Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Ayadi, Ahmad; Nafari, Amir Hossein; Sakhaee, Fatemeh; Rajabi, Kimia; Ghaderi, Yaser; Jamnani, Fatemeh Rahimi; Vaziri, Farzam; Siadat, Seyed Davar; Fateh, Abolfazl

doi:10.1111/hepr.13325

Cited by 5 publications

(5 citation statements)

References 47 publications

(120 reference statements)

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“…Nevertheless, most recently, an Iranian assessment reported 11.3% OCI among 515 cases on CHD. 24 This study is in apparent contradiction with previous Iranian studies as well as ours, which can be explained based on the large sample size, inclusion criteria, and probably regional diversity of the samples.…”

Section: Discussioncontrasting

confidence: 99%

Occult Hepatitis C Virus Infection among Hemodialysis Patients: An Iranian Experience

2020

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Background: Patients with chronic kidney failure and those undergoing chronic hemodialysis (CHD) treatment are at high risk of infection with hepatitis C virus (HCV). The incidence of occult HCV infection (OCI) in CHD remains controversial and the real burden of HCV in this population may be affected by the rate of OCI. This study evaluates the molecular assessment of OCI in CHD in an Iranian population. Methods: All subjects on CHD in the South Khorasan province of Iran were invited for participation in the study. Whole blood samples were taken and serological, clinical, and demographic information was recorded. HCV-RNAs were checked in serum and peripheral blood mononuclear cells (PBMCs) using an in-house semi-nested PCR assay. Viral load was determined using a real-time PCR-based quantification kit. Sequencing was performed to determine genotypes. Results: Overall, 120 cases participated in the study; 57.5% were male and the rest were female. In serum samples, no positive case was found for HCV-RNA. In PBMC samples, 2/120 (1.6%) were positive for HCV-RNA (95% CI, 0.002 to 0.059); the mean age of OCI positive cases was 37.5 ± 19.2 years which was significantly lower than OCI negative cases (P = 0.026). Only one case had detectable viral load which was 49 IU/mL. The only HCV genotype identified was 1a. Conclusion: This study showed that there is a risk of OCI among CHD patients; the very low and undetectable viral loads of OCI warrant further follow-up molecular testing for earlier diagnosis and treatment in the era of DAA.

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Section: Discussioncontrasting

confidence: 99%

Occult Hepatitis C Virus Infection among Hemodialysis Patients: An Iranian Experience

2020

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“…Basal liver necroinflammation and fibrosis scores were higher for patients who were later diagnosed with OCI after reaching treatment-induced SVR [55]. Moreover, as mentioned above, polymorphisms within immune-related genes such as chemokine ligand CXCL10 [56] or IL28 [34,37] determine viral persistence. In seronegative patients with hemophilia or kidney disease, OCI is linked with elevated biochemical parameters associated with systemic inflammation, such as cholesterol, triglyceride, low-density lipoprotein, and C-reactive protein level as well as with 25-hydroxyvitamin D deficiency [37,39].…”

Section: Immune Landscape Of Ocimentioning

confidence: 97%

“…Moreover, as mentioned above, polymorphisms within immune-related genes such as chemokine ligand CXCL10 [56] or IL28 [34,37] determine viral persistence. In seronegative patients with hemophilia or kidney disease, OCI is linked with elevated biochemical parameters associated with systemic inflammation, such as cholesterol, triglyceride, low-density lipoprotein, and C-reactive protein level as well as with 25-hydroxyvitamin D deficiency [37,39]. These data show that OCI may actually reflect specific characteristics of the host immune system, including low-level inflammation and reduced responsiveness to stimulation, which allows the virus to persist even after apparent therapeutically-induced resolution of viremia.…”

Section: Immune Landscape Of Ocimentioning

confidence: 99%

“…Genotype TT in IL28 rs12979860 polymorphism is associated with increased cellular IFN signaling, elevated expression levels of IFN-stimulated genes, and a non-response to treatment in CHC patients [36]. Interestingly this genotype correlated also with a higher percentage of dsRNA in liver tissue in CHC patients [33] and associated with the occurrence of both seropositive and seronegative OCI [34,[37][38][39]. Analysis of 5 UTR variants emerging during therapy with peg-IFN and ribavirin showed that the majority (64%) of the new variants were localized in PBMC and all had decreased IRES stability and impaired translational efficiency.…”

Section: Mechanisms Of Occult Hcv Persistencementioning

confidence: 99%

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

Wróblewska

Bielawski

Sikorska

2021

JCM

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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.

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“…14 Thus, many previous studies have reported OCI among certain populations such as HD patients using PMBCs sample. 6,7,12,13,15 Since its discovery, the existence of OCI in HD setting has been documented in several studies with prevalence ranging from 0 to 45%. A study done in Spain reported the highest prevalence of OCI cases with half of their HD patients were found to have the viral RNA in their PBMCs despite testing negative for both serum anti-HCV antibodies and viral RNA.…”

Section: Introductionmentioning

confidence: 99%

Seronegative Occult Hepatitis C Virus Infection (OCI) in a Main Haemodialysis Centre In Pahang, Malaysia

Snf¹,

Ha²,

Mia³

2020

imjm

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Introduction: Occult HCV infection has a predilection for specific populations such as haemodialysis (HD) patients. The exact natural course, epidemiology, pathogenesis and clinical importance of OCI are unknown. We investigated the existence of OCI among local patients undergoing routine HD at a referral hospital in Pahang, Malaysia. Methods: Serum and peripheral blood mononuclear cells (PMBCs) were collected from peripheral venous blood samples of seropositive (anti-HCV positive) and seronegative (anti-HCV negative) HD patients as well as healthy individuals (negative control group). Inclusion criteria for the seronegative patients included elevated liver enzymes. Both conventional PCR and strand-specific PCR were used to detect the viral RNA and to indicate active viral replication in PBMCs respectively. Direct DNA sequencing was done to confirm the viral HCV RNA and their genotypes. Results: In the majority (90-100%) of seropositive chronic hepatitis C patients, viral RNA was detected in both serum and PMBCs . Meanwhile, out of 22 seronegative patients, 6 (27%) showed active viral replication in PBMCs but no detectable viral RNA presence in the serum. None of the negative control group had detectable viral RNA. All seronegative patients with OCI were infected with HCV genotype 3 and two of them (2/6) had a slight elevation of their liver enzymes. Conclusion: Seronegative OCI does exist among local hemodialysis patients, with normal or persistently abnormal liver enzyme values. Further investigation is needed to study the mode of viral transmission and clinical significance of OCI in HD setting.

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Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Cited by 5 publications

References 47 publications

Occult Hepatitis C Virus Infection among Hemodialysis Patients: An Iranian Experience

Occult Hepatitis C Virus Infection among Hemodialysis Patients: An Iranian Experience

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

Seronegative Occult Hepatitis C Virus Infection (OCI) in a Main Haemodialysis Centre In Pahang, Malaysia

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