Search Results (181)

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

Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut microbiota alterations, and antibiotic-driven expansion of the resistome. This narrative review examines the complex immunometabolic interplay linking MetS and MDR infections, focusing on molecular mechanisms, clinical implications, and prospective research directions. A systematic literature search was conducted using major databases, including PubMed and Scopus, targeting studies from the last 15 years that explore the interface between metabolic dysfunction and antimicrobial resistance. Particular attention is given to key immunometabolic pathways such as the IRS–PI3K–AKT–mTOR axis; the contribution of visceral adiposity and Toll-like receptor (TLR)-mediated inflammation; and the role of gut dysbiosis in augmenting both susceptibility to infections and metabolic derangements. Evidence is presented supporting the hypothesis that MetS increases host vulnerability to MDR pathogens, while chronic MDR infections may reciprocally induce systemic metabolic reprogramming. Viral infections with established metabolic sequelae (e.g., HIV, hepatitis C virus [HCV], and cytomegalovirus [CMV]) are also considered to broaden the conceptual framework. Although current data remain largely associative and fragmented, the emerging MetS–MDR syndemic model poses substantial challenges for translational research, antimicrobial stewardship, and personalized therapeutic strategies. Recognizing this reciprocal relationship is pivotal for refining infection risk stratification, optimizing treatment, and informing public health policies. Further investigations are warranted to elucidate the magnitude and directionality of this association and to identify predictive immunometabolic biomarkers that may guide targeted interventions in high-risk populations. Full article

Purpose: This article aims to harmonize the current data from the literature, describe baseline severity, and discuss potential treatment considerations for cases of triple infection. Patients and Methods: We undertook a retrospective, observational study on 1244 patients with viral hepatitis study subgroups: chronic replicative hepatitis with HCV—679 patients, HBV—98 patients, HBV/HCV—25 patients, HBV/HDV—14 patients, and 2 patients with triple-infection (HBV, HCV, and HDV), hospitalized in the Second Department of “Sf. Cuv. Parascheva” Infectious Diseases Clinical Hospital of Galați, Romania, between 1 April 2017 and 1 March 2025. Results: Comparative analysis of biochemical parameters and liver fibrosis—at the initial testing—i.e., at the beginning of the specific antiviral therapy—with direct-acting antivirals on HCV (DAAs) or nucleos(t)ide analogues (NUCs): Entecavir (ETV) or Tenofovir Disoproxyl fumarate (TDF), for HBV, Bulevirtide (BLV) for HDV—revealed clinical forms with higher severity in the case of triple and double infections, in comparison to individuals who have had only one hepatotropic virus infection. Conclusions: Compared to patients with a single hepatotropic viral infection, those with a double or triple infection had more severe hepatic damage. Concomitant therapy with Bulevirtide, DAAs, and NUCs is possible and the therapeutic results from clinical studies, with single-infection patients showing great potential for improving the prognosis of these patients. Full article

Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are severe hepatitis that occur in patients with and without chronic liver diseases and/or cirrhosis, respectively, and both often result in death. Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can cause these severe conditions. We reviewed the role of HAV and HEV, which infect humans through the fecal–oral route, in ALF and ACLF in Asian countries. This narrative review was the derived from a traditional non-systematic review. Hepatitis A should be recognized as one of the sexually transmitted infections, especially among men who have sex with men. HAV genotype IIIA infection seems to present a more severe clinical manifestation. Acute HEV-1 infection is associated with ALF in pregnant women in India. HEV-4, rather than HEV-3, was found in severe hepatitis in Japan. HEV also plays a role as a cause of acute insult and/or chronic liver disease in immunocompromised patients with ACLF. Further studies are needed for the development of vaccines and antivirals against HAV and HEV infections. Despite the limitations of the recording of cases and the extent of specific vaccinations, multidisciplinary cooperation, involving hepatologists, virologists, experts in public health, etc., may improve the treatment of HAV and HEV infection. Full article

Hepatitis E virus (HEV), the causative agent of hepatitis E, is the leading cause of acute viral hepatitis worldwide; under immunosuppression, infection can lead to chronic liver disease. Furthermore, extrahepatic manifestations, particularly renal manifestations, are frequently associated with infection. This is important considering the global burden of chronic kidney disease (CKD). However, the study of chronic hepatitis E has been limited to liver disease, and its definition with respect to renal disease is still incomplete. Recently, through a protocol aimed at identifying HEV seroprevalence in a cohort of patients on hemodialysis, we incidentally identified HEV RNA in a patient with a history of alcoholism, diabetes mellitus, and essential systemic hypertension. In this study, we aimed to follow up this case to characterize hepatitis E in the context of CKD. Notably, we identified the development of chronic HEV genotype 3 infection without seroconversion or evidence of liver damage. Moreover, apparent immunocompetence was identified in the patient. Considering that HEV is still neglected in numerous countries and that it is not included in the differential diagnosis of kidney disease, our findings support the need to consider HEV infection in patients with renal disease, even in the absence of liver deterioration. Full article

Hepatitis E virus (HEV) infection can become chronic in immunocompromised patients, like solid organ transplant recipients (SOTRs). We evaluated HEV prevalence, risk factors, and outcomes among SOTRs in a hyperendemic HEV area. Three hundred SOTRs were enrolled from April to July 2019 and tested for anti-HEV IgM and IgG and HEV RNA. Sixty-three recipients (21%) were positive for any HEV marker. HEV infection was independently associated with older age and pork liver sausage consumption. Three viremic recipients harbored genotype 3e and 3f according to HEV RNA sequencing and phylogenetic analysis. Overall, 10 recipients had markers of active/recent infection (HEV RNA and/or anti-HEV IgM) and were followed up prospectively. Five of them spontaneously resolved their HEV infection. In two recipients, HEV clearance was achieved only through immunosuppression reduction, while three needed ribavirin therapy to achieve virologic resolution. We observed a chronic course in 30% of SOTRs with active/recent HEV infection. No association was found between tacrolimus assumption and chronicization. In conclusion, we found a high prevalence of infection among SOTRs attending a transplant center in a hyperendemic Italian HEV region. Systematic screening for all HEV markers and dietary education for infection control are needed for transplant recipients. Full article

Background/Objectives: Hepatitis E virus (HEV) is one of the leading causes of acute hepatitis, with immunosuppressed individuals, such as oncology patients, being particularly vulnerable to chronic infections that may progress to liver disease or fatal outcomes. Assay variability complicates HEV prevalence assessment in at-risk groups. This study aimed to compare the reliability and concordance of three HEV antibody assays—Wantai, Euroimmun, and Elecsys^®—in immunosuppressed oncology patients. Methods: In this prospective pilot study, serum samples were obtained from oncology patients between September 2020 and October 2021. Samples were collected both at baseline (treatment-naive) and during ongoing treatment. A healthy control group was retrospectively included for comparative analysis. Anti-HEV IgM and IgG antibodies were tested in all samples using enzyme-linked immunosorbent assays (Wantai, Euroimmun) and an electrochemiluminescence immunoassay (Elecsys^®). Demographic and clinical data, along with information on HEV risk factors, were extracted from medical records and patient questionnaires. Results: HEV IgM prevalence ranged from 0% (Wantai) to 6% (Elecsys^®), while IgG prevalence was 12% (Euroimmun), 38% (Wantai), and 53% (Elecsys^®). Concordance was poor, with Cohen’s Kappa values indicating slight to moderate agreement (κ = 0.000–0.553). Patients with hematological malignancies exhibited the highest IgG seroprevalence. Risk factor analysis revealed the highest association between HEV exposure and the consumption of undercooked pork or crop-based agriculture. Conclusions: Significant variability among HEV serological assays highlights the challenges of reliable HEV diagnostics in immunosuppressed oncology patients. Assay selection and improved testing strategies are critical for this high-risk group. Full article

In recent decades, considerable advances have been achieved in the treatment of chronic hepatitis B. However, the currently available drugs have shortcomings. In this context, several natural compounds have been proposed as potential agents to improve either the outcome of antiviral treatment or the progression of chronic infection, with curcumin being one of the most evaluated compounds due to its pleiotropic antiviral activity. The aim of this study was to characterize the effect and mechanism of curcumin on hepatitis B virus (HBV) replication in two different experimental models. Treatment of HepG22.15 and HBV-transfected Huh7 cells with curcumin revealed that the phytochemical differentially modulated HBV replication in both cell lines. In HepG22.15 cells, the addition of curcumin had no effect on viral DNA, pregenomic RNA (pgRNA), and e antigen (HBeAg) levels, while it decreased Precore RNA and s antigen (HBsAg) levels. Conversely, in Huh-7 cells, curcumin significantly increased viral progeny more than tenfold, as well as HBV RNAs and viral antigens. Furthermore, the analysis of the cellular mechanisms associated with the modulation of viral replication revealed that in Huh-7 cells, curcumin-induced cell cycle arrest in the G2/M phase and the modulation of genes involved in proliferation, cell cycle progression, and apoptosis, whereas no changes in cell cycle progression and gene expression were observed in HepG22.15 cells. In conclusion, curcumin elicits a differential cellular response in two hepatoma cell lines, which, in the case of Huh-7 cells, would provide an optimal cellular setting that enhances HBV replication. Therefore, the antiviral effect of this phytochemical remains controversial. Full article

Background: Hepatitis C virus (HCV) infection accelerates the progression of chronic kidney disease (CKD), increasing the risk of kidney failure and end-stage renal disease. Direct-acting antiviral (DAA) therapies for HCV infection inhibit viral replication by 95–97%, leading to a sustained virologic response. Our objective was to assess renal function in patients with chronic HCV infection in Taiwan after receiving DAA therapy. Goal: Our study included 4823 patients with HCV infection who were undergoing DAA therapy. Renal function was evaluated by calculating the glomerular filtration rate (eGFR). eGFR assessed at the initiation of the treatment, during treatment, and at 3 months, 6 months, 1 year, and 3 years after completion of treatment. The baseline demographic and laboratory parameters of the study participants were evaluated, and the results were analyzed using statistical methods. Results: The average age of the study participants was 61.35 ± 12.50 years, and 54.5% of were male. The mean of eGFR in baseline and after treatment showed a decrease. Liver fibrosis scores (FIB4, APRI, Fibroscan) and liver function tests were significantly improved after DAA treatment (p = 0.001). However, white blood count (5.41 ± 1.7 vs. 5.73 ± 1.9), platelet count (168.04 ± 74.0 vs. 182.11 ± 69.4), and creatinine levels (1.05 ± 1.3 vs. 1.12 ± 1.3) increased after treatment (p = 0.001). The number of patients with an eGFR of 60 mL/min/1.73 m² decreased both during and after treatment (p < 0.001). Among patients with CKD, eGFR improved after DAA treatment (n = 690, 35.93 ± 19.7 vs. 38.71 ± 23.8; 95% CI −3.56–1.98; p = 0.001). Logistic regression analysis revealed that renal function improved in patients with CKD who had an eGFR of less than 60 mL/min/1.73 m² before DAA treatment (OR 1.62, 95% CI 1.37–1.91, p = 0.001). Conclusions: In individuals with CKD and a baseline eGFR < 60 mL/min per 1.73 m², eGFR level was increased during DAA treatment. This suggests that initiating DAA therapy in HCV-infected patients, even those without clinical manifestations, could be a crucial strategy to prevent further decline in renal function. Full article

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several studies have investigated the impact of HEV on the male reproductive system; however, the available data are limited and conflicting. Assessment of the patients’ ejaculates/semen samples revealed that HEV particles are excreted in these fluids in cases of chronic infection but not acute infection. The excreted HEV particles are infectious to in vivo animal models and in vitro cell culture. However, the effect of HEV infection on male infertility is not confirmed. One study including human samples showed male infertility associated with HEV genotype 4 infection. Studies of HEV infection in animal models such as pigs, gerbils, and mice showed that HEV infection caused distortion on the testes, damage of the blood–testis barrier, and induction of inflammatory responses leading to abnormalities in the sperm. The excretion of HEV in the semen fluids raises concerns about HEV transmission via sexual transmission. However, all available data do not confirm the transmission of HEV through sexual intercourse. This review aims to summarize and critically assess the available studies investigating the influence of different HEV genotypes on the male reproductive system, providing insights into whether HEV contributes to reproductive impairment in men. Full article

Thalassemia is an inherited hematological disorder characterized by a decrease in the synthesis of or absence of one or more globin chains. Hepatitis E virus (HEV) is a major cause of acute viral hepatitis, constituting a major global health burden and emerging as a critical public health concern. HEV infection is mainly transmitted via the fecal–oral route; however, parenteral transmission through blood components has been reported in both developing and developed countries. Although HEV infection is typically self-limiting, immunocompromised individuals, patients with chronic liver disease, and thalassemic patients are at a heightened risk of contracting the infection and may develop chronic hepatitis and life-threatening complications that require treatment. The reported prevalence rates of HEV in thalassemia patients vary significantly by country. Age, gender, residential area, and the cumulative amount of blood transfusions received have been identified as associated risk factors for HEV infection. In order to enhance blood safety and ensure the protection of vulnerable patient populations, such as thalassemia patients, several countries have introduced universal or targeted HEV screening policies in blood donations. Other preventive measures include vigilant monitoring of thalassemic patients and screening for anti-HEV antibodies. The aim of this review is to explore the prevalence, risk factors, clinical impact and management of HEV infection in patients with thalassemia. Full article

Hepatitis E virus (HEV) is a global health problem, causing an estimated 20 million infections annually. Thus, the management of HEV requires special consideration. In developed countries, hepatitis E is mainly recognized as a foodborne disease (mainly transmitted via undercooked meat consumption) that is generally caused by genotype 3 and 4 circulating in various animals, including pigs and wild boars. The current absence of officially recognized protocols for the analysis of HEV in foods and the lack of awareness of this disease among healthcare workers, together with the high percentage of asymptomatic cases, make HEV infection highly underestimated. Most HEV-3 infections in immunocompetent individuals are self-limited. Nevertheless, the possibility of serious forms of liver disease, especially in patients with co-morbidities, should be considered because it can lead to a fatal outcome. Here, we report a case of fatal hepatitis related to HEV-3 infection in a 67-year-old male patient with underlying chronic liver disease (CLD) and living in a region where a high prevalence and genetic heterogeneity of HEV-3 in wild boar has been recently demonstrated. Our case report describes the interdisciplinary approach used (from the diagnosis to the virus phylogenetic characterization) in order to improve epidemiologic HEV surveillance in central Italy. Full article

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, primarily transmitted through contaminated water and food. In patients with chronic liver disease (CLD), HEV infection might worsen the prognosis. This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in CLD patients. A decision tree–Markov cohort model was used to assess the cost-effectiveness of universal-vaccination, vaccination-following-screening, and no-vaccination strategies in 100,000 CLD patients over their lifetimes, simulating cohorts aged ≥16 years, ≥40 years, and ≥60 years, based on the licensed vaccination ages and typical ages of CLD onset, from a societal perspective. Model parameters were retrieved and estimated from previous publications and government data. The outcomes included HEV-related cases, costs, and the incremental cost-effectiveness ratio (ICER). Compared to no-vaccination, universal-vaccination reduced HEV-related cases by 32.8% to 39.6%, while vaccination-following-screening reduced them by 38.1% to 49.3%. Furthermore, universal-vaccination showed ICERs of USD 6898.33, USD 6638.91, and USD 6582.69 per quality-adjusted life year (QALY) for cohorts aged ≥16, ≥40, and ≥60 years, respectively. Moreover, the vaccination-following-screening strategy significantly enhanced cost-effectiveness, with ICERs decreasing to USD 6201.55, USD 5199.46, and USD 4919.87 per QALY for the cohorts. Additionally, one-way sensitivity analysis identified the discount rate and utility for CLD patients as the key factors influencing ICER. Probabilistic sensitivity analysis indicated the vaccination-following-screening strategy was cost-effective with probabilities of 92.50%, 95.70%, and 95.90% for each cohort. Hepatitis E vaccination in CLD patients costs less than GDP per capita for each QALY gained in China. The vaccination-following-screening strategy may be the optimal option, especially in those over 60 years. Full article

Hepatitis E virus (HEV) is a common cause of acute hepatitis, with increasing incidence in Europe, including Romania. Concurrently, Romania has a high prevalence of chronic hepatitis B (CHB). There is limited research on the clinical presentation and outcomes of HEV infection in patients with pre-existing chronic hepatitis B (CHB), especially in resource-rich settings. Most literature data come from South, East, and Southeast Asia. A review of the literature on HEV and HBV co-infection indicates a severe prognosis, particularly in patients with underlying liver disease. However, the cases in this study, which did not display cirrhosis, showed varied outcomes. The role of anti-HBV treatment in improving prognosis remains uncertain and warrants further investigation. Acute HEV infection superimposed on chronic HBV infection poses significant clinical challenges, with outcomes ranging from full recovery to fatality. Preventive measures, including sanitation and vaccination against HBV, are crucial. More studies are needed to establish effective treatment protocols for this co-infection. In this study, we will analyze the clinical setting, diagnosis, particularities, and outcomes of five such cases of dual hepatotropic viral infection recorded over a period of 6 years (2018–2023) at a large Infectious Diseases clinic in Bucharest, Romania. Full article

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage. Full article