Association between persistent lymphatic infection by hepatitis C virus after antiviral treatment and mixed cryoglobulinemia

Giannini, Carlo; Petrarca, A.; Monti, Monica; Arena, Umberto; Caini, Patrizio; Solazzo, Vera; Gragnani, Laura; Milani, Stefano; Laffi, Giacomo; Zignego, Anna Linda

doi:10.1182/blood-2007-09-112490

Cited by 26 publications

(24 citation statements)

References 10 publications

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“…[12][13][14] Accordingly, the detection of viral RNA in the plaque tissue of patients in the absence of detectable viremia (pts. 3-5; Table 1) points out the possibility of a compartmentalization of the virus in this district with pathogenetic consequences.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Recently, the possibility of viral persistence in extrahepatic reservoirs after apparent HCV eradication has also been shown. [12][13][14] Data supporting a possible role of HCV in atherosclerosis have been reported. 2,10,[15][16][17][18] In particular, large cross-sectional studies in the general Japanese population showed an association between HCV infection and increased risk of carotid artery plaques.…”

Section: Introductionmentioning

confidence: 99%

“…14,26 Both in case of positive-and negative-strand HCV RNA testing, several stringent controls of PCR specificity were systematically used to avoid the risk of contamination by amplification products from different tests, as previously described. 24 In addition, samples were blindly tested by three different laboratory technicians.…”

Section: Methodsmentioning

confidence: 99%

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Hepatitis C virus RNA localization in human carotid plaques

Boddi

Abbate

Chellini

et al. 2010

Journal of Clinical Virology

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a b s t r a c tBackground: Hepatitis C virus (HCV) infection has certain characteristics that enable it to play an important role in atherosclerosis. Some studies report its association with an increased risk of carotid artery plaque. Objectives: The aim of this study was to evaluate the presence of HCV genomic sequences and replicative intermediates in plaque tissues. Study Design: A cohort of consecutive, prospectively recruited patients with HCV infection and chronic ischemic heart disease from the Cardiology, Vascular Surgery and Hepatology Units of a University Hospital in Florence, Italy, were studied. Results: Positive-strand HCV RNA was detected in seven carotid plaque tissues from anti-HCV-positive patients and was not detected in the nine carotid plaque tissues obtained from anti-HCV-negative patients. In three patients, HCV RNA was found in carotid plaque and not in serum. HCV replicative intermediates were detected in three plaque samples. Direct sequencing of HCV RNA from the plaque and serum showed HCV genotypes 2 (five cases) and 1 (two cases). Conclusions: The novel finding of HCV RNA sequences in plaque tissue strongly suggests an active local infection. This in turn makes it conceivable that the virus may exert local action in carotid atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatitis C virus RNA localization in human carotid plaques

Boddi

Abbate

Chellini

et al. 2010

Journal of Clinical Virology

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130

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“…25 The determination and quantification of HCV RNA in serum samples were performed by a sensitive real-time polymerase chain reaction technique that has been extensively described in previous studies. 26,27 In some cases, peripheral blood mononuclear cell samples were tested for the presence of isolated HCV infection in this compartment, as previously described. 27 Evaluation of liver ultrastructure.…”

Section: Evaluation Of Treatment Responsementioning

confidence: 99%

“…26,27 In some cases, peripheral blood mononuclear cell samples were tested for the presence of isolated HCV infection in this compartment, as previously described. 27 Evaluation of liver ultrastructure. Transjugular biopsies for microscopy were obtained in 2 patients (no.…”

Section: Evaluation Of Treatment Responsementioning

confidence: 99%

Safety and efficacy of rituximab in patients with hepatitis C virus–related mixed cryoglobulinemia and severe liver disease

Petrarca

Rigacci

Caini

et al. 2010

Blood

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112

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The effectiveness of rituximab in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC) has been shown. However, the risk of an increase in viral replication limits its use in cirrhosis, a condition frequently observed in patients with MC. In this prospective study, 19 HCV-positive patients with MC and advanced liver disease, who were excluded from antiviral therapy, were treated with rituximab and followed for 6 months. MC symptoms included purpura, arthralgias, weakness, sensory-motor polyneuropathy, nephropathy, and leg ulcers.

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Long‐term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open‐label, cohort study

et al. 2015

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Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC), especially concerning the long-term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long-term effects of viral eradication on MC. We prospectively enrolled 424 HCV 1 patients belonging to the following groups: MC syndrome (MCS)-HCV (121 patients with symptomatic MC), MC-HCV (132 patients with asymptomatic MC), and HCV (158 patients without MC). Pegylated interferon plus ribavirin treatment was administered according to standard protocols. Posttreatment follow-up ranged from 35 to 124 months (mean 92.5 months). A significant difference was observed in the rate of sustained virological response between the HCV group and both the MC-HCV (P 5 0.009) and MC-HCV1MCS-HCV (P 5 0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of nonresponse. The clinical-immunological response in MCS-HCV correlated with the virological one. All patients with sustained virological response also experienced a sustained clinical response, either complete or partial. In the majority of sustained virological response patients all MCS symptoms persistently disappeared (36 patients, 57%); in only two (3%) did definite MCS persist. All virological nonresponders were also clinical nonresponders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of interferon-based therapy on HCV patients with and without MC and with and without symptoms, as well as the long-term effects of viral eradication on MC. Conclusion: MC is a negative prognostic factor of virological response. Clearance of HCV led to persistent resolution or improvement of MCS, strongly suggesting the need for a next generation of highly effective antiviral drugs. (HEPATOLOGY 2015;61:1145-1153 M ixed cryoglobulinemia (MC) is an autoimmune/lymphoproliferative disorder characterized by circulating immune complexes named cryoglobulins (CGs) that reversibly precipitate at low temperatures. The CGs are comprised of polyclonal immunoglobulin Gs (including anti-hepatitis C virus [HCV] immunoglobulin) and mono-or polyclonal immunoglobulin M with rheumatoid factor activity, sustained by the clonal expansion of rheumatoid factor B cells.

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Association between persistent lymphatic infection by hepatitis C virus after antiviral treatment and mixed cryoglobulinemia

Cited by 26 publications

References 10 publications

Hepatitis C virus RNA localization in human carotid plaques

Hepatitis C virus RNA localization in human carotid plaques

Safety and efficacy of rituximab in patients with hepatitis C virus–related mixed cryoglobulinemia and severe liver disease

Long‐term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open‐label, cohort study

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