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Keywords = Hepatitis B and C

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15 pages, 986 KB  
Article
Epidemiology and Clinical Outcomes in the 20-Year HepCoVe Cohort: Progress Toward Elimination of HCV Infection in North-East Italy
by Luisa Cavalletto, Elisabetta Bernardinello, Ilenia Mezzocolli, Silvia De Carlo, Mirko Schipilliti, Eleonora Bertoli and Liliana Chemello
Livers 2026, 6(1), 7; https://doi.org/10.3390/livers6010007 (registering DOI) - 23 Jan 2026
Abstract
Background and Objectives: The increase in rates of cirrhosis and hepatocellular carcinoma (HCC) due to HCV infection supported the implementation of screening programs for control of this infection in Italy. The HepCoVe network has collected cases with chronic hepatitis C (CHC) in the [...] Read more.
Background and Objectives: The increase in rates of cirrhosis and hepatocellular carcinoma (HCC) due to HCV infection supported the implementation of screening programs for control of this infection in Italy. The HepCoVe network has collected cases with chronic hepatitis C (CHC) in the Veneto region of North-East Italy since the 2000s. This platform allowed us to (a) compare the characteristics of the HCV cohort exposed to parenteral risk before or after 1995 (introduction of mandatory HCV testing), and (b) track the changes induced by IFN-based therapy and the novel direct-acting antivirals (DAA). Methods: From January 2000 to December 2005, 2703 prospectively recruited cases with CHC were analyzed and followed up for 16.2 ± 8.4 years, by a per protocol analysis. Results: Two epidemic waves occurred; the first, related to blood transfusions and infection with the HCV-1b and 2a/2c genotypes, affecting an elderly population, and the second, spread through drug addiction, among young people and with a prevalence of HCV-1a, 3a/3b and 4c/4d. Patients treated with DAA had more advanced liver disease; despite this, they achieved the highest SVR rate, compared to those who received an IFN-based regimen (95.1% vs. 61.5%; p < 0.01). The 10-year HCC incidence rate by KM was 0.81, 3.75, and 1.26 per 100 person-years (p-y) in cases with or without SVR and in the untreated group, respectively (p < 0.001). Conclusions: The period of exposure to HCV in Italy (born from 1939 to 1989) was supported by two epidemic waves. Unknowing cases of HCV infection are disappearing, particularly those included in the first cohort, among the “boomers”. Despite the eradication of HCV in all treated cases, antiviral therapy does not completely eliminate the risk of HCC onset. Full article
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21 pages, 1237 KB  
Article
Unveiling the Hidden Reservoir: High Prevalence of Occult Hepatitis B and Associated Surface Gene Mutations in a Healthy Vietnamese Adult Cohort
by Huynh Hoang Khanh Thu, Yulia V. Ostankova, Alexander N. Shchemelev, Elena N. Serikova, Vladimir S. Davydenko, Tran Ton, Truong Thi Xuan Lien, Edward S. Ramsay and Areg A. Totolian
Microorganisms 2026, 14(1), 238; https://doi.org/10.3390/microorganisms14010238 - 20 Jan 2026
Abstract
Background: Vietnam faces a hyperendemic burden of hepatitis B virus (HBV) infection, but the prevalence of occult HBV infection (OBI) and its underlying molecular mechanisms in healthy populations remain poorly understood. This study aimed to characterize the serological and molecular HBV profile [...] Read more.
Background: Vietnam faces a hyperendemic burden of hepatitis B virus (HBV) infection, but the prevalence of occult HBV infection (OBI) and its underlying molecular mechanisms in healthy populations remain poorly understood. This study aimed to characterize the serological and molecular HBV profile of a healthy Vietnamese adult cohort in Southern Vietnam. We assessed the prevalence of occult HBV infection (OBI) and HBsAg-positivity (serving as a proxy for probable chronic infection). Methods: In this cross-sectional study, 397 healthy adults from Southern Vietnam underwent serological screening for HBsAg, anti-HBs, and anti-HBc. All participants were screened for HBV DNA using a high-sensitivity PCR assay (LOD ≥ 5 IU/mL). For all viremic cases, the full Pre-S/S region was sequenced to determine genotype and characterize escape mutations. Results: We uncovered a high prevalence of both HBsAg-positivity (17.6%) and OBI (9.3% HBsAg-negative, HBV DNA-positive). Serological analysis revealed a massive, age-dependent reservoir of past exposure (63.7% anti-HBc) characterized by a high and increasing prevalence of the anti-HBc only profile (31.5%), a key serological marker for OBI. This trend contrasted sharply with a steep age-related decline in protective anti-HBs. The viral landscape was dominated by genotypes B (73.8%) and C (26.2%), with sub-genotypes B4 and C1 being the most prevalent. Critically, individuals with OBI carried a significantly higher burden of S gene escape mutations compared to those with HBsAg-positivity (p < 0.001). Canonical escape variants, including sG145R (21.6%), sK141R/T/E/Q (24.3%), and sT116N/A/I/S (18.9%), were exclusively or highly enriched in the OBI group. A LASSO-logistic model based on this mutational profile successfully predicted occult infection with high accuracy (AUC = 0.83). Conclusions: A substantial hidden reservoir of occult HBV infection exists within the healthy adult population of Vietnam, driven by a high burden of S gene escape mutations. These findings highlight the significant limitations of conventional HBsAg-only screening. They also underscore the need for comprehensive molecular surveillance to address the true scope of HBV viremia, hopefully enabling a reduction in hidden transmission of clinically significant viral variants. Full article
(This article belongs to the Section Virology)
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16 pages, 2240 KB  
Article
Assessment of Liver Fibrosis Stage and Cirrhosis Regression After Long-Term Follow-Up Following Sustained Virological Response
by Lidia Canillas, Dolores Naranjo, Teresa Broquetas, Juan Sánchez, Anna Pocurull, Esther Garrido, Rosa Fernández, Xavier Forns and José A. Carrión
Diagnostics 2026, 16(2), 279; https://doi.org/10.3390/diagnostics16020279 - 15 Jan 2026
Viewed by 161
Abstract
Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study [...] Read more.
Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study evaluating hepatic biopsies and liver stiffness measurement by vibration-controlled transient elastography (VCTE-LSM) after the end of treatment (EOT) in patients with compensated advanced chronic liver disease (cACLD). Fibrosis was evaluated according to two semi-quantitative grading systems (METAVIR and Laennec) at 6 years after EOT (LB6) and compared with biopsies at 3 years (LB3). Results: Fifty-four patients with LB6 (34 with paired LB3–LB6) were included. Median (IQR) age was 53.9 (48.5–59.3), 38 (70.4%) were men, and 13 (24.1%) were HIV-coinfected. The VCTE-LSM was >15 kPa in 30 (55.6%). The LB6 (81.4 months after EOT) showed non-advanced fibrosis (F1–F2) in 12 (22.4%) patients, bridging (F3) in 26 (48.2%), and cirrhosis (F4) in 16 (29.6%): F4A in 7 (13.0%), F4B in 4 (7.4%), and F4C in 5 (9.3%). The 1-year post-EOT follow-up VCTE-LSM ≤ 8.6 kPa identifies patients without advanced fibrosis (AUROC = 0.929), with a negative predictive value of 88.9% and a positive predictive value of 95.2%. Paired biopsies showed regression in 9 (47.4%) out of 19 patients with cirrhosis: 8 (61.5%) of 13 with F4A but only 1 (16.7%) of 6 with F4B–F4C. Conclusions: Advanced fibrosis persists in most patients with advanced chronic liver disease after HCV eradication. Regression is possible in mild cirrhosis. However, it is a limited and slow event. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Liver Diseases)
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21 pages, 4904 KB  
Article
Full-Genome Hepatitis B Virus Genotyping: A Juxtaposition of Next-Generation and Clone-Based Sequencing Approaches—Comparing Genotyping Methods of Hepatitis B Virus
by Li-Ping Hu, Qin-Yan Chen, Mei-Lin Huang, Wen-Jia Zhang, Xiao-Qian Huang, Xian-Feng Yi and Hui-Hua Jia
Viruses 2026, 18(1), 112; https://doi.org/10.3390/v18010112 - 15 Jan 2026
Viewed by 248
Abstract
Background: The enhanced sensitivity of next-generation sequencing (NGS) for assessing hepatitis B virus (HBV) quasispecies heterogeneity over clone-based sequencing (CBS) is well documented. However, its comparative reliability for genotype determination remains an open question. Objective: This study aimed to directly compare the performance [...] Read more.
Background: The enhanced sensitivity of next-generation sequencing (NGS) for assessing hepatitis B virus (HBV) quasispecies heterogeneity over clone-based sequencing (CBS) is well documented. However, its comparative reliability for genotype determination remains an open question. Objective: This study aimed to directly compare the performance of NGS and CBS for genotyping HBV using the entire viral genome. Methods: We selected five challenging clinical samples that previously could not be subgenotyped or showed conflicting results when using direct sequencing of the S open reading frame (ORF). The full HBV genome from these subjects was amplified and then analyzed in parallel by both NGS and CBS. Phylogenetic analysis was subsequently used to assign genotypes. Results: Both methods identified a range of genotypes, including B, C, and I, as well as aberrant and recombinant forms. For three of the five subjects, genotyping results were identical between the two platforms. In the remaining two cases, however, CBS revealed greater complexity, identifying additional subgenotypes and recombinant/aberrant strains not detected by NGS. Notably, for three individuals, the genotypes determined by both modern methods contradicted earlier results from 2011 based on direct S ORF sequencing. Furthermore, the specific mutations detected were incongruent between the platforms, with CBS identifying a higher number of variants than NGS. Conclusions: Our findings indicate that genotyping results from NGS and CBS can be discordant. Contrary to expectations, CBS may uncover more genetic diversity, including a greater number of subgenotypes and mutations, than NGS in certain contexts. The study also confirms that genotyping based solely on direct sequencing of the S ORF can be unreliable and lead to misclassification. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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8 pages, 1301 KB  
Article
Evidence from Outcomes: Gender-Neutral 2vHPV Vaccination at Moderate Coverage Drives Rapid Depletion of HPV16/18 Among Vaccinated and Unvaccinated Women
by Matti Lehtinen, Ville N. Pimenoff, Tiina Eriksson, Camilla Lagheden, Anna Söderlund-Strand, Heljä-Marja Surcel and Joakim Dillner
Viruses 2026, 18(1), 99; https://doi.org/10.3390/v18010099 - 12 Jan 2026
Viewed by 196
Abstract
Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against [...] Read more.
Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these communities (n = 80,272) were invited to participate. Overall, 11,662 males and 20,513 females consented, corresponding to vaccination coverages of 25% and 45%, respectively, in 2007–2009. Between 2010 and 2014, 11,396 cervical samples were collected from 18-year-old participants and subjected to high-throughput PCR-based HPV genotyping. In addition, serum samples were obtained from 8022 unvaccinated women under 23 years of age residing in Arm A (n = 2657), Arm B (n = 2691), or Arm C (n = 2674) communities during the pre-vaccination (2005–2010) and post-vaccination (2011–2016) periods. To assess indirect vaccine effects using PCR and serological outcomes in unvaccinated women, we compared reductions in HPV16/18 prevalence from baseline within the gender-neutral and girls-only vaccination arms, using the control arm as a reference. A significant decrease in seroprevalence between the pre- and post-vaccination periods was detected in the gender-neutral communities for both HPV16 (seroprevalence ratio = 0.64) and HPV18 (0.72), whereas no comparable reductions were observed in the girls-only or control communities. In contrast, a significant reduction in HPV18 PCR-based prevalence from baseline to the post-vaccination period was observed in both the gender-neutral (0.32) and girls-only (0.61) communities. However, after accounting for ratios of seroprevalence rations for secular trends, the corresponding decrease in HPV18 seroprevalence was no longer statistically significant. Vaccine efficacy (VE) in Arm A or Arm B versus Arm C of vaccinated women measured the direct protection of vaccinated women by vaccination strategy. HPV16/18 VEs varied between 89% and 96% with some indication of herd effect against HPV18. Robust effectiveness of vaccination against PCR-confirmed cervical HPV16/18 infections, along with rapid indirect protection against HPV16/18 and HPV18 infections, was evident even with vaccination reaching only 25% and 45% coverage. Our results suggest that vaccine efficacy and herd effect induced by gender-neutral 2vHPV vaccination sets the stage for comprehensive HPV eradication, including the unvaccinated in the vaccinated communities. Full article
(This article belongs to the Special Issue HPV-Associated Cancers 2025)
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18 pages, 1752 KB  
Article
GLP-1 Receptor Agonist Exenatide Protects Against Doxorubicin-Induced Cardiotoxicity Through the SIRT1 Pathway: An Electrocardiographic, 99mTc-PYP Scintigraphic, and Biochemical Study
by Musa Salmanoglu, Gulcin Ercan, Hanife Seyda Genç, Serdar Savaş Gül and Hatice Aygün
Medicina 2026, 62(1), 143; https://doi.org/10.3390/medicina62010143 - 10 Jan 2026
Viewed by 175
Abstract
Background and Objectives: This study was designed to evaluate the potential cardioprotective effect of Exenatide against doxorubicin (DOX)-induced myocardial injury in rats by assessing scintigraphic alterations together with oxidative stress and inflammation. Materials and Methods: This study included 28 adult male Wistar albino [...] Read more.
Background and Objectives: This study was designed to evaluate the potential cardioprotective effect of Exenatide against doxorubicin (DOX)-induced myocardial injury in rats by assessing scintigraphic alterations together with oxidative stress and inflammation. Materials and Methods: This study included 28 adult male Wistar albino rats that were randomized to 4 groups (n = 7): control, Exenatide alone, DOX (receiving DOX (18 mg/kg, i.p) on days 5–7; Exenatide + DOX (treated with Exenatide together with the DOX). On day 8, ECG, 99mTc-PYP scintigraphy, and biochemical parameters were evaluated. Results: DOX caused ECG abnormalities—bradycardia, significant QT prolongation, and elevated ST-segment amplitude—along with increased myocardial PYP uptake. Exenatide + DOX group significantly improved ECG changes. Biochemically, DOX markedly increased cardiac injury biomarkers (cTnT, CK, CK-MB), hepatic and renal injury markers (ALT, AST, LDH, BUN, creatinine), SIRT-1 level, inflammatory marker (NF-κB, TNF-α, IL-6, NO) and oxidative stress indicators (MDA, TOS), while decreasing antioxidant defenses (GSH, TAS, Nrf2). Exenatide co-treatment significantly attenuated all DOX-induced changes. Conclusions: Exenatide markedly attenuates DOX-induced cardiotoxicity by improving electrical conduction, reducing myocardial radiotracer uptake, and restoring oxidative–inflammatory balance through partial recovery of the SIRT-1/Nrf2/NF-κB pathway. Full article
(This article belongs to the Section Pharmacology)
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18 pages, 301 KB  
Article
Impact of Social Drivers of Health, Self-Efficacy, and Substance Use on COVID-19 Preventative Behaviors Among Persons Who Inject Drugs with Hepatitis C: The HERO Study
by Snehal S. Lopes, Irene Pericot-Valverde, Paula J. Lum, Lynn E. Taylor, Shruti H. Mehta, Judith I. Tsui, Judith Feinberg, Arthur Y. Kim, Brianna L. Norton, Kimberly Page, Cristina Murray-Krezan, Jessica Anderson, Alison Karasz, Julia Arnsten, Phillip Moschella, Moonseong Heo, Alain H. Litwin and the HERO Study Group
Int. J. Environ. Res. Public Health 2026, 23(1), 93; https://doi.org/10.3390/ijerph23010093 - 9 Jan 2026
Viewed by 186
Abstract
Background: Personal protective measures help prevent infection and disease transmission during health crises such as Coronavirus disease 2019 (COVID-19). Populations facing barriers to adhering to these measures are more vulnerable to the health crisis. This study investigated the association of social drivers of [...] Read more.
Background: Personal protective measures help prevent infection and disease transmission during health crises such as Coronavirus disease 2019 (COVID-19). Populations facing barriers to adhering to these measures are more vulnerable to the health crisis. This study investigated the association of social drivers of health (SDoH), self-efficacy, and adverse substance use behavior changes with ability to practice COVID-19 personal protective behaviors among persons who inject drugs (PWID) with hepatitis C virus (HCV) infection history. Methods: This study used the Hepatitis C Real Options (HERO) study’s COVID-19 survey data (n = 157). The association of inability to practice COVID-19 personal protective behaviors (hand washing, social distancing, etc.) with (a) SDoH difficulties (employment, housing, etc.); (b) adverse substance use behavior change (overdose, injecting behavior, etc.); and (c) self-efficacy was tested using logistic regression. Results: Inability to practice any personal protective behaviors was more likely among those experiencing any vs. no SDoH difficulties [adjusted odds ratio (aOR) (95% confidence interval (CI))] = 4.57 (1.57, 16.40); p = 0.003] but less likely for those with higher overall self-efficacy [aOR (95% CI) = 0.55 (0.32, 0.93); p = 0.025] and self-efficacy for setting goals [aOR (95% CI) = 0.63 (0.40, 0.96); p = 0.031]. The association between adverse substance use behavior changes and the outcome was not significant. Conclusions: Greater SDoH difficulties and lower self-efficacy were associated with greater inability to practice COVID-19 personal protective behaviors. Interventions to meet SDoH-related challenges and increase self-efficacy could help encourage practice of personal protective behaviors and economically reduce disease burden during health crises. Full article
29 pages, 980 KB  
Review
Ketamine in Diabetes Care: Metabolic Insights and Clinical Applications
by Shiryn D. Sukhram, Majandra Sanchez, Ayotunde Anidugbe, Bora Kupa, Vincent P. Edwards, Muhammad Zia and Grozdena Yilmaz
Pharmaceutics 2026, 18(1), 81; https://doi.org/10.3390/pharmaceutics18010081 - 8 Jan 2026
Viewed by 312
Abstract
Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a [...] Read more.
Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a scoping review following PRISMA-ScR. MEDLINE/PubMed, CINAHL, and APA PsycInfo were searched (January 2020–31 May 2025). Eligible human and animal studies evaluated ketamine, esketamine, or norketamine in the context of diabetes (type 1 [T1DM], type 2 [T2DM], gestational [GDM]), or DN, and reported psychiatric, analgesic, metabolic, or mechanistic outcomes. Two reviewers independently screened and charted data; no formal risk-of-bias assessment was performed. Results: Eleven studies met inclusion criteria: four human case reports/series (three T1DM, one T2DM), one randomized trial in GDM, two narrative reviews of topical ketamine for DN, and four preclinical rodent studies using streptozotocin- or diet-induced diabetes models. Short-term improvements were reported for treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative analgesia in GDM. Glycemic effects varied across settings, with both hyperglycemia and hypoglycemia reported. Mechanistic and clinical drug–drug and drug-disease interactions (particularly involving metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and CYP3A4/CYP2B6 modulators) remain insufficiently studied. We outline a forward-looking population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK-PD) research agenda, including priority covariates (eGFR, hepatic function, inflammatory status, HbA1c, genotype, co-medications) and sparse-sampling windows for future model-informed precision dosing. Conclusions: Current evidence supports cautious, selective use of ketamine for refractory depression and DN within multidisciplinary diabetes care. Purpose-built popPK/PK-PD studies in both human and preclinical diabetic models cohorts are needed to quantify variability, define drug–disease–drug interactions and glycemic risk, and inform individualized dosing strategies. Full article
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17 pages, 922 KB  
Article
Demographics and Prevalence of HBV, HCV, and Syphilis Among the Female Sex Workers of Daulatdia, Bangladesh: A Cross-Sectional Study
by Md. Ahsanul Haque, Rahima Begum, Md. Zulfekar Ali, Dewan Zubaer Islam, Ashikur Rahman, Ismail Khalil and Shahad Saif Khandker
Venereology 2026, 5(1), 3; https://doi.org/10.3390/venereology5010003 - 7 Jan 2026
Viewed by 446
Abstract
Background: In Bangladesh, a number of sex workers are involved in commercial sex work in different brothels in both legal and illegal settlements due to reasons such as lack of social support, depression, forced sex, abuse, violence, polyamory, being kidnapped, and unemployment. [...] Read more.
Background: In Bangladesh, a number of sex workers are involved in commercial sex work in different brothels in both legal and illegal settlements due to reasons such as lack of social support, depression, forced sex, abuse, violence, polyamory, being kidnapped, and unemployment. In this study, we tried to evaluate the demographic characteristics and prevalence of viral and sexually transmitted diseases (STDs) among the study population. Methods: A total of 250 female sex workers were interviewed and tested from the Daulatdia brothel of Rajbari district, Bangladesh, who had been working there for at least 1 month. Through questionnaires, demographic data were collected. Primarily, lateral flow immunoassay (LFIA) tests were used to investigate HCV (Hepatitis C Virus), HBV (Hepatitis B Virus), and Syphilis, which were reconfirmed using enzyme-linked immunosorbent assay (ELISA) in cases of positive results. Results: The mean age was 27.51 ± 6.69 years with a range of 18–50 years. Most of them (n = 243, 97.98%) had elementary knowledge of STDs. We determined that overall, 96 (38.40%) were positive for either of these diseases. Individually, 10 (4.00%), 18 (7.20%), and 68 (27.20%) were positive for HCV, HBV, and syphilis, respectively. Conclusions: Our observation indicates that females of all ages should be strictly protected from forced sex work. Current sex workers should be educated regarding the dangers and protective mechanisms of STDs. In addition, as a public health concern, regular clinical check-ups and STD associated diagnoses are necessary to ensure the safety of FSW from these highly infectious and concerning diseases. Due to their socio-economic condition, proper treatment and rehabilitation are highly recommended. Full article
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12 pages, 1068 KB  
Article
Microvesicle Profiles in Patients with HIV, HBV, and HCV Infections: An Exploratory Pilot Study
by Georgios Dryllis, Sotirios P. Fortis, Nikolaos Martsoukos, Vasiliki Pantazatou, Evgenia Spyropoulou, Despoina Pontikaki, Christelos Kapatais, Nikolaos Tsakalis, Andrianna Konstantelou, Eleni Myrto Trifylli, Andreas G. Tsantes, Effie G. Papageorgiou, Serena Valsami, Andreas Kapatais, Olga Kosmopoulou and Anastasios G. Kriebardis
Microorganisms 2026, 14(1), 124; https://doi.org/10.3390/microorganisms14010124 - 7 Jan 2026
Viewed by 230
Abstract
Microvesicles (MVs) are extracellular vesicles released from many cell types under physiological and pathological conditions, influencing viral transmission, immune regulation, and inflammation. This exploratory pilot study characterized and compared plasma MV profiles in patients infected with human immunodeficiency virus (HIV), hepatitis B virus [...] Read more.
Microvesicles (MVs) are extracellular vesicles released from many cell types under physiological and pathological conditions, influencing viral transmission, immune regulation, and inflammation. This exploratory pilot study characterized and compared plasma MV profiles in patients infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Plasma samples (n = 125; HIV: 25, HBV: 50, HCV: 50) were analyzed using nanoparticle tracking analysis (NanoSight NS300) to assess MV size and concentration, classifying them as small (<300 nm) or large (>300 nm). Patients with HBV exhibited significantly larger mean MV size compared with both patients with HIV (131.5 ± 14.6 nm vs. 113.1 ± 14.0 nm, p < 0.0001) and HCV (131.5 ± 14.6 nm vs. 118.0 ± 18.5 nm, p = 0.0002). HCV infection showed higher concentrations of large MVs than HIV (p = 0.0022), while total and small MV levels did not differ. No sex-related differences were detected. Distinct MV size distributions appear linked to chronic viral infections, with HBV and HCV showing greater alterations than HIV. MVs may serve as potential biomarkers reflecting infection-associated biological processes; however, mechanistic, or functional roles were not assessed in this study and will require dedicated future investigations in larger controlled studies. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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24 pages, 2198 KB  
Article
Impact of SLCO1B1 Polymorphism and Vitamin D Status on Statin Efficacy and Tolerability in Postmenopausal Women
by Romana Marušić, Dunja Šojat, Tatjana Bačun, Nenad Nešković, Željko Debeljak, Mirna Glegj, Melita Vukšić Polić and Saška Marczi
Biomedicines 2026, 14(1), 113; https://doi.org/10.3390/biomedicines14010113 - 6 Jan 2026
Viewed by 290
Abstract
Background: Interindividual differences in statin efficacy and tolerability are partly determined by genetic and metabolic factors. The SLCO1B1 c.521T>C polymorphism affects hepatic statin transport, while vitamin D deficiency may influence lipid metabolism and muscular tolerance. This study aimed to assess the impact [...] Read more.
Background: Interindividual differences in statin efficacy and tolerability are partly determined by genetic and metabolic factors. The SLCO1B1 c.521T>C polymorphism affects hepatic statin transport, while vitamin D deficiency may influence lipid metabolism and muscular tolerance. This study aimed to assess the impact of SLCO1B1 genotype and vitamin D status on lipid-lowering response and adverse events in postmenopausal women treated with atorvastatin or rosuvastatin. Methods: A total of 145 Croatian postmenopausal women were prospectively followed for 16 weeks. Participants received atorvastatin or rosuvastatin with dose titration to achieve low-density lipoprotein cholesterol (LDL-C) targets. Serum lipids, liver enzymes, and creatine kinase were monitored monthly. Serum levels of 25-hydroxyvitamin D were quantified by LC–MS/MS, while SLCO1B1 c.521T>C genotyping was performed using real-time PCR. Results: Rosuvastatin achieved a higher LDL-C target attainment rate compared with atorvastatin (81.1% vs. 67.6%, p = 0.02). The SLCO1B1 genotype was not associated with lipid response but was significantly associated with adverse effects. In multivariable regression analysis, patients with the T/C genotype had a significantly higher risk of developing adverse effects compared with those with the T/T genotype (OR 7.4, 95% Cl 2.1–26.7, p = 0.002). Vitamin D status showed no significant association with lipid outcomes or adverse events, although participants with severe deficiency exhibited a weaker LDL-C response. Conclusions: Rosuvastatin demonstrated superior lipid-lowering efficacy and tolerability compared with atorvastatin in postmenopausal women. The SLCO1B1 c.521T>C variant primarily affected safety rather than efficacy, while severe vitamin D deficiency might contribute to diminished statin response. Integrating pharmacogenetic and endocrine profiling could enhance individualized statin therapy and cardiovascular prevention in women. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Current Progress and Future Challenges)
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16 pages, 937 KB  
Review
The Dawn of Precision Medicine in Pediatric Nephrology: Lumasiran and the Era of siRNA Therapies for Primary Hyperoxaluria Type 1
by John Dotis and Maria Fourikou
J. Pers. Med. 2026, 16(1), 15; https://doi.org/10.3390/jpm16010015 - 2 Jan 2026
Viewed by 297
Abstract
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that causes progressive renal failure, nephrolithiasis, and nephrocalcinosis in children. It is characterized by hepatic overproduction of oxalate. Conventional management, which involves combined liver–kidney transplantation, vitamin B6 supplementation, and intense hydration, does [...] Read more.
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that causes progressive renal failure, nephrolithiasis, and nephrocalcinosis in children. It is characterized by hepatic overproduction of oxalate. Conventional management, which involves combined liver–kidney transplantation, vitamin B6 supplementation, and intense hydration, does not address the underlying metabolic defect for most patients and it generally provides only supportive care. The first approved disease-modifying treatment for pediatric PH1 is Lumasiran, a small interfering RNA (siRNA) therapeutic. By specifically inhibiting the hepatic glycolate oxidase mRNA, Lumasiran lowers the production of oxalate at its origin. Along with fewer kidney stone events and stabilization of nephrocalcinosis, clinical trials (ILLUMINATE-A/B/C) showed significant decreases in urinary oxalate excretion. The most frequently reported adverse event is mild injection-site reactions, which are generally well tolerated. The molecular mechanism, pharmacokinetics, and clinical effectiveness of Lumasiran in children with PH1 are compiled in this review. We go over possible long-term safety concerns, the impact of early intervention on renal outcomes, and the function of siRNA therapies in pediatric precision medicine. Furthermore, we highlight Lumasiran’s importance as a model for targeted treatment in uncommon pediatric kidney diseases by considering it in the larger context of RNAi-based therapies. A paradigm shift in pediatric nephrology is signaled by Lumasiran, which changes the therapeutic approach from supportive care to precision, targeted medicine. Further research and empirical data will clarify its long-term advantages, the best ways to treat it, and the possible use of siRNA technologies for other genetic renal disorders. Full article
(This article belongs to the Section Mechanisms of Diseases)
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Article
Alleviation of Aflatoxin B1-Induced Hepatic Damage by Propolis: Effects on Inflammation, Apoptosis, and Cytochrome P450 Enzyme Expression
by Sevtap Kabalı, Neslihan Öner, Ayca Kara, Mehtap Ünlü Söğüt and Zehra Elgün
Curr. Issues Mol. Biol. 2026, 48(1), 56; https://doi.org/10.3390/cimb48010056 - 1 Jan 2026
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Abstract
AflatoxinB1 (AFB1) is a hepatotoxic mycotoxin whose bioactivation by cytochrome P450 (CYP450) enzymes generates reactive metabolites that drive oxidative stress, inflammation, and apoptosis. Propolis is a bee-derived product with antioxidant and immunomodulatory properties. To investigate whether propolis supplementation attenuates AFB1-induced hepatic injury [...] Read more.
AflatoxinB1 (AFB1) is a hepatotoxic mycotoxin whose bioactivation by cytochrome P450 (CYP450) enzymes generates reactive metabolites that drive oxidative stress, inflammation, and apoptosis. Propolis is a bee-derived product with antioxidant and immunomodulatory properties. To investigate whether propolis supplementation attenuates AFB1-induced hepatic injury by modulating inflammatory mediators, Nrf2–HO-1 signaling, mitochondrial apoptosis, and CYP450 expression in rats, twenty-four male Sprague-Dawley rats were randomly allocated to four groups (n = 6): control, AFB1 (25 µg/kg/day), propolis (250 mg/kg/day), and AFB1 + propolis. Treatments were given by oral gavage for 28 days. Hepatic IL-1β, IL-6, TNF-α, Nrf2 and HO-1 levels were measured by ELISA. Histopathology was assessed on H&E-stained sections. Bax, Bcl-2, caspase-3, CYP1A2, CYP3A4, CYP2C19 and cytochrome P450 reductase expressions were evaluated immunohistochemically and quantified by ImageJ. Data were analyzed using one-way ANOVA with Tukey’s post hoc test. AFB1 significantly increased hepatic IL-1β and IL-6 and reduced Nrf2 levels, while propolis supplementation restored Nrf2, elevated HO-1 and significantly lowered IL-6 compared with AFB1 alone (p < 0.05). AFB1 induced marked hydropic degeneration, sinusoidal congestion, and mononuclear infiltration, alongside increased Bax and caspase-3 and decreased Bcl-2 expression; these changes were largely reversed in propolis-treated groups. AFB1 upregulated CYP1A2, CYP3A4 and cytochrome P450 reductase, whereas propolis co-treatment significantly suppressed their expression without affecting CYP2C19. Propolis supplementation attenuated AFB1-induced liver injury through coordinated anti-inflammatory, antioxidant, anti-apoptotic and metabolic regulatory effects, notably via restoration of Nrf2–HO-1 signaling and down-regulation of key CYP450 isoenzymes. Propolis may represent a promising natural dietary strategy against AFB1-associated hepatotoxicity, warranting further translational research. Full article
(This article belongs to the Section Molecular Pharmacology)
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14 pages, 17952 KB  
Case Report
Primary Hepatic Squamous Cell Carcinoma
by Soo Ryang Kim, Soo Ki Kim, Hisato Kobayashi, Toyokazu Okuda, Yumi Fujii, Makiho Sakamoto, Yu-ichiro Koma, Osamu Nakashima, Motoko Sasaki, Akira Asai and Hiroki Nishikawa
Diagnostics 2026, 16(1), 120; https://doi.org/10.3390/diagnostics16010120 - 1 Jan 2026
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Abstract
Background and Clinical Significance: We present an 85-year-old male case of primary hepatic SCC manifesting as multiple liver nodules with atypical imaging findings. Case Presentation: The patient was negative for hepatitis B surface antigen and hepatitis C virus antibody. Serum tumor markers were [...] Read more.
Background and Clinical Significance: We present an 85-year-old male case of primary hepatic SCC manifesting as multiple liver nodules with atypical imaging findings. Case Presentation: The patient was negative for hepatitis B surface antigen and hepatitis C virus antibody. Serum tumor markers were all within normal limits. Contrast-enhanced ultrasonography with perflubutane demonstrated hypervascular nodules in the early vascular phase, early washout in the portal phase, and a defect in the postvascular phase (10 mm in S5 and 25 mm in S6). Histopathological examination revealed irregularly shaped tumor cells with large hyperchromatic nuclei and basophilic cytoplasm, surrounded by dense fibrous stroma forming cords, solid nests, and sheet-like structures. Immunohistochemical analysis showed positivity for AE1/AE3, p40, CK5/6, c-kit, and NCAM. Conclusions: The lesions were diagnosed as primary hepatic squamous cell carcinoma and suggested the possible involvement of hepatic progenitor cells, supporting the hypothesis of de novo carcinogenesis. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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32 pages, 1753 KB  
Review
Vaccination Strategies Against Hepatic Diseases: A Scoping Review
by Zahra Beyzaei, Bita Geramizadeh, Sara Karimzadeh and Ralf Weiskirchen
Vaccines 2026, 14(1), 49; https://doi.org/10.3390/vaccines14010049 - 31 Dec 2025
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Abstract
Background/Objectives: Viral hepatitis remains a significant global cause of chronic liver disease, highlighting the importance of effective vaccination strategies. This review assesses recent evidence on vaccine safety and effectiveness. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Scopus [...] Read more.
Background/Objectives: Viral hepatitis remains a significant global cause of chronic liver disease, highlighting the importance of effective vaccination strategies. This review assesses recent evidence on vaccine safety and effectiveness. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Scopus identified English-language studies published from January 2000 to September 2025. Eligible studies evaluated vaccination for hepatitis A, B, C, or E, as well as vaccine responses in individuals with chronic liver disease or HIV infection. Of 5254 records screened, 166 studies met the inclusion criteria. Results: Hepatitis A vaccines demonstrated excellent safety, 95–100% short-term seroprotection, and durable immunity for both inactivated and live-attenuated formulations, with population-level reductions in disease incidence. Hepatitis B vaccines showed consistently strong immunogenicity across age groups, with over 90% seroprotection from recombinant and CpG-adjuvanted formulations. Effective prevention of mother-to-child transmission required maternal antiviral therapy, timely birth-dose vaccination, hepatitis B immunoglobulin (HBIG) administration, and post-vaccination serologic testing. Long-term data demonstrated immune persistence for up to 35 years and significant reductions in liver cancer following neonatal HBV vaccination. Limited studies in hepatitis C populations showed impaired responses, partially improved with higher or booster doses. Hepatitis E vaccines showed excellent safety and over 99% seroconversion. In non-viral liver disease and post-transplant populations, vaccine responses were reduced but remained clinically meaningful, especially with adjuvanted or higher-dose HBV vaccines. Among HIV-infected individuals, HAV vaccination was generally effective, while enhanced HBV regimens markedly improved seroprotection. Conclusions: Hepatitis A, B, and E vaccines are safe, immunogenic, and effective, with neonatal hepatitis B vaccination critical for preventing maternal transmission. No licensed HCV vaccine exists, and therapeutic HCV vaccines show limited efficacy. Optimized and targeted vaccination strategies are needed for individuals with chronic liver disease, HIV infection, HCV infection, transplant recipients, and other immunocompromised populations to maximize public health impact. Full article
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
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