BACKGROUND

More than 4 million people in the United States are chronically infected with hepatitis C virus (HCV) and approximately 800,000 will develop liver cirrhosis or present with several other extrahepatic conditions such as porphyria cutanea tarda, lichen planus, vitiligo, mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and bone marrow hypoplasia. Several studies with relatively small convenience samples of HCV-infected patients seen at referral centers present controversial results regarding the association between HCV infection and B-cell lymphomas.

METHODS

Using the computerized database of the Department of Veterans Affairs, Fresno, California, we carried out a cross-sectional study to examine whether B-cell non-Hodgkin’s lymphoma (NHL) and other hematologic malignancies might be associated with chronic HCV infection. We examined all cases of chronic HCV infected patients (n=992) diagnosed between 1991 and 2004 and randomly matched control subjects HCV naïve (n=1,929).

Demographic Distribuition

Cases (n=992)Controls (n=1,929)
Alive at enrollment 880 (88.7%) 1,761 (91.3%) 
Age (years) 53.13 53.14 
gender (male) 869 (98.8%) 1,725 (98%) 
Period of military service (Vietnam Era) 578 (66%) 1,149 (62%) 
Exposure to Agent Orange 12 (2%) 35 (2%) 
Cases (n=992)Controls (n=1,929)
Alive at enrollment 880 (88.7%) 1,761 (91.3%) 
Age (years) 53.13 53.14 
gender (male) 869 (98.8%) 1,725 (98%) 
Period of military service (Vietnam Era) 578 (66%) 1,149 (62%) 
Exposure to Agent Orange 12 (2%) 35 (2%) 
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RESULTS

An increased prevalence of hematologic malignancies was found among the chronic HCV infected patients compared to the control group with an odds ratio (OR) of 3.4 (95% confidence interval [95%CI]=1.4–10, p=0.009). The prevalence of NHL (OR=4.2, 95%CI=0.7–22, p=0.1), Hodgkin’s lymphoma (p=0.1), myeloproliferative disorders (OR=4.2, 95%CI=0.7–22, p=0.1), myelodysplastic syndrome (p=0.6) and myeloma (p=0.3) was each independently statistically not significant. The chronic HCV infected group showed a prevalence of 2% for hepatocellular carcinoma (p<0.0001) and had a significantly higher rate of HIV co-infection compared to the control group (OR=6, 95%CI=3–13, p<0.0001). However, none of the chronic HCV and HIV co-infected patients presented a concomitant hematologic malignancy. The overall mortality rate in the chronic HCV infected patients was 11.3% and of the control group 8.7% (OR=1.3, 95%CI=1–1.7, p=0.028). Patients with chronic HCV infection died significantly earlier (mean age 56.7 years) compared to the subjects in the control group (mean age 63.5 years) (p<0.0001).

Chronic HCV Infection and Hematologic Malignancies

Cases n=880 (%, 95%CI)Controls n=1,761 (%, 95%CI)OR95%CIp
NHL 4 (0.5%, 0.2–1.2) 2 (0.1%, 0.04–0.4) 4.2 0.7–22 0.1 
Hodgkin’s lymphoma 2 (0.3%, 0.07–0.8) 0 (0%, 0.001–0.2) - - 0.1 
Myeloproliferative disorders 4 (0.5%, 0.2–1.2) 2 (0.1%, 0.04–0.4) 4.2 0.7–22 0.1 
Myelodysplastic syndromes 0 (0%, 0.003–0.4) 2 (0.1%, 0.04–0.4) - - 0.6 
Multiple Myeloma 1 (0.1%, 0.03–0.6) 0 (0%, 0.001–0.2) - - 0.3 
Overall Hematologic Malignancies 11 (1.3%, 0.7–2.2) 6 (0.34%, 0.2–0.7) 3.4 1.4–10 0.009 
Cases n=880 (%, 95%CI)Controls n=1,761 (%, 95%CI)OR95%CIp
NHL 4 (0.5%, 0.2–1.2) 2 (0.1%, 0.04–0.4) 4.2 0.7–22 0.1 
Hodgkin’s lymphoma 2 (0.3%, 0.07–0.8) 0 (0%, 0.001–0.2) - - 0.1 
Myeloproliferative disorders 4 (0.5%, 0.2–1.2) 2 (0.1%, 0.04–0.4) 4.2 0.7–22 0.1 
Myelodysplastic syndromes 0 (0%, 0.003–0.4) 2 (0.1%, 0.04–0.4) - - 0.6 
Multiple Myeloma 1 (0.1%, 0.03–0.6) 0 (0%, 0.001–0.2) - - 0.3 
Overall Hematologic Malignancies 11 (1.3%, 0.7–2.2) 6 (0.34%, 0.2–0.7) 3.4 1.4–10 0.009 
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CONCLUSIONS

We report the prevalence of several hematologic malignancies in chronic HCV-infected veterans. Our study suggests that chronic HCV infection is a significant risk factor for lymphatic and stem-cell malignancies. Further larger studies are required to confirm this finding.

Topics:
hematologic neoplasms, hepatitis c, chronic, infections, b-cell lymphomas, hodgkin's disease, multiple myeloma, myelodysplastic syndrome, myeloproliferative disease, agent orange, bone marrow, hypocellular

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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