scholarly journals Occult Infection with Hepatitis C Virus: Looking for Clear-Cut Boundaries and Methodological Consensus

2021 ◽  
Vol 10 (24) ◽  
pp. 5874
Author(s):  
Anna Wróblewska ◽  
Krzysztof Piotr Bielawski ◽  
Katarzyna Sikorska
Keyword(s):  
Hepatitis C ◽  
Virologic Response ◽  
Hcv Rna ◽  
Published Data ◽  
Careful Study ◽  
Clear Cut ◽  
Monitoring Strategies ◽  
New Information ◽  
Clinical Background ◽  
Epidemiological Significance

The sustained virologic response and elimination of HCV is widely viewed as a true cure of chronic hepatitis C as it associates with amelioration of histological liver damage and improved clinical outcomes. Therefore, the existence and clinical burden of occult HCV infection (OCI) has been a controversial issue for many years. In this review, we summarize recently published data that adds new information on the molecular and clinical background of OCI and its epidemiological significance. We also identify and discuss the most important methodological pitfalls, which can be a source of inconsistency between studies. Data that have accumulated so far, strongly support the existence of extrahepatic HCV replication in individuals negative for serum HCV-RNA by conventional clinical tests. OCI emerges as a condition where the immune system is unable to fully resolve infection but it is continuously stimulated by low levels of HCV antigens, leading to progression of liver pathology and extrahepatic HCV-related complications. Moreover, the development of monitoring strategies or management guidelines for OCI is still hampered by the lack of clear definition and the confusion regarding its clinical significance. Careful study design and the introduction of uniform protocols for the detection of low-level HCV-RNA are crucial for obtaining reliable data on OCI.

Rituximab plus Peg-interferon-α/ribavirin compared with Peg-interferon-α/ribavirin in hepatitis C–related mixed cryoglobulinemia

Blood ◽  
2010 ◽  
Vol 116 (3) ◽  
pp. 326-334 ◽  
Author(s):  
David Saadoun ◽  
Mathieu Resche Rigon ◽  
Damien Sene ◽  
Benjamin Terrier ◽  
Alexandre Karras ◽  
...  
Keyword(s):  
Hepatitis C ◽  
B Cell ◽  
Complete Response ◽  
Mixed Cryoglobulinemia ◽  
Virologic Response ◽  
Interferon Α ◽  
Hcv Rna ◽  
Cell Suppression ◽  
N 93 ◽  
Cell Clonal Expansion

AbstractTreatment of hepatitis C (HCV)–mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m2) once a week for 1 month followed by Peg-interferon-α (Peg-IFN-α; 2a, 180 μg or 2b, 1.5 μg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-α/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-α/ribavirin, rituximab plus Peg-IFN-α/ribavirin–treated patients had a shorter time to clinical remission (5.4 ± 4 vs 8.4 ± 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69+ B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-α/ribavirin is well tolerated and more effective than Peg-IFN-α/ribavirin in HCV-MC.

scholarly journals Hepatitis C testing and linkage to care among adults on probation in a large US city

2021 ◽  
Author(s):  
Kevin F Kamis ◽  
David L Wyles ◽  
Matthew S Minturn ◽  
Tracy Scott ◽  
Dean McEwen ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Point Of Care ◽  
Linkage To Care ◽  
Virologic Response ◽  
Patient Navigator ◽  
Hcv Rna ◽  
Study Cohort ◽  
Hcv Treatment ◽  
Hiv Test ◽  
Hcv Testing

Abstract Background Despite constituting the largest segment of the correctional population, individuals on probation remain largely unstudied with respect to hepatitis C virus (HCV) testing and linkage-to-care. We implemented an HCV testing and patient navigation program at an adult probation department. Methods Adults were tested at a local probation department with a rapid point-of-care HCV antibody (Ab) assay followed by a lab-based HCV RNA assay if anti-HCV positive. All individuals received counseling rooted in harm-reduction principles. Individuals testing positive for HCV Ab were immediately linked to a patient navigator in person or via telephone. The patient navigator assisted patients through cure unless lost to follow-up. Study participation involved an optional survey and optional point-of-care HIV test. Results Of 417 individuals tested, 13% were HCV Ab positive and 65% of those tested for HCV RNA (34/52) had detectable HCV RNA. Of the 14 individuals who linked to an HCV treatment provider, 4 completed treatment as measured by pharmacy fill documentation in the electronic medical record, and 1 obtained sustained virologic response. 193 individuals tested for HIV; none tested positive. Conclusions The study cohort had a higher HCV seroprevalence than the general population (13% vs 2%), but linkage-to-care, completion of HCV treatment, and successful test-of-cure rates were all low. This study indicates that HCV disproportionately impacts adults on probation and prioritizing support for testing and linkage-to-care could improve health in this population. Co-localization of HCV treatment within probation programs would reduce the barrier of attending a new institution and could be highly impactful.

scholarly journals Treatment outcomes of patients with chronic hepatitis C receiving sofosbuvir-based combination therapy within national hepatitis C elimination program in the country of Georgia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tengiz Tsertsvadze ◽  
Amiran Gamkrelidze ◽  
Muazzam Nasrullah ◽  
Lali Sharvadze ◽  
Juliette Morgan ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Response Rate ◽  
Response Rates ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Hcv Rna ◽  
Genotype 3 ◽  
Treatment Regimens ◽  
Genotype 2 ◽  
Chronic Hcv

Abstract Background Georgia has one of the highest HCV prevalence in the world and launched the world’s first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia. Methods Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed. Results Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P < 0.0001). In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05–1.15]) and genotype 3 (RR = 1.14, CI [1.11–1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93–0.98]), receiving treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR = 0.85, CI [0.81–0.91]; RR = 0.86, CI [0.82–0.92]; RR = 0.88, CI [0.85–0.91] and RR = 0.92, CI [0.87–0.98], respectively) were less likely to achieve SVR. Conclusions Georgia’s real world experience resulted in high overall response rates given that most patients had severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs, significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.

scholarly journals Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir Regimen in Haemodialysis Patients With Hepatitis C Virus Infection

2020 ◽  
Vol 39 (1) ◽  
pp. 23-27
Author(s):  
Antonija Verhaz ◽  
Tatjana Roganović ◽  
Ljiljana Pašić ◽  
Olja Čuković ◽  
Tanja Macanović-Kostić
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Concomitant Medication ◽  
Demographic Data ◽  
Virologic Response ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Stage Renal Disease

Background: Hepatitis C virus (HCV) infection is common among patients on haemodialysis (HD) therapy and is an important cause of morbidity and mortality. In patients with chronic kidney disease (CKD), the risks for negative outcomes are significantly higher in HCV-infected patients than in those without HCV infection, including progression to cirrhosis, hepatocellular carcinoma and liver-related mortality. Ombitasvir (OBV), paritaprevir (PTV), ritonavir (r), and dasabuvir (DSV) are all hepatically metabolized and, therefore, require no dose adjustment in patients with any degree of renal impairment. Aims: We studied the safety and efficacy of OBV/PTV/r + DSV in a small group of HCV infected patients on haemodialysis therapy. Methods: Treatment course with ombitasvir/paritaprevir/ritonavir and dasabuvir; (3-DAA regimen of OBV/PTV/r+DSV±RBV) was analysed. Pre-treatment evaluation of HCV infection included HCV RNA, genotype, and liver fibrosis assed by transient fibroelastography (FibroScan). The stage 5 CKD was defined as an eGFR of &lt;15 mL/min/1.73 m2, respectively; those on haemodialysis were considered to have stage 5 CKD or end-stage renal disease (ESRD). Demographic data and concomitant medication were retrieved from patients’ records. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Among 7 treated patients, 6 were male and 1 female, all were infected with genotype 1 (5 GT1b, 2 GT1a). Patient had compensated liver cirrhosis and six patients did not have liver cirrhosis, none were liver transplant recipients. All of seven patients completed 12 weeks of treatment and achieved SVR12. Concomitant medication had to be modified with the treatment initiation in 5 out of 7 patients. One of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, diarrhoea. Adverse events were primarily mild, and no patient discontinued treatment due to an AE. Conclusions: Treatment with OBV/PTV/r +DSV ± RBV was well-tolerated and resulted in high rates of SVR12 (100%) for patients with HCV GT1b/1a on haemodialysis.

scholarly journals Clinical Implications of Detectable Baseline Hepatitis C Virus-Genotype 1 NS3/4A-Protease Variants on the Efficacy of Boceprevir Combined With Peginterferon/Ribavirin

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
John A. Howe ◽  
Jianmin Long ◽  
Stuart Black ◽  
Robert Chase ◽  
Patricia McMonagle ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Failure ◽  
Virologic Response ◽  
Phase Iii ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Virus Genotype ◽  
The Impact

Abstract Background.  We analyzed the impact of pretreatment variants conferring boceprevir-resistance on sustained virologic response (SVR) rates achieved with boceprevir plus peginterferon-α/ribavirin (P/R) for hepatitis C virus (HCV)-genotype-1 infection. Methods.  NS3-protease-polymorphisms emerging coincident with virologic failure on boceprevir/P/R regimens were identified as resistance-associated variants (RAVs). Baseline samples pooled from 6 phase II or phase III clinical trials were analyzed for RAVs by population sequencing. Interferon (IFN)-responsiveness was predefined as &gt;1 log reduction in HCV-RNA level during the initial 4-week lead-in treatment with P/R before boceprevir was added. The effective boceprevir-concentration inhibiting RAV growth by 50% (EC50) was determined using a replicon assay relative to the wild-type referent. Results.  Sequencing was performed in 2241 of 2353 patients (95.2%) treated with boceprevir. At baseline, RAVs were detected in 178 patients (7.9%), including 153 of 1498 genotype-1a infections (10.2%) and 25 of 742 genotype-1b infections (3.4%) (relative risk, 3.03; 95% confidence interval [CI], [2.01, 4.58]). For IFN-responders, SVR24 (SVR assessed 24 weeks after discontinuation of all study medications) rates were 78% and 76% with or without RAVs detected at baseline, respectively. For the 510 poor IFN-responders, SVR24 rates were 8 of 36 subjects (22.2% [11.7%, 38.1%]) when baseline RAVs were detected vs 174 of 474 subjects (36.7% [32.5%, 41.1%]) when baseline RAVs were not detected (relative likelihood of SVR24 [95% CI], 0.61 [0.32, 1.05]). Sustained virologic response was achieved in 7 of 8 (87.5%) IFN-nonresponders with baseline variants exhibiting ≤2-fold increased EC50 for boceprevir in a replicon assay, whereas only 1 of 15 (7%) IFN-nonresponders with baseline RAVs associated with ≥3-fold increased EC50 achieved SVR. Conclusions.  Baseline protease-variants appear to negatively impact SVR rates for boceprevir/P/R regimens only when associated with decreased boceprevir susceptibility in vitro after a poor IFN-response during the lead-in period.

scholarly journals An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTime HCV RNA Assay

2015 ◽  
Vol 53 (4) ◽  
pp. 1264-1269 ◽  
Author(s):  
Christoph Sarrazin ◽  
Inge Dierynck ◽  
Gavin Cloherty ◽  
Anne Ghys ◽  
Katrien Janssen ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Similar Proportion ◽  
Hcv Rna ◽  
Pure System ◽  
Treatment Naïve ◽  
Total Therapy

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.)

scholarly journals A Follow-up Study for Chinese Chronic Hepatitis C Patients Treated with the Combination of PEG-IFNα-2a (PEGASYS) and Ribavirin

2014 ◽  
Vol 3 (3) ◽  
pp. 103-107
Author(s):  
Zhu Chen ◽  
Yi-lan Zeng ◽  
Li Wang ◽  
Rong Hu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Adverse Events ◽  
Chronic Hepatitis C ◽  
Virologic Response ◽  
Interferon Alfa ◽  
Hcv Rna ◽  
Peginterferon Alfa ◽  
To Receive

Abstract Objective To compare the efficacy of peginterferon alfa-2a (PEGASYS) plus ribavirin (RBV) with interferon alfa-2a plus RBV, and evaluate the safety. Methods Total of 117 patients with chronic hepatitis C were enrolled to receive either PEGASYS (135 μg or 180 μg) subcutaneously once per week, plus RBV (800 mg-1 200 mg) per day for 48 weeks (79 patients, PEGASYS group), or 5 million units of interferon alfa-2a subcutaneously every other day, plus RBV as above dosage for 48 weeks (38 patients, IFNα group). Results Sixty-three of 79 (79.7%) patients reached sustained virological response (SVR) in PEGASYS group, while 14 of 38 (36.8%) patients reached SVR in IFNα group. PEGASYS group was associated with a higher rate of virologic response than IFNα group at week 4, 12, 36, 48 and week 72. Sustained normalization of serum ALT concentrations at week 36, 48 and week 72 was also more common in PEGASYS group than in IFNα group. Baseline levels of ALT and HCV RNA had no effect on SVR in either PEGASYS group or IFNα group. Both groups were similar in the frequency and severity of adverse events. Conclusions PEGASYS plus RBV produced similar adverse events but higher rate of SVR. Meanwhile, complications should be prevented and treated promptly in order to increase compliances and effects.

Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Mohamed Yousef ◽  
Maha Mohsen Mohamed Kamal El Din ◽  
Tari Magdy Aziz George ◽  
Amr Adel Elzohary Mohamed
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Virologic Response ◽  
Hcv Rna ◽  
Occult Hepatitis ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Occult Hepatitis C ◽  
Direct Acting Antiviral Agents

Abstract Background Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. Objectives The aim of the study to detect the prevalence of occult hepatitis C Virus infection in patients who achieved a sustained virologic response (SVR) to direct-acting antiviral agents and to outline predictors of OCI. Patients and Methods This study included 100 patients with chronic HCV infection without liver cirrhosis attending to hepatitis C clinics at Ain Shams University Hospital, Ahmed Maher Teaching hospital and Elgomhorya Teaching Hospital.who received sofosbuvir (400mg) plus daclatasvir (60mg) daily for 12 weeks with or without ribavirin according to National committee to combat viral hepatitis (NCCVH) protocol. Results We tested peripheral blood for HCV RNA in PBMCs to detect OCI. Occult HCV was found positive in 12% of the studied cases. Occult HCV was positive more in male cases. Positive cases had significantly lower age, and higher total bilirubin, direct bilirubin, AST and ALT levels. Age had significant moderate diagnostic performance in predicting occult HCV, while direct bilirubin has significant low diagnostic performance in predicting occult HCV. Conclusion OCI following direct antiviral therapy may be present in some cases, and this may require further testing of patients with SVR particularly in younger male patients with persistantly high liver enzymes.

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