Hepatitis C Virus RNA Viral Load Research Articles

Reflex Hepatitis C Virus Viral Load Testing Following an Initial Positive Hepatitis C Virus Antibody Test: A Global Systematic Review and Meta-analysis.

Many people who have a positive hepatitis C virus (HCV) antibody (Ab) test never receive a confirmatory HCV RNA viral load (VL) test. Reflex VL testing may help address this problem. We undertook a systematic review to evaluate the effectiveness of reflex VL testing compared with standard nonreflex approaches on outcomes across the HCV care cascade. We searched 4 databases for studies that examined laboratory-based reflex or clinic-based reflex VL testing approaches, with or without a nonreflex comparator, and had data on the uptake of HCV RNA VL test and treatment initiation and turnaround time between Ab and VL testing. Both laboratory- and clinic-based reflex VL testing involve only a single clinic visit. Summary estimates were calculated using random-effects meta-analyses. Fifty-one studies were included (32 laboratory-based and 19 clinic-based reflex VL testing). Laboratory-based reflex VL testing increased HCV VL test uptake versus nonreflex testing (RR: 1.35; 95% CI: 1.16-1.58) and may improve linkage to care among people with a positive HCV RNA test (RR: 1.47; 95% CI: .81-2.67) and HCV treatment initiation (RR: 1.03; 95% CI: .46-2.32). The median time between Ab and VL test was <1 day for all laboratory-based reflex studies and 0-5 days for 13 clinic-based reflex testing. Laboratory-based and clinic-based HCV reflex VL testing increased uptake and reduced time to HCV VL testing and may increase HCV linkage to care. The World Health Organization now recommends reflex VL testing as an additional strategy to promote access to HCV VL testing and treatment. PROSPERO CRD42021283822.

Outcome of direct-acting antiviral treatment in patients with hepatitis C virus/hepatitis B virus coinfection

BackgroundOral direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection have greatly improved treatment efficacy, with sustained virological response (SVR) rates of > 95% for HCV monoinfected patients. However, hepatitis B virus (HBV)/HCV coinfection is more complex than monoinfection with HBV or HCV alone. We evaluated the SVR rate at 12 weeks post-treatment with DAAs in patients with HCV/HBV and evaluated the rate of HBV reactivation during and 6 months after treatment.ResultsAmong the included patients, 191 (95.5%) achieved SVR. Older age, low platelet count, high serum creatinine, and higher liver stiffness value measured by fibroscan were predictors of failure to achieve SVR. The 16 patients (8%) with HBV reactivation patients had significantly higher ALT and serum creatinine and a high HCV RNA viral load at baseline compared with that of those without HBV reactivation.ConclusionPatients who received DAAs to treat HCV/HBV coinfection showed a high SVR. However, it is important to be aware of the potential risk for HBV reactivation during and after treatment with DAAs.

The Relationship between Neutrophil Lymphocyte Ratio and Hepatitis C Virus RNA in Hepatitis C Coinfected HIV Patients Receiving Direct-Acting Antiviral Therapy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Background: Hepatitis C is an inflammatory disease of the liver caused by infection with the hepatitis C virus (HCV). Inflammatory markers are significant in assessing the course of an infectious or inflammatory disease. One of them is the neutrophil-lymphocyte ratio (NLR) and the amount of HCV RNA viral load, which combines neutrophils as an active inflammatory component and lymphocytes as a regulatory and protective component in a single parameter. Research on the relationship between NLR and HCV RNA in HIV patients coinfected with HCV is still limited. This study aimed to determine the relationship between NLR and HCV RNA in HIV-HCV coinfected patients who received DAA therapy and went to the outpatient polyclinic at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.&#x0D; Methods: Analytic observational study. A total of 38 research subjects participated in this study. Observation of NLR was carried out using hematology analyzer, and observation of HCV RNA levels was carried out using the PCR technique. Data analysis was carried out using SPSS univariate and bivariate.&#x0D; Results: There was a difference between pre-post therapy NLR and pre-post therapy HCV RNA viral load, p&lt;0.05. NLR is in line with HCV RNA viral load as a prognostic tool for successful DAA therapy in HIV patients coinfected with hepatitis C.&#x0D; Conclusion: There is a relationship between HIV and HCV RNA in hepatitis C coinfected HIV patients receiving direct-acting antiviral therapy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.

Impact of hepatitis C virus point-of-care RNA viral load testing compared with laboratory-based testing on uptake of RNA testing and treatment, and turnaround times: a systematic review and meta-analysis

Point-of-care (POC) hepatitis C virus (HCV) RNA nucleic acid test viral load assays are being used increasingly as an alternative to centralised, laboratory-based standard-of-care (SOC) viral load assays to reduce loss to follow-up. We aimed to evaluate the impact of using POC compared with SOC approaches on uptake of HCV RNA viral load testing and treatment, and turnaround times from testing to treatment along the HCV care cascade. We searched PubMed, Embase, and Web of Science for studies published in English between Jan 1, 2016, and April 13, 2022. We additionally searched for accepted conference abstracts (2016-20) not identified in the main search. The contacts directory of the WHO Global Hepatitis Programme was also used to solicit additional studies on use of POC RNA assays. We included studies if they evaluated use of POC HCV RNA viral load with or without a comparator laboratory-based SOC assay, and had data on uptake of viral load testing and treatment, and turnaround times between these steps in cascade. We excluded studies with a sample size of ten or fewer participants. The POC studies were categorised according to whether the POC assay was based onsite at the clinic, in a mobile unit, or in a laboratory. Studies using the POC assay or comparator SOC assays were further stratified according to four models of care: whether HCV testing and treatment initiation were performed in the same or different site, and on the same or a different visit. The comparator was centralised, laboratory-based HCV RNA SOC assays. For turnaround times, we calculated the weighted median of medians with 95% CIs. We analysed viral load testing and treatment uptake using random-effects meta-analysis. The quality of evidence was rated using the GRADE framework. This study is registered with PROSPERO, CRD42020218239. We included 45 studies with 64 within-study arms: 28 studies were in people who inject drugs, were homeless, or both; four were in people incarcerated in prison; nine were in the general or mixed (ie, includes high-risk groups) populations; and four were in people living with HIV. All were observational studies. The pooled median turnaround times between HCV antibody test and treatment initiation was shorter with onsite POC assays (19 days [95% CI 14-53], ten arms) than with either laboratory-based POC assays (64 days [64-64], one arm) or laboratory-based SOC assays (67 days [50-67], two arms). Treatment uptake was higher with onsite POC assays (77% [95% CI 72-83], 34 arms) or mobile POC assays (81% [60-97], five arms) than with SOC assays (53% [31-75], 12 arms); onsite and mobile POC assay vs SOC assay p=0·029). For POC and SOC arms, higher RNA viral load testing uptake was seen with the same-site models for testing and treatment than with different-site models (all within-category p≤0·0001). For onsite and mobile POC arms, there was higher treatment uptake for same-site than different-site models (within-category p<0·0001). Four studies had direct within-study POC versus SOC comparisons for RNA viral load testing uptake (pooled relative risk 1·11 [95% CI 0·89-1·38]), and there were ten studies on treatment uptake (1·32 [1·06-1·64]). Overall, the quality of evidence was rated as low. Compared with use of laboratory-based SOC HCV viral load testing, the use of POC assays was associated with reduced time from antibody test to treatment initiation and increased treatment uptake. The effect of POC viral load testing is greatest when positioned within a simplified care model in which testing and treatment are provided at the same site, and, where possible, on the same day. POC HCV RNA viral load testing is now recommended in WHO guidelines as an alternative strategy to laboratory-based viral load testing. Unitaid.

Sofosbuvir plus velpatasvir for 8 weeks in patients with acute hepatitis C: The HepNet acute HCV-V study

EASL guidelines recommend 8 weeks of treatment with sofosbuvir plus velpatasvir (SOF/VEL) for the treatment of acute or recently acquired HCV infection, but only 6- and 12-week data are available. Therefore, the aim of this study was to evaluate the safety and efficacy of a shortened 8-week SOF/VEL treatment for acute HCV monoinfection. In this investigator-initiated, prospective, multicentre, single-arm study, we recruited 20 adult patients with acute HCV monoinfection from nine centers in Germany. Patients received SOF/VEL (400/100mg) as a fixed-dose combination tablet once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). The median HCV RNA viral load at baseline was 104,307 IU/ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: n= 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking medication for HIV pre-exposure prophylaxis. SVR12 was achieved in all patients who complied with the study protocol (n= 18/18 [100%], per protocol analysis), but the primary endpoint was not met in the intention-to-treat analysis (n= 18/20 [90%]) because two patients were lost to follow-up. One serious adverse event (unrelated to study drug) occurred during 12 weeks of post-treatment follow-up. The 8-week treatment with SOF/VEL was well tolerated and highly effective in all adherent patients with acute HCV monoinfection. Early treatment of hepatitis C might effectively prevent the spread of HCV in high-risk groups. NCT03818308. The HepNet acute HCV-V study (NCT03818308), an investigator-initiated, single-arm, multicenter pilot study, demonstrates the efficacy and safety of 8 weeks of daily treatment with the fixed-dose combination sofosbuvir/velpatasvir (400/100mg) in patients with acute hepatitis C virus (HCV) infection. All patients who completed therapy and were followed-up achieved sustained virologic response. Thus, early treatment with SOF/VEL which might effectively prevent the spread of HCV in high-risk groups can be recommended for patients with acute HCV monoinfection.

Risk Factors for Treatment Failure with Oral Antivirals in HCV

Introduction: Chronic hepatitis C virus (HCV) infection is one of the major cause of cirrhosis of liver and leads to significant morbidity and mortality. In past, HCV therapy was limited to subcutaneous peg interferon plus oral ribavirin, a regimen that was generally poorly tolerated and provided low efficacy, with cure rates below 40% for HCV genotypes 1 and 4, and below 75% for HCV genotypes 2 or 3. The availability of oral direct-acting antiviral (DAA) as treatment for chronic hepatitis C has revolutionized the field. Although current HCV therapies rarely fail to achieve viral eradication, a subset of patients experience treatment failure. Aim: To study the risk factors associated with treatment failure with oral antiviral drugs in patients of Chronic hepatitis C. Materials &amp; Methods: It was a retrorospective study done at Medical Gastroenterology Department, PGIMS, Rohtak in which six years data i.e.from 01.01.2015 to 31.12.2020, pertainining to Eighty Six (86) chronic hepatitis C patients who had treatment failure i.e. SVR failure on oral antiviral drugs was analyzed. Observations: Out of the total 86 patients, there was clear cut male predominance i.e. 54 (62.79 %) with rural background (villages) i.e.73 (84.88%). The age distribution in these 86 patients varied between 10-80 yrs of age and characterstically peak was seen in 31-40 yrs age group i.e.25 patients (29.06 %). The majority of patients had high baseline HCV viral load (&gt; 4 lakhs I.U. /ml) i.e. 52 patients (60.46%). Out of total 86 patients, , 50 patients (58.13%) were cirrhotic, 34 patients (39.53 %) were smokers, 33 patients (38.37%) were alcoholic, 26 patients (30.23 %) had past history of surgical intervention, 9 patients (10.46 %) were diabetic, 9 patients (10.46 %) had got tattoo, 8 patients (9.30%) had history of previous blood transfusion and 13 patients (15.11%) gave history of use of alternative medications. Results: The direct risk factors associated with development of failed SVR in HCV patients are high baseline HCV RNA viral load, cirrhosis, rural background and indirect risk factors are smoking, alcohol and Diabetes Mellitus but large scale studies in future are required to confirm the same.

Distribution of HCV genotypes and HCV RNA viral load in hepatitis infected patients of Kolar region, Karnataka, India.

Decisions and disease progression prediction, understanding the distribution of the hepatitis C virus (HCV) genotype and its association with viral load is significant for treatment. Therefore, it is of interest to document the distribution pattern of HCV genotypes and their association with viral load among HCV infected patients in Kolar, Karnataka. Seventy-four HCV-positive patients and not on antiviral therapy were enrolled from R.L. Jalappa hospital in Kolar, Karnataka. Blood samples were taken and demographics were recorded. HCV RNA was isolated after plasma was separated. qPCR was performed to measure the viral load, and RT-PCR was performed to determine the genotype. Genotype 3 was the prevalent (n=11, 40.7%) followed by genotype 4 (n=8, 29.6%), 2 (n=6, 22.2%), 1 (n= 13.7%), and mix (n=1, 13.7%). The median viral load of genotype 3 was a 2,87,835 IU/mL (IQR 10, 780-3, 71, 66) , genotype 2 was 81,030 IU/mL (IQR 66,495-95,565), genotype 4 was 43, 410 IU/mL (IQR 38, 355-48, 465) belongs to viral load less than 8,00,000 IU/mL. The median viral load genotype 3 was a 1, 05, 19, 500 IU/mL (IQR 49, 37, 250-2, 36, 71, 500), genotype 2 was 2,55,99,000 IU/mL (IQR 2,00,10,000-32,725,500), genotype 4 was 1,67,40,000 IU/mL (IQR 1,45,50,000-17,493,000) belonging to viral load more than 8,00,000 IU/mL category. A correlation between genotype and viral load was observed (p =1.5x10-12), of which genotype 3 showed a high viral load. Thus, HCV genotypes 1 2, 3, 4, and mixed genotype was observed in the patients studied. HCV genotype was associated with viral load in patient plasma. This data finds use in the treatment and prevention of hepatitis C in Kolar, Karnataka.

Investigation of Hepatitis C Virus (HCV) Genotypes by "Reverse Hybridisation Strip Assay" and DNA Sequence Analysis Methods

Hepatitis C Virus (HCV) is a virus that is estimated to infect approximately 185 million people worldwide and causes 350 000 deaths each year. The target in HCV treatment is the sustained virological response (SVR), and the most important virological factors determining SVR are genotype and baseline HCV-RNA levels. In this study, it was aimed to compare the HCV genotypes and subtypes detected by the "line probe assay (LIPA)" method with sequence analysis. HCV genotypes and subtypes were investigated by line probe assay (LIPA) (NLM analytica, Italy) and sequence analysis methods in 212 patients with chronic HCV diagnosis and with HCV RNA viral load of 10⁴ IU/ml and above. 5'UTR and core regions were studied in LIPA method and NS5B gene region was studied in the sequencing method. After amplifying 340 bp region in the NS5B gene region with the hemi-nested PCR method, sequence analysis (ABI 3500 Genetic Analyzer [Applied Biosystems, USA]) was performed. Statistical analysis of the study was determined by using TURCOSA Analytics program. In the study, HCV genotypes and subtypes that were determined in 212 patients by LIPA method were; 40 (18.8%) genotype 1a, 97 (45.75%) genotype 1b, 7 (3.3%) genotype 2, 12 (5.6%) genotype 2a/c, 2 (0.94%) genotype 2b, 19 (8.96%) genotype 3, 16 (7.55%) genotype 4, 1 (0.47%) genotype 4a, 15 (7.5%) genotype 4c/d, 1 (0.47%) genotype 4h and 2 (0.94%) genotype 5. The HCV genotypes and subtypes determined in 212 patients by sequence analysis were; 20 (9.43%) genotype 1a, 118 (55.6%) genotype 1b, 16 (7.55%) genotype 2a, 4 (1.89%) genotype 2b, 1 (0.47%) genotype 2k, 21 (9.91%) genotype 3a, 2 (0.94%) genotype 4a, 28 (13.21%) genotype 4d and 2 (0.94%) genotype 5a. The difference in results between the two methods was found to be statistically significant (p< 0.001). According to the viral load-genotype relationship, the highest viral load was detected in genotype 1a patients (p< 0.001). In conclusion, in order to determine HCV genotypes and subtypes in our study, LIPA and sequence analysis methods were compared and the genotype compatibility between the two methods were determined as 97.5% on the basis of genotype and 19% on the basis of subtype. Since the direct-acting antiviral (DEA) treatment protocol in chronic HCV patients is planned according to the genotype/subtype determination, the inconsistency of the results obtained in the LIPA method, which is routinely widely used, with the sequence analysis method is remarkable, and it was concluded that these results should be supported by studies containing more samples.

Maternal viral load and risk of vertical transmission in patients with Hepatitis C

Hepatitis C virus (HCV) affects approximately 8% of pregnant people and should be screened for during every pregnancy. Risk of vertical transmission (VT) is about 6% but has not been well quantified based on maternal HCV RNA viral load (VL). We sought to assess thisbased on VL as a continuous variable and other potential maternal risk factors.

CORRELATION BETWEEN HCV RNA VIRAL LOAD AND HOMA-IR IN CHRONIC HEPATITIS C PATIENTS

Background: Insulin resistance (IR) is one of the extrahepatic complications of hepatitis C virus (HCV) infection that needs to be recognized early. HOMA-IR is an effective way to measure insulin resistancy. Core proteins, NS-3, and NS-5 are the main components of HCV RNA proteins which are involved in the incidence of IR. Seeing this, a hypothesis was developed that the level of HCV RNA viral load was related to the HOMA-IR. This study was designed to identify the correlation between HCV RNA viral load with HOMA-IR in chronic hepatitis C patients.Method: We conducted a cross-sectional approach from the medical record of chronic hepatitis C patients at the outpatient clinic dr. Soetomo Hospital, Surabaya. A total of 30 patients aged &gt;19 years old with complete medical records were included. Clinical and laboratory (including HCV RNA viral load level and HOMA-IR) data were obtained from the availability of medical records.Result: A total of 30 chronic hepatitis C patients, 17 (56.7%) were women and 13 (43.3%) were men, with mean age was 50.90 ± 7.17 years. The median of HCV RNA viral load level was 3,14 x106 IU/ml and the median of HOMA-IR was 4.50. The result of the Spearman correlation test showed a moderate positive association between HCV RNA viral load and HOMA-IR (r=0.537 ; p=0.002).Conclusion: A positive moderate correlation was obtained between HCV RNA viral load with HOMA-IR in chronic hepatitis C patients.

Hepatitis C core antigen: a simple predictive marker for treatment response to the new direct-acting antiviral drugs in chronic HCV Egyptian patients

BackgroundSuccessful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new direct-acting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays. Our main objectives were to correlate between serum levels of HCVcAg and HCV RNA loads in chronic HCV patients as well as to explore the potential value of HCVcAg assay in predicting treatment response to the new DAAs. The study enrolled a total of 280 chronic HCV-infected patients scheduled to start the new regimen for treatment of chronic HCV by all-oral, interferon-free DAAs. According to the viral load, the studied individuals were arranged into three groups corresponding to mild, moderate, and sever viremia. Serum level of HCVcAg was determined by ELISA technique and HCV RNA viral loads were quantified using the real-time PCR system. The assays were performed three times for all participants: prior to initiation of treatment, at the end of treatment (week 12), and 3 months post-treatment cessation (week 24).ResultsA statistically significant difference between HCV RNA and HCVcAg baseline levels among different viremia groups was detected (P < 0.001). There was a significant positive correlation between HCV RNA and HCVcAg baseline values among all the studied cases (P < 0.05) with a correlation coefficient of 0.752, 0.976, and 1.00 respectively for mild, moderate, and severe viremia groups. 92.9% (260/280) of the studied patients achieved sustained virologic response, 3.6% (10/280) were non-responders, and 3.6% (10/280) had recurrent viremia/relapse as regards RT-PCR results.ConclusionHCVcAg is a promising alternative to HCV RNA assay. The ELISAs for HCVcAg proved excellent correlations with HCV RNA levels. Moreover, HCVcAg can be introduced as a simple and highly specific tool for monitoring the new DAA regimens particularly in low-resource settings.

The Impact of Hepatitis C Virus Genotypes on Oxidative Stress Markers and Catalase Activity.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide. Chronic HCV infections are usually associated with increased oxidative stress in the liver tissue. The intensity of oxidative stress may be a detrimental factor in liver injury and may determine the severity of the disease. The aim of the present case-control study was to determine the level of lipid peroxidation (TBARS), protein oxidative modification (AOPP), and catalase activity in sera of patients infected with HCV, in relation to different HCV genotypes and viral load. Considering the HCV patients with chronic hepatitis C (52) and control subject (50) recruitment, the study was designed as a case–control-type. The HCV RNA isolation, viral load, and HCV genotyping were performed according to the standard protocols. A significant difference compared to control healthy subjects was reported for TBAR (p < 0.001), AOPP (p = 0.001), and catalase activity (p = 0.007). In a gender-based comparison, a significantly higher level of AOPP for females was reported (p < 0.001). As stratified by HCV genotype, the most common was HCV-1 (HCV-1a and HCV 1b), with the overall participation of more than 60%, followed by genotype 3, while the least represented was genotype 2. No significant difference was documented among genotypes in regard to oxidative stress markers, although somewhat higher TBARS level, but not significant, was registered in patients infected with genotype 1b. A statistically significant positive correlation was found between the concentration of HCV genome copies and AOPP (r = 0.344; p = 0.012). A high level of HCV viral load was more likely to have a higher TBARS, but still without statistical significance (p = 0.072). In conclusion, the results obtained confirmed an imbalance between the ROS production and antioxidative defense system in HCV-infected patients. Since oxidative stress may have a profound influence on disease progression, fibrosis, and carcinogenesis, our results may meet the aspirations of mandatory introduction of antioxidants as early HCV therapy to counteract ROS consequences.

Investigating utilising the Alinity m platform to detect hepatitis C virus RNA in dried blood spot samples

Elimination of Hepatitis C virus (HCV) relies on increasing HCV diagnostic rates in hard to reach populations. Dried blood spot (DBS) samples are a convenient sample type for HCV testing, as they can be collected in non-traditional settings such as drug services and prison settings, increasing access to HCV testing. Herein we investigate an off-label DBS protocol for use on the Abbott Alinity m platform. A dilution series of HCV RNA positive blood was used to determine the analytical sensitivity of the test. We assess the sensitivity and specificity of HCV RNA detection in 50 mock DBS specimens compared to associated plasma viral load, and re-test 66 clinical DBS, previously tested on the m2000 to determine the clinical sensitivity and specificity of the assay. The dilution panel suggested that the Alinity m DBS assay is one log more sensitive than our current DBS HCV RNA assay. Mock DBS demonstrated 100% specificity, and 100% sensitivity for samples with plasma HCV RNA viral loads > 2.7 log10 IU/mL, however four samples with viral loads between 1.3 and 2.4 log10 IU/mL were not detected. The clinical sensitivity and specificity of previously tested DBS was 94% and 100% respectively, with two samples reported as low level RNA positive on the m2000 testing negative on Alinty m. The data suggests that DBS can be used as an off-label specimen type on the Alinity m HCV assay. Allowing continuous, random access testing of DBS simultaneously alongside other Alintiy m assays, potentially improving test turn-around times.

Validation of hepatitis C virus RNA detection using capillary blood by finger prick (GenXpert system)-Hepatitis C fingerprick study.

To achieve the ambitious goals of the WHO to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030, innovative approaches are needed to improve the uptake for screening and treatment in people who inject drugs (PWID). Important barriers to care are difficult venous access and the two-step approach in current point-of-care tests, using an HCV antibody screening test followed by a confirmatory HCV RNA test. In this study, we aimed to validate the new GenXpert instrument to diagnose HCV RNA by finger prick. This prospective study was conducted in a cohort of PWID in 6 alcohol/drug clinic sites and 1 outreach project in Belgium between January 2018 and March 2019. Plasma and capillary whole-blood samples were collected by venepuncture and finger prick, respectively. Sensitivity and specificity of the GenXpert system were compared to the gold standard Artus HCV RNA kit. Of 153 participants enrolled, 147 (96.1%) had results of both the GenXpert system and Artus HCV RNA kit available. HCV RNA was detected in 35 of 147 (23.8%) by the Artus HCV RNA kit and in 36 of 147 (24.8%) by the GenXpert. Median quantitative HCV RNA viral load on finger prick was 28700IU/mL (IQR 4070-65875) vs 1900000IU/mL (IQR 416,466-2,265,510) on plasma. The GenXpert instrument had a sensitivity of 100% (95% CI 90%-100%) and a specificity of 99.1% (95.1%-99.9%). The overall diagnostic accuracy was 99.3% (96.3%-99.9%). This study validates the excellent performance of the GenXpert instrument to assess HCV RNA in capillary whole blood by finger prick in a PWID cohort.

Hepatitis C screening, diagnosis, and cascade of care among people aged >\u200940\u2009years in Brasilia, Brazil

BackgroundIdentifying patients with hepatitis C virus (HCV) infection and enhancing the cascade of care are essential for eliminating HCV infection. This study aimed to estimate the prevalence of positive anti-HCV serology in Brasilia, Brazil, and evaluate the efficiency of the cascade of care for HCV-positive individuals.MethodsThis cross-sectional study analyzed 57,697 rapid screening tests for hepatitis C in individuals aged > 40 years between June 2018 and June 2019. HCV-positive patients were contacted and scheduled to undergo the HCV RNA viral test, genotyping, and transient elastography.ResultsThe prevalence of positive serology was 0.27%. Among 161 patients with positive anti-HCV serology, 124 (77%) were contacted, 109 (67.7%) were tested for HCV RNA viral load, and 69 (42.8%) had positive results. Genotype 1 (75%) was the most prevalent genotype. Among 65 patients (94.2%) who underwent transient elastography, 30 (46.2%) presented with advanced fibrosis. Additionally, of the 161 patients, 55 (34.1%) were referred for treatment, but only 39 (24.2%) complied, with 36 (22.4%) showing sustained virological response. By the end of the study, 16 patients were still awaiting to receive medication.ConclusionsThe prevalence of HCV-positive patients was low in Brasilia, and the gaps in the cascade of care for these patients were significantly below the targets of HCV infection elimination. This study opens new avenues for eliminating HCV infection and suggests that partnerships with clinical laboratories to conduct anti-HCV tests are a useful strategy to improve HCV diagnosis.Trial registrationResearch Ethics Committee of the Faculty of Health Sciences of the University of Brasília - UNB (CAAE number 77818317.2.0000.0030) and by the Ethics Committee of the Health Science Teaching and Research Foundation - FEPECS/SES/DF (CAAE number 77818317.2.3001.5553).

Thyroid dysfunction in Egyptian patients with hepatitis C virus: prevalence and possible triggering

BackgroundThe contribution of chronic hepatitis C virus (HCV) infection per se in thyroid autoimmunity and dysfunction remains controversial. We investigate the prevalence of thyroid disorders and the possible association between thyroid dysfunction and different factors in a cohort of HCV-untreated patients.Patients and methodsA total 1050 patients with untreated HCV infection were enrolled in this study. Thyroid function tests, antiperoxidase (TPO-Ab), antithyroglobulin, thyroid ultrasound, real-time PCR to assess HCV RNA viral load, and fibroscan to determine degree of hepatic fibrosis were done.ResultsThyroid dysfunction was found in 17.1% of patients: 11.5% hypothyroidism and 5.6% hyperthyroidism. Subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism were detected in 8.6, 2.8, 3.3, and 2.3% of patients, respectively. Thyroid ultrasound showed abnormality in 10.2% of patients. TPO-Ab and antithyroglobulin were positive in 5.1 and 6.4% of patients, respectively. TPO-Ab was more frequently positive in hyperthyroid patients compared with euthyroid (P<0.001) and hypothyroid (P<0.001) patients. Positive TPO-Ab was only significantly associated with thyroid state (P<0.001) and duration of HCV infection (P=0.02).ConclusionThe prevalence of thyroid dysfunction is 17.1% among patients with HCV infection. Furthermore, thyroid disorder is related mainly to thyroid autoimmunity independent of age, sex, or level of viremia.

306. CD8+ T-Cell Responses to Chronic Hepatitis C in Pregnancy

BackgroundChronic hepatitis C virus (HCV) infection is marked by stable, high -level viremia and a failed T-cell response. HCV-specific CD4+ helper T cells are rare, and CD8+ cytotoxic T cells are functionally exhausted or ineffective due to viral escape mutations. Postpartum, a subset of infected women experience a substantial drop in viremia. Preliminary data indicate that this unusual viral decline may be linked to a resurgence of HCV-specific CD4+ T cells producing Th1 cytokines. How improved CD4+ helper T-cell function might affect viral replication in this scenario is not established. Here we tested the hypothesis that improved CD4+ T cell help mediates control of chronic HCV replication through enhanced CD8+ T-cell function.MethodsWe examined plasma HCV RNA viral load (VL) and HCV-specific T-cell responses in 33 women with chronic HCV during the third trimester (T3) and at 3 months postpartum (3P). HCV-specific CD4+ and CD8+ T-cell IL2 and IFNγ responses were measured by intracellular cytokine staining following stimulation of peripheral blood mononuclear cells with peptide pools corresponding to the HCV proteins NS3, NS4a, and NS4B.ResultsMedian VL dropped from 5.87 log10 at T3 to 5.25 log10 at 3P (P < 0.0001, Wilcoxson signed rank), with a wide range from +0.4 log10 to -4.2 log10. The degree of decline correlated significantly with improved frequencies of HCV-specific CD4+ T cells producing IFNγ (P = 0.015 Spearman) but did not correlate with CD8+ T-cell changes. Nevertheless, improved T helper function correlated with increased HCV-specific CD8+ T-cell function (ΔCD4+IL2+ vs. ΔCD8+IFNγ+, P = 0.015 Spearman, graph 1; ΔCD4+IFNγ+ vs. CD8+IFNγ+ at 3P, P = 0.004 Spearman, graph 2).ConclusionDespite no significant association between virus-specific CD8+ T-cell Tc1 cytokine production and postpartum viral control, our data suggest that recovery of CD4+ T-cell help may augment CD8+ T-cell function. Further study incorporating viral genomic sequences to focus on intact class I epitopes is needed to clarify the relationship of improved CD8+ function and viral control in this unique model of immune restoration. Disclosures All authors: No reported disclosures.

Outcome of sofosbuvir based regimen in chronic hepatitis C patients with chronic kidney diseases on maintenance hemodialysis from western India

Introduction: The introduction of direct-acting antiviral (DAA)-based therapies for hepatitis C virus (HCV) has revolutionized the approach to HCV treatment. The data of sofosubvir based regimen in HCV infected Chronic Kidney Diseases (CKD) Patients on maintenance hemodialys (MHD) is not widely available. Our study was aimed to evaluate the effect of sofosbuvir–Ledipasvircombinationregimen in HCV positive CKD patient on MHD. Materials and Methods: Patients aged more than 12 years with HCV RNA positive and on MHD were included. Patients having liver cirrhosis and already started DAAs were excluded. Before starting treatment genotype, viral load routine clinical and laboratory data (CBC, SGPT, S.Albumin, S.Fetoprotein) were collected at baseline and also at 4, 12, and 24weeks during the treatment. All patients irrespective of genotypes were started sofosbuvir 400mg plus Ledipasvir 90 mg combination alternate day for 12 weeks. HCV RNA viral load was assessed at the end of 4, 12 and 24wks.We evaluated early virological response (EVR) at end of 4th weeks, end of treatment response (ETR) at the end of 12 weeks and sustained virological response (SVR) at the end of 24 weeks after initiation of therapy. Results: We had enrolled 210 HCV RNA patients with male (n=166) predominance with mean age of 31.6±10 years. Genotype 1 in 179 (85.2%) and genotype 3 in 31(14.8%) were found. 208 patients (99.03%) had achieved complete response at 12 wks (SVR12). 2 patients (1b,3) did not respond even at 24 wks. None of patient discontinued therapy because of side effects. No significant change in hemoglobin, platelet count and bilirubin. Conclusions: Sofosbuvir-Ledipasvir therapy on alternate day for 12 weeks was found effective therapy for HCV?infected CKD patients on MHD. Keywords: Sofosbuvir, Ledipasvir, HCV treatment, Haemodialysis, Western India.

964 Patient Flow Across Physician Specialties Over the Course of the Hepatitis C Care Cascade: A Real World Analysis From the United States

INTRODUCTION: Hepatitis C virus (HCV) infection is a major cause of hepatic and extrahepatic morbidity and mortality. In spite of recommendations for HCV screening, diagnosis, linkage to care and treatment, significant gaps remain in the cascade of care for HCV. As the role of physician specialties for closing these gaps is poorly understood, this study assesses the flow of HCV patients across physician specialties in the US, over the course of the care cascade. METHODS: This retrospective real-world study used two large de-identified national laboratory datasets (2013–2016). Screened patients had a HCV antibody (AB) test and/or HCV RNA viral load test. Diagnosed patients had a positive HCV RNA viral load test, and among this group, fibrosis assessment, genotype test and treatment were evaluated. Treatment was inferred with an algorithm based on changes in viral load. The number/proportion of patients at each step in the care cascade was calculated by physician specialty. Patient flow by physician specialty over the course of care cascade was assessed using Sankey Diagrams. RESULTS: Approximately 17 million patients received HCV screening, and 913,529 were diagnosed. Over the course of the care cascade, there was an increase in the proportion of patients switching to HCV specialists (gastroenterologist, hepatologist, and infectious disease specialist). Generalists (primary care, family practice, internal medicine) ordered 37% of the AB tests, and 15% initiated treatment. HCV specialists ordered 3% of screening tests and 37% initiated treatment. Most of the fibrosis assessment (30%) and genotype tests (29%) were ordered by HCV specialists. Obstetricians/gynecologists ordered 11% of screening tests but only 0.3% initiated treatment. Among 974,277 patients who received a positive AB test, 46% did not receive a confirmatory RNA test. Among diagnosed patients, 57% did not receive fibrosis assessment, 47% did not receive genotype test and 90% did not receive treatment. CONCLUSION: Generalists account for more than one third of all HCV screening tests, however, HCV specialists play a more prominent role in patient assessment (fibrosis status, genotype testing) and treatment. Significant gaps remain in all stages of the cascade of care for HCV, and improved efforts are needed for every physician specialty to address them. Timely screening, monitoring and linkage to care by generalists coupled with early treatment by specialists could effectively reduce the hepatic and extrahepatic burden of HCV.

Severe Guillain-Barr\xe9 syndrome associated with chronic active hepatitis C and mixed cryoglobulinemia: a case report

BackgroundWe describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported.Case presentationA 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center.ConclusionsOur case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations.