Search

This article discusses the detection of blood-borne pathogens in clotting factor concentrates from the 1970s and 1980s. The study found that concentrated coagulation factors derived from human blood donations during this time period were contaminated with viruses such as HIV-1 and hepatitis C. The authors used qPCR assays to test the clotting factor samples for various viruses and found that HCV, B19V, and HPgV-1 were the most frequently detected viruses. The study highlights the need for continued screening of blood products and the development of safer clotting products. [Extracted from the article]

Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus‐like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell‐culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross‐neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV‐specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector‐based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus‐like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health. [ABSTRACT FROM AUTHOR]

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID‐19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL‐18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL‐18 function can help understand COVID‐19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. angiotensin‐converting enzyme 2 (ACE‐2) receptors on cholangiocytes suggest liver involvement in SARS‐CoV‐2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL‐18, and interferon‐Alpha as diagnostic tools in HCV, COVID‐19, and dual HCV‐COVID‐19 pathogenesis. The current study was a prospective cross‐section conducted on 188 participants classified into the following four groups: Group 1 COVID‐19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV‐COVID‐19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL‐18, and interferon‐alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV‐COVID‐19 had high ferritin levels compared to other biomarkers while those with COVID‐19 infection had high levels of D‐Dimer. The histamine, acetylcholine, and IL‐18 biomarkers in both COVID‐19 and dual HCV‐COVID‐19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN‐Alpha test performed well in the HCV‐COVID‐19 group and was fair in the COVID‐19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL‐18, and interferon‐Alpha in HCV, COVID‐19, and dual HCV‐COVID‐19 infection. Circulating levels of acetylcholine, histamine, IL‐18, and interferon‐Alpha can be potential early indicators for HCV, COVID‐19, and dual HCV‐COVID‐19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases. [ABSTRACT FROM AUTHOR]

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009−2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV‐1, and HSV‐2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26−1.70; OR 1.09, 95% CI 1.05−1.13; OR 1.06, 95% CI 1.01 ‐ 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29−1.77; OR 1.08, 95% CI 1.04−1.12; OR 1.05, 95% CI 1.01−1.10, respectively) after adjusting all relevant co‐factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV‐1 infection, while the relationship between HSV‐2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to the development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct‐acting antiviral drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection‐related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth‐arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to the development of HCC. [ABSTRACT FROM AUTHOR]

The genetic diversity of killer cell immunoglobulin‐like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA‐A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case‐control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA‐A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA‐A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection. [ABSTRACT FROM AUTHOR]

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop‐mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 103 genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point‐of‐care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources. [ABSTRACT FROM AUTHOR]

Comparison of diagnostic accuracy for commercial hepatitis C virus (HCV) genotyping (Abbott RealTime HCV Genotyping II, Roche Cobas Genotyping) and investigational Abbott HCV Genotype plus RUO assays designed to discriminate genotype (GT)‐1a, 1b or 6 in cases of ambiguous GT from the Abbott commercial assay remains limited. 743 HCV‐viremic samples were subjected to analysis using Abbott and Roche commercial as well as Abbott HCV Genotype plus RUO assays. Next‐generation sequencing (NGS) targeting core region was employed as the reference standard. Diagnostic accuracy was reported as the number of participants (percentages) along with 95% confidence intervals (CIs). Using NGS, 741 samples (99.7%) yielded valid genotyping results. The diagnostic accuracies were 97.6% (95% CI: 96.1%–98.5%) and 95.3% (95% CI: 93.4%–96.6%) using Abbott and Roche commercial assays (p = 0.0174). Abbott commercial assay accurately diagnosed HCV GT‐6a and 6w, whereas Roche commercial assay accurately diagnosed HCV GT‐6a. Both assays demonstrated low accuracies for HCV GT‐6b, 6e, 6g, and 6n. Abbott HCV Genotype plus RUO assay discriminated 13 of the 14 samples (92.9%; 95% CI: 64.2%–99.6%) that yielded ambiguous GT. Both assays were capable of diagnosing mixed HCV infections when the minor genotype comprised >8.4% of the viral load. The diagnostic performance of commercial HCV genotyping assays is commendable. Abbott assay demonstrated superior performance compared to Roche assay in diagnosing HCV GT‐6. Abbott HCV Genotype plus RUO assay aids in discriminating ambiguous GT. Both commercial assays are proficient in diagnosing mixed HCV infections at a cut‐off viral load of 8.4% in minor genotype. [ABSTRACT FROM AUTHOR]

Early confirmation of sustained virologic response (SVR) or viral relapse after direct‐acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow‐ups. A total of 1011 patients who achieved end‐of‐treatment virologic response, including 526 receiving fixed‐dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off‐treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off‐treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0–98.9) and 100% (95% CI: 66.4–100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed‐dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9–100] vs. 97.1% [95% CI: 96.2–97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off‐treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off‐treatment week 12 among patients with HCV who are treated with fixed‐dose pangenotypic DAAs. [ABSTRACT FROM AUTHOR]

Hepatitis C remains a global health problem, especially in poverty‐stricken areas. A rapid and sensitive point‐of‐care (POC) diagnostic tool is critical for the early detection and timely treatment of hepatitis C virus (HCV) infection. Here, for the first time, we reported a novel molecular diagnostic assay, termed reverse transcription multiple cross displacement amplification integrated with a gold‐nanoparticle‐based lateral flow biosensor (RT‐MCDA‐AuNPs‐LFB), which was developed for rapid, sensitive, specific, and visual identification of HCV. HCV‐RT‐MCDA induced rapid isothermal amplification through a specific primer set targeting the 5′untranslated region gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a that are prevalent in China. The optimal reaction temperature and time for RT‐MCDA‐AuNPs‐LFB were 68°C and 25 min, respectively. The limit of detection of the assay was 10 copies per test, and the specificity was 100% for the experimental strains. The whole detection procedure, including crude nucleic acid isolation (~5 min), RT‐MCDA (68°C, 25 min), and visual AuNPs‐LFB result confirmation (less than 2 min), was performed within 35 min. The preliminary results indicated that the HCV‐RT‐MCDA‐AuNPs‐LFB assay could be a valuable tool for sensitive, specific, visual, cost‐saving, and rapid detection of HCV and has potential as a POC diagnostic platform for field screening and early clinical detection of HCV infection. [ABSTRACT FROM AUTHOR]

High‐risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost‐effective HCV testing strategies for high‐risk populations to identify potential undiagnosed HCV‐infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high‐risk populations. Among the 2093 samples from high‐risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV‐positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high‐risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti‐HCV screening, followed by HCV RNA testing on reactive samples. [ABSTRACT FROM AUTHOR]

Liver cirrhosis remains a major health concern globally, but its epidemiology and etiology evolve with time. However, the changing pattern in etiology and cause of liver‐related mortality for patients with cirrhosis are not fully elucidated. Herein, our aim was to characterize the temporal trend of the etiological spectrum and evaluate the impact of etiology on liver‐related death among patients with compensated cirrhosis (CC) in Beijing, China. Clinical profiles of patients with CC discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. The mortalities of different etiologies of cirrhosis were calculated. The risks of readmission and liver‐related death associated with etiologies were evaluated by the Cox regression model. A total of 23 978 cirrhotic patients were included. The predominant cause was hepatitis B virus (HBV) (58.93%), followed by alcohol (21.35%), autoimmune (14.85%), miscellaneous etiologies (3.55%), and hepatitis C virus (HCV) (1.32%). From 2008 to 2015, the proportion of HBV‐related cirrhosis decreased to 28.11%. Meanwhile, the proportions of autoimmune‐ and miscellaneous‐related cirrhosis increased to 28.54% and 13.11%. The risk of liver‐related death ranked the highest in patients with miscellaneous cirrhosis, followed by HBV‐related cirrhosis, alcohol‐related cirrhosis, autoimmune‐related cirrhosis, and HCV‐related cirrhosis. The 5‐year rates of liver‐related death were 22.56%, 18.99%, 18.77%, 16.01%, and 10.76%, respectively. HBV‐related cirrhosis caused the highest risk of hepatocellular carcinoma (HCC)‐related death, whereas alcohol‐ and miscellaneous‐related cirrhosis caused higher risks of decompensation (DC)‐related death than HBV‐related cirrhosis, with hazard ratios of 1.35 (95% confidence interval [CI]: 1.24–1.48) and 1.20 (95% CI: 1.03–1.40), respectively. HBV remained a common cause of liver cirrhosis but gradually decreased. Mortality disparities existed in etiologies, with higher risks of HCC‐related death in HBV‐related cirrhosis, and DC‐related death in alcohol‐ and miscellaneous‐related cirrhosis. [ABSTRACT FROM AUTHOR]

Early neutralizing antibodies against hepatitis C virus (HCV) and CD8 + T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus undefined additional antiviral immune mechanisms are required. In recent years, Fc‐receptor‐dependent antibody effector functions, particularly, antibody‐dependent cellular phagocytosis (ADCP) were shown to offer immune protection against several RNA viruses. However, its development and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti‐envelope 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralization function are also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti‐E2 antibody levels and neutralization function regardless of clinical outcome and genotype of infecting virus, while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titer in patients with chronic disease while maintained in clearers due to the quality (affinity) of their anti‐E2 antibodies despite having lower antibody titers. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. Among its 8 genotypes (GT), GT3 has a relatively lower sustained virological response to highly effective direct‐acting antiviral agents (DAA). Sofosbuvir (SOF), an anti‐NS5B polymerase inhibitor, is a core component of many anti‐HCV DAA cocktail regimens, and its resistant mutations are rare in clinics because these mutations usually severely impair the NS5B polymerase activity, including a mutation S282T in NS5B, the most frequently reported SOF‐resistant mutation. In this study, we selected SOF‐resistant variants of a previously developed GT3 subgenomic replicon (PR87A7). Two mutations were identified in the viral genome of SOF‐resistant PR87A7 variants, Q606R in nontargeted NS3 and S282T in targeted N5SB. We demonstrated that Q606R could rescue the replication defect of S282T in PR87A7, and the resulting double mutant confers the SOF resistance. Finally, we showed that NS3‐606R could not compensate for the replication defect of S282T in other GTs. In conclusion, we identified a novel GT3‐specific combination of two mutations that confers SOF resistance. Our result calls for attention to potential mutations that may arise in nontargeted viral proteins during the SOF‐based DAA treatment of chronic HCV. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection remains a challenge to human public health despite the development of highly effective direct‐acting antivirals (DAAs). Sofosbuvir (SOF), a key component in most DAA‐based anti‐HCV cocktail regimens, is a potent viral RNA polymerase (NS5B) inhibitor with a high barrier to drug resistance. The serine‐to‐threonine mutation at NS5B 282 (S282T) confers the SOF resistance, but severely impairs viral replication in most HCV genotypes (GTs) and cannot be stably maintained after the termination of the SOF‐based therapies. In this study, we first developed a new HCV GT‐6a subgenomic replicon PR58D6. Next, we selected SOF‐resistant PR58D6 variants by culturing the replicon cells in the presence of SOF. Interestingly, unlike many other HCV replicons which require additional mutations to compensate for the S282T‐inducing fitness loss, S282T alone in PR58D6 is genetically stable and confers the SOF resistance without significantly impairing viral replication. Furthermore, we showed that amino acid residue at NS5B 74 (R74) and 556 (D556) which are conserved in GT 6a HCV contribute to efficient replication of PR58D6 containing S282T. Finally, we showed that the G556D mutation in NS5B could rescue the replication deficiency of the S282T in JFH1, a GT‐2a replicon. In conclusion, we showed that a novel GT‐6a HCV replicon may easily render SOF resistance, which may call for attention to potential drug resistance during DAA therapies of HCV GT‐6a patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) accounts for 80% of liver cancers, while 70%–80% of HCC developed from chronic liver disease with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as the major etiology. Immunotherapy is assuming a role as a pillar of HCC treatment, but the remarkable immune‐mediated responses are restricted in a minority of patients. Nucleic acid sensing (NAS) pathways are the central pathway of the innate immune system and antiviral immune response to viral infection, but their role in hepatitis virus‐related HCC remains undetermined. In our study, we performed a comprehensive bioinformatics analysis based on transcriptomic data of hepatitis virus related‐HCC tissues collected from multiple public data sets. Two subgroups were validated based on NAS‐related genes in virus‐related HCC patients, which were defined as NAS‐activated subgroups and NAS‐suppressed subgroups based on the expression of NAS‐related genes. On this basis, a NAS‐related risk score (NASRS) predictive model was established for risk stratification and prognosis prediction in the hepatitis virus‐related HCC (TCGA‐LIHC and ICGC cohorts). The predictive values of the NASRS in prognosis and immunotherapy were also verified in multiple data sets. A nomogram was also established to facilitate the clinical use of NASRS and demonstrate its effectiveness through different approaches. Additionally, six potential drugs binding to the core target of the NAS signature were predicted via molecular docking strategy. We subsequently evaluated the cytotoxic capabilities of potential drug in vitro and in vivo. Based on these results, we conclude that the NASRS model could serve as a power prognostic biomarker and predict responses to immunotherapy, which is meaningful in clinical decision‐making of hepatitis virus‐related HCC patients. [ABSTRACT FROM AUTHOR]

Although the prevalence of hepatitis C virus (HCV) infection has decreased significantly with the advent of direct‐acting antiviral agents, HCV is known to spread as a sexually transmitted disease among men who have sex with men (MSM), and this study aims to provide a perspective on the future prevalence of HCV in Japan. We examined incidence in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to 2019 and from 2020 to May 2023 and investigated their background factors. Twenty‐two cases were newly confirmed to be HCV infection in 2009–2019 and a total of 9 cases in 2020–2023, with an incidence rate of 5.04 per 1000 person‐years in 2009–2019 and 5.55 per 1000 person‐years in 2020–2023. All of them were diagnosed at routine outpatient visits for HIV, and few cases were considered to have symptoms of suspected hepatitis that led to a visit to the hospital and a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would not have been diagnosed without testing at regular visits as in the case of people with HIV, and that the true prevalence rate among MSM, including non‐HIV‐infected persons, may be much higher. [ABSTRACT FROM AUTHOR]

As an intracellular parasite, the virus usurps cellular machinery and modulates cellular metabolism pathways to replicate itself in cells. Lipid droplets (LDs) are universally conserved energy storage organelles that not only play vital roles in maintaining lipid homeostasis but are also involved in viral replication. Increasing evidence has demonstrated that viruses take advantage of cellular lipid metabolism by targeting the biogenesis, hydrolysis, and lipophagy of LD during viral infection. In this review, we summarize the current knowledge about the modulation of cellular LD by different viruses, with a special emphasis on the Hepatitis C virus, Dengue virus, and SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Killer‐cell immunoglobulin‐like receptors 2DL4 (KIR2DL4) and the human leukocyte antigen class I‐G (HLA‐G) display vital parts in immune responses against hepatitis C virus (HCV) infection. We select four potentially functional single nucleotide polymorphisms (SNPs) of KIR/HLA to explore the associations between KIR2DL4/HLA‐G genetic variants and HCV infection results. In the present case‐control study, a total of 2225 HCV‐infected high‐risk subjects, including 1778 paid blood donors (PBD) and 447 drug users were consecutively recruited before treatment from 2011 to 2018. KIR2DL4‐rs660773, KIR2DL4‐rs660437, HLA‐G‐rs9380142, and HLA‐G‐rs1707 SNPs were sorted as genotypes in the subdivided groups, involving 1095 uninfected controls subjects, 432 spontaneous HCV clearance subjects and 698 HCV persistent infection subjects. After genotyping experiments using the TaqMan‐MGB assay, modified logistic regression was used to calculate the correlation among the SNPs and HCV infection. The SNPs were functionally annotated using bioinformatics analysis. Following adjusting by age, sex, alanine aminotransferase, aspartate aminotransferase, IFNL3‐rs12979860, IFNL3‐rs8099917, and the infection route, the logistic regression analysis discovered that KIR2DL4‐rs660773 and HLA‐G‐rs9380142 were correlated with vulnerability to HCV infection (all p < 0.05). In a locus‐dosage way, compared with subjects carrying the rs9380142‐AA or rs660773‐AA genotypes, subjects with rs9380142‐AG or rs660773‐AG/GG (all p < 0.05) were more vulnerable to HCV infection; the overall impact of their risk genotypes (rs9380142‐AGrs660773‐AG/GG) was correlated with an elevated incidence of HCV infection (ptrend < 0.001). In the Haplotype analysis, patients with haplotype AG were more likely to contract HCV compared to those with the highest common AA haplotype (p = 0.002) were higher in susceptibility to infect HCV. The SNPinfo web server estimated that rs660773 is a transcription factor binding site, whereas rs9380142 is a potential microRNA‐binding site. In two Chinese high‐risk population (PBD and drug uesrs), KIR2DL4 rs660773‐G and HLA‐G rs9380142‐G alleles polymorphisms are related to HCV susceptibility. KIR2DL4/HLA‐G pathway genes might affect the innate immune responses by regulating KIR2DL4/HLA‐G transcription and translation play a potential role in HCV infection. [ABSTRACT FROM AUTHOR]

Dried blood spots (DBS) are a reliable tool to diagnose viremic hepatitis C virus (HCV) infection. We evaluated the clinical performance of a DBS‐based molecular assay for the assessment of cure and reinfection after on‐site treatment at a harm reduction center (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. People who inject drugs (PWID) from an ongoing test‐and‐treat pilot at the largest HRC in Barcelona were included in the study. HCV‐RNA detection from DBS collected after treatment (with follow‐up at 12, 36, and 60 weeks) was compared with a molecular point‐of‐care test using finger‐stick blood (GeneXpert). Baseline and follow‐up DBS samples were genotyped by NS5B sequencing or commercial real‐time PCR. Among treated patients, 193 follow‐up DBS samples were tested. The DBS‐based assay showed 100% specificity (129/129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut‐offs (from detectable to 3000 IU/mL). Sensitivity as test of cure (follow‐up 12) ranged from 85.1% to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IU/mL); HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and posttreatment follow‐up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended. [ABSTRACT FROM AUTHOR]

In Egypt, hepatocellular carcinoma (HCC) ranks as the second largest cause of cancer mortality. PRDM1 is a tumor suppressor gene essential for the differentiation and regulation activity of plasma cells and T cells. It plays a vital role in T cell exhaustion of chronic viral infection and HCC. We aimed to study the role of PRDM1 gene polymorphism in HCV and HCC‐related to hepatitis C virus (HCV) progress in Egyptians. The case‐control study included 300 Egyptian patients divided into 100 HCC,100 cirrhosis, and 100 control. Laboratory investigations were done for some clinicopathological biomarkers, including liver function tests, complete blood picture, serum alpha‐fetoprotein, and hepatitis markers (HBsAg, anti‐HCV‐Ab). TaqMan allelic discrimination assay technique was used to genotype PRDM1 gene polymorphism. Multivariant analysis (logistic regression) assessed the association between the polymorphisms with HCC progression and designed the suggested model for HCC prediction. The frequencies of the G allele and GG phenotype in the control group were significantly more than that of the HCC and cirrhosis group. However, GA genotypes and A allele frequencies significantly increased in the HCC patients than in cirrhosis and controls. In addition, by comparing the HCC group and the non‐HCC group (controls and cirrhotic patients), the subjects carrying AA or GA have 2 times more risk to develop HCC than those carrying GG genotypes (odd ratio = 2.045% and 95% confidence interval are (1.123−3.722) p = 0.019). Multivariate analysis results suggested a model of Aspartate transaminase (AST), Albumin, and PRDM1 polymorphism to predict the risk of HCC in Egyptians. In addition, PRDM1 polymorphism has an association with HCC prognosis (tumor size). For PRDM1 polymorphism, the A allele and AA might be considered as HCC‐related to the HCV risk factor. In addition, AST, Albumin, and PRDM1 polymorphism predict the risk of HCC in Egyptians Therefore, the polymorphism might help in identifying the susceptible Egyptians to HCC. In addition, polymorphism might have a role in HCC prognosis. [ABSTRACT FROM AUTHOR]

Background and Aims: The newly developed direct‐acting antivirals have revolutionized the treatment of chronic hepatitis C virus (HCV), with cure rates as high as 98% in some cohorts. Although genome sequencing has demonstrated that some subtypes of HCV naturally harbor drug resistance associated substitutions (RAS), these are often overlooked as "rarities." Furthermore, commercial subtyping assays and associated epidemiological findings are skewed towards Western cohorts and whole‐genome sequencing can be problematic to deploy without significant infrastructure and training support. We thus aimed to develop a simple, robust and accurate HCV subtyping pipeline, to optimize and streamline molecular detection and sequence‐based typing of diverse RAS‐containing subtypes. Methods: HCV serum derived from 146 individuals, whose likely source of infection was from sub‐Saharan Africa (SSA) was investigated with a novel panel of single round polymerase chain reaction (PCR) assays targeting NS5B and NS5A genomic regions. Virus subtype assignments were determined by pairwise‐distance analysis and compared to both diagnostic laboratory assignments and free‐to‐use online typing tools. Results: Partial NS5A and NS5B sequences were respectively obtained from 131 to 135 HCV‐positive patients born in 19 different countries from SSA but attending clinics in the UK. We determined that routine clinical diagnostic methods incorrectly subtyped 59.0% of samples, with a further 6.8% incorrectly genotyped. Of five commonly used online tools, Geno2Pheno performed most effectively in determining a subtype in agreement with pairwise distance analysis. Conclusion: This study provides a simple low‐cost pathway to accurately subtype in SSA, guide regional therapeutic choice and assist global surveillance and elimination initiatives. [ABSTRACT FROM AUTHOR]

Liver disease is a growing burden among people living with HIV (PLHIV) in resource‐limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre‐cART ALT measurement and at least one follow‐up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10‐year follow‐up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis‐4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow‐up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82–8.77, p < 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00–5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person‐years). Those HCV‐antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75–8.18, p < 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23–3.45, p = 0.006) were associated with liver cirrhosis. HCV‐antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV‐antibody and those who consume alcohol. [ABSTRACT FROM AUTHOR]

Almost all chronic hepatitis C (CHC) patients can achieve sustained virological response (SVR) with direct‐acting antivirals. However, the development of hepatocellular carcinoma (HCC), even after the achievement of SVR, continues to be a serious problem. The aim of this study was to assess the association between host genetic factors and de novo HCC after SVR. This single‐center, retrospective study consisted of 442 consecutive CHC patients without a history of HCC who achieved SVR through interferon (IFN)‐based and IFN‐free therapy. Predictive factors associated with the development of HCC were determined by the Cox proportional hazards model. The single‐nucleotide polymorphism (SNP) genotyping data of 223 patients were available for analysis. Of the seven SNPs analyzed in this study, only the patatin‐like phospholipase domain containing 3 (PNPLA3) rs738409 GG genotype was significantly, positively associated with the development of de novo HCC after adjusting for age, sex, and fibrosis status (adjusted hazard ratio [aHR] 5.66, p = 0.003). In multivariable analysis, age (aHR 1.05, p = 0.007), advanced fibrosis (aHR 2.69, p = 0.019), α‐fetoprotein at post‐12 weeks of treatment ≥7.0 ng/ml (aHR 3.85, p = 0.001), and PNPLA3 GG genotype (aHR 3.02, p = 0.004) were extracted as independent predictors of the development of de novo HCC. In conclusion, the PNPLA3 genotype was independently associated with the de novo HCC of CHC patients who achieved SVR. Such detailed knowledge of host genetic factors will be useful for HCC surveillance after HCV elimination. [ABSTRACT FROM AUTHOR]

Data on sofosbuvir‐based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti‐HCV antibody during the 1‐year follow‐up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow‐up year one. In conclusion, this case series study found that sofosbuvir‐based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir‐based therapy as a reference when similar severe CHC situations are encountered during clinical practice. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection can generate a systemic inflammatory response, characterized by a cytokine storm and associated with an exaggerated release of proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IL‐17, all of which can affect the liver. Here, we aimed to evaluate the cytokine profiles of patients suffering from coronavirus disease (COVID)‐19 and/or hepatitis. We subjected 87 patients to serology and/or polymerase chain reaction analysis for the hepatitis C virus. They were also tested for TNF‐α, IL‐6, and IL‐17 using commercial immunoassay kits. The test results of the COVID‐19/hepatitis C patients (n = 8) were compared with that of the negative controls (n = 28), hepatitis C patients (n = 29), and COVID‐19 patients (n = 22). All COVID‐19 patients (mono‐ and coinfected) expressed high levels of cytokines. The COVID‐19/hepatitis patients exhibited higher levels of IL‐6 (6.33 ± 3.9 pg/ml) and IL‐17 (102.23 ± 2.7 pg/ml); however, TNF‐α values were lower (68.08 ± 15.88 pg/ml), as compared with that of the hepatitis patients (p < 0.001), and lower than that of the COVID‐19 patients and exceptionally for TNF‐α (p < 0.05). These data highlight the importance of monitoring patients with hepatitis and COVID‐19. Highlights: A significant increase in the serological levels of IL‐6, IL‐17, and interesting results of TNF‐α in the SARS‐CoV‐2‐infected patients were found.Coinfection with HCV and SARS‐CoV‐2 needs to be more investigated and can help to elucidate the relevant aspects of the inflammatory process that is necessary for monitoring post‐COVID affections in patients with previous liver disorders. [ABSTRACT FROM AUTHOR]

Treatment of hepatitis C virus (HCV) infection with direct‐acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow‐up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment‐emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty‐eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug‐unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis‐dependent patients with genotype 1b AHC. Highlights: 1.All AHC patients undergoing hemodialysis achieved SVR12 after 12 weeks of GZR/EBR treatment.2.Low baseline HCV RNA levels were related to early viral clearance during GZR/EBR treatment.3.GZR/EBR treatment was tolerable and most patients had only mild AEs including fatigue, headache, and nausea during treatment. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Treatment of hepatitis C virus (HCV) genotype 4 patient with fixed dose combination of ombitasvir‐paritaprevir‐ritonavir plus ribavirin (OBV/rPTV/RBV) has been proven efficacy and safety in many clinical trials. The current study reports the efficacy and safety of OBV/rPTV/RBV (for treatment‐naïve), and OBV/rPTV/RBV/sofosbuvir (SOF) (for treatment‐experienced), in chronic HCV genotype 4 patients in real life settings. Methods: Prospective cohort study including all adult chronic HCV genotype 4 patients who were scheduled to receive OBV/rPTV/RBV ± SOF for 12 or 24 weeks in New Cairo Viral Hepatitis Treatment Center. The primary efficacy endpoint was a virologic response at posttreatment week 12 (SVR12). Changes in hematological parameters, liver biochemical profile and fibrosis‐4 index (FIB‐4), as well as clinical and laboratory adverse events (AEs) across follow up visits (week 4, end of treatment [EOT], and SVR12), were recorded. Results: Our study included 325 patients (age; 47.63 ± 12.63 years, 55.38% [n = 180] men). Most of the included patients (89.85%, n = 292) were treatment naïve and only 7% (n = 23) had liver cirrhosis. Overall, SVR12 was attained by 98.44% (316 of 321) of the patients; 97.15% (307 of 316) of patients who received 12 weeks of OBV/rPTV/RBV ± SOF and 100% (9 of 9) of patients who received 24 weeks of OBV/rPTV/RBV as assessed by modified intention to treat analysis. There was a significant improvement of baseline alanine aminotransferase, aspartate aminotransferase, hemoglobin, FIB‐4 at SVR12 (P < 0.05). The most common reported AEs were anemia (n = 106), fatigue (n = 41) and elevated indirect bilirubin (n = 37). Conclusion: OBV/rPTV/RBV (±SOF) is a highly effective therapy for chronic HCV patients in real life settings. Highlight: Treatment of chronic HCV patients with ombitasvir‐paritaprevir‐ritonavir was highly effective in real life settings (cure rate 98.44%).We noticed significant improvement of baseline hepatic necroinflammatory markers, hemoglobin, FIB‐4 at SVR12 (p < 0.05).The most common reported treatment related adverse events were anemia, fatigue and indirect hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Hepatitis, a significant cause of mortality worldwide, results in around 1.34 million deaths each year globally. Africa is not exempt from the plague of Hepatitis. Around 100 million estimated individuals are infected with Hepatitis B or C. Egypt has the highest prevalence of cases of Hepatitis followed by Cameroon and Burundi. The continent is severely affected by the onset of the COVID-19 pandemic, as the virus has added an additional burden on the already fragile continent. With the pandemic, it is presumable that Hepatitis like other viral diseases will pose a threat to collapsing healthcare system. Therefore, for Africa to become more resilient in the face of such menaces, including Hepatitis, further prevention policies are required to be implemented. [ABSTRACT FROM AUTHOR]

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane‐bound receptors such as Toll‐like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen‐associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR‐dependent way. The TLR‐viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development. Highlights: 1. The TLR‐viral protein relationship plays an important role in innate immunity activation2. we review viral proteins serving as pathogen‐associated molecular patterns and their corresponding TLRs.3. Respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR‐dependent way. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an arbovirus belonging to the flaviviridae family with a risk assessment that has been increasing in recent years and was labeled a global health emergency by the World Health Organization in 2016. There are currently no Food and Drug Administration‐approved treatment options available for ZIKV, so expeditious development of treatment options is urgent. To expedite this process, an on‐market drug, tamoxifen (TAM), was selected as a promising candidate for repurposing due to its wide range of biological activities and because it has already been shown to possess activity against hepatitis C virus, a flavivirus in a separate genus. Anti‐ZIKV activity of TAM was assessed by compound screens using an infectious virus and mechanistic details were gleaned from time of addition and virucidal studies. TAM and an active metabolite, 4‐hydroxytamoxifen (TAM‐OH), both showed promising antiviral activity (EC50 ≈9 and 5 µM, respectively) in initial compound screening and up to 8‐h postinfection, though the virucidal assay indicated that they do not possess any direct virucidal activity. Additionally, TAM was assessed for its activity against ZIKV in the human male germ cell line, SEM‐1, due to the sexually transmitted nature of ZIKV owing to its extended survival times in germ cells. Virus titers show diminished replication of ZIKV over 7 days compared to controls. These data indicate that TAM has the potential to be repurposed as an anti‐ZIKV therapeutic and warrants further investigation. [ABSTRACT FROM AUTHOR]

Currently, there is no well‐established algorithm predicting hepatocellular carcinoma (HCC) development in untreated hepatitis C virus (HCV) patients. We aimed to validate an algorithm (risk evaluation of viral load elevation and associated liver disease/HCV [REVEAL‐HCV]: age, AST, ALT, HCV RNA, HCV genotype, and cirrhosis) developed in Taiwanese patients. We analyzed 1381 (50.1% White, 14.7% Hispanic, 13.8% Asian of diverse origin, and 7.8% African American) adult treatment‐naïve HCV patients (no viral co‐infection, no HCC within 6 months) at 4 U.S. and one Hong Kong centers (11/1994–10/2017). Compared to the non‐Asian cohort, the Asian cohort had a higher percentage of patients in the low‐risk group (46.1% vs. 26.1%) and a lower percentage in the high‐risk group (12.0% vs. 20.3%, p < 0.01). Overall, 5‐year HCC incidence were 1.75%, 4.71%, and 24.4% for low, medium, and high‐risk patients, respectively (p < 0.0001). For the overall cohort, area under receiving operating characteristic curve (AUROC) for HCC prediction were 0.83 (95% confidence interval [CI]: 0.72–0.93), 0.82 (95% CI: 0.75–0.88), and 0.84 (95% CI: 0.77–0.89) for 1‐, 3‐, and 5‐year HCC risk, respectively. There was a slightly lower AUROC for Asians compared to the non‐Asian cohort at 3 years (0.75 vs. 0.83) and 5 years (0.78 vs. 0.84), though this was not statistically significant. In multivariable analysis, we found male sex, presence of metabolic syndrome as well as the risk score categories to be independently associated with HCC but not ethnicity. The REVEAL‐HCV risk score has good validity for both Asian and non‐Asian populations. Further studies should consider additional factors, such as sex, metabolic syndrome, and treatment status. Highlights: We have provided cross‐validation of the REVEAL‐HCV risk score which predicts HCC development in untreated HCV patients.We found that REVEAL‐HCV, while developed using a cohort in Taiwan, can predict HCC risk in untreated non‐Asian as well as Asian HCV patients with reasonable accuracy.We found that male sex, presence of metabolic syndrome, medium and high‐risk REVEAL‐HCV score category were associated with HCC.The finding of sex and metabolic syndrome as significant risk factors suggest they may be important in the development or modification of future risk scores. [ABSTRACT FROM AUTHOR]

Globally, 13% of all hepatitis C virus (HCV) infections are caused by genotype 4 (GT4), which consists of 17 subtypes with various levels of susceptibility to anti‐HCV therapy. This genotype is endemic in the Middle East and Africa and has considerably spread to Europe lately. The molecular features of HCV‐GT4 infection, as well as its appropriate therapeutics, are poorly characterized as it has not been the subject of widespread basic research. As such, in this review, we aim to gather the current state of knowledge of this genotype with a particular emphasis on its heterogeneity, sequence signatures, resistance‐associated substitutions, and available in vivo and in vitro models used for its study. We urge developing more cell‐culture models based on different GT4 subtypes to better understand the virology and therapeutic response of this particular genotype. This review may raise more awareness about this genotype and trigger more basic research work to develop its research tools. This will be critical to design better therapeutics and help to provide adequate guidelines for physicians working with HCV‐GT4 patients. Highlights: We raised awarness on the fast growing prevalence of HCV‐GT4 beyong the endemic region.We analysed the genetic diversity of GT4 subtypes.We summarized the succeptibility of HCV‐GT4 to the current standart treatment.We reported the GT4‐specific sequence signatures.We summarized the availabe in vivo and in vitro research tools for study HCV‐GT4. [ABSTRACT FROM AUTHOR]

The real‐world virological efficacy and safety of interferon‐free direct‐acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1‐ and 2‐infected patients with decompensated cirrhosis. A total of 65 patients with HCV‐related decompensated cirrhosis (Child‐Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5–89.9) (52/64), 98.4% (95% CI, 91.2–100.0) (60/61), and 98.5% (95% CI, 91.7–100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0–97.5) (60/65). Albumin–bilirubin (ALBI) scores decreased during and after treatment (p < 0.001), and there were significant differences between baseline and end of treatment and between baseline and SVR12. Subgroup analyses showed no significant differences in SVR rates according to patient age, sex, HCV genotype (subtype), Child‐Pugh classification, modified ALBI grade, presence of ascites, presence of hepatic coma, or history of hepatocellular carcinoma. In all subpopulations, the SVR rates were higher than 80%. There were no severe adverse events associated with the treatment. The SOF/VEL regimen showed good virological efficacy and acceptable safety even in patients with HCV‐related decompensated cirrhosis. Highlights: The efficacy and safety of sofosbuvir and velpatasvir were assessed in hepatitis C virus patients with decompensated cirrhosis.The overall sustained virological response rate was 92.3% and albumin–bilirubin scores decreased during and after treatment (p <0.001).There were no severe adverse events associated with the treatment. [ABSTRACT FROM AUTHOR]

The use of direct‐acting antiviral agents (DAAs) in patients with chronic HCV genotype (GT) 1 infection results in sustained virologic response (SVR) rates of 95%–97%, but 3%–5% of patients experience virologic failure. We observed 41 patients infected with HCV subtype 1b who failed previous treatment with DAAs, including 37 subjects (90.2%) with liver cirrhosis. In total, 30 (73.2%) subjects previously received NS5A inhibitors of the first generation (ledipasvir, daclatasvir, or ombitasvir) and 11 subjects (26.8%) received NS5A inhibitors of the second generation (velpatasvir). All patients received retreatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutation (L31M/V/I and/or Y93H), and the generation of previously used NS5A inhibitors. Observed SVR12 rates were as follows: 97.6% (40/41 patients) overall; 100% in patients without cirrhosis (n = 4) versus 97.3% in those with cirrhosis (n = 37); 100% with single L31M/V/I or Y93H mutation (n = 22) versus 94.4% with double mutations (n = 18); 100% in patients who failed previous treatment with first‐generation (n = 30) versus 90.9% in those who failed previous treatment with second‐generation NS5A inhibitors (n = 11). Retreatment with 3D + SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection, including those with liver cirrhosis, who failed previous treatment with DAA containing NS5A inhibitors. Fibrosis stage and single or simultaneous presence of NS5A RASs L31M/V/I and Y93H at the baseline, as well as the generation of previously used NS5A inhibitors, did not impact SVR12 rates. [ABSTRACT FROM AUTHOR]

In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co‐infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro‐fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR‐101, miR‐122, miR‐155, miR‐192, miR‐200c, miR‐338, and miR‐532 was determined by quantitative real‐time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV‐infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post‐LT. None of the patients was treated with direct‐acting anti‐HCV drugs. All co‐infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR‐101 (p =.03), miR‐122 (p =.012), and miR‐192 (p =.038) were significantly downregulated in HCV/HIV co‐infected and HCV mono‐infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co‐infected ones. Moreover, in co‐infected recipients but not in mono‐infected ones, miR‐101 inversely correlated with the peripheral HCV‐RNA levels (r =.41, p =.04) and miR‐122 inversely correlated with peripheral HCV‐RNA levels (r =.49, p =.03) and with the histological grading (r =.51, p =.02). In conclusion, as early as 6 months after LT, the presence of HIV‐HCV co‐infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation. [ABSTRACT FROM AUTHOR]

Female sex workers (FSWs) represent a high vulnerability group for the acquisition of sexual and parenteral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. The present study aimed to determine the prevalence of serological markers and risk factors associated with exposure to HBV and HCV among FSWs in the state of Pará, Brazil. A cross‐sectional study using principles of the time location sampling (TLS) method was conducted in four cities (Belém, Bragança, Barcarena, and Augusto Corrêa) of the state of Pará, from 2005 to 2006. In total, 365 FSWs were interviewed using a standardized questionnaire. Blood samples were collected and tested for serological markers of exposure to HBV and HCV using an enzyme immunoassay. The overall prevalence of exposure to HBV and HCV was 36.7% and 7.7%, respectively. The prevalence of surface antigen of HBV was 3.0%. The prevalence of anti‐HBc and anti‐HBc+ anti‐HBs antibodies were 6.3% and 27.4%. Very few (4.7%) FSWs had vaccine immunity against HBV (anti‐HBs antibodies only). The prevalence of anti‐HCV antibodies was 7.7%. Low monthly income, drug usage, and unprotected sex were some of the social characteristics associated with exposure to the viruses using different analysis. The seroprevalence of HBV and HCV infections among FSWs in four cities of the state of Pará is high when compared to the general population of Brazil, but similar to those found in FSWs in other nondeveloped countries. The prevalence of HBV was higher in Belém, while the prevalence of HCV was higher in the other three cities, highlighting the importance of establishing control and prevention programs to reduce the risk of acquiring these viruses in Pará. [ABSTRACT FROM AUTHOR]

Combination regimens of direct‐acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment‐naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single‐center, open‐label trial to receive 2 weeks of the highly potent and selective non‐nucleoside inhibitor (NNI) CDI‐31244 concurrent with 6 weeks of sofosbuvir/velpatasvir. The main efficacy endpoints were sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks after treatment completion. In all patients, plasma HCV RNA levels rapidly decreased during the first 2 days of treatment and were below the lower limit of quantification by the end of the 6‐week treatment period. Eight of 12 (67%) patients achieved both SVR12 and SVR24. Four patients had virological relapse at Week 10, 4 weeks after end of treatment. The most common adverse event was headache, occurring in five (42%) patients. Pharmacokinetic analysis showed no relevant drug interactions between CDI‐31244, sofosbuvir, and velpatasvir. In this pilot study of short‐duration combination therapy involving a novel NNI with a fixed‐combination DAA, 8 of 12 treatment‐naïve patients with chronic genotype 1 HCV infection without cirrhosis achieved virologic cure. Future trials might evaluate whether extending the NNI duration beyond 2 weeks with combination DAAs results in higher cure rates comparable with currently approved longer duration therapy. [ABSTRACT FROM AUTHOR]

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti‐hepatitis C virus antibody (anti‐HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at‐risk population, such as immunocompromised hosts and end‐stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at‐risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at‐risk patients who require monitoring of HCV infection and reinfection. Highlights: ‐ Anti HCV antibody is used as screening test/ ‐ Anti HCV antibody test is falsely negative in immunocompromised hosts. ‐ HCV antigen testing can be used as screening test in this group. [ABSTRACT FROM AUTHOR]

Retraction: "Small Interfering RNA Effectively Inhibits Protein Expression and Negative Strand RNA Synthesis From a Full‐Length Hepatitis C Virus Clone" by Prabhu, R., Vittal, P., Yin, Q., Flemington, E., Garry, R., Robichaux, W.H. and Dash, S, J. Med. Virol 2005, 76: 511‐519. The above article, published online on 23 June 2005, in Wiley Online Library (https://doi.org/10.1002/jmv.20391), has been retracted by agreement between the journal Editor‐in‐Chief, Shou‐Jiang Gao, and Wiley Periodicals, LLC. The retraction has been agreed due to following publication concerns which were raised by third parties regarding Figure 3. The authors were unable to provide a satisfactory explanation and could not provide the original data. The retraction has been agreed because of concerns that the images were manipulated, affecting the interpretation of the data and results presented. [ABSTRACT FROM AUTHOR]

Comments on "Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C" Keywords: Anti-hepatitis C virus DAA (directly acting antivirals); Antiviral agents; Hepatitis C virus; Hepatitis virus; Virus classification EN Anti-hepatitis C virus DAA (directly acting antivirals) Antiviral agents Hepatitis C virus Hepatitis virus Virus classification 436 438 3 12/13/21 20220201 NES 220201 Elhence et al.1 assessed the retreatment outcomes of direct-acting antivirals (DAAs) therapy failure in a cohort of 40 patients with chronic hepatitis C (HCV) and previous virological failure (VF) to DAAs. Addressing hesitancy in HCV retreatment prescription and nonadherence to second-line DAAs with a tailored approach is crucial to scale up HCV treatment and eradicate HCV infection in people with previous VF to DAAs. [Extracted from the article]

This study investigated the safety and efficacy of ravidasvir (RDV) plus ritonavir‐boosted danoprevir (DNVr) and ribavirin (RBV) regimens for treatment‐naïve non‐cirrhotic patients with hepatitis C virus (HCV) genotype 1b in mainland China. We also gained insight into HCV‐host interactions during anti‐HCV treatment. 16 patients with HCV and 10 healthy people enrolled the study. Three of 16 patients received 12‐weeks' placebo treatment first and served as the placebo controls. All (n = 16) patients received 12‐weeks' RDV plus DNVr and RBV treatment. The adverse effects (AEs), viral loads, alanine transaminase, and aspartate aminotransferase were recorded during study. We also performed multianalyte profiling of 48 cytokines/chemokines in 16 patients with HCV and 10 normal controls. Seventy‐five percent patients treated with RDV plus DNVr and RBV experienced AEs. No death, treatment‐related serious AEs or AEs leading to discontinuation were reported. The serum HCV‐RNA levels remained extremely high in 3 placebo controls after treated with placebo. After RDV plus DNVr and RBV treatment, all patients achieved sustained virologic response (SVR) at posttreatment week 12, but 1 patient experienced viral relapse at SVR 24. The cytokine/chemokine expression pattern was markedly altered in patients with HCV as compared with healthy controls. The interferon‐inducible protein‐10 (IP‐10) decreased after anti‐HCV treatment, and dramatically increased in one patient with viral relapse. The regimen of RDV and DNVr plus RBV represents a highly safe and effective treatment option for HCV patients in mainland China. The IP‐10 has the potential to be an indicator of innate immune viral recognition. Highlights: Ravidasvir plus ritonavir‐boosted danoprevir and ribavirin regimens are safe and effective for HCV patients.The cytokine/chemokine expression pattern was markedly altered in HCV patients.The IP‐10 level was changed during the HCV infection and elimination. [ABSTRACT FROM AUTHOR]

Introduction: Although the effectiveness of direct‐acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real‐world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. Methods: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). Results: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full‐course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non‐SVR12 was 4.5% (95% CI, 3.5‐5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child‐Pugh score B OR, 2.09 (P =.06), Child‐Pugh C OR, 11.7 (P <.0001); and liver transplant (LT) recipient OR, 3.75 (P =.01). Conclusion: In this real‐life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time‐point of DAA treatment (NCT03775798; www.clinicaltrials.gov). Highlights: SVR12 failure in clinical practice is low in Latin America (4.5%). End stage liver disease (Child B/C scores) and liver transplantation were independent predictors of DAA failure. Early DAA treatment to prevent disease progression is needed to avoid nonresponse to treatment. [ABSTRACT FROM AUTHOR]

Hepatitis B and C viruses (HBV and HCV) are common causative pathogens of viral hepatitis. Progression of both infections is determined by virus‐ and host‐related factors. Cytokines are important host genetic factors that may have a predisposing role in HBV and HCV infections. This case‐control study evaluated the genetic association of IL4RA+1902 (rs1801275), IL6−174 (rs1800795), IL6−597 (rs1800797), and IL12B−1188 (rs3212227) variants with chronic HBV and HCV infections among Iraqi patients. A total of 220 viral hepatitis patients were enrolled in the study (113 HBV and 107 HCV), together with 141 healthy subjects. Sequence‐specific primer polymerase chain reaction assay was the genotyping method. Results revealed that under a dominant genetic model, IL6−174 variant was significantly associated with HBV infection, whereas no association with the HCV risk was reported. However, the risk for both infections was markedly associated with IL6−597 variant under recessive, dominant, and codominant genetic models. Estimation of IL6−174‐IL6−597 haplotypes depicted that G‐A haplotype was significantly associated with an increased risk to develop HBV infection, whereas a significantly decreased risk was associated with G‐G and C‐G haplotypes. For HCV, G‐G and C‐A haplotypes were significantly associated with risk of HCV infection. IL4RA+1902 and IL12B−1188 variants showed no association with HBV or HCV risk. Analysis of variance revealed no significant association between genotypes of the four determined single‐nucleotide polymorphisms and HBV or HCV viral load. In conclusion, the study supports the concept that IL6−597 variant is associated with susceptibility to HBV and HCV infections among Iraqis. The risk of HBV infection is further associated with IL6−174 variant. Highlights: IL6‐597 variant is associated with susceptibility to HBV and HCV infections.IL6‐174 variant is a further risk factor for HBV infection.IL4RA+1902 and IL12B‐1188 variants are not associated with HBV− or HCV‐risk. [ABSTRACT FROM AUTHOR]

CD8+ T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+ T‐cell subsets were confirmed to be closely related to HCV infection such as TCM, TEM, TEMRA, Tc17, and CD8+ Treg. Herein, we report a new subset of interleukin (IL)‐17/interferon (IFN)‐γ producing CD8+ T (Tc17/IFN‐γ) cells that markedly correlate with CD28+CD244+ cells, IL‐17 levels, and HCV RNA in HCV patients. During early treatment with peg‐IFN‐a2a plus ribavirin, the imbalance of these Tc17/IFN‐γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4‐week course of treatment with peg‐IFN‐a2a plus ribavirin and found that the percentage of CD8+CD28+CD244+ T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+CD244+ T cells were the only CD8+ T‐cell group that secreted both IL‐17 and IFN‐γ in this axis and blockade with anti‐CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+CD244+ Tc17/IFN‐γ cells may play an important role in persistent HCV infection. Highlights: A new subset of IL‐17/IFN‐γ producing CD8+ T (Tc17/IFN‐γ) cells that markedly correlate with CD28+CD244+ cells, IL‐17 levels, and HCV RNA in HCV patients.The imbalance of these Tc17/IFN‐γ cells could be partially restored afterearly treatment with peg‐IFN‐a2a plus ribavirin, the imbalance of these Tc17/IFN‐γ cells could be partially restored. [ABSTRACT FROM AUTHOR]

Infectious diseases during pregnancy remain a public health concern, especially in a resource‐limited setting. The study aimed to determine the seroprevalence and determinants of HIV and co‐infection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis among pregnant women attending antenatal care in Luanda, the capital city of Angola. A cross‐sectional study was conducted with 1612 pregnant women screened for HIV during antenatal care. HIV‐reactive were also screened for the HBV, HCV, and syphilis using immunoassay kits. A logistic regression model, adjusted odds ratios (AOR) and their 95% confidence interval (CI) were calculated with a level of significance set at 5%. The overall seroprevalence of HIV was 2.6%. About 13% of HIV‐positive pregnant women were coinfected. From which, 7.5% were reactive to HBV and 5% to syphilis. There was no reactivity to HCV. Pregnant women younger aged than 25 years were significantly protected from HIV‐infection (AOR, 0.43 [95% CI, 0.20‐0.91], P =.026). The co‐infection was 1.3 times (AOR, 0.04‐41.0) in younger aged than 25 years, 7.0 times (AOR, 0.50‐99.2) to residents in urbanized areas, and 1.4 times (AOR, 0.10‐20.9) in pregnant women with a high educational level. In conclusion, infectious diseases are a public health burden among pregnant women in Luanda. However, include an integrated antenatal screening mainly in urbanized areas is crucial to reduce the spread of infectious diseases in different communities of Angola. Highlights: Infectious diseases such as HIV, HBV, and syphilis are a public health burden among pregnant women attending antenatal care in Luanda, which highlights the need to strengthen biomedical interventions.An integrated antenatal program including HBV vaccination and screen of syphilis should be widely applied in all pregnant women attending antenatal care in Luanda regardless of HIV prevention strategies.Health education to prevent the spread of infectious diseases in Angola, should begin in urbanized areas and expand into rural areas.Investigate demographic and behavioral factors that influence the emergence of infectious agents is crucial to reduce costs related to public health planning, the spread of infectious diseases, maternal transmission, and adverse effects on neonates. [ABSTRACT FROM AUTHOR]

Earlier observation suggests that hepatitis C virus (HCV) is a single‐stranded RNA virus which encodes at least 10 viral proteins. F protein is a novel protein which has been discovered recently. These studies suggest three mechanisms for the production of this protein concerning ribosomal frameshift at codon 10, initial translation at codons 26 and 85 or 87. In this study, the association between protein F and chronicity of hepatocellular carcinoma (HCC) has been reviewed. Evidence suggests that humoral immune system can recognize this protein and produce antibodies against it. By detecting antibodies in infected people, investigators found that F protein might have a role in HCV infection causing chronic cirrhosis and HCC as higher prevalence was found in patients with mentioned complications. The increment of CD4+, CD25+, and FoxP3+ T cells, along with CD8+ T cells with low expression of granzyme B, also leads to weaker responses of the immune system which helps the infection to become chronic. Moreover, it contributes to the survival of the virus in the body through affecting the production of interferon. F protein also might play roles in the disease development, resulting in HCC. The existence of F protein affects cellular pathways through upregulating p53, c‐myc, cyclin D1, and phosphorylating Rb. This review will summarize these effects on immune system and related mechanisms in cellular pathways. Highlights: There are different types of F protein with different production mechanism, which is also genotype specific.F protein can induce antibody production in HCV patients. Anti‐F antibody prevalence is significantly higher in chronic HCV patient, patients with cirrhosis and hepatocarcinoma cases.F protein can weaken the innate immune responses by increasing the apoptosis of dendritic cells, reduction of IFN‐α, IFN‐γ and also causing some changes in cytokine secretion which helps the infection to persist and become chronicF protein increases CD4+ CD25+ FoxP3 T cells and also IL‐10 producing CD4+ CD25+ T cells. Also with induction of generation of CD8+ and CD4+ T cells with low granzyme B expression and contribution to a bias in Th1/Th2 responses can weaken the cellular immune responses.Modifications causes by F protein in cell cycle may contribute the infection to lead to hepatocarcinoma. These modifications include upregulation of c‐myc, downregulation of p53, increasing the cyclin D1 and pRb levels. [ABSTRACT FROM AUTHOR]

Pakistan has the second‐highest burden of hepatitis C patients in the world. A total of 683 individuals, who visited the Liver Clinic during the study period, were screened for the presence of hepatitis C virus (HCV) infection. A total of 534 individuals who showed positive HCV infection were grouped into the case group and 149 individuals with HCV negative status were grouped into the control group. A detailed questionnaire was used to collect demographic, clinical, HCV risk factor, and familial clustering data. HCV familial clustering was found in 30.1% in the case group compared with 17.4% in the control group. We also found 17% of patients had spouses who were also infected with HCV compared to 4% spouse infection in the control group. Only 3.7% of patients had HCV positive mothers. These results were further expanded by regression analysis that showed that family history and sexual history are independent risk factors for transmission of hepatitis C infection and mother's history has no significance as a risk factor for transmission. The major risk factor for getting HCV infection are dental procedures, unsafe injections, surgery, and blood transfusions. There is a strong need to increase awareness about HCV transmission routes among positive patients to reduce the chances of HCV familial clustering. Highlights: Pakistan has second highest burden of HCV in the world. There is joint family system in Pakistan and the number of people living in a house is very high as compared with Western countries. Our study shows 30.1 of HCV familial clustering. The major risk factor for HCV transmission in Pakistan are dental procedures, unsafe injection, surgery, and blood transfusion. There is strong need to increase awareness about HCV transmission routes among positive patients to reduce the chances of HCV familial clustering. [ABSTRACT FROM AUTHOR]

Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg‐negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV‐infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management. Highlights: In recent years, a progressive increase in the use of immunosuppressive treatments has been observed in developed countries. Occult B infection (OBI) is a virological entity to be considered when evaluating immunocompromised patients, as well as subjects with chronic liver diseases or blood donors. The prevalence of OBI significantly varies in different studies according to the methods used and the population considered. Our review outlines the epidemiology of OBI in Western countries and its implications in clinical practice. [ABSTRACT FROM AUTHOR]

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology. Highlights: The development of liver pathology as a result of HCV infection is not straightforward to characterise.Serial biopsies from infected individuals are clinically impractical and unlikely to be available from early infection.We have characterised pathology in tamarins at various time‐points during infection with GBV‐B ‐ a surrogate model of HCV infection.We identified changes in the liver soon after infection; we also noted development of fibrosis which has not been reported previously in tamarins.This report highlights refinement of the tamarin model and its value in the pre‐clinical evaluation of antiviral treatments and vaccines. [ABSTRACT FROM AUTHOR]