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In this study, a stable observer‐based feedback controller has been designed for treatment of hepatitis C infectious disease under interferon (IFN) therapy. In order to consider the memory behavior and uncertain nature of this biological system, an unknown dynamics fractional‐order (FO) model has been utilized for describing the interactions between the healthy cells, infected cells, and hepatitis C virus (HCV). To cope with unknown dynamics, the fuzzy logic system (FLS) has been utilized. Limitation of the drug efficacy due to its negative side effects has been taken into account as an input saturation. In order to estimate the unknown states which are required for treatment, a full‐order fuzzy observer has been designed. Stability of the closed‐loop system in the presence of observer dynamics, input limitation, and unknown system dynamics has been established via the Lyapunov stability theorem. Finally, the effectiveness of the proposed controller has been demonstrated via a simulation study. Simulation results indicate that under the proposed treatment strategy, all system states remain bounded, and the infected cells concentration decreases to the cure boundary. [ABSTRACT FROM AUTHOR]

For a hepatitis C virus (HCV) mathematical model considering host immune system which is studied by Blé et al. (2018), uniform persistence and global asymptotic stability of the endemic equilibrium of the model are considered, and a set of feasible sufficient conditions are obtained by constructing appropriate Lyapunov functions. Our results largely improved those in related works. [ABSTRACT FROM AUTHOR]

Ageing with a chronic hepatitis B (HBV) or hepatitis C (HCV) infection is an emerging public health priority. For people living with chronic viral hepatitis, their disease progression into old age is both underpinned by their existing blood borne virus and the potential emergence of other infectious and non‐infectious conditions. These twinned pathways bring additional challenges to the care and support for people as they near end of life. This scoping review sought to examine what is known about the experiences of the end‐of‐life phase of an increasing population ageing with HBV and HCV in studies conducted in high‐income settings and published in peer reviewed literature (2010–2021). In interpreting this literature, we found that challenges in determining the end‐of life phase for people with lived experience of HBV or HCV are exacerbated by the conflation of aetiologies into a singular diagnosis of end‐stage liver disease. Studies overwhelmingly reported the clinical aspects of end‐of‐life care (i.e. prognosis assessment and symptom management) with less attention paid to educative aspects (i.e. advance care directives and surrogate decision makers, discussion of treatment options and determining goals of care). Psychosocial interventions (i.e. quality of life beyond symptom management, including emotional/spiritual support and family and bereavement support) received limited attention in the literature, though there was some recognition that psychosocial interventions should be part of end‐of‐life care provision. Given the focus on the prominent disease presentation of liver cirrhosis and/or end‐stage liver disease, the social and cultural dimensions of these infections have received less attention in the literature on end‐of‐life in the context of chronic viral hepatitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment of hepatitis C virus (HCV) infection with direct‐acting antivirals (DAAs) is monitored by assessing plasma HCV‐RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative. Aim: To evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV‐infected patients Methods: We performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV‐RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end‐of‐treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT). Results: We selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity = 0.40, specificity = 0.96, positive likelihood ratio (PLR) = 9.16, negative likelihood ratio (NLR) = 0.63, and area under the summary receiver operating curve (SROC) = 0.57), fair at week 4 (sensitivity = 0.30, specificity = 0.90, PLR = 3.18, NLR = 0.77, and AUC = 0.79), acceptable at EOT (sensitivity = 0.40, specificity =0.98, PLR = 16.54, NLR = 0.62, and AUC = 0.97) and excellent for SVR (sensitivity = 0.94, specificity = 0.99, PLR = 107.54, NLR = 0.06, and AUC = 0.99). Conclusions: The HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV‐infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance. [ABSTRACT FROM AUTHOR]

Cryoglobulinemic Vasculitis (CV) is an autoimmune/lymphoproliferative disorder associated with HCV infection that in 5%–10% of cases evolves into a B cell Non‐Hodgkin's Lymphoma (NHL). B‐cell activating factor (BAFF) is a key regulator in B‐cell development and survival. Particular genetic variants are responsible for BAFF signaling impairment in autoimmune and neoplastic diseases. We evaluated BAFF and BAFF‐receptor (BAFF‐R) polymorphisms in order to determine if they predispose to HCV‐related CV and NHL. The analysis was performed on 416 HCV‐chronically infected patients: 136 HCV without signs/symptoms of lymphoproliferations/autoimmunity (HCV), 166 HCV with CV (HCV‐CV) and 114 HCV with NHL (HCV‐NHL). Rs9514828 SNP on BAFF promoter, rs61756766 on BAFF‐R and rs12428930 on the BAFF gene were evaluated by Real‐Time PCR. Concerning rs9514828, the frequency of C/T genotype was significantly higher in HCV‐CV than in HCV. The difference in the distribution of the T/T mutant genotype in HCV‐CV compared to HCV was significant as well as the distribution of C/T and T/T genotype in HCV‐NHL versus HCV. T minor allele was more frequent in HCV‐NHL and HCV‐CV than in HCV. The distribution of C/T + T/T (for the dominant model of penetrance C/T + T/T vs. C/C) was significantly higher in HCV‐CV and HCV‐NHL than in HCV. Genotyping of rs61756766 on BAFF‐R coding gene, revealed C/T heterozygosis at a frequency of 11% in HCV‐NHL versus 3% in HCV. The T minor allele frequency was higher in HCV‐NHL than in HCV. No differences emerged by genotyping rs12428930 SNP on BAFF coding gene. Our results reinforce the hypothesis that BAFF/BAFF‐R genetic pattern has a role in the pathogenesis of HCV‐related lymphoproliferations. BAFF/BAFF‐R variants could identify a risk haplotype for HCV related CV and NHL and a BAFF/BAFF‐R genetic profile assessment could potentially contribute to tailoring anti‐BAFF therapy by identifying patients with BAFF alterations in which the treatment could be more beneficial. [ABSTRACT FROM AUTHOR]

Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy. [ABSTRACT FROM AUTHOR]

In 2020, the Australian state of Victoria experienced the longest COVID- 19 lockdowns of any jurisdiction, with two lockdowns starting in March and July, respectively. Lockdowns may impact progress towards eliminating hepatitis C through reductions in hepatitis C testing. To examine the impact of lockdowns on hepatitis C testing in Victoria, de-identified data were extracted from a network of 11 services that specialize in the care of people who inject drugs (PWID). Interrupted time-series analyses estimated weekly changes in hepatitis C antibody and RNA testing from 1 January 2019 to 14 May 2021 and described temporal changes in testing associated with lockdowns. Interruptions were defined at the weeks corresponding to the start of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre-COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C. [ABSTRACT FROM AUTHOR]

In 2020, Centers for Disease Control and Prevention (CDC) released guidelines recommending HCV screening in all adults 18 years and older. In the current study, we aimed to identify risk factors for HCV infection in an ED population. We performed a retrospective analysis of ED patients ≥ 18 years who were screened for HCV between 28 November 2018, and 27 November 2019, at a single urban, quaternary referral academic hospital. An HCV-antibody immunoassay (HCV-Ab) was used for screening; positive results were confirmed by measuring HCV ribonucleic acid (RNA). The outcome of interest was the number of new HCV diagnoses (presence of viremia by HCV RNA testing). Multiple logistic regression models were used to identify risk factors associated with a new HCV diagnosis. 16,722 adult patients were screened for HCV (mean age: 46 ± 15 years; 51% female). HCV seroprevalence was 5%. Independent risk factors for HCV included increasing age [10-year aOR 1.26 (95% CI 1.23, 1.30)], male sex [aOR 1.25 (95% CI 1.03, 1.51)], undomiciled housing status [aOR 2.8 (95% CI 2.3, 3.5)], history of tobacco use [aOR 3.0 (95% CI 2.3, 3.9)], history of illicit drug use [aOR 3.6 (95% CI 2.9, 4.5)], Medicaid insurance status [aOR 4.0 (95% CI 2.9, 5.5)] and Medicare insurance status [aOR 1.6 (95% CI 1.1, 2.2)].The ED services a high-risk population with regards to HCV infection. These data support universal screening of ED patients for HCV. Risk factor profiles could improve targeted screening at institutions without universal testing protocols. [ABSTRACT FROM AUTHOR]

Linear, blotchy, reticular, and perifollicular patterns have also been described.1,2 Poikilodermatous lichen planus pigmentosus is a rare variant of lichen planus pigmentosus that was first reported in 2016 by Sharma et al.3 in an Indian female. Based on the clinical, histological, and dermoscopic findings, a final diagnosis of poikilodermic lichen planus pigmentosus with concomitant typical lichen planus and lichen planopilaris was made. Facial pitted scars + epidermal cysts + comedon-like lesions ht The poikilodermatous lichen planus pigmentosus case reported by Sharma et al.3 was accompanied by cicatricial alopecia and typical lichen planus lesions, as our case. [Extracted from the article]

Background: Although the prevalence and mortality of hepatitis is high in the Asia‐Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). Methods: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) cohort, on ART, and with follow‐up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co‐infection if they ever tested positive for HCV antibody (anti‐HCV) or HBV surface antigen (HBsAg), respectively. Results: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti‐HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti‐HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. Conclusion: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment. [ABSTRACT FROM AUTHOR]

Background: The prevalence of liver complications is increasing among people living with HIV, and microbial translocation (MT) might play a vital role. We conducted a prospective cohort study to evaluate the association between plasma biomarkers of MT and liver fibrosis (LF) among people living with HIV in southwest China. Method: A total of 665 people living with HIV were enrolled at baseline and had at least one follow‐up visit during the 3‐year study period. We calculated the Liver Fibrosis Index (FIB‐4) to evaluate LF and measured plasma soluble CD14 (sCD14) and lipopolysaccharide‐binding protein (LBP) as surrogate biomarkers for MT. We used ordinal logistic regression to investigate correlates of LF at baseline and used a linear mixed model to examine the association between dynamic changes in MT biomarkers and LF. Results: Of the participants, 61 (9.17%) had advanced LF (FIB‐4 >3.25), and 193 (29.02%) had moderate LF (1.45 ≤ FIB‐4 ≤ 3.25). Patients with advanced LF had higher plasma levels of sCD14 and LBP than those with moderate or no LF, both at baseline and at follow‐up. The following factors were significantly associated with advanced LF: the highest quartile of LBP (adjusted odds ratio [aOR] = 1.69; 95% confidence interval [CI] 1.02~2.81), current intravenous drug use (aOR = 1.82; 95% CI 1.06~3.12), baseline CD4 <200 cells/μl (aOR = 3.25; 95% CI 2.13~4.95), hepatitis C virus coinfection (aOR = 2.52; 95% CI 1.41~4.51) and age >50 years (aOR = 32.66; 95% CI 15.89~66.36). LF progression (increasing FIB‐4) was significantly associated with increasing sCD14 level (β = 1.11; 95% CI 0.97~1.26; p < 0.001) with covariate adjustment. Conclusion: The significant relationship between MT and LF may reveal pathogenic mechanisms and potential intervention targets of liver complications among people living with HIV in China. [ABSTRACT FROM AUTHOR]

This article discusses two models, with two different needle assumptions for the transmission of hepatitis C virus (HCV) between people who inject drugs (PWIDs) who share needles and syringes. Our analysis demonstrates that the basic reproduction number R0 determines how the model behaves. R0=1 is a crucial threshold parameter which divides two qualitatively different scenarios. It has been shown that if R0≤1 only a disease‐free equilibrium point exists. On the other hand if R0>1 a unique endemic equilibrium point exists as well as the disease‐free one. The disease‐free equilibrium point is globally asymptotically stable if R0≤1 otherwise unstable. We look at an approximation to this model by using the fact that the timescale on which the individual PWIDs inject with needles or syringes is much faster than the timescale of epidemiological change. Also, we showed that if R0>1 the endemic equilibrium point is locally asymptotically stable for our approximation to this model. Additionally, we perform some simulations with realistic parameter values which confirm that if R0>1 then the solutions to this model tend to this endemic equilibrium value giving a steady‐state nonzero HCV prevalence. With realistic parameter values for both assumptions we find that R0=2.9987 and the total endemic equilibrium fraction of infectious PWIDs is 0.5348 and the total equilibrium fraction of antibody positive PWIDs is 0.65. The total fraction of infectious needles is 0.275. [ABSTRACT FROM AUTHOR]

Objective. This systematic review and meta-analysis aimed to compare the diagnostic performance of transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE) for staging liver fibrosis in patients with chronic viral hepatitis (CVH). Methods. Pubmed, Embase, Web of Science, and Cochrane Library were searched (-01/08/2021) for studies comparing TE with 2D-SWE in patients with CVH. Other etiologies of chronic liver disease (CLD) and articles not published in SCI journals were excluded. The bivariate random-effects model was used to pool the performance of the TE and 2D-SWE. Results. Eight articles with a total of 1301 CVH patients were included. The prevalence of significant fibrosis (fibrosis stage ≥ 2), advanced fibrosis (fibrosis stage ≥ 3), and cirrhosis was 50.8%, 44.8%, and 34.7%, respectively. 2D-SWE expressed higher overall accuracy than TE in detecting significant fibrosis (0.93 vs. 0.85, P = 0.04). No significant difference among the overall diagnostic accuracy of TE and 2D-SWE in staging advanced fibrosis and cirrhosis was found. Conclusion. TE and 2D-SWE express good to excellent diagnostic accuracies to stage fibrosis in CVH patients. 2D-SWE compares favorably with TE especially for predicting significant fibrosis. [ABSTRACT FROM AUTHOR]

The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV‐associated symptoms and functional well‐being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well‐being using the disease‐specific HCV‐PRO instrument. Survey assessments were administered at baseline, early post‐treatment (median = 6 months) and late post‐treatment (median = 21 months). Constrained longitudinal linear mixed‐effects models were used to evaluate within‐treatment change and between‐treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post‐treatment, 5 out of 6 symptoms and functional well‐being significantly improved (all p's <.05). In the LDV/SOF arm, mean changes ranged from −3.73 for nausea to −6.41 for fatigue and in the EBR/GZR, mean changes ranged from −2.19 for cognitive impairment to −4.67 for fatigue. Change of >3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well‐being that were sustained during the late post‐treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well‐being up to two years after SVR. [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]

Background and Aims: In moving towards the elimination of hepatitis C virus (HCV) infection among people living with HIV, understanding HCV transmission patterns may provide insights to guide and evaluate interventions. In this study, we evaluated patterns of, and factors associated with HCV phylogenetic clustering among people living with HIV/HCV co‐infection in Australia in the direct‐acting antiviral era. Methods: HCV RNA was extracted from dried blood spot (DBS) samples collected between 2014 and 2018 in the CEASE cohort study. The HCV Core‐E2 region was amplified by a polymerase chain reaction and Sanger sequenced. Maximum likelihood phylogenetic trees (1000 bootstrap replicates) were used to identify patterns of clustering (3% genetic distance threshold). Mixed‐effects logistic regression was used to determine correlates of phylogenetic clustering. Factors assessed were sexual risk behavior, education, injecting drug use, housing, employment, HIV viral load, age, sex, and sexuality. Results: Phylogenetic trees were reconstructed for HCV subtype 1a (n = 139) and 3a (n = 63) sequences, with 29% (58/202) in a pair or cluster. Overall (n = 202), phylogenetic clustering was positively associated with younger age (under 40; adjusted odds ratio [aOR] 2.52, 95% confidence interval [CI] 1.20–5.29), and among gay and bisexual men (n = 168), was positively associated with younger age (aOR 2.61, 95% CI 1.10–6.19), higher education (aOR 2.58, 95% CI 1.09–6.13), and reporting high‐risk sexual behavior (aOR 3.94, 95% CI 1.31–11.84). During follow‐up, five reinfections were observed, but none were in phylogenetic clusters. Conclusion: This study found a high proportion of phylogenetic relatedness, predominantly among younger people and gay and bisexual men reporting high‐risk sexual behavior. Despite this, few reinfections were observed, and reinfections demonstrated little relationship with known clusters. These findings highlight the importance of rapid HCV treatment initiation, together with monitoring of the phylogeny. [ABSTRACT FROM AUTHOR]

Background: Sharps injuries and the related risk of infections such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) represent one of the major occupational health risks for healthcare workers (HCWs). Literature Review: An overview of available data on the incidence of sharps injuries and the related HBV, HCV and HIV infections and ensuing costs is provided. Results: Literature reported incidence rates of sharps injuries ranging from 1.4 to 9.5 per 100 HCWs, resulting in a weighted mean of 3.7/100 HCWs per year. Sharps injuries were associated with infective disease transmissions from patients to HCWs resulting in 0.42 HBV infections, 0.05-1.30 HCV infections and 0.04-0.32 HIV infections per 100 sharps injuries per year. The related societal costs had a mean of €272, amounting to a mean of €1,966 if the source patient was HIV positive with HBV and HCV co-infections. Conclusion: Sharps injuries remain a frequent threat amongst HCWs. The follow-up and treatment of sharps injuries and the deriving consequences represent a significant cost factor. [ABSTRACT FROM AUTHOR]

The incidence rate of hepatocellular carcinoma (HCC) is expected to increase, with most cases occurring in Asia. In some parts of Asia, the occurrence of HCC developing from metabolic-related liver disease has markedly increased in recent years, whereas the occurrence of HCC developing from viral-hepatitis-related liver disease has decreased. Advancements in the treatment of HCC over the past few decades has been remarkable, with most treatment strategies to remove or control liver tumours (hepatic resection, local ablation, radiation therapy, transarterial chemoembolisation, hepatic arterial infusion chemotherapy) primarily developing in Asia. In addition, recent progress in systemic therapies has prolonged the prognosis of advanced HCC. Nowadays, six regimens of systemic therapies have become available in most countries, according to phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). In a global randomised phase III trial (IMbrave 150 trial), the most effective of the latest drug designs was newly emerged combination immunotherapy (atezolizumab plus bevacizumab), which has shown significantly prolonged overall survival compared with sorafenib, which was the first-line systemic therapy for more than a decade. Now, the treatment dynamics for HCC are undergoing a major transition as a result of two important changes: the replacement of viral-related HCC by metabolic-related HCC and the emergence of combination immune therapy. [ABSTRACT FROM AUTHOR]

Approximately 80% of primary healthcare facilities in China were ready to deliver hepatitis care services by 2021. This study aimed to assess hepatitis B and C test uptake, identify the factors associated with testing and determine the predictors of hepatitis stigma among primary care patients. We conducted a cross‐sectional survey among patients seeking care in the family medicine and primary care unit of the University of Hong Kong‐Shenzhen Hospital, China. Participants were 30 years or older and had not tested for HBV and HCV in the preceding 12 months. Test uptake was defined as self‐reported previous HBV and HCV testing. Descriptive statistics, Chi‐square test, forward multivariable logistic regression and stepwise multiple linear regression were conducted, and a p‐value <.05 was deemed statistically significant. A total of 750 eligible patients completed the survey, and 54.5% (404 ± 0.9) were between 30 and 40 years old. Most participants were heterosexuals 98.0% (n = 735), female 57.5% (n = 431), married 78.3% (587) and earned ≤1500 USD per month 54.4% (n = 408). A 66.1% (n = 496) and 13.7% (n = 103) self‐reported previous HBV and HCV testing, respectively, and 62% (n = 468) were vaccinated. HCV testing was associated with HBV testing (aOR = 13.7, 95% CI:2.1–91.5); and HBV testing was associated with family history of HBV (aOR = 2.4, 95%CI:1.1–5.5). Overall hepatitis stigma was about average and decreased with family history of HBV (p =.017). In conclusion, HCV testing uptake among primary care patients was low and needs to be further promoted. Integrating HBV and HCV testing interventions and fostering family‐based support for disclosure could effectively improve testing uptake. [ABSTRACT FROM AUTHOR]

In the Netherlands, hepatitis C virus (HCV) transmission occurs primarily in men who have sex with men (MSM). By early diagnosis and immediate treatment of acute HCV infections, HCV micro‐elimination in MSM is within reach. In cooperation with the community affected, we developed an online HCV‐RNA home‐based self‐sampling test service. This service combined online HCV self‐risk assessment with the possibility to test anonymously for HCV‐RNA. The service was available in the Netherlands from February 2018 till December 2020 and was promoted online on various dating sites and offline by community volunteers. Using website user data, test results and an online post‐test user survey, we evaluated the service and user experiences. The website page with information about testing was visited by 3401 unique users, of whom 2250 used the HCV‐risk assessment tool, 152 individuals purchased 194 HCV‐RNA tests, and 104 tests were used, of which 101 gave a conclusive result. The target population of MSM at risk was successfully reached with 44.1% of users receiving the advice to test. The test service had a satisfactory uptake (6.8%, 152/2250), a very high HCV‐RNA positivity rate (10.9%, 11/101) and was considered acceptable and easy to use by most MSM. We demonstrate that an HCV‐RNA home‐based self‐sampling test service is successful in diagnosing HCV infections among MSM. This service could be a valuable addition to existing sexual healthcare services as it may reach men who are otherwise not tested. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) treatment in people who inject drugs (PWID) is delivered within settings frequented by PWID, such as needle and syringe programs (NSP). The optimal direct‐acting antiviral (DAA) dispensing regimen among NSP clients is unknown. This study compared cures (Sustained virologic response 12 weeks post‐treatment, [SVR12]) across three dispensing schedules to establish non‐inferiority of fortnightly dispensing versus directly observed therapy. The ADVANCE HCV study was a randomized, unblinded trial, recruiting PWID attending NSP in Tayside, Scotland, between January 2018 and November 2019. HCV‐positive participants were randomized to receive DAAs via directly observed therapy, fortnightly provision or fortnightly provision with psychological intervention. A modified intention to treat analysis was used to identify differences in cures between the three treatment regimes. The study was registered with clinicaltrials.gov; NCT03236506. A total of 110 participants completed the study. 33 participants received directly observed therapy, with 90.91% SVR12; 37 received fortnightly provision, with 86.49% SVR12 and 40 received fortnightly provision and psychological intervention at treatment initiation, with 92.50% SVR12. Analysis showed no significant difference in SVR12 (p = 0.67). This study did not demonstrate a statistically significant difference in cure rate between groups. This provides evidence of the non‐inferiority of fortnightly dispensing of direct‐acting antivirals (DAAs) compared to directly observed therapy among PWID. It suggests that tight control of adherence through directly observed therapy dispensing of DAAs among this population offers no therapeutic advantage. Therefore, less restrictive dispensing patterns can be used, tailored to patient convenience. [ABSTRACT FROM AUTHOR]

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti‐HBc) is the serological marker that indicates HBV exposure. The impact of anti‐HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti‐HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg‐negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in‐house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti‐HBc‐positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti‐HBV antibodies (P < 0.05). There was also an association between anti‐HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P < 0.05). Positive anti‐HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg‐negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti‐HBc positivity, and anti‐HBc‐positive patients should be carefully evaluated for disease progression. [ABSTRACT FROM AUTHOR]

The incidence rate of hepatocellular carcinoma (HCC) is expected to increase, with most cases occurring in Asia. In some parts of Asia, the occurrence of HCC developing from metabolic‐related liver disease has markedly increased in recent years, whereas the occurrence of HCC developing from viral‐hepatitis–related liver disease has decreased. Advancements in the treatment of HCC over the past few decades has been remarkable, with most treatment strategies to remove or control liver tumours (hepatic resection, local ablation, radiation therapy, transarterial chemoembolisation, hepatic arterial infusion chemotherapy) primarily developing in Asia. In addition, recent progress in systemic therapies has prolonged the prognosis of advanced HCC. Nowadays, six regimens of systemic therapies have become available in most countries, according to phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). In a global randomised phase III trial (IMbrave 150 trial), the most effective of the latest drug designs was newly emerged combination immunotherapy (atezolizumab plus bevacizumab), which has shown significantly prolonged overall survival compared with sorafenib, which was the first‐line systemic therapy for more than a decade. Now, the treatment dynamics for HCC are undergoing a major transition as a result of two important changes: the replacement of viral‐related HCC by metabolic‐related HCC and the emergence of combination immune therapy. [ABSTRACT FROM AUTHOR]

Cost-effectiveness analysis of an active search to retrieve HCV patients lost to follow-up (RELINK-C strategy) and the impact of COVID-19 Keywords: cost-effectiveness analysis; COVID-19 pandemic; hepatitis C elimination; linkage to care; lost to follow-up patients EN cost-effectiveness analysis COVID-19 pandemic hepatitis C elimination linkage to care lost to follow-up patients 579 583 5 06/10/22 20220701 NES 220701 Abbreviations ALT Alanine Aminotransferase AST Aspartate Aminotransferase DAA direct-acting antivirals HCV Hepatitis C virus LTFU Lost to follow-up RNA Ribonucleic acid INTRODUCTION Hepatitis C virus (HCV) infection affects 71 million people worldwide. Cost-effectiveness analysis, lost to follow-up patients, COVID-19 pandemic, hepatitis C elimination, linkage to care A higher percentage of patients was located (65% vs 62%) among candidates to contact during the COVID-19 pandemic, and a larger number of patients located attended the physician's appointment (88% vs 41%) than during pre-COVID-19. [Extracted from the article]

In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management such as the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care and evaluate the impact of what‐if scenarios on the future burden of disease using modelling analysis. A dynamic Markov model was used to forecast the HCV disease burden in Germany. Model inputs were retrieved through literature review, unpublished sources and expert input. Next, three "what‐if" scenarios were developed to evaluate the status quo, COVID‐19 pandemic, and steps needed to achieve the WHO targets for elimination. At the beginning of 2020, there were 189,000 (95% UI: 76,700–295,000) viremic infections in Germany, a decline of more than 85,000 viremic infections since 2012. Annual treatment starts went down since 2015. Compared with 2019, the COVID‐19 pandemic resulted in a further 11% decline in 2020. If this continues for two years, it could result in 110 excess HCC cases and 200 excess liver related deaths by 2030. To achieve the WHO targets, 81,200 people need to be diagnosed, with 118,600 initiated on treatment by 2030. This could also avert 1,020 deaths and 720 HCC cases between 2021 and 2030. Germany has made strides towards HCV elimination, but more efforts are needed to achieve the WHO targets by 2030. [ABSTRACT FROM AUTHOR]

Innovative testing approaches and care pathways are required to meet global hepatitis B virus (HBV) and hepatitis C virus (HCV) elimination goals. Routine blood‐borne virus (BBV) testing in emergency departments (EDs) in high‐prevalence areas is suggested by the European Centre for Disease Prevention and Control (ECDC) but there is limited evidence for this. Universal HIV testing in our ED according to UK guidance has been operational since 2015. We conducted a real‐world service evaluation of a modified electronic patient record (EPR) system to include opportunistic opt‐out HBV/reflex‐HCV tests for any routine blood test orders for ED attendees aged ≥16 years. Reactive laboratory results were communicated directly to specialist clinical teams. Our model for contacting patients requiring linkage to care (new diagnoses/known but disengaged) evolved from initially primarily hospital‐led to collaborating with regional health and community service networks. Over 11 months, 81,088 patients attended the ED; 36,865 (45.5%) had a blood test. Overall uptake for both HBV and HCV testing was 75%. Seroprevalence was 0.9% for hepatitis B surface antigen (HBsAg) and 0.9% for HCV antigen (HCV‐Ag). 79% of 140 successfully contacted HBsAg+patients required linkage to care, of which 87% engaged. 76% of 130 contactable HCV‐Ag+patients required linkage, 52% engaged. Our results demonstrate effectiveness and sustainability of universal ED EPR opt‐out HBV/HCV testing combined with comprehensive linkage to care pathways, allowing care provision particularly for marginalized at‐risk groups with limited healthcare access. The findings support the ECDC BBV testing guidance and may inform future UK hepatitis testing guidance. [ABSTRACT FROM AUTHOR]

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti‐HCV, HCV‐RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta‐analysis, meta‐regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory‐based anti‐HCV and HCV‐RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti‐HCV, sensitivity was 95% (95% CI: 92%–97%) and specificity was 99% ([95% CI: 98%–99%]; n = 25; I2 = 81%; moderate certainty). For the detection of HCV‐RNA, the sensitivity was 95% (95% CI: 93%–97%) and specificity was 97% ([95% CI: 94%–98%]; n = 20; I2 = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%–91%) and specificity was 98% ([95% CI: 94%–99%]; n = 5; I2 = 37%; low certainty) compared with HCV‐RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti‐HCV and then HCV‐RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow‐up and support international efforts towards HCV elimination in both high and low prevalence settings. [ABSTRACT FROM AUTHOR]

Background: This systematic review was aimed to estimate hepatitis C virus (HCV) seroprevalence and burden in disease in WHO South East Asia Region (SEAR). Methods: Electronic databases (PubMed, Scopus, Embase, and Google Scholar) and websites of non‐indexed national medical journals, government and international health agencies were searched to identify English language literature published between 1991 and June 2020. We selected the studies reporting HCV seroprevalence in asymptomatic general (low‐risk) and high‐risk adult populations, that is, persons living with HIV (PLHIV), persons who inject drugs (PWID), sex workers, persons on maintenance hemodialysis (MHD), people in prison, and men sex with men (MSM). Seroprevalence data were combined to estimate weighted pooled prevalence (95% confidence interval) in each group and in each country, using the random‐effects model. Estimated pooled seroprevalences were multiplied with estimated populations at risk to estimate the overall HCV burden. Results: The analysis included 538 studies (35 Bangladesh, 6 Bhutan, 2 DPR Korea, 323 India, 43 Indonesia, 2 Maldives, 18 Myanmar, 29 Nepal, 11 Sri Lanka, 67 Thailand, and 2 Timor‐Leste). In SEAR, the weighted pooled anti‐HCV seroprevalence was estimated as 0.84% (0.56–1.12) in low‐risk population and 13.67% (10.95–16.40) in PLHIV, 51.44% (43.67–59.20) in PWID, 25.80% (20.34–32.09) in MHD, 8.39% (5.84–11.51) in prison inmates, 2.69% (1.43–4.13) in people with high‐risk sex behavior, and 11.43% (8.61–14.74) in MSM. The total HCV burden in low‐risk and high‐risk populations in SEAR countries was estimated as 12.45 million and 1.65 million, respectively. Conclusion: Our estimates of HCV seroprevalence and burden should help the respective countries in planning their HCV elimination strategies. [ABSTRACT FROM AUTHOR]

Background and Aims: Estimates of paediatric hepatitis C virus (HCV) seroprevalence are needed to aid treatment scaling‐up, screening and detection approach in this age range, with the ultimate goal of global HCV eradication. The aim of this study was to gather all of the available information on HCV seroprevalence in children all around the world. Methods: We searched PubMed, Scopus, Web of Science (WOS), Wiley and EBSCO databases for all studies evaluating HCV seroprevalence in children; however, studies examining seroprevalence in high‐risk children or specific groups were excluded. Results: Only 20 articles with 48 963 people met our inclusion criteria, with an overall prevalence of 0.904% and a 95% confidence interval (CI) of 0.543 to 1.355. Seroprevalence was higher in research published prior to 2010 than in those published after 2010 (0.77% vs. 0.53%). Conclusion: Few studies were conducted to assess the seroprevalence of HCV in children worldwide. However, the worldwide pooled seroprevalence of HCV in children in these studies is low (less than 1%). [ABSTRACT FROM AUTHOR]

This paper reviews the modern management of viral hepatitis: hepatitis A, hepatitis B, hepatitis D and non-A non-B hepatitis. It describes the treatment of uncomplicated acute viral hepatitis, complicated acute viral hepatitis, and chronic viral hepatitis. The roles for corticosteroids, synthetic nucleotides, and interferons are reviewed. Finally, passive and active immunization against viral hepatitis are discussed.

Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. The prevalence of hepatitis B and hepatitis C infection in HTX recipients is over 10%. Despite its increased prevalence, the long-term outcome in this cohort is still not clear. There is a reluctance to place these patients on transplant waiting list given the increased incidence of viral reactivation and chronic liver disease after transplant. The emergence of new antiviral therapies to treat this cohort seems promising but their long-term outcome is yet to be established. The aim of this paper is to review the literature and explore whether it is justifiable to list advanced heart failure patients with coexistent hepatitis B/C infection for HTX. [ABSTRACT FROM AUTHOR]

Keywords: automatic referral; bundle; hepatitis B; hepatitis C; hepatitis delta; HIV; integrated diagnosis; viral hepatitis EN automatic referral bundle hepatitis B hepatitis C hepatitis delta HIV integrated diagnosis viral hepatitis 1145 1147 3 04/28/23 20230501 NES 230501 Key points The global elimination of viral hepatitis elimination is within reach, and will be facilitated by improving testing tools. Global health sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022-2030; 2022 Available from: https://www.who.int/publications/i/item/9789240053779 9 Degasperi E, Anolli MP, Lampertico P. Bulevirtide for patients with compensated chronic hepatitis delta: a review. Bundle, hepatitis B, hepatitis C, hepatitis delta, automatic referral, HIV, viral hepatitis, integrated diagnosis With a single blood sample, it is now possible to screen and to perform a comprehensive diagnosis for hepatitis B, hepatitis C, hepatitis D and other blood-borne viruses like HIV to link those in need to treatment and care. [Extracted from the article]

Rationale Electronic medical record (EMR) systems are commonly included in health care reform discussions. However, their embrace by the health care community has been slow. Methods At Addiction Research and Treatment Corporation, an outpatient opioid agonist treatment programme that also provides primary medical care, HIV medical care and case management, substance abuse counselling and vocational services, we studied the implementation of an EMR in the domains of quality, productivity, satisfaction, risk management and financial performance utilizing a prospective pre- and post-implementation study design. Results This report details the research approach, pre-implementation findings for all five domains, analysis of the pre-implementation findings and some preliminary post-implementation results in the domains of quality and risk management. For quality, there was a highly statistically significant improvement in timely performance of annual medical assessments ( P < 0.001) and annual multidiscipline assessments ( P < 0.0001). For risk management, the number of events was not sufficient to perform valid statistical analysis. Conclusions The preliminary findings in the domain of quality are very promising. Should the findings in the other domains prove to be positive, then the impetus to implement EMR in similar health care facilities will be advanced. [ABSTRACT FROM AUTHOR]

Background. Prior study showed HCV-infected patients have increased serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP) and a possible left ventricular diastolic dysfunction. The objectives of the present paper were to investigate the characteristics of hs-CRP and its correlation with clinical profiles including NT-proBNP and echocardiographic variables in HCVinfected patients.Methods and Results. A total of 106 HCV-infected patients and 106 control healthy individuals were enrolled. The level of serum hs-CRP (median 1.023 mg/L, range 0.03∼5.379 mg/L) was significantly lower in all 106 patients than that in controls (median 3.147 mg/L, range 0.08∼7.36 mg/L, P = 0.012). Although hs-CRP did not correlate significantly with NT-proBNP when all patients and controls were included (r = 0.169, P = 0.121), simple regression analysis demonstrated a statistically significant linear correlation between hs-CRP and NT-proBNP in HCV-infected patients group (r = 0.392, P = 0.017). Independent correlates of hs-CRP levels (R² = 0.13) were older age (β' = 0.031, P = 0.025) and NT proBNP (β' = 0.024, P = 0.017). Conclusions. Although the level of serum hs-CRP decreased significantly, there was a significant association between hs-CRP and NT-proBNP in HCV-infected patients. [ABSTRACT FROM AUTHOR]

Background. The prognostic importance of α-fetoprotein (AFP) level elevation in patients with chronic hepatitis C and its clinical significance in steatosis associated with HCV infection remain to be determined. The present paper assessed clinical significance of elevated AFP in patients with CHC with and without steatosis. Methods. One hundred patients with CHC were divided into 50 patients with CHC and steatosis and 50 patients with CHC and no steatosis based on liver biopsy. Results. AFP was significantly increased in CHC with steatosis than patients without steatosis (P < 0.001). Highly significant positive correlation was found between serum AFP and necroinflammation as well as the severity of fibrosis/cirrhosis and negative significant correlation with albumin level in chronic HCV with steatosis (P < 0.001) but negative nonsignificant correlation with ALT and AST level (P + 0.778 and 0.398), respectively. Highly significant increase was found in chronic hepatitis patients with steatosis than CHC without steatosis regarding necroinflammation as well as the severity of fibrosis/cirrhosis and AFP (P < 0.001). Conclusion. Patients with chronic HCV and steatosis have a higher AFP levels than those without steatosis. In chronic HCV with steatosis, elevated AFP levels correlated positively with HAI and negative significant correlation with albumin level. [ABSTRACT FROM AUTHOR]

It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers to be presented at the 47th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology (ANZSN) including "Generation of Stem Cells From Patients With Genetic Kidney Disease," S. Ricardo and colleagues, "PD Outcomes in Units Where Physicians Insert PD Catheters Versus Others," by R. Pandy and S. May, and "Source of Erythropoietin in an Anephric Patient With Hepatitis C?" by A. Ziad and S. May.

The Hepatitis C virus E1 and E2 envelope proteins are the major players in all events required for virus entry into target cells. In addition, the recently developed HCV cell culture system has indicated that E1E2 heterodimer formation is a prerequisite for viral particle production. In this paper, we explored a new genetic approach to construct intergenotypic 2a/1b chimeras, maintaining the structural region of the infectious strain JFH1 and substituting the soluble portion of E1 and/or E2 proteins. This strategy provides useful information on the role of the surface-exposed domain of the envelope proteins in virus morphogenesis and allows comparative analysis of different HCV genotypes. We found that substituting the E2 protein ectodomain region abolishes the production of chimeric infectious particles. Our data indicate that the soluble part of the E2 protein is involved in a genotypespecific interplay with remaining viral proteins that affect the HCV assembly process. [ABSTRACT FROM AUTHOR]

Hemodialysis (HD) patients are recognized as one of the high-risk groups for hepatitis C virus (HCV) infection. The prevalence of HCV infection varies widely between 5.5% and 24% among different Iranian populations. Preventive programs for reducing HCV infection prevalence in these patients require accurate information. In the present study, we estimated HCV infection prevalence in Iranian HD patients. In this systematic review, we collected all published and unpublished documents related to HCV infection prevalence in Iranian HD patients from April 2001 to March 2008. We selected descriptive/analytic cross-sectional studies/surveys that have sufficiently declared objectives, a proper sampling method with identical and valid measurement instruments for all study subjects, and proper analysis methods regarding sampling design and demographic adjustments. We used a meta-analysis method to calculate nationwide prevalence estimation. Eighteen studies from 12 provinces (consisting 49.02% of the Iranian total population) reported the prevalence of HCV infection in Iranian HD patients. The HCV infection prevalence in Iranian HD patients is 7.61% (95% confidence interval: 6.06-9.16%) with the recombinant immunoblot assay method. Iran is among countries with low HCV infection prevalence in HD patients. [ABSTRACT FROM AUTHOR]

Aims To review the evidence on the effectiveness of harm reduction interventions involving the provision of sterile injecting equipment in the prevention of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). The interventions assessed were needle and syringe programmes (NSP), alternative modes of needle/syringe provision (pharmacies, vending machines and outreach) and the provision of injecting equipment other than needles/syringes. Methods Systematic searches of the English language literature to March 2007 were undertaken to identify systematic, narrative or meta-analytical reviews (also known as a review of reviews) of the impact of interventions on HCV transmission, HIV transmission or injecting risk behaviour (IRB). Critical appraisal criteria classified the reviews as either high quality (‘core’) or supplementary: a framework based on the quality of reviews, the reviewers' conclusions and the designs/findings of the primary studies was used to derive evidence statements. Results Three core and two supplementary reviews of injecting equipment interventions were identified. According to the proposed framework, this study found (a) insufficient evidence to conclude that any of the interventions are effective in preventing HCV transmission; (b) tentative evidence to support the effectiveness of NSP in preventing HIV transmission; (c) sufficient evidence to support the effectiveness of NSP (and tentative evidence of an additional impact of pharmacy NSP) in reducing self-reported IRB; and (d) little to no evidence on vending machines, outreach or providing other injecting equipment in relation to any of the outcomes. Conclusions The evidence is weaker than given credit for in the literature. The lack of evidence for effectiveness of NSP vis-à-vis biological outcomes (HCV and HIV incidence/prevalence) reflects the limitations of studies that have been undertaken to investigate these associations. Particularly for HCV, low levels of IRB may be insufficient to reduce high levels of transmission. New studies are required to identify the intervention coverage necessary to achieve sustained changes in blood-borne virus transmission. [ABSTRACT FROM AUTHOR]

Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is one of the leading known causes of liver disease in the world. The HCV is a single-stranded RNA virus. The genomes of HCV display significant sequence heterogeneity and have been classified into types and subtypes. Types from 1 to 11 have so far been recognized, each type having a variable number of subtypes. It has been confirmed that 90% approximately of the isolates HCV infections in Egypt belong to a single subtype (4a) [10]. In this paper, we construct a mathematical model to study the spread of HCV-subtype 4a amongst the Egyptian population. The relation between HCV-subtype 4a and the other subtypes has also been studied. The values of reproduction numbers R01, R02 have been derived [5]. Also, threshold conditions for the value of the transmission rates k1 and k02, in terms of R01, R02 and the mutation factor μ have been determined to insure that the disease will die out. If the conditions fail to happen the disease takes off and becomes endemic. [ABSTRACT FROM AUTHOR]

Buprenorphine and methadone are the two established substitution drugs licensed in many countries for the treatment of opioid dependence. Little is known, however, about how these two drugs are applied and how they work in clinical practice. In this paper we present the aims, methods, design and sampling issues of a collaborative multi-stage epidemiological study (COBRA) to address these issues. Based on a nationally representative sample of substitution physicians, the study is designed as an observational, naturalistic study, consisting of three major parts. The first part was a national survey of substitution doctors (prestudy, n = 379 doctors). The second part was a cross-sectional study (n = 223 doctors), which consisted of a target-week assessment of 2m694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross-sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration. The third part consists of a prospective-longitudinal cohort study of 48 methadone-treated and 48 buprenorphine-treated patients. The cohort is followed up over a period of 12 months to investigate whether course and outcome of the patients differ by type or treatment received in terms of clinical, psychosocial, pharmaco-economic and other related measures. The response rate among substitution doctors was 57.1%; that among eligible patients was 71.7%. Comparisons with the federal registers reveal that the final samples of doctors and patients may be considered nationally representative with regard to regional distribution, training, type of setting as well as the frequency of patients treated with buprenorphine or methadone. The COBRA study provides a unique comprehensive database, informing about the natural allocation and intervention processes in routine care and about the course and outcome of patients treated with buprenorphine or methadone. [ABSTRACT FROM AUTHOR]

The human leukocyte antigen (HLA) system is one of the most crucial host factors influencing disease progression in bacterial and viral infections. This review provides the basic concepts of the structure and function of HLA molecules in humans. Here, we highlight the main findings on the associations between HLA class I and class II alleles and susceptibility to important infectious diseases such as tuberculosis, leprosy, melioidosis, Staphylococcus aureus infection, human immunodeficiency virus infection, coronavirus disease 2019, hepatitis B, and hepatitis C in populations worldwide. Finally, we discuss challenges in HLA typing to predict disease outcomes in clinical implementation. Evaluation of the impact of HLA variants on the outcome of bacterial and viral infections would improve the understanding of pathogenesis and identify those at risk from infectious diseases in distinct populations and may improve the individual treatment. [ABSTRACT FROM AUTHOR]

Effect decomposition is a critical technique for mechanism investigation in settings with multiple causally ordered mediators. Causal mediation analysis is a standard method for effect decomposition, but the assumptions required for the identification process are extremely strong. Moreover, mediation analysis focuses on addressing mediating mechanisms rather than interacting mechanisms. Mediation and interaction for mediators both contribute to the occurrence of disease, and therefore unifying mediation and interaction in effect decomposition is important to causal mechanism investigation. By extending the framework of controlled direct effects, this study proposes the effect attributable to mediators (EAM) as a novel measure for effect decomposition. For policymaking, EAM represents how much an effect can be eliminated by setting mediators to certain values. From the perspective of mechanism investigation, EAM contains information about how much a particular mediator or set of mediators is involved in the causal mechanism through mediation, interaction, or both. EAM is more appropriate than the conventional path‐specific effect for application in clinical or medical studies. The assumptions of EAM for identification are considerably weaker than those of causal mediation analysis. We develop a semiparametric estimator of EAM with robustness to model misspecification. The asymptotic property is fully realized. We applied EAM to assess the magnitude of the effect of hepatitis C virus infection on mortality, which was eliminated by controlling alanine aminotransferase and treating hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Introduction. Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods. Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results. The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion. The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct‐acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18–65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD‐7]), QoL (SF‐36 ver.2) and computer‐based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR‐12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR‐12 had mean percentage reduction in BDI (11.3%, p =.000), GAD (8.6%, p =.001) and Stroop test (58.4%, p =.001), with improved NCT (1.7%, p =.001), visual memory (13.7%, p =.001) and digit span (23.8%, p =.002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80–110.50], p =.000), high ALT (OR 1.02 [95% CI 1.00–1.05]), and BDI score (OR 1.73 [95% CI 1.42–3.26] p =.039) predicted cure. SVR‐12 was associated with improved visual memory ≥5.5 (AUC‐0.708; sensitivity 62.5%, specificity 63%, p =.000) and % correct Stroop test responses >26.6% (AUC‐0.918, sensitivity 94.4% specificity 80.4%, p =.000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality‐of‐life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination. [ABSTRACT FROM AUTHOR]

Issues Non‐medical prescription opioid use (NMPOU) contributes substantially to the global burden of morbidity. However, no systematic assessment of the scientific literature on the associations between NMPOU and health outcomes has yet been undertaken. Approach: We undertook a systematic review evaluating health outcomes related to NMPOU based on ICD‐10 clinical domains. We searched 13 electronic databases for original research articles until 1 July 2021. We employed an adaptation of the Oxford Centre for Evidence‐Based Medicine 'Levels of Evidence' scale to assess study quality. Key Findings: Overall, 182 studies were included. The evidence base was largest on the association between NMPOU and mental and behavioural disorders; 71% (129) studies reported on these outcomes. Less evidence exists on the association of NMPOU with infectious disease outcomes (26; 14%), and on external causes of morbidity and mortality, with 13 (7%) studies assessing its association with intentional self‐harm and 1 study assessing its association with assault (<1%). Implications: A large body of evidence has identified associations between NMPOU and opioid use disorder as well as on fatal and non‐fatal overdose. We found equivocal evidence on the association between NMPOU and the acquisition of HIV, hepatitis C and other infectious diseases. We identified weak evidence regarding the potential association between NMPOU and intentional self‐harm, suicidal ideation and assault. Discussion and Conclusions: Findings may inform the prevention of harms associated with NMPOU, although higher‐quality research is needed to characterise the association between NMPOU and the full spectrum of physical and mental health disorders. [ABSTRACT FROM AUTHOR]

Introduction: Ageing patients with haemophilia (PWH) develop cardiovascular risk factors impacting care. Little is known about the prevalence of diabetes in PWH and its relation to other comorbidities. Aim: To examine the risk of diabetes for adult PWH compared to men from the general United States population (National Health and Nutrition Examination Surveys [NHANES]) and outpatients attending a Veterans Affairs Medical Center (VAMC) clinic. Methods: Retrospective cross‐sectional design. PWH from four haemophilia centres (n = 690) were matched with random samples from NHANES and VAMC. Diabetes (yes/no) was the outcome, while age, body mass index (BMI), race and Hepatitis C (HCV; by serology) and human immunodeficiency virus (HIV) positivity were covariates. We fitted semiparametric generalized additive models (GAMs) in order to compare diabetes risk between cohorts. Results: Younger PWH were at lower risk of diabetes than NHANES or VAMC subjects irrespective of BMI. However, the risk of diabetes rose in older PWH and was closely associated with HCV. For HCV‐negative subjects, the risk of diabetes was considerably lower for PWH than NHANES and VAMC subjects. The difference persisted after controlling for BMI and age, indicating that the low risk of diabetes in PWH cannot be explained by lean body mass alone. Conclusion: Since many ageing PWH are HCV positive and therefore at heightened risk for diabetes, it is important to incorporate diabetes screening into care algorithms in Haemophilia Treatment Centers, especially since PWH are not always followed in primary care clinics. [ABSTRACT FROM AUTHOR]

Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co‐exist. Furthermore, much evidence suggests a role of OBI in the hepato‐carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non‐HCV‐related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field. [ABSTRACT FROM AUTHOR]