HCV Monoinfection Research Articles

Performance of Elecsys® HCV Duo Immunoassay for Diagnosis and Assessment of Treatment Response in HCV Patients with or without HIV Infection

Background/Objectives: The Elecsys® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. Methods: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12–24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. Results: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82–99.97%), 100% (95%CI, 95.39–100%), and 0.998 (95%CI, 0.992–1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24–88.19%), 97.41% (95%CI, 93.73–99.04%), and 0.773 (95%CI, 0.543–1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. Conclusions: Our study showed that the Elecsys® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings.

B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.

Chronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear. We sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors. We identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT. We provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination.

Characterization and Outcomes of Hepatocellular Carcinoma in Chronic HCV or HBV Monoinfection

Characterization and Outcomes of Hepatocellular Carcinoma in Chronic HCV or HBV Monoinfection

Qualitative Evaluation of a Program to Integrate Hepatitis C Care Into HIV Care Inclusive of Task Shifting to Nonspecialist Providers.

The treatment and cure of hepatitis C (HCV) in people with HIV is particularly important as progression of their liver disease is quicker compared with those who have HCV monoinfection. Innovative approaches are needed to maximize access to curative HCV treatment. Integration of HCV care into HIV primary care with education and support of nonspecialist providers via telementoring offers a solution to specialist workforce shortages. Using focus group qualitative methodology, health care workers' perspectives regarding this approach, particularly with the Extension for Community Healthcare Outcomes (ECHO) telementoring model, were obtained and are described. Successful integration of HCV care into HIV primary care has demonstrated benefits to patients, including allowing them to remain in their medical home for care. Factors beyond disease that influence their health and wellbeing must also be considered.

Особенности ведения периоперационного периода у пациентов с хроническим гепатитом и циррозом печени при выполнении офтальмохирургических операций

Purpose. Study of frequency and structure of hepatitis and cirrhosis among ophthalmic surgical patients. Material and methods. Among 1706 patients, 43 patients with chronic hepatitis and cirrhosis were selected. A clinical assessment of their etiology, severity, and possibility of performing ophthalmic surgery in these patients was carried out. Results. The average age of the selected 43 patients was 64.1 ± 9.7 years, in 72.1 % they conasist in elderly age group. 88.4 % had viral hepatitis (B, C, chronic HBV and HCV coinfection), 9.3 % had a toxic hepatitis, and one patient (2.3 %) had autoimmune hepatitis. Among hepatitis, HCV monoinfection prevailed (55.4 %). The vast majority (97.7 %) had minimal disease activity. Although violations of hemostasis system were detected in 9 patients, signs of significant hypocoagulability were observed in 3 people (6.9 %). After 3-days course of intramuscular injections of vitamin K 2–3 times a day, all 3 patients underwent successful ophthalmic surgery. 97.7 % of patients were admitted to surgery: 39 people. – in planned manner, 3 people – after medical preparation. In one patient with suspected acute viral hepatitis B, planned surgical treatment was postponed. Conclusion. In general structure of ophthalmic surgical patients, the proportion of patients with hepatitis and cirrhosis was 2.5 %. Viral hepatitis B and C prevailed (88.4 %), HCV monoinfection dominated (55.4 %). The vast majority of patients (97.7 %) had minimal hepatitis activity, 6.9 % had signs of significant hypocoagulability, which required their preoperative preparation. Keywords: hepatitis, cirrhosis, ophthalmic surgery

Effect of HCV treatment with DAAs on serum intestinal fatty acid binding protein (I-FABP) as a marker of intestinal permeability in HCV/HIV co-infected patients

BackgroundHCV and HIV co-infected patients develop cirrhosis more rapidly than HCV mono-infection. Intestinal injury and microbial translocation are postulated mechanisms for the rapid progression of cirrhosis.AimStudy the effect of HCV treatment with DAAs on serum intestinal fatty acid binding protein (I-FABP) as a marker of intestinal injury in HCV/HIV co-infected patients and its relation to hepatic fibrosis. Comparing the level of I-FABP in HCV mono-infection and HCV/HIV co-infection was a secondary aim.MethodsI-FABP levels were measured in 50 non-cirrhotic HCV/HIV co-infected patients pre- and post-HCV treatment (SVR 12) (25 patients were HIV treatment naive, and 25 patients were on HAART) and in 25 chronic HCV patients as a control group. Hepatic fibrosis was assessed by FIB4 score, APRI score, and transient elastography.ResultsHCV/HIV co-infected patients had significantly higher levels of I-FABP compared to the HCV-mono-infected patients (P = 0.001). After HCV treatment in HCV/HIV co-infected patients, I-FABP level was significantly elevated (P < 0.001) and was positively correlated with baseline FIB4 values and serum ALT levels (r = 0.283, P-value = 0.047) and (r = 0.340, P-value = 0.016), respectively.ConclusionHCV/HIV co-infection is associated with significantly higher intestinal injury and subsequent hepatic fibrosis than HCV mono-infection. HIV infection is associated with intestinal epithelial injury and microbial translocation and may play a role in the persistence of systemic inflammation after HCV eradication.

HCV Genotype Distribution and Clinical Characteristics of HCV Mono-Infected and HCV/HIV Co-Infected Patients in Liangshan Prefecture, Sichuan Province, China.

Objective: The present study aimed to characterize the genotype distribution and clinical characteristics of HCV monoinfected and HCV/HIV coinfected patients in the Liangshan Prefecture, Sichuan Province, China. Methods: All the patients were divided into HCV monoinfection and HCV/HIV coinfection groups according to whether they were complicated with HIV infection. The data from the two groups were collected. Results: In this study, HCV genotype 3 was the most common genotype in both groups, while HCV genotype 6 was significantly higher in the coinfection group than in the monoinfection group (p = 0.046). The white blood cell count, total bilirubin level, and HCV RNA were significantly higher in the HCV monoinfection group than that in the HCV/HIV coinfection group (p = 0.031; p < 0.001; p = 0.027, respectively). Conclusion: HCV prevalence was high in HIV-positive patients in the Liangshan Prefecture. Thus, incorporating screening and management of HCV monoinfection and HCV/HIV coinfection is needed in local region programs.

Comparative outcomes of direct-acting antiviral treatment in patients with HIV-Hepatitis C co-infection: insights from a single center experience in Colombia.

Direct-acting antivirals (DAA) were introduced to Latin America with the aim of eliminating hepatitis C (HCV) in the region. There are scarce data on the outcomes of people living with HIV and HCV treated with these medications in Colombia. This study compares the outcomes of patients with HIV-HCV co-infection and HCV mono-infection treated with DAAs. Retrospective observational study including patients ≥18 years old with HCV infection treated with DAAs from August 2017 to December 2019 in a comprehensive center in Colombia. The main outcome was sustained virologic response (SVR). Secondary outcomes included reinfection, relapse and adverse events. We included 223 individuals with HCV treated with DAAs; 142 (63.6%) individuals were mono-infected and 81 (36.3%) co-infected. Genotypes 1b (49.7%) and 4 (33.9%) were the most common. Overall SVR after DAA treatment was 96.8%. Relapse rate was 2.24%, reinfection rate was 6.28% and adverse events occurred in 27.8% of cases. SVR was comparable in patients with co- and mono-infection (95% vs 97.8%, p=0.245). DAA were effective in mono-infected (HCV) and co-infected (HCV/HIV) patients and reinfection was high in this last group.

Longitudinal Assessment of Multiple Immunological and Inflammatory Parameters during Successful DAA Therapy in HCV Monoinfected and HIV/HCV Coinfected Subjects.

In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group. Activated CD4+ and CD8+ T-lymphocytes, mDCs, pDCs, MDC8 and classical, non-classical and intermediate monocytes were detected using flow cytometry. IP-10, sCD163 and sCD14 were assessed by ELISA while matrix metalloproteinase-2 (MMP-2) was measured by zymography. At baseline, increased levels of IP-10, sCD163 and MMP-2 were found in both HIV/HCV and mHCV patients compared to HD, whereas sCD14 increased only in HIV/HCV patients. After therapy, IP-10, sCD163 and sCD14 decreased, whereas MMP-2 persistently elevated. At baseline, activated CD8+ T-cells were high in HIV/HCV and mHCV patients compared to HD, with a decrease at SVR12 only in HIV/HCV patients. Activated CD4+ T-cells were higher in HIV/HCV patients without modification after DAAs therapy. These results suggest complex interactions between both viruses and the immune system, which are only partially reversed by DAA treatment.

PrEP Indications and PrEP Knowledge, Access, and Interest Among Individuals With HCV.

BackgroundIndividuals with hepatitis C (HCV) represent a population that may benefit from pre-exposure prophylaxis (PrEP), given the overlapping risk factors and transmission networks of HCV and HIV. This analysis assesses the prevalence of PrEP indications among individuals with HCV monoinfection and PrEP awareness, interest, and access in this population.MethodsGRAVITY was an observational study for the collection of epidemiologic data from individuals with HCV and/or HIV in Washington DC and Baltimore, with the present analysis limited to HCV-monoinfected patients. The prevalence of PrEP indications was determined using epidemiologic survey responses. Bivariate and multivariable analyses assessed for associations between PrEP indications and PrEP awareness, access, and interest.ResultsAmong 314 HCV-monoinfected participants, 109 (35%) had an indication for PrEP. Forty-eight (44%) had a drug use indication alone, 40 (37%) had a sexual indication alone, and 21 (19%) had both drug use and sexual indications. Eighty-five (27%) participants had heard of PrEP, 32 (10%) had been offered PrEP by a provider, 114 (38%) were interested or maybe interested in PrEP, and 6 (2%) were currently taking PrEP. On bivariate analysis, PrEP awareness was significantly associated with study site (P < .0001), race (P = .0003), age (P < .0001), and sexual PrEP indication (P = .04). However, only study site remained significant (P = .0002) on regression analysis.ConclusionsThough indications for PrEP were prevalent among individuals with HCV in this cohort, most patients were unaware of PrEP, had never been offered PrEP, and were not using PrEP. These data support the need for improved PrEP implementation among people with HCV.

Management of patients with chronic hepatitis and cirrhosis during the periooperative period of ophthalmic surgery

Aim. To study the frequency and structure of hepatitis and cirrhosis among ophthalmic surgery patients.Material and methods. Among 1706 ophthalmic surgery patients, 43 patients with chronic hepatitis and cirrhosis were selected. A clinical assessment of the etiology and severity of their condition was carried out and the possibility of performing ophthalmic surgery was determined.Results. The average age of the patients included in the study comprised 64.1 ± 9.7 years, with 72.1% of the patients belonging to the elderly age group. 88.4%, 9.3%, and 2.3% (one patient) of the patients suffered from viral hepatitis (B, C, chronic HBV and HCV coinfection), toxic hepatitis, and autoimmune hepatitis, respectively. Among hepatitis patients, HCV monoinfection prevailed (55.4%). The majority (97.7%) of patients demonstrated minimal disease activity. Although violations of the hemostatic system were detected in nine patients, signs of significant hypocoagulability were observed in three patients (6.9%). Following a 3-day course of intramuscular vitamin K injections 2 to 3 times per day, these three patients underwent successful ophthalmic surgery. Out of 97.7% of patients admitted to surgery, 39 people were operated in a planned manner and 3 people required medical preparation. In one patient with suspected acute viral hepatitis B, planned surgical treatment was postponed.Conclusions. The share of patients with hepatitis and cirrhosis in the general structure of ophthalmic surgery patients comprised 2.5%. Among them, viral hepatitis B and C prevailed (88.4%) with dominated HCV monoinfection (55.4%). The vast majority of patients (97.7%) showed minimal hepatitis activity; 6.9% had signs of significant hypocoagulability, thus requiring preoperative medical preparation.

Gamma-Delta T-Cell Phenotype and Function in DAA-Treated HIV-HCV Co-Infected and HCV-Mono-Infected Subjects

HIV-HCV co-infected subjects are at risk of liver fibrosis which may be linked to immune imbalances. Direct-acting antivirals (DAAs) represent the mainstay of HCV treatment in co-infected individuals, yet their effects on immune cell populations playing a role in fibrogenesis is unknown. We assessed γδ T-cell phenotype and function, Treg and Th17 frequencies, as well as γ-globulins and B-cell activation in 47 HIV-HCV co-infected and 35 HCV mono-infected individuals prior to and following DAA treatment (SVR12). Γδ T-cell activation decreased in both groups yet persisted at higher levels in the HIV-HCV co-infected subjects. No differences were registered in terms of γδT-cell function. Of note, the Vδ2/Th17 ratio, inversely linked to liver damage, increased significantly in the two groups upon treatment, yet a negative correlation between the Vδ2/Th17 ratio and liver function enzymes was found in the co-infected subjects alone. B-cell activation and γ-globulin levels decreased in both settings, yet B-cell activation remained higher in the HIV-HCV co-infected individuals. In HIV-HCV co-infected and HCV mono-infected participants, the effect of DAA was limited to γδ T- and B-cell activation as well as γ-globulin concentrations and the Vδ2/Th17 ratio, with no changes in γδ T-cell function and Treg frequencies. Importantly, γδ T- and B-cell activation remained at higher levels in the co-infected individuals than in those with HCV mono-infection alone. The persistence of such alterations within these cell subsets may be associated with the risk of hepatic and extrahepatic complications.

Improvements in liver transplant outcomes in patients with HCV/HIV coinfection after the introduction of direct-acting antiviral therapies.

In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. Using Organ Procurement and Transplant Network/United Network for Organ Sharing data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post-DAAs introduction. We categorized these patients into two eras: pre-DAA (2008-2012 [pre-DAA era]) and post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting was used to adjust patient characteristics. A total of 17215 LT recipients were eligible for this study (HCV/HIV [n=160]; HIV mono-infection [n=188]; HCV mono-infection [n=16867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of 1- and 3-year graft loss post-DAA, compared pre-DAA (1-year: adjusted hazard ratio [aHR] 0.29, 95% confidence interval (CI) 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; 3-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95% CI 0.58-0.70, respectively). The hazards of 1- and 3-year graft loss post-DAA in HIV mono-infection were comparable to those in pre-DAA. HCV/HIV coinfection had significantly lower patient mortality post-DAA, compared to pre-DAA (1-year: aHR 0.30, 95% CI 0.17-0.55; 3-year: aHR 0.31, 95% CI 0.15-0.63). Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection.

Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection.

The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.

The predictive value indicators of first trimester biochemical screening in assessing unfavorable factors of pregnancy course in women with HIV as well as hepatitis B and C

Aim: to find out the predictive value of blood serum biochemical parameters PAPP-A (pregnancy-associated plasma protein A) and β-hCG (beta subunit of human chorionic gonadotropin) in the assessment of unfavorable pregnancy outcomes in women infected by human immunodeficiency virus (HIV) as well as viral hepatitis B (HBV) and C (HCV).Materials and Methods. A retrospective study of the medical records from 52 women was carried out, including 19 HIV-infected women, 9 women with monoinfection HBV or HCV, 11 pregnant women who were co-infected (HIV/HBV or HIV/HCV) and 13 uninfected women. PAPP-A and β-hCG levels, expressed as MoM (multiple of median), were evaluated in all women.Results. Our study revealed that only PAPP-A was prognostically significant for developing chronic placental insufficiency in women with HIV infection and co-infection of HIV together hepatitis B and C. None of the parameters examined were significant in women with HBV or HCV monoinfection. PAPP-A and β-hCG in pregnant women without infections were effective in predicting development of chronic placental insufficiency.Conclusion. PAPP-A can be used as a diagnostic parameter of developing chronic placental insufficiency in pregnant women with monoinfection HIV and co-infection with HIV/HBV or HIV/HCV.

CCR5+ T-Cells Homed to the Liver Exhibit Inflammatory and Profibrogenic Signatures in Chronic HIV/HCV-Coinfected Patients.

Liver fibrosis is accelerated in patients coinfected with hepatitis C virus and human immunodeficiency virus (HIV), compared with HCV monoinfected patients, although the underlying mechanisms are unknown. We hypothesize that T cells expressing the HIV co-receptor, chemokine receptor 5 (CCR5), preferentially migrate to the inflamed liver and contribute to enhanced fibrogenesis. We compared the peripheral and intrahepatic CCR5 expression on CD4+ and CD8+ T cells in 21 HIV/HCV-coinfected patients with 14 chronic HCV monoinfected patients. Using 12-color flow cytometry, phenotypic and functional characterization of CCR5+ and negative cells pre- and post-stimulation with HCV genotype specific overlapping pooled peptides was conducted. Patients with HIV/HCV coinfection had significantly more CD4+CCR5+ and CD8+CCR5+ T cells in the liver as compared with peripheral blood (p = 0.0001 for both). Compared with patients with HCV monoinfection, patients with HIV/HCV coinfection also had fewer peripheral CD4+CCR5+ and CD8+CCR5+ T cells (p = 0.02, p = 0.001 respectively), but more intrahepatic CD4+CCR5+ and CD8+CCR5+ cells (p = 0.0001 for both). Phenotypic analysis of CCR5+ sorted cells demonstrated an increased expression of markers of exhaustion, senescence, immune activation and liver homing (PD1, CD57, CD38, HLADR, and CXCR3). Post-stimulation with HCV peptides, CCR5+ T cells secreted more proinflammatory and profibrogenic cytokines and chemokines rather than antiviral cytokines. Phenotypic and functional analyses of CCR5+ T cells in HIV/HCV-coinfected patients revealed a pathogenic role for CCR5+ T cells in hepatic fibrogenesis. These cells are functionally proinflammatory, pro-fibrogenic and preferentially accumulate in liver, accelerating fibrosis. These findings suggest that targeting CCR5 may be a therapeutic strategy for be ameliorating liver fibrosis.

HDV Seroprevalence in HBsAg-Positive Patients in China Occurs in Hotspots and Is Not Associated with HCV Mono-Infection.

HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany. We found that the HDV seroprevalence in HBsAg-positive patients in China is limited to geographic hotspots (Inner Mongolia: 35/251, 13.9%; Xinjiang: 7/180, 3.9%) and high-risk intravenous drug users (HBV mono-infected: 23/247, 9.3%; HBV-HCV co-infected: 34/107, 31.8%), while none of the 2634 HBsAg carriers from other metropolitan regions were anti-HDV-Ab-positive. In Germany, we recorded an HDV seroprevalence of 5.3% in a university hospital environment. In a cohort of HBsAg-negative, anti-HCV-positive patients that were not exposed to HBV before (anti-HBc-negative), HDV was not associated with HCV mono-infection (Chinese high-risk cohort: 0/365, 0.0%; German mixed cohort: 0/263, 0.0%). However, 21/1033 (2.0%) high-risk HCV patients in China with markers of a previously cleared HBV infection (anti-HBc-positive) were positive for anti-HDV-Ab, with two of them being positive for both HDV and HCV RNA but negative for HBV DNA. The absence of anti-HDV-Ab in HCV mono-infected patients shows that HCV cannot promote HDV transmission in humans.

Late presentation of chronic hepatitis C patients in the era of direct-acting antivirals-Data from the German Hepatitis C-Registry.

Late presentation for care in chronic viral hepatitis has been estimated to occur in approximately 25% of patients initiating treatment with direct acting antivirals. We evaluated the extent of late presentation since the implementation of direct acting antivirals and established differences between HCV monoinfected and HIV/HCV coinfected patients. The German Hepatitis C Registry is a multicenter non-interventional registry study. We analysed patients enrolled between 02/2014 and 12/2018. Advanced liver disease was defined as an aspartate aminotransferase to platelet-ratio-index score ≥ 1.5, a FibroScan ≥ 9.5 kPa or a METAVIR stage ≥ F3. HCV monoinfected and HIV/HCV coinfected patients were analysed separately and baseline characteristics of both subgroups were compared. 8003 treatment naive patients were analysed. Overall, 2197/8003 (28%) patients presented late for care (HCV monoinfection: 2067/7452 (28%); HIV/HCV coinfection: 130/551 (24%)). Late presentation decreased comparing the year 2014 to the years 2015 (p≤0.001), 2017 (p≤0.001) and 2018 (p≤0.001) and was significantly lower in 2018 in HIV/HCV coinfected patients compared to HCV monoinfected patients (HIV/HCV: 15/89 (17%) vs. 415/1566 (27%); p=0.047). We observed a significant decrease of late presentation from 2014 to 2018. Despite the decrease during the observation period, approximately one in four patients continued to be affected in 2018, with a lower proportion of late presentation being seen in patients coinfected with HIV/HCV. This trend might indicate effects of a closer linkage to care and a more frequent detection of acute HCV infections of HIV+ patients.

Time to HCV Treatment Disfavors Patients Living with HIV/HCV Co-infection: Findings from a Large Urban Tertiary Center.

This study aimed to assess time to hepatitis C (HCV) treatment (i.e., the time between the initial clinic visit for HCV evaluation and the HCV treatment start date), to compare clinical characteristics between patients who received HCV treatment ≥ and &lt; 6 months, and to identify predictors of longer time to HCV treatment in patients living with HCV. This study conducted a retrospective secondary analysis of patients living with HCV mono-infection and HIV/HCV co-infection who received HCV treatment with DAAs (n=214) at a HIV Clinic. Binomial logistic regression was used to identify predictors of longer time to treatment (i.e., ≥ 6 months). The median time to HCV treatment was 211 days. Compared to patients who were treated &lt; 6 months, a higher proportion of patients who were treated ≥ 6 months had HIV/HCV co-infection (31% vs. 49%, p=0.01) and chronic kidney disease (8% vs. 18%, p=0.03). In multivariate analysis, HIV/HCV co-infection was positively associated with a longer time to HCV treatment (adjusted odds ratio, aOR=2.0, p=0.03). Time to HCV treatment disparities between African American and White American did not emerge from the analysis, but time to HCV treatment disfavored patients living with HIV/HCV co-infection. Studies are needed to identify and eliminate factors that disfavor patients living with HIV/HCV co-infection.

Anti-HCV antibody titer highly predicts HCV viremia in patients with hepatitis B virus dual-infection

Hepatitis C Virus (HCV) infection is diagnosed by the presence of antibody to HCV and/or HCV RNA. This study aimed to evaluate the accuracy of anti-HCV titer (S/CO ratio) in predicting HCV viremia in patients with or without hepatitis B virus (HBV) dual infection. Anti-HCV seropositive patients who were treatment-naïve consecutively enrolled. Anti-HCV antibodies were detected using a commercially chemiluminescent microparticle immunoassay. HCV RNA was detected by real-time PCR method. A total of 1321 including1196 mono-infected and 125 HBV dually infected patients were analyzed. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001). Of the entire cohort, the anti-HCV cut-off value of 10 provided the best accuracy, 96.8%, with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96.3%, 98.9%, 99.7% and 87.3% respectively. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001) and 9.36 (AUROC 1.00, P<0.0001) in patients with HCV mono-infection and HBV dual-infection respectively. Among the HBV dually infected patients, the accuracy of anti-HCV titer in predicting HCV viremia reached up to 100% with the cut-off value of 9. All the patients were HCV-viremic if their anti-HCV titer was greater than 9 (PPV 100%). On the other hand, all the patients were HCV non-viremic if their anti-HCV titer was less than 9 (NPV 100%). Anti-HCV titer strongly predicted HCV viremia. This excellent performance could be generalized to either HCV mono-infected or HBV dually infected patients.