Prevalence of Monoclonal Gammopathies in Patients with Hepatitis C Virus Infection

Andreone, Pietro; Zignego, Anna Linda; Cursaro, Carmela; Gramenzi, Annagiulia; Gherlinzoni, Filíppo; Fiorino, Sirio; Giannini, Carlo; Boni, P; Sabattini, Elena; Pileri, Stefano; Tura, S; Bernardi, Mauro

doi:10.7326/0003-4819-129-4-199808150-00005

Cited by 107 publications

(73 citation statements)

References 15 publications

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“…1,29 In some studies, a high frequency of type 2a/c was detected in HCV-related LPDs including type II MC, B-cell NHL, and monoclonal gammopathies. 1,4,30,31 In light of present and past observations, it is possible that different viral types exert a lesser or more important influence on favoring the appearance of LPDs. Concerning more specifically type 2a/c, a correlation with the above-reported observations may possibly be found in the fact that this viral variant has been associated with a more intense stimulation of the lymphatic system.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] The mechanisms involved in LPDs, either virusrelated or virus-independent, are complex and still poorly defined. MC, the LPD most strictly associated with HCV infection, is a borderline (benign/malignant) disorder in that it frequently coexists with bone-marrow aspects of NHL and evolves, in about 5% to 8% of cases, into a clinically frank B-cell malignancy.…”

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confidence: 99%

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T(14;18) translocation in chronic hepatitis C virus infection

et al. 2000

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Pathogenic mechanisms of B-cell lymphoproliferative disorders in chronic hepatitis C virus (HCV) infection are unclear. We studied t(14;18) translocation by polymerase chain reaction in peripheral blood mononuclear cells from 50 patients with HCV-related liver disease (group A), 7 with mixed cryoglobulinemia syndrome (group B), 55 with HCV-negative liver disease (group C), and 30 with HCVnegative chronic rheumatic disorders or chronic infection by nonhepatotropic agents (group D). T(14;18) was significantly more frequent in group A (13/50 patients ‫؍‬ 26 %) and group B (5/7 ‫؍‬ 71.4%) patients than in group C (1/55 ‫؍‬ 3.6%) and group D (1/30 ‫؍‬ 3.3%) ones. Immunoblot analysis showed bcl-2 over-expression in all t(14;18)-positive samples. In group A, 10/13 (77%) patients with t(14;18) and 13/37 (35%) without t(14;18) had serum cryoglobulins in the absence of mixed cryoglobulinemia symptoms (P F .05). These data indicate that t(14;18) and bcl-2 over-expression in lymphoid cells are frequent in chronic HCV infection and suggest that this event may contribute to the pathogenesis of HCV-related lymphoproliferative disorders. (HEPATOLOGY 2000;31:474-479.)Hepatitis C virus (HCV) infection has been associated with a series of B-cell lymphoproliferative disorders (LPDs), including essential mixed cryoglobulinemia (MC), B-cell non-Hodgkin' s lymphoma (NHL), and monoclonal gammopathies. [1][2][3][4] The mechanisms involved in LPDs, either virusrelated or virus-independent, are complex and still poorly defined. MC, the LPD most strictly associated with HCV infection, is a borderline (benign/malignant) disorder in that it frequently coexists with bone-marrow aspects of NHL and evolves, in about 5% to 8% of cases, into a clinically frank B-cell malignancy. 5,6 In addition, clonal expansion of IgMproducing B cells has been detected in patients with HCVpositive MC (HCV/MC). 7 Recently, 1 patient with HCV/MC has been shown to develop a monoclonal multistep lymphoproliferative disorder associated with t(14;18) translocation in the benign phase of the disease and additional genetic alterations in the accelerated one. 8 Over-expression of bcl-2 oncoprotein has been shown by immunohistochemistry in liver lymphocyte aggregates not only in the majority of HCV-positive MC, but also in about 45% of patients with chronic HCV-related hepatitis without MC. 9 The recombination of anti-apoptotic bcl-2 proto-oncogene [t(14;18)] has been widely investigated in the field of lymphomagenetic studies. Following t(14;18), the bcl-2 locus, normally located in chromosome 18, is juxtaposed with the immunoglobulin heavy chain locus (IgH), leading to bcl-2 activation. This genetic aberration, which occurs during early B-cell development, appears to be 1 step toward the progression of a normal cell to a cancer cell 10 ; in particular, its importance in regards to cooperative activities with different oncogenes, such as c-myc, has been experimentally shown. T(14;18) characterizes most follicular B-cell lymphomas as well as some diffuse ones. Recent data...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

T(14;18) translocation in chronic hepatitis C virus infection

et al. 2000

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“…Taking into account the relatively low number of cases, we found trends for a better lymphoma response in patients with extranodal disease and paraproteinemia, features typically associated with HCVassociated NHLs. [22][23][24] Lastly, for CLL/SLL, which is frequently not epidemiologically associated with HCV infection, 3,25 no LDRs were achieved despite virus clearance. Altogether, these findings confirm that HCV clearance per se is beneficial in patients with non-CLL/SLL HCV-associated B-NHL and support a stepwise model of lymphomagenesis induced by chronic antigenic stimulation in this setting.…”

Section: Discussionmentioning

confidence: 99%

Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection

Arcaini

Besson

Frigeni

et al. 2016

Blood

160

131

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Key Points• Direct-acting antiviral agents are able to induce lymphoma response in patients with HCV-associated indolent nonHodgkin lymphoma.• The highest rate of lymphoma response (73%) was observed in patients with marginal zone lymphoma.Regression of hepatitis C virus (HCV)-associated lymphoma with interferon (IFN)-based antiviral treatment supports an etiological link between lymphoma and HCV infection. In addition, a favorable impact of antiviral treatment on overall survival of patients with HCVrelated lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty. We analyzed the virological and lymphoproliferative disease response (LDR) of 46 patients with indolent B-cell non-Hodgkin lymphomas (NHLs) or chronic lymphocytic leukemia (CLL) and chronic HCV infection treated with DAAs. The histological distribution was 37 marginal zone lymphomas (MZLs), 2 lymphoplasmacytic lymphomas, 2 follicular lymphomas, 4 CLL/small lymphocytic lymphomas (CLL/SLLs), and 1 low-grade NHL not otherwise specified. Thirty-nine patients received a sofosbuvir-based regimen and 7 patients received other DAAs. The median duration of DAA therapy was 12 weeks (range, 6-24 weeks). A sustained virological response at week 12 after finishing DAAs was obtained in 45 patients (98%); the overall LDR rate was 67%, including 12 patients (26%) who achieved a complete response. The LDR rate was 73% among patients with MZL, whereas no response was observed in CLL/SLL patients. Seven patients cleared cryoglobulins out of 15 who were initially positive. After a median follow-up of 8 months, 1-year progression-free and overall survival rates were 75% (95% confidence interval [CI], 51-88] and 98% [95% CI, 86-100], respectively. DAA therapy induces a high LDR rate in HCV-associated indolent lymphomas. These data provide a strong rationale for prospective trials with DAAs in this setting.

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“…12,13 Serum cryoglobulin levels and characterization, levels of complement fractions, rheumatoid factor, and autoantibodies were evaluated as described. [13][14][15] The mean duration of MC was 88 months (range, 24-172 months). The main MC symptoms are presented in Table 1.…”

Section: Introductionmentioning

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

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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Prevalence of Monoclonal Gammopathies in Patients with Hepatitis C Virus Infection

Abstract: The prevalence of monoclonal gammopathies in patients with HCV-related chronic liver disease is striking and is often associated with genotype 2a/c infection.

Cited by 107 publications

References 15 publications

T(14;18) translocation in chronic hepatitis C virus infection

T(14;18) translocation in chronic hepatitis C virus infection

Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection

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

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