scholarly journals A New Twist to a Chronic HCV Infection: Occult Hepatitis C

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Bashar M. Attar ◽  
David Van Thiel

Background. The prevalence of occult hepatitis C infection (OCI) in the population of HCV-RNA negative but anti-HCV positive individuals is presently unknown. OCI may be responsible for clinically overt recurrent disease following an apparent sustained viral response (SVR) weeks to years later.Purpose. To review the available current literature regarding OCI, prevalence, pathogenic mechanisms, clinical characteristics, and future directions.Data Sources. SearchingMEDLINE, article references, and national and international meeting abstracts for the diagnosis of OCI (1990–2014).Data Synthesis. The long-term followup of individuals with an OCI suggests that the infection can be transient with the loss of detectable HCV-RNA in PPBMCs after 12–18 months or alternatively exist intermittently and potentially long term. The ultimate outcome of HCV infection is decided by interplay between host immune responses, antiviral therapies, and the various well-identified viral evasion mechanisms as well as the presence of HCV infection within extrahepatic tissues.Conclusion. The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Siti Nurul Fazlin Abdul Rahman ◽  
Hairul Aini binti Hamzah ◽  
Mohammed Imad Mustafa ◽  
Mohamed Hadzri Hasmoni

Introduction: The existence of new entity called occult hepatitis C virus (HCV) has become a raising and escalating concern among healthcare professionals worldwide. It is defined by the presence of viral RNA in liver and/or peripheral blood mononuclear cells (PBMCs) within non HCV-infected patients. Previous study had shown the occult HCV is infectious and capable of transmitting the virus to another host. Till today, HCV infection remains common among hemodialysis patients despite having the best preventive plans. Because of this, there is a significant concern about the source of viral transmission. The aim of the study was to identify and characterize occult HCV infection in PBMC sample of hemodialysis patients. This was an observational and cross sectional study. Materials and method: PBMCs were isolated from the whole blood using Ficoll-gradient centrifugation technique. The PBMCs were then subjected for cell counting and stored in -70O C until further used. HCV RNA were extracted from these cells and viral RNA were subjected for molecular assays, immune cells analysis and cells culture. Results: PBMCs were isolated from eleven (11) study patients and five (5) anti-HCV positive (control) patients. By using automated flow cytometry, PBMCs of each sample were counted and the average number of cells obtained range from 2x104 to 5x106 cells/ ml. Viral RNAs were extracted and quantitatively measured by using NanoDrop Spectrophotometers. The viral RNAs concentration obtained were between 24.7 and 258.9 ng/ml. The RNAs would be subjected for purification (ethanol precipitation) and further assays. Conclusion: The final findings might contribute to the clinical management of dialysis patients.


2020 ◽  
Vol 34 ◽  
pp. 205873842096120
Author(s):  
Abeya A Lotfi ◽  
Asmaa E Mohamed ◽  
Nahela A Shalaby ◽  
Deena S Eissa ◽  
Ehab El-Dabaa ◽  
...  

Despite the link between HCV and malignant lymphoproliferative disorders has been established, the association between occult hepatitis C virus infection and malignant lymphoproliferative disorders remains obscure. The present study intended to identify the possible association between occult HCV infection and malignant lymphoproliferative disorders. Newly diagnosed patients with LPDs were screened for the presence of HCV-RNA in both plasma and PBMCs. PBMCs of the subjects were also, examined by transmission and immuno-electron microscopy. LPD patients showed a high percentage of HCV infection (71.9%): OCI-HCV (37.5%) and HCV (34.38%). Meanwhile, 28.13% of LPD patients did not show any evidence of HCV infection. Ultrastructural examination of PBMCs revealed the presence of intracytoplasmic vacuoles enclosing viral like particles, which were less prominent in occult HCV patients. The possibility of occult HCV should be considered in patients with LPDs which can be helpful in the management of the treatment protocol in order to set up a balance between the control of the tumor progression and minimizing post chemotherapy complications related to HCV infection.


Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1704-1709 ◽  
Author(s):  
JP Hanley ◽  
LM Jarvis ◽  
J Andrew ◽  
R Dennis ◽  
PC Hayes ◽  
...  

In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.


2009 ◽  
Vol 23 (6) ◽  
pp. 594-601 ◽  
Author(s):  
Florence Nicot ◽  
Nassim Kamar ◽  
Bernard Mariamé ◽  
Lionel Rostaing ◽  
Christophe Pasquier ◽  
...  

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1704-1709 ◽  
Author(s):  
JP Hanley ◽  
LM Jarvis ◽  
J Andrew ◽  
R Dennis ◽  
PC Hayes ◽  
...  

Abstract In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.


2016 ◽  
Vol 144 (7-8) ◽  
pp. 418-423 ◽  
Author(s):  
Pavlina Dzekova-Vidimliski ◽  
Igor Nikolov ◽  
Nadica Matevska-Geshkovska ◽  
Yana Boyanova ◽  
Nina Nikolova ◽  
...  

Introduction. Occult hepatitis C is defined by the presence of virus in the peripheral blood mononuclear cells (PBMCs) and/or liver cells, in the absence of serum viremia. Objective. To detect the persistence of occult hepatitis C in hemodialysis (HD) patients and patients without renal disease (non-renal) with treatment-induced clearance of hepatitis C virus (HCV) infection, using assays with a very low detection limit of viremia. Methods. A group of 13 HD patients and a group of 43 non-renal patients, with treatment-induced HCV infection clearance were investigated in the study. The HD patients were treated with pegylated interferon alpha (PEG-IFN-?) only, while the non-renal patients were treated with a combination therapy of PEGIFN- ? and ribavirin. Detection of a possible persistence of HCV RNA in the PBMCs and plasma samples was assessed by an ultrasensitive reverse transcription polymerase chain reaction (RT-PCR) assay (2 IU/ml). Results. HCV RNA was not detected in the PBMCs and plasma samples of HD patients and of non-renal patients, when assessed by the ultrasensitive RT-PCR assay. Conclusion. When a sensitive RT-PCR assay was applied, to determine if treatment induced clearance of HCV infection had been successful, occult hepatitis C could not be detected by an ultrasensitive assay, neither in HD nor in non-renal patients.


2007 ◽  
Vol 81 (14) ◽  
pp. 7710-7715 ◽  
Author(s):  
Javier Bartolomé ◽  
Juan Manuel López-Alcorocho ◽  
Inmaculada Castillo ◽  
Elena Rodríguez-Iñigo ◽  
Juan Antonio Quiroga ◽  
...  

ABSTRACT Occult hepatitis C virus (HCV) infection of patients with abnormal liver function tests of unknown origin who are anti-HCV and serum HCV RNA negative but who have HCV RNA in the liver has been described. As HCV replicates in the liver cells of these patients, it could be that the amount of circulating viral particles is under the detection limit of the most sensitive techniques. To prove this hypothesis, serum samples from 106 patients with occult HCV infection were analyzed. Two milliliters of serum was ultracentrifuged over a 10% sucrose cushion for 17 h at 100,000 × g av, where av means average, and HCV RNA detection was performed by strand-specific real-time PCR. Out of the 106 patients, 62 (58.5%) had detectable serum HCV RNA levels after ultracentrifugation, with a median load of 70.5 copies/ml (range, 18 to 192). Iodixanol density gradient studies revealed that HCV RNA was positive at densities of 1.03 to 1.04 and from 1.08 to 1.19 g/ml, which were very similar to those found in the sera of patients with classical chronic HCV infection. Antigenomic HCV RNA was found in the livers of 56 of 62 (90.3%) patients with detectable serum HCV RNA levels after ultracentrifugation, compared to 27 of 44 (61.4%) negative patients (P < 0.001). No differences in the median loads of antigenomic HCV RNA between patients with an those without serum HCV RNA (4.5 × 104 [range, 7.9 × 102 to 1.0 × 106] versus 2.3 × 104 [range, 4.0 × 102 to 2.2 × 105]) were found. Alanine aminotransferase and gamma-glutamyl transpeptidase levels, liver necroinflammatory activity, and fibrosis did not differ between both groups. In conclusion, HCV RNA can be detected in the sera of patients with occult HCV infection after circulating viral particles are concentrated by ultracentrifugation.


2018 ◽  
Vol 75 (12) ◽  
pp. 1233-1236
Author(s):  
Maja Ruzic ◽  
Milotka Fabri ◽  
Tomislav Preveden ◽  
Katarina Baculov ◽  
Maria Pete ◽  
...  

Introduction. We are aware of the risk of late virological relapse (LVR) years after sustained viral response (SVR) by pegylated interferon and ribavirin alfa (PegIFN? + RBV) of chronic hepatitis C viral (HCV) infection. We presented three patients with LVR, treated by PegIFN? and ribavirin 5 years after the SVR was established. Case report. We analysed 129 (38.8% female, 61.2% male, mean age 37.02 ? SD 11.99) patients treated for chronic HCV with PegIFN? + RBV, with at least 5 years from the establishment of SVR. In addition to the biochemical parameters of liver function, the qualitative HCV RNA polymerase chain reaction (PCR) and the quantitative PCR HCV RNA test were made. Five years after establishing SVR in 2.3% (3/129) of patients, the relapse of HCV infection was registered by qualitative and quantitative PCR HCV RNA assay and all of these patients had additional autoimmune diseases: vasculitis, autoimmune hepatitis, and vasculitis of central nervous system. Conclusion. The existence, but low rate of LVR HCV infection was confirmed, dominantly in patients with additional autoimmune diseases. Due to this SVR after therapy by PegIFN? + RBV should be considered as an indicator of successful HCV suppresion, not its complete eradication.


2020 ◽  

Background and Objectives: Most patients with untreated chronic hepatitis C virus (HCV) infection develop hepatic fibrosis. Hepatic disease progression is monitored with hematological markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin and platelet [PLT] count, AST/ALT ratio, AST/PLT ratio index [APRI], and fibrosis 4 score [FIB-4]) and FibroScan. The present study aimed to investigate the association between Duffy antigen/chemokines receptor (DARC) polymorphisms and clinical parameters in the Han people with chronic hepatitis C infection in Dalian, China. Materials and Methods: This cohort study was performed on 245 Han people with chronic HCV at Dalian infectious hospital during April-December 2015. The participants of the research were selected using the consecutive sampling method. The DARC genotyping was performed using the TaqMan probe method and transient elastography was measured by FibroScan. Results: Based on the findings, DARC polymorphisms correlated with ALT concentrations (FY*A/FY*A vs. FY*A/FY*B, P=0.025). However, the DARC polymorphism did not have an association with HCV RNA titers (FY*A/FY*A vs. FY*A/FY*B, P=0.241) or hepatic fibrosis (FY*A/FY*A vs. FY*A/FY*B, P=0.325). Moreover, correlation analyses showed that APRI (P<0.001, rho=0.603) and FIB-4 (P<0.001, rho=0.698) were useful predictors of hepatic fibrosis in chronic HCV infection. Besides, HCV RNA titers (P=0.327) and hepatic injury markers (P=0.814, 0.198, 0.767, and 0.171 for ALT, AST, ALB, and AST/ALT, respectively) were not useful for the estimation of the fibrosis stage in patients with chronic hepatitis C. Conclusion: The FY*A allele is a potentially valuable protective factor against hepatocyte damage in chronic HCV-infected patients.


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
William W. Thompson ◽  
Mohammed A. Khan ◽  
Jay Soh ◽  
Lauren Canary ◽  
Michael Blank ◽  
...  

ObjectiveUsing data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters, we sought to assess the relationship between mental health outcomes and chronic hepatitis C infection after adjusting for important confounders. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in fee-for-service plans were included in the analysisIntroductionHepatitis C virus (HCV) infection is a leading cause of liver disease-related morbidity and mortality in the United States and HCV incidence has been increasing. Mental illness may impact the likelihood of initial HCV infection, progress and adherence to treatment along the hepatitis C care cascade, and risk of subsequent reinfection for those cured of hepatitis C. The relationship between HCV infection and mental illness is not well understood and many studies have lacked sufficient sample size to adjust for important confounders. We sought to explore the association between chronic HCV infection and mental illness after adjusting for important confounders.MethodsWe obtained data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. These data consist of inpatient and outpatient service claims for persons with employer-sponsored health insurance coverage and their dependents. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in a fee-for-service plan were included in the analysis. Chronic HCV infection was defined by a positive HCV RNA test result. Controls without chronic HCV infection had a negative HCV antibody test result and no positive HCV antibody or RNA test result in the preceding or following year. The index date was defined by the date of the earliest positive HCV RNA or negative HCV antibody test. Demographic characteristics were obtained from the MarketScan® enrollment tables. All enrollees in the study population were at least 18 years old during the year of the index date. The analysis sample was restricted to persons who were identified as receiving outpatient prescription drug claims data feeds. We estimated adjusted odds ratios (OR) for the association between mental illness (ICD-9 code 295 or 296) and HCV RNA status. Multivariate models included age (18-44, 45-64, 65+ years), sex, region, and an adjusted Charlson Comorbidity Index which excluded liver disease and hepatocellular carcinoma.ResultsWe identified 2,847 individuals with chronic HCV infection (HCV RNA+) and 57,418 controls who were HCV antibody negative. With respect to age, 83% of HCV RNA+ individuals were aged 45-64 years while only 43% of the HCV antibody negative individuals were in the same age range. Similarly, for sex, 62% and 40% of HCV RNA+ individuals and controls, respectively, were male. For unadjusted analyses, age, sex, region, comorbid conditions, and mental illness (OR= 2.25 [95% CI; 1.52 - 3.34]) were all statistically associated with HCV RNA+. For the multivariate adjusted models, these same variables remained statistically significant. For the multivariate model, individuals with a mental illness were more likely to be HCV RNA+ relative to HCV antibody negative controls. (OR= 1.95 [95% CI; 1.30 - 2.93]).ConclusionsThis study demonstrated a strong association between mental illness and HCV chronic infection after adjusting for important confounders including other comorbid conditions. A growing body of research suggests that persons with mental illness are at increased risk for contracting and transmitting HCV due to high rates of substance use and high-risk sexual behavior among infected persons as well as high rates of sexual victimization. HCV prevention efforts should be directed toward individuals with mental illness or seeking treatment for mental illness. 


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