Hepatitis C virus genotypes implicated in mixed cryoglobulinemia

Nguyen, Quang Tri; Leruez‐Ville, Marianne; Ferrière, Françoise; Cohen, Pascal; Roulot-Marullo, D.; Coste, T.; Dény, Paul; Guillevin, Loı̈c

doi:10.1002/(sici)1096-9071(199801)54:1<20::aid-jmv4>3.0.co;2-r

Cited by 16 publications

(8 citation statements)

References 45 publications

(78 reference statements)

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“…MC vasculitis is the most frequent clinical manifestation related to HCV infection, and the prevalence ranges from 12 to 50 % in patients with chronic hepatitis C (CHC), with a higher rate in the Mediterranean area [35], probably due to genetic factors that are not yet understood. Some factors related to the prevalence of cryoglobulinemia in HCV-infected patients were analyzed in several studies, with conflicting results; Nguyen et al [25] reported an association with MC and HCV genotype 2, while Leone et al [20] with genotype 1b. Conversely, other authors did not demonstrate a role of HCV genotype in the occurrence of MC [17,39].…”

Section: Introductionsupporting

confidence: 38%

Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

et al. 2015

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The role of interleukin (IL) 28B in the treatment of chronic hepatitis C (CHC) has recently been examined in many studies, while a possible relationship between IL28B and the presence of mixed cryoglobulinemia (MC) remains to be clarified. In this study, we analyzed the influence of IL28B rs8099917/rs12979860 on the presence of MC and the role in treatment with PEG-IFN. We retrospectively examined 541 patients affected by CHC who were treated with pegylated interferon (PEG-IFN) and ribavirin from 2003 to 2012. We included all treatment-naïve patients without other viral co-infections or major contraindications to the PEG-IFN and ribavirin standard of care. One hundred seventy-five patients (32.3 %) had MC; 49 of these (33.3 %) had symptomatic MC. The IL28B rs8099917/rs12979860 TT/CC genotype was the most frequent in MC-positive patients with sustained virological response (SVR) (p < 0.001), while the TG/TC genotype was most frequent in non-SVR (p < 0.001). The TT/CC genotype was found to be the main positive predictive factor of MC in HCV patients (OR = 11.914; IQR = 7.092-18.776; p < 0.001); HCV genotype 2/3 was the strongest positive predictive factor of SVR (OR = 10.448; IQR = 8.352-21.561; p < 0.001); IL28B rs8099917/rs12979860 TT/CC was a better predictive factor than rs12979860 CC alone (OR = 9.829 vs. 2.663). Negative predictive factors were Metavir score F3-F4 (OR = 0.625; IQR = 0.416-0.779; p = 0.008), insulin-resistance (OR = 0.315; IQR = 0.224-0.585; p < 0.001) and presence of symptoms (OR = 0.716; IQR = 0.492-0.855; p < 0.001). IL28B rs8099917/rs12979860 is useful in the treatment of MC-positive HCV patients with PEG-IFN and ribavirin; the TT/CC genotype is associated with SVR, the TG/TC with non-SVR; TT/CC is also predictive of MC in HCV patients.

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Section: Introductionsupporting

confidence: 38%

Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

et al. 2015

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“…The HCV genotype of our patient was 1b, a type that occurs frequently throughout Europe [12,14]. The 1b genotype is associated with 58.3% of HCV patients showing cryoglobulinemia and hepatopathy [14], supporting the hypothesis that 1b is more aggressive than other genotypes [12,14]. However, our patient tested negative for cryoglobulinemia.…”

Section: Discussionmentioning

confidence: 91%

Hepatitis C virus infection and myositis: a polymerase chain reaction study

et al. 2000

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Muscle biopsy tissue from a patient with chronic hepatitis, who was hepatitis C virus (HCV) positive and showed slight weakness of the right arm and leg associated with increased serum creatine kinase levels, was studied using immunocytochemical and polymerase chain reaction (PCR) techniques. Muscle biopsy showed changes compatible with an inflammatory myopathy. Immunohistochemical studies included the use of monoclonal antibodies against human T lymphocytes, macrophages, immunoglobulins, major histocompatibility complex class I molecules (MHC-I), and the neoantigens of the terminal C5b-9 complement membrane attack complex (MAC). In addition to confirming the potential importance of cytotoxic T cells and MHC-I antigen expression in inducing muscle pathology, we demonstrated MAC deposition and the presence of HCV-RNA in the muscle of our patient, suggesting that direct involvement of the virus leading to complement activation might be important in inducing muscle damage.

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“…It is interesting to point out that genotypes 1 and 2 are mainly found in patients with mixed cryoglobulinemia (MC) (39), suggesting that these two genotypes might also be the major mediators of HCV-related extrahepatic disorders. Two hypotheses can explain the presence of two distinct genotypes.…”

Section: Discussionmentioning

confidence: 99%

Specialization of Hepatitis C Virus Envelope Glycoproteins for B Lymphocytes in Chronically Infected Patients

Douam

Bobay

Maurin

et al. 2016

J Virol

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Hepatitis C virus (HCV) productively infects hepatocytes. Virion surface glycoproteins E1 and E2 play a major role in this restricted cell tropism by mediating virus entry into particular cell types. However, several pieces of evidence have suggested the ability of patientderived HCV particles to infect peripheral blood mononuclear cells. The viral determinants and mechanisms mediating such events remain poorly understood. Here, we aimed at isolating viral determinants of HCV entry into B lymphocytes. For this purpose, we constructed a library of full E1E2 sequences isolated from serum and B lymphocytes of four chronically infected patients. We observed a strong phylogenetic compartmentalization of E1E2 sequences isolated from B lymphocytes in one patient, indicating that E1E2 glycoproteins can represent important mediators of the strong segregation of two specialized populations in some patients. Most of the E1E2 envelope glycoproteins were functional and allowed transduction of hepatocyte cell lines using HCV-derived pseudoparticles. Strikingly, introduction of envelope glycoproteins isolated from B lymphocytes into the HCV JFH-1 replicating virus switched the entry tropism of this nonlymphotropic virus from hepatotropism to lymphotropism. Significant detection of viral RNA and viral proteins within B cells was restricted to infections with JFH-1 harboring E1E2 from lymphocytes and depended on an endocytic, pH-dependent entry pathway. Here, we achieved for the first time the isolation of HCV viral proteins carrying entry-related lymphotropism determinants. The identification of genetic determinants within E1E2 represents a first step for a better understanding of the complex relationship between HCV infection, viral persistence, and extrahepatic disorders. IMPORTANCEHepatitis C virus (HCV) mainly replicates within the liver. However, it has been shown that patient-derived HCV particles can slightly infect lymphocytes in vitro and in vivo, highlighting the existence of lymphotropism determinants within HCV viral proteins. We isolated HCV envelope glycoproteins from patient B lymphocytes that conferred to a nonlymphotropic HCV the ability to enter B cells, thus providing a platform for characterization of HCV entry into lymphocytes. This unusual tropism was accompanied by a loss of entry function into hepatocytes, suggesting that HCV lymphotropic variants likely constitute a distinct but parallel source for viral persistence and immune escape within chronically infected patients. Moreover, the level of genetic divergence of B-cell-derived envelopes correlated with their degree of lymphotropism, underlining a long-term specialization of some viral populations for B-lymphocytes. Consequently, the clearance of both hepatotropic and nonhepatotropic HCV populations may be important for effective treatment of chronically infected patients.

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Hepatitis C virus genotypes implicated in mixed cryoglobulinemia

Cited by 16 publications

References 45 publications

Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

Hepatitis C virus infection and myositis: a polymerase chain reaction study

Specialization of Hepatitis C Virus Envelope Glycoproteins for B Lymphocytes in Chronically Infected Patients

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