Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia

Abstract

Because a close relationship has been established between mixed cryoglobulinemia and hepatitis C virus (HCV) infection, the clinical, histologic, and virologic findings of 31 patients affected by mixed cryoglobulinemia have been determined. HCV infection was investigated by the presence of anti-HCV antibodies and by polymerase chain reaction (PCR) amplification of the 52 untranslated region (52UTR), and the genotype of HCV was also determined according to Okamoto et al (J Gen Virol 73:673, 1992). A bone marrow (BM) biopsy was performed in all patients, and liver and kidney biopsies were performed when indicated. The prevalence of anti-HCV antibodies was high (83.9%); polymerase chain reaction amplification of the 52 untranslated region was positive in 26 subjects (83.9%), and Core region amplification in 26 of 27 subjects (96.2%). A high prevalence of genotype II was found (76.6%). Chronic liver disease was present in 15 (48%) patients. BM biopsy specimens showed the presence of low-grade non-Hodgkin's lymphomas in 12 cases (38.7%), whereas, in 11 patients (35.5%), the BM infiltration was not monoclonal (reactive). Mixed cryoglobulinemia is closely associated with HCV infection. Apparently, only 1 patient was not infected by the virus. Several HCV genotypes are involved in the pathogenesis of mixed cryoglobulinemia. The disease is associated with a high prevalence of low-grade non-Hodgkin's lymphomas.

Pegylated‐interferon plus ribavirin for HCV‐positive indolent non‐Hodgkin lymphomas

“…Hepatitis C virus (HCV) causes not only chronic liver disease, but is also implicated in several lymphoproliferative disorders (Pozzato et al, 1994). The identification of CD81 as the main HCV receptor could explain this lymphotropism because this receptor is expressed in B lymphocytes (Pileri et al, 1998).…”

Hepatitis C virus‐related extra‐hepatic disease — aetiopathogenesis and management

“…HCV‐related cryoglobulinaemia is the most common extra‐hepatic manifestation: in three studies with 101 patients with mixed cryoglobulinaemia, up to 95% presented signs of HCV infection 5–7 . Patients with chronic hepatitis C have cryoglobulins in 36–54% of cases, 8 , 9 although most show no clinical or physical manifestations of syndromic cryoglobulinaemia.…”

“…Before the association of mixed cryoglobulinaemia with HCV infection was established, prednisone and cytotoxic drugs (cyclophosphamide and chlorambucil) were often used as maintenance therapy in patients with slow progression, although with limited success 24 . Immunosuppressive therapy may present two disadvantages: possible enhancement of HCV replication and possible exacerbation of low‐grade non‐Hodgkin's lymphoma 6 ,. 24 At present, IFNα or, preferably, pegylated IFNα represent the therapy of choice for HCV‐related mixed cryoglobulinaemia, as the improved rate of sustained virological response is accompanied by a reduction in circulating cryoglobulin levels and potential clinical remission of mixed cryoglobulinaemia symptoms 7 ,.…”

“…Lymphoproliferative disorders may represent an advanced stage of cryoglobulinaemia in HCV‐infected patients, as a result of the chronic stimulation of the immune system 1 . Data indicate that up to 56% of chronic hepatitis C patients with cryoglobulinaemia present abnormal bone marrow morphology [focal lymphoid aggregates suggestive of lymphoma (44%) or non‐Hodgkin's lymphoma (13%)], or even flow cytometric and molecular findings diagnostic of B‐cell non‐Hodgkin's lymphoma 6 ,. 37 The cellular and molecular mechanisms mediating the progression from cryoglobulinaemia to lymphoma remain unknown, although the above‐mentioned bcl‐2 over‐expression, bcl‐2 rearrangements and t(14;18) translocations in HCV‐infected mixed cryoglobulinaemia patients may play a role 19 ,.…”

Adverse drug reactions in the mouth

“…5 Researchers have suggested that mixed cryoglobulinaemia may be associated with a high prevalence of low-grade NHL and that intermediate or high-grade lymphomas can also develop during the long-term follow-up in these patients. 6 In addition, the association between HCV infection and age in patients with lymphoma may reflect the cumulative risk of infection and the long interval of time that is hypothesized to elapse from the beginning of infection to clonal lymphoid proliferation. 7 We propose that while HCV may be important in the aetiology of certain subgroups of NHL, this effect may be a multifactorial process; the malignancy could be the result of interaction among one or more viral agents in combination with genetic and environmental factors.…”