GBV-C Infection and Risk of NHL among U.S. Adults

Abstract

Some retrospective studies suggest an association between infection with GB-virus C (GBV-C) and non-Hodgkin lymphoma (NHL). We evaluated this association prospectively in a nested case-control study within the U.S. Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Cases (N=658) and controls (N=1,316) were individually-matched by age, sex, race/ethnicity, timing of study entry and sample selection. Pre-diagnostic PLCO serum samples were tested for GBV-C RNA (as a measure of active infection) and E2 antibody (active or resolved infection). Logistic regression was used to estimate odds ratios (ORs) for the association between GBV-C and NHL overall and NHL subtypes. Twelve cases (1.8%) and 7 controls (0.5%) were GBV-C RNA positive. GBV-C RNA positivity was associated with NHL overall (OR=3.43, 95% CI=1.35-8.71) and, based on small numbers, diffuse large B-cell lymphoma (OR=5.31, 95% CI=1.54-18.36). The association with NHL persisted when the interval between testing and selection was greater than 4 years (OR=6.00, 95% CI= 1.21-29.73). In contrast, E2 antibody-positivity was not associated with NHL risk (OR=1.08, 95% CI=0.74-1.58). Our study demonstrates that GBV-C infection precedes development of NHL. GBV-C infection may play an etiologic role in a small proportion of NHL cases, perhaps by causing chronic immune stimulation or impaired immunosurveillance.

Cytokine/chemokine expression associated with Human Pegivirus (HPgV) infection in women with HIV

“…The viral genome consists of a single open reading frame (ORF) of ∼3000 amino acids that encodes for multiple structural and non‐structural genes. Most investigations have failed to demonstrate any pathogenic consequence of HPgV replication on human disease reviewed in reference although it may be weakly associated with non‐Hodgkin lymphoma . HPgV is transmitted efficiently via intravenous and sexual routes, and the prevalence varies widely based on geographic location and the population studied.…”

“…There was no conclusive evidence for an association between survival and HPgV infection early in HIV disease; however, there was a significant reduction in mortality when HPgV infection was present later in HIV disease. Clearance of HPgV viremia is associated with accelerated HIV disease compared to non‐clearance …”

Characterization of human pegivirus infection in liver transplantation recipients

“…Previous studies showed that HPgV is not hepatotropic, but rather lymphotropic . In several studies, the correlation of HPgV infection with lymphoma has been reported . To note, HPgV infection is a risk factor of lymphoma, especially non‐Hodgkin's lymphoma, as demonstrated in a large‐scale study …”

Human pegivirus (HPgV) infection in sub‐Saharan Africa—A call for a renewed research agenda

“…Following its discovery, multiple studies evaluated the possible association of HPgV infection with a variety of clinical diseases. While a weak association between HPgV infection and non‐Hodgkin's lymphoma has been reported recently, all other studies found no causal link between HPgV infection and any clinical disease . In contrast, several studies reported that HPgV infection is associated with delayed HIV disease progression .…”