137
8.3.2 HCV Infection and Non-Hodgkin Lymphoma (NHL)
Although there is a low incidence of HCV infection (about 2.5%) in non-Hodgkin
lymphoma (NHL) patients [ 101 ], chronic HCV infection is associated with B-cell
non-Hodgkin lymphoma (B-NHL) as HCV eradication by antiviral therapy induces
B-NHL regression, suggesting a causal relationship between HCV infection and
lymphoma development [ 102 ]. HCV MC may represent an antigen-driven B-cell
proliferation that occasionally develops NHL [ 100 ]. The molecular mechanism of
HCV-induced lymphomagenesis may include continuous stimulation of lympho-
cyte receptors by viral antigens, viral replication in B cells, and permanent B-cell
damage [ 102 ].
HCV glycoprotein E2 binds the CD81 for virus entry [ 103 ]. HCV may bindsimultaneously to CD81 and a specific B-cell receptor (BCR) on B cells to trigger
B-cell activation and proliferation. Although there are reports to show no binding
ability of lymphoma BCRs from B-NHL patients to HCV antigens [ 104 ], chronic
viral antigen stimulation may play an import role in aberrant B-cell proliferation.
Expression of HCV viral proteins in B cells from HCV-infected patients upregulates
BCR signaling. HCV nonstructural protein NS3/4A modulates HuR-mediated post-
transcriptional regulation of a network of mRNAs that is associated with B-cell
lymphoproliferative disorders [ 105 ]. The pro-inflammatory cytokines such as IL-6
and some chemokines may also contribute to aberrant B-cell proliferation [ 106 ].
HCV infection in B cells is controversial. A B-cell line (SB) from a HCV-infected B-NHL patient supports HCV replication and produces HCV virions.
Epstein-Barr virus-immortalized B-cell lines from PBMCs of HCV-positive
patients are positive for HCV RNA and protein, suggesting HCV infection in B
cells [ 107 ]. Using a cell- cultured HCV, Marukian et al. did not observe HCV infection
in peripheral blood mononuclear cells (PBMC), and PBMC is unlikely to support
HCV viral translation [ 108 ].
8.4 Effect of Anti-HCV Treatment on HCC Occurrence
and Recurrence
8.4.1 Anti-HCV Treatment with Interferon (IFN)
Before the emergence of direct-acting antivirals before 2011, interferon (IFN)-
based therapies are the standard treatment for HCV. The endpoint of treatment is a
6-month-long sustained virological response (SVR) after drug withdrawal. SVR is
defined by undetectable HCV RNA below 10–15 international units [IU]/ml.
Administration of a combination of pegylated IFN-α with ribavirin for 24 or
48 weeks yielded viral eradication in approximately 80% patients infected with
HCV genotypes 2 and 3 or 40–50% of patients infected with HCV genotype 1
[ 109 ]. Probably due to the relative low efficacy of IFN therapy, a decreased
8 HCV-Associated Cancers