, was confirmed to have HIV/HBV/HDV infection. All HBsAg-positive patients should undergo routine anti-HDV testing. Vaccination programmes are vital in preventing the spread of HDV. Dual screening strategies are essential for identifying infected individuals and developing prevention and treatment programmes. Anti-HDV positivity indicates advanced liver fibrosis, emphasising the importance of screening and monitoring. However, the limited accuracy of the APRI and FIB-4 scores for detecting coinfections highlights the need to integrate noninvasive methods with molecular diagnostics for precise management. Full article

The Hepatitis B Virus (HBV) presents a formidable global health challenge, impacting hundreds of millions worldwide and imposing a considerable burden on healthcare systems. The elusive nature of the virus, with its ability to establish chronic infection and evade immune detection, and the absence of curative agents have prompted efforts to develop novel therapeutic approaches beyond current antiviral treatments. This review addresses the challenging concept of a functional cure for HBV, a state characterized by the suppression of HBV and HBsAg, mitigating disease progression and transmission without a complete cure. We provide an overview of HBV epidemiology and its clinical impact, followed by an exploration of the current treatment landscape and its limitations. The immunological basis of a functional cure is then discussed, exploring the intricate interplay between the virus and the host immune response. Emerging therapeutic approaches, such as RNA interference-based interventions, entry inhibitors, nucleic acid polymers, and therapeutic vaccines, are discussed with regard to their success in achieving a functional cure. Lastly, the review underscores the urgent need for innovative strategies to achieve a functional cure for HBV. Full article

Italy was one of the first countries to implement a hepatitis B (HBV) immunization strategy in 1991; since its introduction, the epidemiology of this disease has significantly changed. The aim of this retrospective study was to assess the seroprevalence of three HBV markers (anti-HBs, anti-HBc, and HBsAg) and describe the acquired immunity in a representative sample of the adult general population in the province of Florence (Italy) between April 2018 and December 2019. We conducted an enzyme-linked immunosorbent assay on 430 serum samples collected from the adult general population to quantify anti-HBs titers and assess the presence of anti-HBc and HBsAg. For the interpretation of hepatitis B serologic results, we referred to the US CDC guidelines. We conducted two multivariate logistic regression analyses (applied to the entire enrolled population and to the unvaccinated) to assess predictors of immunity against HBV using sex, age, and nationality as predictors. The overall anti-HBs prevalence was 30%, with a significant decreasing trend in seropositivity with increasing age. The overall anti-HBc prevalence was 11.6%, with seropositivity increasing with age. Only one subject tested positive for HBsAg (0.2%). Approximately 67.4% (290/430) of the study population was susceptible, 20.9% (90/430) was vaccinated, 9.1% (39/430) had naturally acquired immunity, and 0.2% (1/430) had an acute infection. Older age and foreign nationality were identified as risk factors in both multivariate logistic regression models. The comparison highlights a reduction in the circulation of HBV infection markers (anti-HBc and HBsAg) over 30 years in Tuscany, particularly in younger age groups. Our seroprevalence study demonstrated a good level of protection against hepatitis B, primarily among individuals under 40 years old, the target group of the vaccination strategy. Full article

Background: Hepatitis B virus (HBV) remains a significant global health concern, particularly in sub-Saharan Africa, where endemicity is high. Occult hepatitis B infection (OBI) presents a unique challenge to transfusion safety, as HBV DNA may persist in HBsAg-negative individuals. This study examines the prevalence of HBcAb positivity among blood donors at Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, and assesses the risk of HBV transmission. Methods: A cross-sectional study was conducted among 200 blood donors. Samples were screened for HBsAg and HBV serological markers using a rapid assay and ELISA. HBcAb-positive samples were analyzed for HBV DNA using real-time polymerase chain reaction (qRT-PCR). Viral loads were quantified, and socio-demographic characteristics were recorded. Results: HBcAb was detected in 57 (28.5%) of the 200 donors. The most common serological pattern among donors was HBsAg-negative and HBcAb-negative (69%). Among these HBcAb-positive donors, HBV DNA was detected in three cases (1.5%), with viral loads of 753.1, 2.193 × 10⁴, and 4.538 × 10⁴ IU/mL. The presence of HBV DNA in these donors confirms the risk of OBI transmission through transfusion. Socio-demographic analysis revealed that 48.5% of donors were aged 26–35 years, 23.5% were aged 18–25 years, 23% were aged 36–42 years, and 2.5% were either 43–50 or above 50 years of age, of which 99.5% were male. These findings highlight a significant prevalence of HBcAb positivity and OBI, aligning with studies in similar high-endemic settings. Conclusions: HBcAb positivity and OBI represent significant transfusion risks in endemic regions. The presence of HBV DNA in 1.5% of HBcAb-positive donors in the study population highlights the limitations of HBsAg-based screening. Incorporating nucleic acid testing (NAT) into routine blood donor screening protocols is critical to enhancing transfusion safety. Further research is needed to evaluate the feasibility and cost-effectiveness of such interventions in resource-limited settings. Full article

Background/Objectives: Immunization with the hepatitis B vaccine is the most effective means of preventing acute HBV infection. However, whether the primary vaccination of infants confers lifelong immunity remains controversial. Therefore, the ongoing surveillance of vaccine recipients is required. Methods: A longitudinal study was carried out based on LongAn county, one of the five clinical trial centers for hepatitis B immunization in China in the 1980s. Serum samples were collected and tested for HBV serological markers and DNA. Results: A total of 637 subjects born in 1987–1993 were recruited, including 503 males and 134 females. The total prevalence of HBsAg was 3.9%. The prevalence in females (8.2%) was significantly higher than that in males (2.8%) (p = 0.004). The prevalence of anti-HBc in females (52.2%) was also significantly higher than that in males (41.2%) (p = 0.021). The prevalence of anti-HBs was 42.7% and did not differ significantly between males (41.7%) and females (46.3%) (p = 0.347). Compared to data from surveillance over the last ten years, the positivity rate of HBsAg did not increase. The positivity rate of anti-HBs decreased significantly (p = 0.049) while that of anti-HBc increased significantly (p = 0.001). The prevalence of occult HBV infection (OBI) in 2024 (6.0%) was significantly higher than that in 2017 (1.6%) (p = 0.045). Subjects diagnosed with OBI in 2017 maintained occult infection in 2024. Conclusions: Neonatal HBV vaccination maintained effective protection for at least 37 years. However, the prevalence of OBI increases with age in those vaccinated at birth, raising a new issue of how to prevent and control OBI in the post-universal infant vaccination era. Full article

Background: Hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis and is a significant global health challenge. Bulevirtide (BLV) is a novel therapeutic treatment that has resulted in variable response rates in HBV/HDV-coinfected patients. We evaluated clinical, virological, and polymorphic factors for the purpose of predicting BLV treatment success. Methods: Thirty HBV/HDV-coinfected patients received BLV monotherapy (2 mg/day) for 24 to 48 weeks. Baseline (BL) serum samples were collected to assess clinical parameters and virological markers (HDV RNA, HBV DNA, HBsAg, HBcrAg, anti-HBc IgG) at treatment weeks 24 (TW24) and 48 (TW48). Additionally, full-genome HDV sequencing and a phylogenetic analysis were performed. Finally, analyses of the HDAg protein sequence and HDV RNA secondary structure were conducted to evaluate potential associations with treatment response. Results: A significant reduction in HDV RNA levels was observed at TW48, with a virological response (HDV RNA undetectable or ≥2 Log decline from BL) achieved by 58% of patients. Median BL levels of anti-HBc IgG were significantly different between virological responders (39.3 COI; interquartile range [IQR] 31.6–47.1) and virological non-responders (244.7 COI; IQR 127.0–299.4) (p = 0.0001). HDV genotype 1e was predominant across the cohort, and no specific HDAg polymorphisms predicted the response. However, secondary structure analysis of HDV RNA revealed that a specific pattern of internal loops in the region 63–100 nucleotides downstream of the editing site may influence treatment response by impacting editing efficacy. Conclusions: This study revealed key factors influencing BLV efficacy in HBV/HDV coinfection. Lower baseline anti-HBc IgG levels strongly correlated with a positive virological response, suggesting that the liver’s inflammatory state affects treatment success. Additionally, the analysis of HDV RNA secondary structure in patients receiving BLV treatment revealed a higher editing efficiency in virological responders, highlighting areas for further research. Full article

About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases are potentiated by alcohol. HBV replicates in hepatocytes, but other liver non-parenchymal cells can sense the virus. In this study, we aimed to investigate the regulatory effects of macrophages on HBV marker and interferon-stimulated genes (ISGs) expressions in hepatocytes. This study was performed on HBV-replicating HepG2.2.15 cells and human monocyte-derived macrophages (MDMs). We found that exposure of HepG2.2.15 cells to an acetaldehyde-generating system (AGS) increased HBV RNA, HBV DNA, and cccDNA expressions and suppressed the activation of ISGs, APOBEC3G, ISG15, and OAS1. Supernatants collected from IFNα-activated MDMs decreased HBV marker levels and induced ISG activation in AGS-treated and untreated HepG2.215 cells. These effects were reversed by exposure of MDMs to ethanol and mimicked by treatment with exosome release inhibitor GW4869. We conclude that exosome-mediated crosstalk between IFN-activated macrophages and HBV-replicating hepatocytes plays a protective role via the up-regulation of ISGs and suppression of HBV replication. However, ethanol exposure to macrophages breaks this protection. Full article

Achieving HBsAg seroclearance is a key goal in treating chronic hepatitis B virus (HBV) infection but remains difficult with nucleos(t)ide analogues (NAs). Tenofovir alafenamide fumarate (TAF), a recommended NA for managing chronic HBV infection (CHB), has uncertain effects on HBsAg levels and potential adverse events when used long-term after switching from entecavir (ETV). We retrospectively evaluated 77 CHB patients, including 47 who switched from ETV to TAF with a median follow-up of 40 months post-switch and a median of 60 months of HBsAg monitoring pre-switch. No significant change in HBsAg levels was observed in the overall cohort post-switch, consistent with the ETV continuation group. However, a significant decrease in HBsAg was noted in patients with HBsAg < 100 IU/mL at the time of switching. HBsAg loss occurred in three patients who switched to TAF. No adverse effects were observed, and TAF was well tolerated. The most significant factor associated with achieving HBsAg < 100 IU/mL was the Fib-4 index, a marker of liver fibrosis, at the time of switching. Switching from ETV to TAF is an effective strategy in CHB management, with hepatic inflammation potentially playing an essential role in achieving HBsAg decrease. Patients with increased Fib-4 index were significantly more likely to show decreased HBsAg. This finding suggests patients with mild to moderate fibrosis may respond better to TAF in terms of HBsAg reduction. Full article

Background: This study addresses a particular aspect of the biological behavior of the Spike subunit S1 of SARS-CoV-2. Researchers observed S1 acting freely in the human organism during and after COVID-19 and vaccination. One of its properties is that it interacts one-to-one with human proteins. S1 interacts with 12 specific human proteins in the liver. Methods: We used these proteins as seeds to extract their functional relationships from the human proteome through enrichment. The interactome representing the set of metabolic activities in which they are involved shows several molecular processes (KEGG), including some linked to HBV (hepatitis B) and HCC (hepatocellular carcinoma) with many genes/proteins involved. Reports show that, in some COVID patients, HBV reactivated or progressed to cancer. Results: We analyzed the interactome with several approaches to understand whether the two pathologies have independent progressions or a common progression. All our efforts consistently showed that the molecular processes involving both HBV and HCC are significantly present in all approaches we used, making it difficult to extract any useful information about their fate. Through BioGRID, we extracted experimental data in vivo but derived it from model cell systems. The lack of patient data in STRING results prevents diagnosis or prediction of real disease progression; therefore, we can consider them “aseptic” model data. Conclusion: The interactome tells us that genes involved in HCC and HVB-related pathways have the potential to activate disease processes. We can consider them as a gold standard. It is the comparison with similar molecular interactions found in individual human phenotypes that shows us whether the phenotype favors or hinders their progression. This also suggests how to use these features. These sets of proteins constitute a molecular “toolkit”. In fact, if we compare them with similar molecular sets of the patient, they will provide us with information on the level of the phenotypic state that is driving the disease. The information derived from the composition of an entire group of proteins is broader and more detailed than a single marker. Therefore, these protein compositions can serve as a reference system with which doctors can compare specific cases for personalized molecular medicine diagnoses. Full article