Hepatitis C virus infection is significantly associated with malignant lymphoma in Taiwan, particularly with nodal and splenic marginal zone lymphomas

Department of Pathology, Chi-Mei Medical Centre, Tainan, Taiwan.
Journal of clinical pathology (Impact Factor: 2.92). 07/2010; 63(7):595-8. DOI: 10.1136/jcp.2010.076810
Source: PubMed


Hepatitis C virus (HCV) is a hepatotropic and lymphotropic RNA virus causally linked to lymphoma with a strong geographic variation. The aim of this study was to investigate the association of HCV and lymphoma in Taiwan, in which HCV is endemic.
Patients diagnosed with lymphoma from January 2004 to December 2008 were investigated for serum anti-HCV, and the infection rate was compared with that in healthy controls. Various lymphoma types were investigated for HCV infection. Immunohistochemistry was performed for HCV non-structural (NS)3 protein, and genotyping was performed by reverse transcriptase PCR.
Thirty-eight (11.0%) of 346 patients with lymphoma were positive for anti-HCV, as compared with 15 (1.8%) of 824 healthy controls (p<0.001, chi(2) test) with an age-adjusted and sex-adjusted OR of 4.57 (95% CI 2.41 to 8.68). Only nodal (five of eight cases) and splenic (two of two cases) marginal zone lymphomas (MZLs) as a group were significantly associated with HCV, as compared with mucosa-associated lymphoid tissue (MALT) lymphomas (1 of 15; p=0.002, Fisher's exact test). All 26 anti-HCV-positive cases stained for HCV-NS3 were negative. The most common genotypes were 1b (22%) and 2a (56%), with no statistical difference from 203 patients with HCV-related chronic liver disease.
The incidence of HCV infection among lymphoma patients in Taiwan was significantly higher than that for healthy controls. Furthermore, non-MALT (nodal and splenic) MZL was the only group significantly associated with HCV. A larger national study is warranted to re-confirm our findings and to elucidate if any particular HCV genotypes were related to the pathogenesis of lymphoma.

9 Reads
  • Source
    Journal of clinical pathology 10/2010; 63(11):1040. DOI:10.1136/jcp.2010.082461 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis B reactivation is a serious and well-documented complication in hepatitis B carriers receiving chemotherapy. Because of high prevalence of hepatitis B in Taiwan region, our National Health Insurance has commenced subsidizing prophylactic anti-viral drugs in these chronic hepatitis B patients since October 2009. In order to clarify the impact of acute hepatitis flare on our patients, we retrospectively reviewed medical records of patients newly diagnosed with breast, colorectal and lung cancer in 2009 and fresh lymphoma patients diagnosed between 2008 and 2009 in our hospital. The incidence of acute hepatitis, screening rate of viral hepatitis marker and outcomes of these patients were analyzed. This study enrolled 913 patients, who included 142 lymphoma patients, 289 breast cancer patients, 289 colorectal cancer patients, and 193 lung cancer patients. There were 65.5% of lymphoma patients (n=93), 60.2% of breast cancer patients (n=174), 52.2% of colorectal cancer patients (n=151), and 96.9% of lung cancer patients (n=187), who received chemotherapy. Acute hepatitis was defined as elevation of alanine aminotransferase (ALT) from a normal baseline till more than 100 mg/dL, a 3-fold elevation from an abnormal baseline, or an elevated total bilirubin level to 2.0mg/dL or more. Acute hepatitis was detected in 26.9%, 6.3%, 13.9%, and 16.1% of lymphoma, breast cancer, colorectal cancer and lung cancer patients (p<0.001); in addition, the screening rates of viral hepatitis markers for hepatitis B or hepatitis C were 91.4%, 9.2%, 21.2% and 18.2% respectively (p<0.001). HBsAg-positive significantly increased the risk of acute hepatitis (p=0.027). Furthermore, acute hepatitis proved to be an independent poor prognostic factors in the multivariate analysis of overall survival (Hazard ratio 1.852; 95% of CI 1.185-2.894; p=0.007). Percentage of acute hepatitis was significantly lower in solid tumor and the screening rate of viral hepatitis markers was also lower, hence the possibility of viral hepatitis reactivation had probably been underestimated in the past. Based on the strong evidence from clinical trials and with the sponsor of the National Health Insurance system, routine screening of viral hepatitis markers in patients undergoing chemotherapy is strongly recommended for prevention of hepatitis reactivation and to avoid possible legal problems.
    Journal of Internal Medicine of Taiwan 10/2010; 21(5):350-358.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV) is one of the main causes of chronic liver disease. Although infection of hepatocytes is mainly responsible for manifestations of hepatitis C, the virus also invades the immune system by a yet-to-be-identified mechanism. Using human T cell lines and primary T lymphocytes as targets and patient-derived HCV as inocula, we aimed to identify how HCV gains entry into these cells. HCV replication was determined by detection of the HCV RNA replicative (negative) strand and viral proteins, while specific antibodies, knocking down gene expression and making otherwise-resistant cells prone to HCV, were employed to identify a receptor molecule determining T lymphocyte permissiveness to HCV infection. The results revealed that T cell susceptibility to HCV requires CD5, a lymphocyte-specific glycoprotein belonging to the scavenger receptor cysteine-rich family. Blocking of T cell CD5 with antibody or silencing with specific short hairpin RNA (shRNA) decreased cell susceptibility to HCV, while increasing CD5 expression by mitogen stimulation had the opposite effect. Moreover, transfection of naturally CD5-deficient HEK-293 fibroblasts with CD5 facilitated infection of these otherwise HCV-resistant cells. In contrast to T cells, hepatocytes do not express CD5. The data revealed that CD5 is a molecule important for HCV entry into human T lymphocytes. This finding provides direct insight into the mechanism of HCV lymphotropism and defines a target for potential interventions against HCV propagating in this extrahepatic compartment.
    Journal of Virology 01/2012; 86(7):3723-35. DOI:10.1128/JVI.06956-11 · 4.44 Impact Factor
Show more