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ABSTRACT Objective Methods Results Conclusion Primary liver cancer (PLC) is projected to be the third leading cause of cancer mortality in the United States in 2040. We examine the burden of PLC in the United States, stratified by sex, state and aetiological risk factors.Data on PLC prevalence, incidence, death and disability–adjusted life years (DALYs) were extracted from the Global Burden of Disease Study 2021. Changes in these parameters were calculated using the Joinpoint regression model.There were 47,970 cases, 31,450 incident cases, 24,770 deaths and 576,920 DALYs from PLC in the United States. The highest prevalence (16,980), incidence (12,040), death (9840) and DALYs (213,410) from PLC were due to chronic hepatitis C virus infection. From 2000 to 2021, PLC incidences increased by 141%, and PLC deaths increased by 136%. Age–standardised incidence rates (ASIRs) and death rates (ASDRs) per 100,000 population for PLC increased, primarily driven by alcohol–related liver disease (ALD) (ASIR: annual percent change [APC]: +2.40%; ASDR: APC: +2.22%) and metabolic dysfunction–associated steatotic liver disease (MASLD) (ASIR: APC: +2.32%; ASDR: APC: +2.04%).The burden of PLC in the United States has risen in the past two decades, driven mainly by ALD and followed by MASLD. These findings offer policymakers an accurate assessment of the PLC burden and emphasise the need for targeted risk factor mitigation, especially regarding alcohol related policy. [ABSTRACT FROM AUTHOR]

Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH. Aims: In the US multicentre SHUNT‐V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy. Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut‐off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%. Results: SHUNT‐V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child–Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%–100% for LEV and 97.3%–100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%–35% of EGDs could have been avoided with 0%–3.7% of LEV and 0%–2.7% of all significant PH lesions missed. Conclusions: HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal‐systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child–Pugh A cirrhosis. Trial Registration: The SHUNT‐V study was registered at ClinicalTrials.gov (NCT03583996) [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains a significant global health issue. Drug-resistant TB and comorbidities exacerbate its burden, influencing treatment outcomes and healthcare utilization. Despite the growing prevalence of TB comorbidities, research often focuses on single comorbidities rather than comorbidity patterns. This study aims to evaluate comorbidity patterns among TB inpatients in Northeastern China from 2013 to 2021 and investigate the association between comorbidities and drug-resistance with length of hospital stay (LOS). Our findings could enhance the understanding of TB comorbidity interactions and provide evidence for targeted morbidity management strategies. Methods: Network analysis was used to evaluate comorbidity patterns, estimating centrality indices to understand the structural importance of each comorbidity. The Walktrap algorithm was used to identify clusters of highly connected comorbidities. Networks of drug-susceptible and drug-resistant TB inpatients were compared. Multivariable linear regression models were used to assess the associations between LOS with comorbidities and drug resistance. Results: A total of 2,352 TB inpatients were included, with a median LOS of 31 (IQR: 16–51) days. Inpatients with multidrug-resistant TB (β = 12.88, 95%CI = 8.03–17.73), chronic hepatitis C (β = 31.89, 95%CI: 4.41–59.37), pneumonia (β = 37.14, 95%CI: 12.53 – 61.76), pneumoconiosis (β = 28.40, 95%CI: 11.92 – 44.87), pneumothorax (β = 19.88, 95%CI: 4.97 – 34.80), and dermatitis/eczema (β = 56.54, 95%CI: 8.18 – 104.89) were significantly associated with longer LOS. Frequent comorbidities included liver dysfunction(15.2%), hypoproteinemia (14.4%), diabetes (14.2%), pleural effusion (11.3%), and emphysema (10.2%). Hypoproteinemia showed high structural importance in the network, ranking second in strength and highest in betweenness. Nine clusters of comorbidities were detected. No significant differences were found between the networks of drug-sensitive and drug-resistant TB inpatients, except for the greater strength of cholecystitis among drug-resistant inpatients. Conclusions: Early detection and management of drug-resistant TB and comorbidities that prolong LOS, as well as those with structural importance or within the same cluster in the comorbidity network, are crucial for improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Neprilysin (NEP) is a metalloprotease that has become a therapeutic target for the treatment of heart failure and hypertension. However, the significance of NEP in chronic liver diseases has rarely been investigated. In this study, we investigated the serum NEP levels in patients with chronic liver disease and their relationship with clinical parameters. Methods and results: Thirty-seven patients with chronic hepatitis C (CHC) who achieved sustained virologic response (SVR) after antiviral treatment and 73 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled. Serum neprilysin levels were measured using an enzyme-linked immunosorbent assay. The median NEP levels were 2.2 ng/mL in CHC and 4.1 ng/mL in MASLD, with the latter being significantly higher. Notably, in patients with MASLD, a significant correlation was observed between NEP and gamma-glutamyltransferase (GGT) levels at baseline. In contrast, there was no significant correlation between NEP levels and progression of liver fibrosis in either group. In the MASLD group, obesity and lifestyle diseases were significantly more prevalent, and the patients exhibited significantly higher NEP levels. In patients with CHC, NEP levels significantly decreased after SVR. NEP mRNA expression in liver tissues was significantly downregulated following SVR. Furthermore, a significant correlation was observed between the degree of NEP and GGT improvement. Conclusions: Elevated NEP levels were observed in both CHC and MASLD groups. Considering the association between NEP levels and obesity, lifestyle diseases, and GGT levels, this suggests that oxidative stress may be involved in the elevation of NEP levels in patients with CHC and MASLD. [ABSTRACT FROM AUTHOR]

Background: Hepatocyte nuclear factors were first identified as liver-enriched transcription factors that might participate in various activities related to the transcription of genes unique to the liver. Objective: The study aimed to reveal the impact of HNF1A gene variations on disease progression in hepatocellular carcinoma (HCC) patients and its relation to serum alpha-fetoprotein level. Methods: Participants in the study were classified as Group I, 32 HCC patients; Group II, 36 chronic hepatitis C patients; and Group III, 26 healthy volunteers as a control group. Each patient underwent full history taking, thorough clinical examination, and radiological examination. Furthermore, tumor staging was done using BCLC staging system. HNF1A gene polymorphisms (rs 2,464,196 and rs 1,169,310) were genotyped by real-time PCR. Results: The findings revealed the highest frequency of AA and GA genotypes of HNF1A (rs2464196) polymorphism in both HCC (P = 0.002) and chronic HCV (P = 0.004) patients in comparison with controls. Regarding rs1169310gene polymorphism, no significant variation was observed across various genotypes when comparing the experimental groups to the control group. Additionally, HCC patients harboring the AA genotype for rs2464196 had significantly increased AFP (≥ 200 ng/ml) levels, whereas HCC patients with rs1169310 SNPs for HNF1A had no significant association regarding the AFP level. Conclusion: The rs2464196 polymorphism of HNF1 is associated with increased AFP levels and HCC disease progression, which may be a prognostic and diagnostic genetic indicator. [ABSTRACT FROM AUTHOR]

Background: The wave of wartime migration from Ukraine has raised a number of concerns about infectious diseases, the prevalence of which is higher in Ukraine than in host countries, with hepatitis C virus (HCV) infection being one of them. Our analysis aimed to assess the percentage of HCV-infected Ukrainian refugees under care in Polish centers providing antiviral diagnosis and therapy, to evaluate their characteristics and the effectiveness of treatment with direct-acting antiviral drugs (DAAs). Methods: The analysis included patients of Polish and Ukrainian nationality treated for HCV infection between 2022 and 2024 in Polish hepatology centers. Data were collected retrospectively and completed online. Results: In the population of 3911 patients with chronic hepatitis C treated with DAAs in 16 Polish centers in 2022–2024, there were 429 war refugees from Ukraine, accounting for 11% of the total treated. The Ukrainian population was significantly younger (45.7 vs. 51 years, p < 0.001) and had a higher percentage of women (50.3% vs. 45.3%, p = 0.048) compared to Polish patients. Patients of Ukrainian origin had less advanced liver disease and were significantly less likely to have comorbidities and the need for comedications. Coinfection with human immunodeficiency virus was significantly more common in Ukrainians than in Polish patients, 16.1% vs. 5.9% (p < 0.001). The distribution of HCV genotypes (GTs) also differed; although GT1b predominated in both populations, its frequency was significantly higher in the Polish population (62.3% vs. 44.5%, p < 0.001), while the second most common GT3 was significantly more common in Ukrainian patients (30.5% vs. 16.2%, p < 0.001). Conclusions: Documented differences in patient characteristics did not affect the effectiveness of antiviral therapy, which exceeded 97% in both populations, but there was a higher rate of those lost to follow-up among Ukrainian patients. [ABSTRACT FROM AUTHOR]

Background The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%–12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. Methods We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. Results The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0–92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0–93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0–87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0–99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0–100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. Discussion At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment. [ABSTRACT FROM AUTHOR]

The article discusses a study on transient CD4 cell recovery in HIV/hepatitis C coinfected patients after successful hepatitis C treatment. The study found a temporary increase in CD4 cell count after hepatitis C treatment initiation, but no sustained effect. The clinical significance of this increase is uncertain, and further research is needed to explore factors influencing immune recovery post-hepatitis C cure in individuals living with HIV. The study highlights the need for larger cohorts and longer follow-up periods to investigate these changes in more detail. [Extracted from the article]

Medical devices made of substances (MDMS) have recently gained great popularity in several specialties of internal medicine, including gastroenterology. In the last decades this discipline has known relevant advances in the cure of severe diseases, such as peptic ulcer, gastroesophageal reflux disease and chronic hepatitis C, thanks to the revolutionary development of new drugs able to act on single receptors changing a particular cell function or blocking microbial and viral replication. However, there are many gastroenterological illnesses that are difficult to treat with traditional medicinal products because of their complex and poorly known pathophysiology, which comprises altered motility, visceral hypersensitivity, gut dysbiosis, intestinal mild inflammation with impaired immune function, increased mucosal permeability and abnormal brain-gut interaction. They are mainly represented by esophageal functional disorders (reflux hypersensitivity, functional heartburn), functional dyspepsia, irritable bowel syndrome, functional constipation and functional diarrhea. Traditional drugs do not provide a definitive resolution of these disorders with a multifactorial pathogenesis and they can benefit from the use of MDMS, which seem to have the ability to act on different factors thanks to the synergistic action of their various components. International medical literature already reports many clinical trials performed with the well-known standards for evaluating their efficacy and safety in a great part of the above-mentioned conditions. [ABSTRACT FROM AUTHOR]

Objective: Hepatitis C virus (HCV) infection is known to influence the seminal and hormonal parameters of infected men. This study was performed to assess the effects of HCV clearance using direct-acting antiviral (DAA) agents on semen and hormonal parameters. Methods: A total of 50 patients with chronic HCV were enrolled, and conventional semen analysis was performed according to World Health Organization guidelines. Basal levels of total testosterone, free testosterone (FT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, and sex hormone-binding globulin (SHBG) were assessed before and 3 months after treatment with DAAs. Results: Following DAA treatment, statistically significant increases were observed in sperm motility and the proportion of grade A sperm. Additionally, the percentage of abnormal forms was significantly decreased after treatment (p=0.000). However, no significant differences were observed in semen volume, concentration, or total sperm count. Sex hormone analysis of patients after DAA treatment revealed significant increases in FT, LH, and FSH levels, along with significant decreases in SHBG, prolactin, and E2 levels. Conclusion: Following HCV clearance, we noted an improvement in sperm motility and an increase in the percentage of sperm with normal morphology. Treatment with DAAs was also associated with increased levels of FT and LH, along with decreased levels of SHBG, prolactin, and E2. [ABSTRACT FROM AUTHOR]

Background & Aims: Pan-genotypic ribavirin-free oral direct-acting antivirals, including the glecaprevir/pibrentasvir combination, are recommended for the treatment of most patients with chronic hepatitis C virus (HCV) infection. In Romania, the HCV-infected patient population receiving glecaprevir/pibrentasvir is not well characterized and data on treatment effectiveness is lacking. The ODYSSEY study aimed to provide insights into the characteristics and treatment outcomes of HCV-infected Romanian patients receiving 8-week therapy with glecaprevir/pibrentasvir. Methods: This observational, retrospective medical chart review study was based on a Patient Support Program for HCV-infected patients (HCV-PSP) attending clinical practices in Romania and initiating glecaprevir/ pibrentasvir between 01 February 2022 and 11 July 2023. Patients ≥18 years of age with compensated liver disease F0-F4 fibrosis grade treatment-naïve or F0-F3 fibrosis grade treatment-experienced on previous interferon-based regimens from the HCV-PSP were included in the ODYSSEY study. Patients received glecaprevir/pibrentasvir for at least 8 weeks. Sustained virological response (SVR) was assessed at 12 weeks after the 8-week treatment (SVR12). Analyses were conducted on the core population (CP) and the CP with sufficient follow-up data (CPSFU). Results: The CP and CPSFU included 2,240 and 2,165 patients, respectively. In both populations, most patients were female (≥67.57%), aged >50 years (≥73.62%), and treatment-naïve (≥96.47%). F4 fibrosis was reported in 19% of patients. Hypertension was the most common relevant comorbidity, reported for 21% of patients; comorbidity rates increased with age. Overall SVR12 rates were 96.1% [95% confidence interval (CI): 95.2-96.8%) and 99.3% (95%CI: 98.9--99.6) in the CP and CPSFU, respectively. When stratified by gender, age category, comorbidities or fibrosis grade, SVR12 rates were >92% in the CP [except for the subgroups of patients with chronic kidney disease (87.5%) and depressive-/anxiety disorders (86.2%)] and ≥97.0% in the CPSFU. SVR12 rates were higher in female patients. In an exploratory analysis, in the CPSFU, the presence of diabetes mellitus [odds ratio (OR)=3.840; 95%CI: 1.093--13.495] and cardiovascular diseases (OR=7.904; 95%CI: 1.719-36.346) were associated with an increased probability to detect HCV RNA at 12 weeks post-treatment. Conclusions: The 8-week treatment with glecaprevir/pibrentasvir resulted in high SVR12 rates for multiple HCV-infected patient profiles encountered in real-life settings in Romania. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and other cardiometabolic risk factors. MASLD has rapidly become the most common cause of liver disease worldwide, currently affecting 38% of the global population. Excess weight causes chronic inflammation and the activation of different pathways involved in liver damage. MASLD can progress from simple steatosis to steatohepatitis, giving way to its inflammatory component, metabolic dysfunction-associated steatohepatitis (MASH), previously recognized as non-alcoholic steatosis hepatitis (NASH). Chronic hepatitis C virus (HCV) infection remains a significant challenge to liver health as it triggers hepatic inflammation, metabolic disruption, and hepatic steatosis. The convergence of MASLD and chronic HCV infection can significantly alter the course of liver disease and accelerate the progression to severe liver damage. Currently, HCV treatment has a high cure rate. However, in patients who achieve a sustained virological response after treatment with direct-acting antivirals, weight gain, and excessive calorie intake may contribute to increased liver steatosis and a higher risk of liver disease progression. Therefore, the effective clinical and nutritional management of HCV patients, both before and after viral eradication, is crucial to reducing the risk of death from hepatocellular carcinoma. Understanding the complex interactions between MASLD and HCV infection is crucial for managing these patients appropriately. Herein, host and viral mechanisms inducing liver damage during the coexistence of MASLD and HCV infection are described, and their therapeutic and dietary management are discussed. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs. [ABSTRACT FROM AUTHOR]

The article discusses the seroconversion of rheumatoid factor (RF) before the onset of rheumatoid arthritis (RA) in patients with interstitial lung disease (ILD). It highlights the detection of RA autoantibodies, including RF and anti-cyclic citrullinated peptide (CCP) antibodies, before the onset of RA in patients with ILD. The study found a significant increase in RF levels in patients with ILD preceding RA, suggesting a potential link between ILD and the development of RA. The research emphasizes the importance of monitoring RF levels in patients with ILD to predict the risk of developing RA. [Extracted from the article]

Objective To construct a risk prediction model for liver cancer in patients with chronic hepatitis C based on seven different machine learning algorithms and select the optimal model. Methods A total of 236 patients with chronic hepatitis C were selected as the research subjects. Patients were divided into a case group and a control group according to whether liver cancer occurs. Prediction models were constructed based on seven machine learning algorithms including classification and regression tree, random forest, gradient boosting decision tree, extreme gradient boosting (XGBoost), logistic regression, K-near neighbor, and support vector machine. The Shapley additive explanations (SHAP) algorithm was used to interpret the best prediction model. Results Among the seven models, the XGBoost model had the best comprehensive prediction performance (accuracy of 0.933, sensitivity of 0.775, specificity of 0.960, area under the ROC curve of 0.956, F1 score of 0.764). The SHAP algorithm suggested that AFP, age, AST, diabetes, BMI, PLT, ALT, liver cysts, FIB-4, and gender contributed to the model decision and are the risk factors for liver cancer in patients with chronic hepatitis C. Conclusion This study develops an interpretable machine learning model based on the XGBoost algorithm, which has a good reference value for individualized monitoring of liver cancer in patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Background: Diagnosis is essential for engagement in care for chronic hepatitis B (CHB) and chronic hepatitis C (CHC), however, many Australians remain undiagnosed, especially for CHB. Primary care represents an important setting for testing, and this study sought to examine coverage in a large representative cohort of patients. Methods: We analysed retrospective data from the electronic medical records of active patients visiting 566 primary care clinics in Victoria, Australia. Pathology records were assessed to identify the proportion of patients with a record of CHB/CHC serology testing based on risk factors identified in national guidelines (ethnicity, Indigenous status, history of injecting drug use, diagnosed HIV, and/or indications of liver disease). Results: Of 1,593,774 patients, 393,948 (24.7%) had an indication for testing for CHB and/or CHC, of which 150,821 (38.3%) had evidence of testing. This proportion was highest in patients with HIV (65.6%) or injecting drug use history (60.0%), and lowest for those whose Indigenous status/ethnicity indicated testing (38.2%) or with elevated liver enzymes (39.1%). The proportion with evidence of testing was only moderate among those with a cirrhosis diagnosis (48.6%) or probable cirrhosis based on laboratory testing (50.6%). Conclusions: This analysis demonstrated considerable gaps in testing for CHB and CHC in a large population of patients, including many with evidence of cirrhosis, suggesting higher risk of adverse outcomes. Primary care practices should be supported to comprehensively offer testing for viral hepatitis, particularly where there is evidence of liver disease, and these findings should be used to guide future interventions. Gaps in diagnosis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) contribute to ongoing adverse outcomes, however, data regarding testing coverage are limited. In a large representative primary care population, a key setting for testing, a substantial proportion of people with established indications for testing had no evidence of it, including many with evidence of liver disease. Primary care practices should be supported to comprehensively offer testing for viral hepatitis for those at risk. [ABSTRACT FROM AUTHOR]

Direct‐acting antivirals (DAA) achieve high virological response rates with minimal side effects for many patients. Despite their significant impact on the progression and epidemiology of hepatitis C virus (HCV) associated liver disease, the global annual incidence of chronic infections is expected to remain relatively constant, averaging 1.42 million new cases each year until 2030. Furthermore, by 2030, there will be a 14–17% increase in end‐stage liver disease outcomes such as liver‐related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis in adults aged 18 years and over. Although reductions in liver decompensation, HCC occurrence, and mortality have been shown in patients with advanced liver disease who achieved sustained virological response (SVR) with DAA, these benefits may be less significant in those with decompensated liver cirrhosis. This review aims to summarise the impact of the virological response to DAA on liver disease progression and outcomes in patients with advanced chronic liver disease, which appears to be crucial for defining patient‐specific follow‐up. [ABSTRACT FROM AUTHOR]

A subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single‐centre retrospective cohort study of adults with HCV infection in the Duke University Health System who received direct‐acting antiviral therapy and achieved SVR. We performed multivariable logistic regression to assess the relationship between potential risk factors and LEE. We used generalised linear mixed‐effects models to explore longitudinal relationships between HIV and LEE. Among 1356 patients, 556 (41.0%) had LEE after achieving SVR. Higher pretreatment alanine aminotransferase (ALT) (adjusted odds ratio [aOR] 1.08 per 10 IU/L increase; 95% confidence interval [CI] 1.05–1.11) and pretreatment cirrhosis (aOR 2.26, 95% CI 1.60–3.21) were associated with higher odds of LEE; male sex was associated with lower odds of LEE (aOR 0.28, 95% CI 0.21–0.38). There was insufficient evidence of an association between HIV and LEE (aOR 0.83, 95% CI 0.47–1.44). Pretreatment ALT, cirrhosis and female sex predicted LEE in this cohort of patients with HCV infection who achieved SVR. These findings can help to identify patients at greatest risk of post‐SVR liver injury. [ABSTRACT FROM AUTHOR]

Diagnostic overshadowing refers to a phenomenon whereby people with mental health conditions encounter inadequate or delayed medical attention and misdiagnosis. This occurs when physical symptoms are mistakenly attributed to their mental health condition. This paper presents a scoping review focusing on direct causes and background factors of diagnostic overshadowing in the context of hepatitis C infection in people who inject drugs and have concurrent mental health conditions. Despite significant strides in hepatitis C treatment with direct‐acting antiviral drugs, the complex interplay of mental health conditions and physical symptoms necessitates a nuanced approach for accurate diagnosis and effective screening. This review was conducted using Joanna Briggs Institute's methodology for scoping reviews. The databases searched included Medline, Embase, PsycInfo, Global Health, CINAHL and Scopus. This review followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR). The search strategies identified 1995 records. Overall, 166 studies were excluded. Forty‐two (42) studies met the inclusion criteria. Three (n = 3) studies represented direct causes, and 39 (n = 39) with background factors related to diagnostic overshadowing. Studies highlighted six key themes encompassing diagnostic overshadowing, with communication barriers, stigma and knowledge deficiencies being the most prominent. Recognising and addressing diagnostic overshadowing in chronic hepatitis C will lead to increased screening, diagnosis and timely administration of life‐saving antiviral therapy, resulting in profound enhancements in well‐being and health outcomes. Moreover, this proactive approach will play a pivotal role in advancing the global effort towards eliminating hepatitis C by 2030. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to directly compare the utility of liver stiffness (LS) and spleen stiffness (SS) at sustained virologic response (SVR) for predicting hepatocellular carcinoma (HCC) and non-HCC events in patients with chronic hepatitis C (CHC) after direct-acting antiviral therapy. This retrospective study included 695 CHC patients who achieved SVR and underwent LS and SS measurements. LS and SS were measured using point shear wave elastography and compared head-to-head. During a median follow-up of 29.5 months, 49 (7.1%) patients developed liver-related events (LREs), including 28 HCC and 22 non-HCC events after SVR. Multivariable Cox regression analysis revealed that age, albumin level, and LS (≥ versus <1.46 m/s) at SVR (adjusted hazard ratio [aHR]: 5.390; 95% confidence interval [CI]: 2.349–12.364; p < 0.001), but not SS at SVR, significantly predicted the overall risk of post-SVR LREs (n = 49). Furthermore, age and LS (≥ versus <1.46 m/s) at SVR (aHR: 6.759; 95% CI: 2.317–19.723; p < 0.001), but not SS at SVR, independently predicted the risk of post-SVR incident HCC. In contrast, SS (≥ versus <2.87 m/s) at SVR (aHR: 11.212; 95% CI: 1.564–20.132; p = 0.021) and albumin level, but not LS at SVR, significantly predicted the risk of post-SVR non-HCC events. Post-SVR LS better predicts HCC risk. Post-SVR SS helps predict non-HCC risk after antiviral therapy for CHC. LS and SS at SVR provide complementary prognostic information regarding risks of HCC and non-HCC events in the post-SVR setting. Further validation is warranted in larger cohorts. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C–related decompensated cirrhosis is associated with lower sustained virologic response (SVR)–12 rates and variable regression of disease severity after direct-acting antiviral agents. We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. Between July 2018 and July 2023, patients with decompensated chronic hepatitis C–related cirrhosis after direct-acting antiviral agents treatment were evaluated for SVR-12 and then had 6-monthly follow-up. Of 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2 ± 11.5 years; 63% men; Model for End-stage Liver Disease–Sodium [MELD-Na]: 16.5 ± 4.6; 87% genotype 3) were enrolled. SVR-12 was 81.8% after 1 course; ultimately SVR was 90.8% after additional treatment. Decompensation events included ascites (1098; 95.3%), hepatic encephalopathy (191; 16.6%), and variceal bleeding (284; 24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284 (24.7%) at a median time of 16.5 (interquartile range, 14.5–20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin (adjusted hazard ratio [aHR], 0.6; 95% confidence interval [CI], 0.5–0.8; P < 0.001), international normalized ratio (aHR, 0.2; 95% CI, 0.1–0.3; P < 0.001), absence of large esophageal varices (aHR, 0.4; 95% CI, 0.2–0.9; P = 0.048), or gastric varices (aHR, 0.5; 95% CI, 0.3–0.7; P = 0.022) predicted recompensation. Portal hypertension progressed in 158 (13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR, 1.6; 95% CI, 1.2–2.8; P = 0.042), and presence of large varices (aHR, 2.9; 95% CI, 1.3-6.5; P < 0.001) were associated with portal hypertension progression. Further decompensation was seen in 221 (19%); 145 patients died and 6 underwent liver transplantation. A decrease in MELDNa of ≥3 was seen in 409 (35.5%) and a final MELDNa score of <10 was seen in 335 (29%), but 2.9% developed hepatocellular carcinoma despite SVR-12. SVR-12 in hepatitis C virus–related decompensated cirrhosis in a predominant genotype 3 population led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and hepatocellular carcinoma developed in 2.9% of patients. (ClinicalTrials.gov , Number: NCT03488485) [Display omitted] In a public health model in resource-constrained regions, treatment of hepatitis C virus with generic, free-of-cost, directly acting antiviral agents in patients with decompensated cirrhosis leads to recompensation in about one-fourth of patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Liver function tests (LFT) are essential for diagnosing and monitoring liver status in patients with chronic hepatitis. In addition, tracking the systemic implications reflected in the changes in metabolic parameters is essential for correctly managing the cases. This study addresses the critical gap in the literature by evaluating the effects of glecaprevir/pibrentasvir on key liver function markers (AST, ALT, GGT, TB) and metabolic parameters (TC, TG, HbA1c) in patients with chronic hepatitis C (CHC). Moreover, this study will evaluate the impact of glecaprevir/pibrentasvir on A2MG, which provides insights into its effects on liver fibrosis. Awareness of these effects is critical for the optimal management of patients during and following antiviral therapy to ensure that therapeutic success does not come at the expense of overall liver and metabolic health. These parameters should be monitored as they supply clinicians with essential data, informing treatment more accurately and ensuring a holistic approach in CH patients. Methods: This study consists of 104 patients with chronic hepatitis C treated with glecaprevir/pibrentasvir and monitored from January to June 2024. Assessments comprised standard liver markers, lipid profiles, glycated hemoglobin, and alpha-2-macroglobulin, as well as specific non-invasive tests of liver injury. Results: 95.2% of the patients experienced a sustained virologic response. Biochemical markers and total cholesterol values were significantly decreased with glecaprevir/pibrentasvir therapy. Non-significant elevations in total bilirubin and glycated hemoglobin support the drug's favorable tolerability profile. Conclusions: In the treatment of chronic hepatitis C patients, glecaprevir/pibrentasvir therapy leads to normalization in biochemical markers (AST, ALT, and GGT), as well as in total cholesterol. [ABSTRACT FROM AUTHOR]

The article in the Annals of the American Thoracic Society discusses a case of a 66-year-old man with a loculated fluid collection in the right hemithorax, diagnosed with empyema. It highlights the challenges in differentiating between lung abscess and empyema based on CT imaging findings and clinical presentation. The treatment for empyema involves antibiotic therapy, prompt drainage with chest tube thoracostomy, and, in some cases, intrapleural administration of tissue plasminogen activator/DNase. The article emphasizes the importance of early recognition of empyema to guide appropriate interventions and reduce morbidity and mortality. [Extracted from the article]

People who inject drugs (PWIDs) experience high rates of hepatitis C virus (HCV) infection, primarily due to needle sharing and limited healthcare access, resulting in a disproportionate disease burden within this population. This prospective study evaluated treatment outcomes in 432 adult patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) at the University Clinical Center of Serbia. Patients were categorized into two groups based on a history of drug addiction: PWIDs (163, 37.7%) and non-PWIDs (269, 62.3%). The PWID group was further categorized into subpopulations of problematic PWIDs (39, 23.9%), ex-PWIDs (124, 76.1%), and PWIDs on OST (96, 58.9%). The PWID group demonstrated significantly lower treatment adherence, with an intention-to-treat (ITT) rate of 82.8%, compared to 96.3% in the control group (p < 0.001). In contrast, no significant differences were observed in per-protocol (PP) outcomes between the two groups. Additionally, PWIDs were significantly younger (p < 0.001) and had higher rates of psychiatric disorders (p < 0.001), alcohol abuse (p < 0.001), and HCV genotype 1a (p < 0.001). Advanced fibrosis was predictor of PP treatment failure among PWIDs, while mood disorders and alcohol use disorder were associated with interruptions before the scheduled completion time. For non-PWIDs, older age and advanced fibrosis emerged as key predictors of PP treatment failure. The loss to follow-up was most commonly observed in the problematic PWID subgroup (p = 0.001). These findings highlight the importance of addressing barriers in PWIDs through integrated care strategies that concurrently manage addiction and HCV. [ABSTRACT FROM AUTHOR]

The continuous search for simple, noninvasive methods for assessing liver fibrosis remains very important to help risk-stratify and follow-up patients with chronic hepatitis C virus (HCV). This study aimed to evaluate the diagnostic performance and accuracy of six serological noninvasive scores for the assessment of liver fibrosis in comparison to liver histopathology. This retrospective cohort study included data from 19501 patients with chronic HCV infection who had liver biopsies as an HCV treatment prerequisite within the Egyptian national HCV treatment program. Six noninvasive scores (FIB-4, APRI, King's score, Fibro-Q, fibrosis index, Fibro-α score) were evaluated and compared to liver histopathology data in assessing different stages of liver fibrosis. The diagnostic performance for each score was assessed using the area under the receiver-operating characteristic curve (AUROC). All six noninvasive scores were statistically significant for predicting different stages of liver fibrosis. Four scores (FIB-4, King's score, APRI, and Fibro Q) had a better diagnostic performance for predicting different fibrosis stages. FIB-4, followed by the King's score, performs better in identifying patients with advanced fibrosis at cutoffs of 2.01 and 16.7, respectively, with AUROC of 0.71 for both, and in predicting cirrhosis at cutoffs of 2.21 and 17.4, respectively with AUROC 0.82 for both. Using noninvasive scores for fibrosis assessment is very important, especially in limited resource settings, to rapidly stratify patients who need more specialized care. [ABSTRACT FROM AUTHOR]

ABSTRACT Progress in treating chronic hepatitis C virus (HCV) infection has been slow amongst people who use drugs (PWUD). This study describes the HCV treatment cascade amongst people accessing a mobile clinic offering integrated low‐threshold buprenorphine and infectious disease services in Baltimore City. From May 1, 2021, to December 31, 2022, 560 people had a rapid HCV antibody test, of whom 201 (36%) had a positive result and amongst those, 117 (58%) had an HCV RNA test performed, 81 (40%) had a documented positive RNA, 45 (22%) were prescribed medication, 42 (21%) started medication, 32 (16%) completed medication, 22 (11%) had blood work to assess for sustained virologic response and 20 (10%) had a documented cure. Challenges including housing instability, insurance barriers and lack of venous access limit progress in this cascade. Providing integrated care models to meet the needs of PWUD in the community is necessary but not sufficient to make progress in improving HCV treatment. Removal of insurance restrictions, availability of point‐of‐care HCV RNA testing, development of rapid HCV treatment guidelines and development of long‐acting injectable HCV treatment are needed to move towards a same‐day, one‐time test and treat model of care. [ABSTRACT FROM AUTHOR]

Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections. The study included patients with acute HCV (n = 29), chronic HCV (n = 54), and SARS-CoV-2 (n = 39 longitudinal, n = 103 cross-sectional), along with 30 healthy controls. Blood samples were collected at baseline, end of treatment/infection, and during follow-up (up to 9 months). SIMs were quantified using the HD-SP-X Imaging and Analysis System™. At baseline, SIM profiles in acute SARS-CoV-2 and HCV infections were significantly elevated compared with controls. During follow-up, SIM decline was less pronounced in acute and chronic HCV infections after successful therapy than in SARS-CoV-2 infections. Most SIM in the SARS-CoV-2 cohort normalized within 3 months. In chronic HCV, SIM were higher in cirrhotic than noncirrhotic patients post-HCV elimination. Dynamics of SIM after viral elimination vary between blood-borne acute and chronic HCV infections and respiratory SARS-CoV-2 infections. Immunological imprints 3–9 months after HCV elimination appear more pronounced than after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

ABSTRACT Background & Aims Methods Results Conclusions Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US‐FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real‐world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC.This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight‐based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data.Sixty‐one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow‐up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment.This study confirmed the real‐life effectiveness and safety of the 8‐week therapy with GLE/PIB for treatment of CHC in children and adolescents. [ABSTRACT FROM AUTHOR]

Introduction: Adherence to direct-acting antivirals (DAAs) could be a predictor of chronic viral hepatitis C (HCV) therapeutic failure. We examined the perceptions of patients receiving DAAs to determine how cognitive factors influence their decision to maintain adherence. Also, we explored the threshold of DAAs adherence for obtaining sustained virologic response (SVR) among patients with HCV, in order to better implement a strategy that improves the DAAs adherence in the future clinical practice. Methods: A single-arm prospective study was performed. Patients with HCV that started and completed DAAs treatment in the County Hospital of Craiova, Dolj, Romania, were enrolled. Patients' medication adherence was assessed using the HCV-AD10 questionnaire, and the cognitive emotion regulation was measured with CERQ questionnaire (five positive/adaptive cognitive emotion-regulation domains and four negative/maladaptive domains). Spearman correlation analysis was conducted to explore the relationships between adherence and different factors. ROC-curves were used to evaluate the adherence threshold to achieve SVR. A linear regression model was performed to analyze the primary outcome (DAAs adherence) to be the target variable based on given independent variables (age, treatment duration, severity of HCV, the nine adaptive and maladaptive strategies). Results: 368 patients (mean age: 61 years) with HCV diagnosed 4.05 ± 6.38 (average) years ago were enrolled. Mean (±SD) adherence via HCV-AD10 was 91.51 ± 8.34, and the proportion of the participants achieving SVR was 96%. Patients with an adherence less than 84% (5 patients, 1.36%) was considered nonadherent and they have a high probability of not achieving response (sensitivity and specificity of 83% and 80%, respectively). We obtained significantly higher values of three adaptive strategies between adherent and nonadherent patients following DAAs treatment: in positive refocusing (p -value = 0.044), refocus on planning (p -value = 0.037), and positive reappraisal (p -value = 0.047). Discussion: The interplay between the three adaptive strategies of the cognitive emotion regulation and the enhancement of DAAs adherence contributes to a more holistic comprehension of patient behavior in the context of HCV treatment. Increasing refocusing and planning using goal setting and assisting patients in establishing specific, achievable goals can be crucial strategies for clinicians aiming to improve adherence among their patients. [ABSTRACT FROM AUTHOR]

Background: The early detection and intervention of liver fibrosis (LF) in patients with chronic liver disease is critical to their management. The accuracy of serum Mac-2 binding protein glycosylation isomer (M2BPGi) in the diagnosis of LF remains controversial. This study aimed to comprehensively assess the value of serum M2BPGi in diagnosing LF. Methods: The PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched. The effect values were combined using a random-effects model. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. In addition, publication bias assessment and sensitivity analysis were conducted. Results: This study includes 12 studies with 2,416 patients. The pooled sensitivity, specificity, and AUROC of M2BPGi in the diagnosis of significant fibrosis (≥F2) were 0.65 (95% CI: 0.57–0.71), 0.79 (95% CI: 0.72–0.84), and 0.78 (95% CI: 0.74–0.81), respectively, while those for predicting extensive fibrosis (≥F3) were 0.76 (95% CI: 0.71–0.80), 0.75 (95% CI: 0.68–0.81), and 0.81 (95% CI: 0.77–0.84). Sensitivity analysis indicated stable results in this study. The disease type, cut-off values, study country, average age, and male proportion were the sources of heterogeneity in diagnosing significant fibrosis of M2BPGi (p < 0.05). Sample size, disease type, study country, publication year, cut-off values, average age, and male proportion were important sources of heterogeneity in diagnosing extensive fibrosis (p < 0.05). Conclusion: Serum M2BPGi has good diagnostic performance for significant fibrosis and extensive fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or nonalcoholic fatty liver disease (NAFLD) and is an effective, non-invasive, and convenient marker. Systematic Review Registration: https://inplasy.com/inplasy-2023-10-0086/. [ABSTRACT FROM AUTHOR]

Objective: Mac-2 binding protein glycosylation isomer (M2BPGi) is produced in the extracellular matrix and serves as an indicator of hepatic stellate cell activation. Assessing M2BPGi levels could aid in predicting hepatocellular carcinoma (HCC) in individuals with hepatitis C virus (HCV). The objective of this study was to evaluate the usefulness of M2BPGi as a biomarker for HCC in HCV patients and its association with disease severity and progression. Methods: This study included patients who were cured of chronic hepatitis C virus. The patients were divided into three subgroups: HCV without cirrhosis, HCV with cirrhosis, and HCV with HCC. These subgroups were then compared to a subgroup of healthy volunteers. In addition to routine laboratory investigations, M2BPGi levels were measured in all the enrolled subjects. Results: The level of serum M2BPGi was significantly greater in the HCV with cirrhosis and HCC groups than in the control group (P < 0.001). Additionally, it was significantly greater in multifocal HCC than in those with unifocal HCC (P < 0.001), and it was directly proportional to the size of the focal lesion of HCC (P = 0.001). The cutoff for serum M2BPGi in diagnosing HCC was ≥ 0.869 (C.O.I), with an AUC of 0.762, a sensitivity of 78.6%, and a specificity of 61.9% (P = 0.004). Furthermore, the cutoff for predicting multifocality was > 0.93 (C.O.I), with an AUC of 0.73, sensitivity of 66.7%, and specificity of 63.8% (P = 0.03). Although the AFP level was still superior in predicting cirrhosis and HCC, the M2BPGi level was better at predicting the size and diagnostic value of HCC when the AFP level was normal. The cutoff for M2BPGi in this case was 0.903(C.O.I), with a sensitivity of 80%, specificity of 75%, and an accuracy of 76.25%. M2BPGi was independently associated with the CRP level (β = 0.484, P = 0.001) and the size of the HCC focal lesion (β = 1.422, P = 0.001). Conclusion: M2BPGi can be used as an effective marker to assess the biological behavior and aggressiveness of HCC. Further studies are warranted on a large scale of patients to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: The risks of heart disease, resistance of insulin, and diabetes mellitus type II are increased in individuals diagnosed with metabolic syndrome. Furthermore, there is an increase in the vascular and neurological effects. This study aimed to assess the isolated independent impact of hepatitis C virus (HCV) on metabolic syndrome, excluding obesity and diabetes mellitus as common risks, this impact was assessed using the metabolic syndrome Severity Z-score (MetS Z-Score) which was initially designed to assess metabolic disease severity itself. Fifty-one HCV patients non-obese and non-diabetic who visited the Tropical Medicine Department from July 2023 to June 2024 were included in our prospective cross sectional study. Results: After calculation of MetS Z-Score, strong correlations were observed between MetS Z-score and the following data: HDL, fasting insulin, fasting blood sugar, HOMA-IR and hypertension (P value < 0.05). Moreover, The MetS Z-Score was found to have higher values in hypertensive patients. Jaundice shows a near to significance correlation with the MetS Z-Score. Anemia, hypoalbuminemia and thrombocytopenia were observed in the included HCV patients. Low density lipoprotein, alanine aminotransferase, aspartate aminotransferase, cholesterol and triglycerides have shown higher levels than normal in the included HCV patients. Conclusion: The MetS Z-score can be used for determining the severity of metabolic abnormalities in HCV patients who are neither diabetic nor obese. [ABSTRACT FROM AUTHOR]

The article discusses a case of chronic hepatitis E in a 47-year-old female patient following chimeric antigen receptor-T cell treatment for diffuse large B-cell lymphoma. The patient developed rapid progression towards decompensated liver cirrhosis, with a confirmed diagnosis of chronic hepatitis E caused by genotype 3 of the hepatitis E virus. Treatment with ribavirin and pegylated interferon led to viral clearance, but also resulted in adverse effects such as haemolysis and autoimmune flare-ups. The case highlights the challenges of diagnosing and treating chronic hepatitis E post-CAR T-cell therapy, emphasizing the importance of monitoring transaminases and raising awareness about preventive measures. [Extracted from the article]

ABSTRACT Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)‐based and IFN‐free therapy. HCV‐infected patients who underwent neuropsychological assessment in previous studies were invited to a follow‐up examination. Patients were grouped according to the treatment status: Sustained virological response (SVR) after IFN treatment (IFN SVR, n = 14) or after therapy with direct acting antivirals (DAA SVR, n = 28) or ongoing HCV infection (HCV RNA+, n = 11). A group of 33 healthy controls served as reference. Patients completed self‐report questionnaires addressing health‐related quality of life (HRQoL), mood and sleep quality and a neuropsychological test battery including tests of memory and attention (Luria's list of words, PSE test, cancelling “d” test, Word–Figure–Memory Test and computer‐based test battery for the assessment of attention [TAP]). At baseline, all three patient groups had worse fatigue, depression, anxiety and HRQoL scores compared to healthy controls. Longitudinal analysis revealed that fatigue and mood slightly improved in all patient groups over time, while HRQoL improved in SVR patients but not in HCV RNA+ patients. Memory test results improved significantly in all patient groups, irrespective of their virological status. In contrast, the attention test results showed no clear change from baseline to follow‐up. Our data can be considered as a hint that HCV eradication—independent of therapy regimen—does not substantially ameliorate neuropsychiatric symptoms in HCV‐afflicted patients. [ABSTRACT FROM AUTHOR]

Background: The high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs). Methods: We performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach. Results: Six studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%). Conclusion: The 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%. [ABSTRACT FROM AUTHOR]

Background Chronic hepatitis C virus (HCV) infection is associated with early onset of chronic diseases and increased risk of chronic disorders. Chronic viral infections have been linked to accelerated biological aging based on epigenetic clocks. In this study, we aimed to investigate the association between HCV infection and clinical measures of biological aging among 8 306 adults participating in the 2015–2018 waves of the National Health and Nutrition Examination Survey (NHANES). Methods NHANES 2015–2018 participants aged 20 years and older who had complete data on clinical blood markers and HCV-related tests were included in the current study. We estimated biological age using 2 approaches including phenotypic age (PhenoAge) and allostatic load (AL) score based on 9 clinical biomarkers. Results After adjusting for demographic and other confounding factors, HCV antibody-positivity was associated with advanced PhenoAge (β = 2.43, 95% confidence interval: 1.51–3.35), compared with HCV antibody-negativity. Additionally, both active HCV infection (HCV RNA (+)) and resolved infection were associated with greater PhenoAge acceleration. The positive association with the AL score was not statistically significant. We did not observe any significant interactions of potential effect modifiers, including smoking and use of drug/needle injection, with HCV infection on measures of biological aging. Conclusions Our findings suggest that HCV infection is independently associated with biological aging measured by phenotypic age in the U.S. general population. Further studies are warranted to confirm the findings. [ABSTRACT FROM AUTHOR]

Mitochondria are subcellular organelles involved in many metabolic events, including oxidative phosphorylation and signaling in tissue-specific processes. They play a key role in cell proliferation, differentiation and death. Diseases in the pathogenesis of which mitochondrial oxidative stress and immunity play a significant role include cancer, cardiovascular, nervous and rheumatic diseases as well as liver, lung and kidney diseases. In addition, mitochondria participate in the pathogenesis of infections and autoimmunity. Mitochondrial dysfunction can be positively influenced by administration of antioxidants, including coenzyme Q10. [ABSTRACT FROM AUTHOR]

Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher (P < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4–25.2) vs.9.7 (7.2–12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated (p < 0.05) with decreased albumin (r=-0.266), elevated APRI (r = 0.288), and elevated FIB-4 (r = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control. [ABSTRACT FROM AUTHOR]

Background and Aims: The impact of hepatitis C virus (HCV) eradication via direct‐acting antiviral (DAA) therapy on overall mortality, particularly non‐liver‐related mortality, is understudied. Methods: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non‐SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all‐cause mortality, including non‐liver‐related diseases, were investigated. Results: Of the 4180 patients, 592 died during the follow‐up period. In the SVR group, the mortality rates from liver‐related and non‐liver‐related diseases were 16.5% and 83.5%, respectively. Compared to the non‐SVR group, mortality rates from liver‐related and non‐liver‐related diseases were 50.1% and 49.9%, respectively (p <.001). In non‐cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver‐related (hazard ratio [HR],.251; 95% confidence interval [CI],.092–.686) and non‐liver‐related (HR,.641; 95% CI,.415–.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver‐related mortality (HR,.151; 95% CI,.081–.279). In propensity score‐matched patients, the eradication of HCV (SVR group) decreased both liver‐related (p <.001) and non‐liver‐related mortality (p =.008) rates compared to persistent HCV infection (non‐SVR group). Conclusions: The elimination of HCV via DAA therapy reduced not only liver‐related mortality but also non‐liver‐related mortality in patients with chronic HCV. [ABSTRACT FROM AUTHOR]

Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. The Treg cell population – especially the activated Treg cell subpopulation – was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection. [Display omitted] • Increased Tregs persist in patients with chronic HCV after DAA-induced viral clearance. • DAA-induced HCV clearance does not abrogate inflammatory features of Tregs. • HCV clearance does not reverse inflammatory imprinting in the epigenome of Tregs. • Increased TNF+ Tregs persist in patients with chronic HCV after viral clearance. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (CHC) is a liver disease caused by the hepatitis C virus. Anti- Saccharomyces cerevisiae (S. cerevisiae) antibodies (ASCA) are frequently reported in autoimmune diseases but rarely in viral infections. We aimed to determine the frequency of ASCA in adult patients with CHC. Eighty-eight patients with CHC and 160 healthy blood donors were included in this study. ASCA-IgG and IgA levels were determined using enzyme linked immunosorbent assay. For statistical analysis, we used open EPI version 3 as software. Correlations were determined by Spearman's test using IBM® SPSS® Statistics. ASCA (IgG or IgA) were present in 31.8 % of patients and in 3.7 % of controls (p < 10−6). ASCA-IgG and ASCA-IgA were more frequent in patients with CHC than in healthy subjects (23.9 % vs. 3.1 %; p < 10−5 and 9.1 % vs. 0.6 %; p = 0.002, respectively). In patients, mean levels of ASCA-IgG and IgA were significantly higher than in controls (9.95 ± 11.78 U/mL vs. 2.28 ± 2.86 U/mL, p < 10−6 and 5.96 ± 7.69 U/mL vs. 0.56 ± 0.12 U/mL, p < 10−6; respectively). In patients with CHC, the mean level of ASCA-IgG was significantly higher than that of ASCA-IgA (9.95 ± 11.78 U/mL vs. 5.96 ± 7.69 U/mL, p = 0.008). The frequency of ASCA was significantly higher in patients with CHC than in healthy controls. [ABSTRACT FROM AUTHOR]

Risk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. A retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. A total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45–3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45–3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65–11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46–16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45–3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. The baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC. [ABSTRACT FROM AUTHOR]

ObjectiveTo construct a risk prediction model for liver cancer in patients with chronic hepatitis C based on seven different machine learning algorithms and select the optimal model. MethodsA total of 236 patients with chronic hepatitis C were selected as the research subjects. Patients were divided into a case group and a control group according to whether liver cancer occurs. Prediction models were constructed based on seven machine learning algorithms including classification and regression tree, random forest, gradient boosting decision tree, extreme gradient boosting (XGBoost), logistic regression, K-near neighbor, and support vector machine. The Shapley additive explanations (SHAP) algorithm was used to interpret the best prediction model. ResultsAmong the seven models, the XGBoost model had the best comprehensive prediction performance (accuracy of 0.933, sensitivity of 0.775, specificity of 0.960, area under the ROC curve of 0.956, F1 score of 0.764). The SHAP algorithm suggested that AFP, age, AST, diabetes, BMI, PLT, ALT, liver cysts, FIB-4, and gender contributed to the model decision and are the risk factors for liver cancer in patients with chronic hepatitis C. ConclusionThis study develops an interpretable machine learning model based on the XGBoost algorithm, which has a good reference value for individualized monitoring of liver cancer in patients with chronic hepatitis C.

Background/Purpose: There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. Methods: From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. Results: Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age 35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). Conclusion: For DAA-treated CHC patients, those with baseline age

Background/Objectives: Liver function tests (LFT) are essential for diagnosing and monitoring liver status in patients with chronic hepatitis. In addition, tracking the systemic implications reflected in the changes in metabolic parameters is essential for correctly managing the cases. This study addresses the critical gap in the literature by evaluating the effects of glecaprevir/pibrentasvir on key liver function markers (AST, ALT, GGT, TB) and metabolic parameters (TC, TG, HbA1c) in patients with chronic hepatitis C (CHC). Moreover, this study will evaluate the impact of glecaprevir/pibrentasvir on A2MG, which provides insights into its effects on liver fibrosis. Awareness of these effects is critical for the optimal management of patients during and following antiviral therapy to ensure that therapeutic success does not come at the expense of overall liver and metabolic health. These parameters should be monitored as they supply clinicians with essential data, informing treatment more accurately and ensuring a holistic approach in CH patients. Methods: This study consists of 104 patients with chronic hepatitis C treated with glecaprevir/pibrentasvir and monitored from January to June 2024. Assessments comprised standard liver markers, lipid profiles, glycated hemoglobin, and alpha-2-macroglobulin, as well as specific non-invasive tests of liver injury. Results: 95.2% of the patients experienced a sustained virologic response. Biochemical markers and total cholesterol values were significantly decreased with glecaprevir/pibrentasvir therapy. Non-significant elevations in total bilirubin and glycated hemoglobin support the drug’s favorable tolerability profile. Conclusions: In the treatment of chronic hepatitis C patients, glecaprevir/pibrentasvir therapy leads to normalization in biochemical markers (AST, ALT, and GGT), as well as in total cholesterol.

Abstract Background The risks of heart disease, resistance of insulin, and diabetes mellitus type II are increased in individuals diagnosed with metabolic syndrome. Furthermore, there is an increase in the vascular and neurological effects. This study aimed to assess the isolated independent impact of hepatitis C virus (HCV) on metabolic syndrome, excluding obesity and diabetes mellitus as common risks, this impact was assessed using the metabolic syndrome Severity Z-score (MetS Z-Score) which was initially designed to assess metabolic disease severity itself. Fifty-one HCV patients non-obese and non-diabetic who visited the Tropical Medicine Department from July 2023 to June 2024 were included in our prospective cross sectional study. Results After calculation of MetS Z-Score, strong correlations were observed between MetS Z-score and the following data: HDL, fasting insulin, fasting blood sugar, HOMA-IR and hypertension (P value

Chronic hepatitis C (CHC) represents a significant public health concern. In the majority of cases, the infection progresses to a chronic form, which is characterised by the development of fibrosis and cirrhosis of the liver. A plethora of cytokines and chemokines are generated as a consequence of inflammatory processes within the liver. These can exert a dual effect, both protective and damaging, particularly in relation to the death of hepatocytes and the progression of liver fibrosis. Furthermore, a number of growth factors have been identified as playing a role in the pathogenesis of CHC. The objective of the study was a comprehensive evaluation of a wide range of cytokines, chemokines and growth factors in the blood plasma of patients with CHC at varying stages of liver fibrosis. The study cohort comprised 63 patients diagnosed with CHC, who were divided into three groups according to the stage of liver fibrosis. The control group comprised healthy individuals (n = 32). Concentrations of the following cytokines were determined in plasma: Interleukins and some cytokines (IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IL-17-E/IL-25, IL-17F, IL-18, IL-27, IFNα, IFNγ, TNFα, TNFβ); chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine) and growth factors (EGF, FGF-2, Flt-3L, G-CSF, M-CSF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF-A) by multiplex analysis based on xMAP technology. Nonparametric statistics methods were used for statistical analysis. As a result of the study, increased concentrations of cytokines IL-12 (p40), IL-15, IL-17E/IL-25, IL-27, IFNγ, TNFα, chemokines CXCL9/MIG and CXCL-10/IP-10 and growth factors FGF-2 and M-CSF were found at all stages of liver fibrosis. Elevated concentrations of cytokines IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-17F, IFNα, TNFβ, chemokines CCL2/MCP-1, CCL11/Eotaxin, CCL22/MDC and growth factors G-CSF, TGF-α, Flt-3L were found in severe liver fibrosis/cirrhosis. Correlation analysis revealed a relationship of high significance between the severity of liver fibrosis and the content of cytokines IL-6, IFNγ, TNFα, IL-7, chemokines CCL2/MCP-1, CCL11/Eotaxin, CXCL9/MIG, CXCL10/IP-10, CXCL1/GROα, growth factors TGF-α, PDGF-AA, PDGF-AB/BB. Thus, a certain profile of cytokines characteristic for CHC was revealed, cytokines, chemokines and growth factors significant for liver fibrosis in CHC were found.