From hepatitis C virus infection to B-cell lymphoma

Abstract

In addition to liver disorders, hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to antiviral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated. Based on reported biological studies, several mechanisms of transformation seem however to emerge. A strong body of evidence supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could play a direct role in cellular transformation, particularly in de novo large B-cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of patients. In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell lymphoproliferation is of prime importance to optimize therapeutic strategies, especially with the recent development of new direct-acting antiviral drugs.

Does cirrhosis associated with well controlled viral hepatitis confer a risk for extrahepatic cancer?

“…This is a well‐defined, large‐scale, prospective cohort study using the ANRS CO12 CirVir database. The clear association between viral hepatitis and lymphoma, which is well established, increases the validity of the study results. However, there are several limitations that should be taken into account when interpreting the study results.…”

“…Therefore, patients with cirrhosis and viral hepatitis may be at a higher risk of malignancy than people in the general population. In additon, it is well established that HBV or HCV infection increases the risk of hematologic malignancies, particularly lymphoma . Both viruses also create immune disturbances in the host, which may affect cancer immune surveillence; correction of these immune alterations with successful antiviral therapy may be too late to prevent cancer as carcinogenesis processes may have already evolved to evade immune surveillence.…”

In vitro knock‐out of miR‐155 suppresses leukemic and HCV virus loads in pediatric HCV‐4–associated acute lymphoid leukemia: A promising target therapy

“…There are many studies illustrating the role of miR‐155 in HCV infection and leukemia, separately. But we also have some limitations: we did not study the mechanistic pathways by which miR_155a inhibition suppresses leukemic cell proliferation and HCV replication in pediatric ALL . We suggest more research to investigate the roles which miR‐155 play in those patients.…”

“…HCV chronic infection can lead to hepatocellular carcinoma and non‐Hodgkin lymphoma (NHL) . New emerging evidence suggets that HCV infection increases the risk of lymphoid neoplasms, with a predominance of large B cell lymphoma . HCV chronic infection may induce B‐cell lymphoma by sustained B cells stimulation through chronic antigenic stimulation, which will lead to increased production of cryoglobulins .…”

Prevention of liver cancer with new curative hepatitis C antivirals: Real‐world challenges

“…A wide constellation of clinical complications, ranging from direct effects of hepatic damage causing decompensated cirrhosis to extrahepatic conditions such as cryoglobulinemia, insulin resistance and type 2 diabetes, and neuropsychiatric abnormalities, can improve after HCV is cured . Even cancers other than HCC (ie, some B‐cell lymphomas) have been associated with persistent HCV infections and could also be prevented with successful DAA therapies …”