Risk of Non-Hodgkin's Lymphoma in HCV Patients in the United States Between 2013 and 2020: A Population-Based Study

Abstract

An association between non-Hodgkin's lymphoma (NHL) and hepatitis C virus (HCV) was recognized two decades ago with no recent studies. We studied database (Explorys, IBM) which includes records of over 72 million patients. Between June 2013 and June 2020, HCV-positive and HCV-negative populations were compared. NHL's risk in HCV positive group was higher than previously reported, with an odds ratio of 2.6. Hepatitis C virus (HCV) is a significant healthcare problem affecting ˜1% of the United States population. Meta-analyses of epidemiological studies reported a strong association between non-Hodgkin's lymphoma (NHL) and HCV. Direct oncogenic properties of HCV proteins and chronic antigenic stimulation are possible etiologies. We explored if NHL's prevalence has changed since older HCV therapy based on interferon that shared antiviral and anti-lymphoma properties was replaced with interferon-free direct-acting antivirals (DAA). We reviewed data from a nationwide database (Explorys, IBM) that aggregates records from 26 health-care-systems. We identified patients with chronic hepatitis C infection between June 2013 and June 2020. The control group was gender, race, and age-matched HCV-negative population. Statistical analysis used the odds ratio (OR) with P value < .001 for significance. There were 940 cases of NHL of 129,970 patients in the HCV group versus 107,480 cases of NHL of 37,961,970 in the control cohort [OR 2.6, 95% confidence interval (CI) 2.4-2.7]. A positive association was present for chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, non-Hodgkin T-cell lymphoma, and primary cutaneous T-cell lymphoma. There were no differences in Mantle cell lymphoma. The increased risk of HCV-associated lymphoma was persistent across genders, Caucasians and Afr ican-Amer icans, and age groups. While the risk of NHL in the HCV-negative population was higher in Caucasians than Afr ican-Amer icans (OR 1.8, 95% CI 1.7-1.8), the risk of HCV-associated NHL was not different. Further prospective studies examining the risk of HCV-associated lymphoma following DAA are warranted.

Chronic hepatitis C infection is associated with higher incidence of extrahepatic cancers in a Canadian population based cohort

“…As with previous studies, including two large population-based case-control and cohort studies conducted in the USA and Denmark, we observed elevated incidence of pancreatic cancer, kidney cancer, lung cancer, and oropharyngeal cancer among people living with HCV infection ( 9 , 25 – 30 ). Among extrahepatic cancers, NHL has been reported to have the strongest association with chronic HCV infection ( 28 , 31 , 32 ). Higher proportions of problematic alcohol consumption, injection drug use, and comorbid medical conditions among individuals living with chronic HCV could partly explain the greater incidence of alcohol and/or tobacco-related cancers, namely oral, larynx, esophagus, lung, kidney, and pancreatic cancers in our cohort ( Table 1 ) ( 27 ).…”

“…Biological mechanisms underlying elevated risks of extrahepatic cancers among individuals living with HCV infection are not well-understood; for NHL, the process seems to involve direct and indirect oncogenic expressions of HCV proteins (e.g., E2) which causes lymphoproliferative disorders such as B-cell continuous replication ( 32 , 35 – 37 ). Chronic kidney disease and oral lichen planus are known HCV-related extrahepatic manifestations which may correspondingly increase the risks of renal and oral cancers among people with HCV infection ( 35 – 37 ).…”

Acute myeloid leukaemia following direct acting antiviral drugs in HCV-infected patients: A 10 years’ retrospective single-center study

“…Aside from liver transplantation, chronic hepatitis C infection is also known to be associated with an increased risk of developing HM predominantly of B-cell type but not AML, whatever the level of liver fibrosis (4,11,12,19). The underlying pathogenesis is most likely the chronic and continuous antigen stimulation leading to a permanent B-cell response with subsequent genetic mutation and finally clonal and malignant B-cell proliferations (20).…”

Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection

“…They also reported that the increased risk of HCV-associated lymphoma was persistent across genders, between Caucasians and African-Americans, and across age groups. While the risk of NHL in the HCV-negative population was higher in Caucasians than African-Americans (OR 1.8, 95% CI 1.7-1.8), the risk of HCV-associated NHL was not different [43]. The researchers also found that there were few cases of NHL in patients under 40 years of age.…”