Hepatitis C Virus Infection In Non-Hodgkin’s Lymphoma: A Case Control Study

Hepatitis C Virus Infection In Non-Hodgkin’s Lymphoma: A Case Control Study

[ID:1491, in press, available in 2012][DOI: 10.5812/kowsar.1735143X.801]
Authors: Muhammad SK,Chandio MA, Soomro MA, Shaikh BA
Correspondence:
Shaikh Khalid Muhammad

Abstract:

Background:
Hepatitis C virus (HCV) is the most common cause of chronic liver disease in Pakistan{%1%} Globally an estimated 170 million persons are infected with HCV and around 3-4 million are newly infected each year with HCV {%2%}{%3%} Currently the prevalence of HCV in Pakistan is 4-7%.{%4%}{%5%}{%6%}HCV is a hepatotropic virus, causing chronic hepatitis in at least 80% of infected with it. If left untreated, 20-30% will eventually develop Cirrhosis with average latency of 15-25 years and Hepato-Cellular Carcinoma at rate of 1-5% per year with average latency of 20-30 years. {%3%}{%7%}.

Objectives: To determine the association between hepatitis C virus (HCV) infection and Non-Hodgkin's Lymphoma (NHL).

Methods & Materials: This 2 year case control study was started on 1st January 2009. 292 cases of NHL underwent staging according to Ann Arbor staging and were graded according to working formulation classification. Blood samples from 292 NHL cases and 1168 age and sex matched controls (2 groups) meeting our selection criteria, were sent for detection of anti-HCV Ab on ELISA. Chi-square test was applied to compare anti-HCV Ab seropositivity in cases and controls and odd ratios were computed. NHL cases were divided in anti-HCV Ab seronegative and seropositive groups to compare the effect of anti-HCV Ab seropositivity on stage and grades of NHL. P value of 0.05 was taken as statistically significant.

Results: 52 (17.8%) cases, 45 (7.7%) controls in group 1(10 Relatives) and 50 (8.6%) controls in group 2 (Non Hematological Malignancy) were anti-HCV Ab positive, with odd ratios of 2.59 (95%CI: 1.69 - 3.97) for group 1 and 2.31 (95%CI: 1.52 - 3.50) for group 2 with P value of 0.000 for both. Anti-HCV Ab positive NHL cases were more likely to be in middle age (40-60years) with odds of 3.68 (95%CI: 2.07 - 6.50). There was no significant effect of anti-HCV Ab seropositivity on grades and stages of NHL.

Conclusion: NHL is strongly associated with Anti-HCV Ab seropositivity, with 2 to 2.5 odd risk and seropositive cases tend to be in middle and young age.

Keywords: Hepatitis C Virus (HCV); Hepatitis C Antibodies; Association; Lymphoma, Non-Hodgkin (NHL).

Discussion Only
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This was first study conducted in Pakistan to observe the association between HCV and NHL and to observe the impact of anti-HCV Ab seropositivity on the stages and grades of NHL. In our study, we excluded NHL patients who had experienced exposure to any known risk factor for lymphoma development such as irradiation exposure, HIV infection, HBV infection, exposure to cytotoxic or immunosuppressive drugs, autoimmune disorders, and connective tissue disorders. We also excluded patients with a history of transfusion or parenteral medication or surgical procedures in the last 6 months as well as known patients with hemophilia or thalassemias since these disorders may falsely elevate the number of patients in the anti-HCV Ab-positive group. After exclusion, a total of 292 patients were enrolled in our study. For the cases, we used age- and sex-matched controls.
Advantages in selecting 1st degree relatives as control group 1 were that the relative belonged to the same locality of origin, experienced the same environmental factors, and had a genetic makeup similar to that of the patient.

Control group 2 consisted of patients with non-hematological malignancy and was used to compute the odds of NHL n HCV, as compared to other non-hematological malignancies. In our study, we identified statistically significant (P <0.000) odds ratio values for HCV in NHL patients. The HCV-infected NHL patients were younger (P < 0.000) than the non-infected individuals, but the risk was higher in young (< 20 years) and middle-aged (40–60 years) patients. There was no significant impact of HCV seropositivity on the stages and grades of NHL. Similar results were reported by researchers in Egypt and Saudi Arabia. In Egypt, Cowgill et al. (30) observed a significant association between NHL and HCV, but they did not evaluate the impact of HCV infection on the stages and grades of NHL. HCV infection in NHL patients is reportedly independent of age. Polymerase chain reaction, which was used in a previous study, was better than ELISA for the detection of HCV infection. In Saudi Arabia, Harakati et al. (31) reported that HCV-infected NHL patients were more likely to have intermediate-grade NHL than non-infected patients. Researchers in Europe also documented a similar association between NHL and HCV infection, but few studies have been conducted to evaluate the impact of the stages and grades of NHL in detail. Mele et al. (32) documented a strong association and concluded that in Italy, 1 of 20 instances of B-NHL may be attributable to HCV infection, and thus, the patients may benefit from antiviral treatment. In Turkey, Isikdogan et al. (33) observed that HCV-seropositive NHL patients were more likely to have intermediate-grade NHL. In France, Seve et al. (34) documented a positive but non-significant trend
towards an association between NHL and HCV infection (odds ratio, 1.31; 95% CI, 0.51–3.36). In Spain, De Sanjose et al. (35) found no significant difference in HCV seropositivity between nodal and extranodal NHL cases.

Similar to our study, all these studies reported a positive association between NHL and HCV. A Spanish study reported results similar to those of our study regarding the impact on the grades of NHL, but a Turkish study reported contradictory results. Studies performed in other countries have also reported a strong association between HCV and NHL. Spinelli et al. (36) in Canada, Takeshita et al. (37) in Japan, Masami et al. (38) and Nieters et al. (39) in a European multicenter case-control study (EPILYMPH), and El-Sayed et al. (40) in Egypt also reported similar results.


Most of these studies did not examine the impact of HCV seropositivity on the stages, grades, and B symptoms of NHL. Our study not only studied the association between NHL and HCV but also examined its impact on the stages and grades of NHL. In addition, this was the first study performed in Pakistan on this issue. The literature supports the concept that hepatitis C and NHL are associated.
However, limited studies have been conducted in Pakistan to explore this issue. The incidences of these disorders are currently increasing. The primary reasons for increase in HCV infections in developing countries such as Pakistan include poverty, lack of public awareness, non-availability of vaccines, and lack of health care facilities. Furthermore, the incidence of NHL is also increasing
at a rate of 1–4% per year. This association of HCV with NHL may put the public at risk of an NHL epidemic, particularly in developing countries such as Pakistan. This may ultimately result in decreased life expectancy and loss of young people in developing nations.

In conclusion, HCV infection is strongly associated with NHL. HCV was 2–3 times more prevalent in NHL patients than in the controls. HCV infection in NHL patients was more frequently observed in young and middle-aged subjects. No statistically significant impact was observed regarding anti-HCV Ab seropositivity on the stages and grades of NHL.

On the basis of our results, larger epidemiological studies can be conducted. Our study results also provide information for health policy and decision makers that can be used to control a combined epidemic.

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