Lymphotropic hepatitis C virus has an interferon‐resistant phenotype

Abstract

Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal B-cell activation and development of lymphoproliferative and autoimmune disorders. This immune perturbation may in turn be associated with the resistance of HCV against the host immune system. The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)-based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non-RVR, sustained viral responder (SVR) vs non-SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non-RVR, non-SVR and NVR groups. Association between the therapy outcome and the positive B-cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B-cell HCV RNA and the minor single-nucleotide polymorphism near the IL28B gene (rs8099917) were independent factors associated with NVR in patients infected with HCV genotype 1. When these two factors were combined, the sensitivity, specificity, positive and negative predictive values for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the presence of one or no mutations in the IFN-sensitivity determining region were associated with higher levels of B-cell HCV RNA. B-cell-tropic HCV appears to have an IFN-resistant phenotype. B-cell HCV RNA positivity is a predictive factor for resistance to IFN-based therapy.

Persistence of Cryoglobulinemia in Patients with Chronic Hepatitis C after Successful Treatment with Direct-acting Antivirals

“…Table 2 shows the clinical characteristics of HCV-infected patients. Cryoglobulinemia was identified in 13.7 of CH-C patients who enrolled in this study, and this prevalence was lower than that previously reported 24 22 . A high prevalence of hypocomplementemia low C3 33.6 , low C4 10.6 , low CH50 59.3 , and high levels of RF 37.6 were detected in the patients before DAAs administration, and interestingly, these findings were identical to the previous report.…”

“…It has been proven epidemiologically that HCV causes a variety of extrahepatic manifestations, including cardiovascular diseases and dysfunction of the central nervous system 15 . In these manifestations, LPDs are most closely associated with HCV infection [22][23][24] . Zignego et al 25 reported the t 14 ; 18 translocation and overexpression of bcl-2 in lymphoid cells of patients with a lymphoproliferative disorder associated with HCV infection.…”

Genetic variations in host IL28B links to the detection of peripheral blood mononuclear cells–associated hepatitis C virus RNA in chronically infected patients

“…Several reports indicate that HCV can efficiently infect extra‐hepatic tissue, including PBMCs . This and other observations collectively suggest that PBMCs may represent a privileged reservoir for HCV. Notably, a recent study demonstrated that host‐based resistance to RBV may occur in HCV patients undergoing combination PegIFN/RBV therapy .…”

“…Some reports, however, do suggest that HCV persists, albeit at very low levels, in circulating lymphoid cells for several years after apparently complete clinical and virological resolution of chronic hepatitis C, suggesting that PBMCs represent a natural reservoir for HCV . Recent reports suggest that HCV‐infected lymphoid cells are resistant to IFN and RBV , suggesting a link between the presence of HCV RNA in PBMCs with a poor response to IFN therapy . Yet, again these observations remain highly controversial .…”

High Level of Rheumatoid Factor is Associated with Hepatitis B Viremia in Patients with Chronic Hepatitis B

“…1A 5 . RNA 1 µl from peripheral blood mononuclear cells derived from the patients with CH-B was reverse transcribed into cDNA and amplified using the GeneAmp EZ rTth RNA polymerase chain reaction kit Applied Biosystems, Inc., Foster City, CA , according to the manufacturer s instructions.…”