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Hepatitis C and Non-Hodgkin’s Lymphoma: An Association Clarified
Abstract & Commentary
Synopsis: In this multicenter Italian study the prevalence of hepatitis C infection (HCV) was 17.5% among 400 newly diagnosed non-Hodgkin’s lymphoma patients compared to 5.6% among controls, confirming an association between these 2 disorders. The suggestion is made that such patients should be studied to both determine the role of the HCV in the pathogenesis of lymphoma and to determine the effects of antiviral therapy on lymphoma progression.
Source: Mele A, et al. Blood. 2003;102:996-999.
Hepatitis C virus (HCV) remains a major cause of chronic liver disease throughout the world and an association with non-Hodgkin’s lymphoma (NHL) has been described.1,2 It has been proposed that hepatitis C may be involved in the pathogenesis of the lymphoma in those patients who have been shown to have both illnesses. If such were the case, then one might expect to see evidence for HVC greater in patients with lymphoma than in the general population. Indeed, a positive association has been found in studies conducted in countries where the prevalence of HCV infection is relatively high (eg, Italy, United States) but not in other countries).
The objective of the current study performed throughout Italy was to evaluate the potential association between B-cell NHL and HCV. A multicenter, case-controlled study was undertaken including only patients with newly diagnosed B-cell NHL. From January 1998 through February, 2001 all new cases of NHL were catalogued. Control patients were individuals from other departments within the same hospitals. Both groups were interviewed, and the prevalence of HCV infection was calculated. Adjusted odds ratio (OR) and HCV-attributable risk (AR) were estimated.
HCV prevalence was 17.5% among the 400 lymphoma patients and 5.6% among the 396 controls. The adjusted odds ratio of NHL (patients vs controls), adjusted by age, sex, level of education, and place of birth was 3.1 (95% confidence interval, 1.8-5.2), and OR indicative of positive association was found for indolent and aggressive B-cell NHL. The estimated AR was 4.6%.
This study confirms an association between HCV and B-cell NHL. In Italy, where the incidence of HCV is considered high, comparable to that in the United States, 1 of 20 B-cell non-Hodgkin lymphoma patients may have coexisting hepatitis C infection. The authors speculate that this may turn out to be useful information inasmuch as antiviral therapy may be important in the management of both the HCV infection and lymphoma in these patients.
Comment by William B. Ershler, MD
The current cooperative investigation has the merits of evaluating only new cases of NHL over a relatively short period of time throughout a country (Italy) in which HCV is known to be fairly prevalent. The findings demonstrate, without a doubt, an association of HCV and lymphoma. In fact, patients with newly diagnosed NHLs were found to be 3.1 times more likely to be infected with HCV than controls. Also of note, the increased risk of HCV infection was observed for both aggressive and nonaggressive lymphoma histologies. Furthermore, there did not seem to be a difference in the hepatitis C genotypes (1b, 2a/2c) when compared to the prevalence of these genotypes in the general Italian community. This would suggest that the association of lymphoma with HCV infection is not genotype specific.
Mele et al were very careful to match, as best possible, the controls (hospitalized patients without lymphoma) with patients. When adjustments were made for age, sex, level of education, place of birth, and other possible confounders, the observed risk of HCV infection remained significantly greater for NHL patients than controls.
This finding warrants consideration and additional investigation. Recently it has been reported that patients with HCV and splenic lymphoma had regression of disease when treated with interferon and Ribavirin, the standard approach for HCV infection.3 Accordingly, as has been the case in other virally associated lymphomas, such as those that occur in the transplant setting, therapeutic trials of antivirals may prove useful in the management of the lymphoproliferative disorder. Clearly, this approach needs to be subjected to rigorous clinical investigation.
Dr. Ershler is INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.
1. Pozzato G, et al. Blood. 1994;84:3047-3053.
2. Ferri C, et al. Br J Haematol. 1994;88:392-394.
3. Hermine O, et al. N Engl J Med. 2002;347:89-94.