SEN Virus Infection in Egyptian Patients With Chronic Hepatitis C and Patients Undergoing Hemodialysis

Maisa Omar, PhD; Samah Saad El-Din, PhD; Nevine Fam, MD; Manal Diab, MD; Mohamed Shemis, PhD; Manar Raafat, MD; Moataz Seyam, MD; Moataz Hssan, MD; Afkar Badawy, PhD; Maha Akl, PhD; Mohamed Saber, PhD

Disclosures

Medscape J Med. 2008;10(12):290 

In This Article

Discussion

The clinical relevance of SEN virus infection alone or in combination with HCV infection remains controversial. Given the high incidence of HCV in Egypt (10%-13%),[22] we investigated the prevalence and clinical effect of SEN virus on coexistent HCV infection. We also determined the prevalence of SEN virus among patients undergoing hemodialysis, a group at high risk of being infected with parenterally transmitted viruses.

Infection with SEN virus has been observed in 22% to 85% of patients with chronic hepatitis C[7,12,13,14] and in 27% to 61% of uremic patients undergoing maintenance hemodialysis.[16,23,24,25] We found that the prevalence of SEN virus infection was 13.5% in patients with chronic HCV infection and 11.1% in patients undergoing hemodialysis; these rates were similar to that in healthy controls. The observed differences in the prevalence of SEN virus DNA between our patients and those in previous studies may be attributed to different routes of transmission, such as injection-drug use, or to the use of slightly different primers.[26] The low prevalence of SEN virus infection relative to HCV infection may be attributed to the rate of clearance of the SEN virus. Umemura and colleagues[1] found that about 77% of posttransfusion infected patients cleared the virus within 6 months after being infected and that 13% appeared to have chronic SEN virus infection.

Dual infection with HCV and either hepatitis A or hepatitis B virus has been associated with a more and rapidly progressive disease.[27] In contrast, in our study, clinical and biochemical evaluations of patients with chronic liver disease and patients undergoing hemodialysis did not significantly differ between those infected with HCV alone and those coinfected with HCV and SEN virus. In this and previous studies,[13,28,29,30] no evidence suggests that SEN virus causes hepatitis when it is the sole agent detected, or worsens the severity or persistence of coexistent chronic HCV. In the present study, coinfection with TTV and hepatitis G virus were detected in 30% and 10% of SEN virus-infected patients, respectively. However, the distribution of TTV or hepatitis G virus did not significantly differ between SEN virus-infected and noninfected patients. Previous studies done in our laboratory found that neither virus was causally associated with chronic liver disease or hepatocellular carcinoma.[31,32] Some authors have suggested a specific link between HCV genotypes 2a and 1b and coinfection with SEN virus among patients with chronic HCV.[14,33] In the present study, the association of SEN virus with HCV serotype 4 may be attributed to the high prevalence of this serotype in Egypt (>90%).[34]

The influence of coinfection with SEN virus on HCV response to combination therapy has been investigated, with contradictory results. Rigas and colleagues [35] reported that coinfection with SEN virus might adversely affect the outcome of combination therapy. However, other studies found that HCV response was not affected by the presence of SEN virus and recorded a significantly higher rate of SEN virus response to combination therapy than the response of HCV.[14,29,33] We could not judge this influence because SEN virus DNA was detected in only 1 patient before receipt of combination therapy. However, clearance of both HCV RNA and SEN virus DNA was observed after 12 weeks of treatment. Additional studies using a large number of patients are required to confirm this finding and to document the duration of response and rate of spontaneous clearance of this virus over time.

Most cases of hepatocellular carcinoma are associated with chronic infection with hepatitis B virus or HCV.[36] In the present study, the prevalence of SEN virus infection was significantly higher in patients with chronic liver disease and hepatocellular carcinoma than in those with chronic liver disease only. This finding may suggest a possible role of SEN virus as a cofactor in the development of hepatocellular carcinoma. However, clinical and virologic measures did not significantly differ between patients with hepatocellular carcinoma who were SEN virus infected and those who were not infected. High prevalence of SEN virus infection among patients with hepatocellular carcinoma may be attributed to increased risk for exposure as a result of multiple medical or radiologic interventions, in addition to the decreased rate of spontaneous clearance due to immunosuppression.[37,38] Whether coexistent SEN virus infection has a role in the etiology of HCV-related hepatocellular carcinoma or is just an innocent bystander requires further investigation.

We found that SEN virus DNA was detected in 7.1% of healthy volunteers, a rate similar to that previously reported in Thailand, Turkey, and Japan (range, 5%-10%)[9,12,30] but higher than that in the United States and Italy (range, 2%-3%)[39,40] and lower than that in China (31%).[7] These data suggest that SEN virus has a global distribution with marked geographic differences in its prevalence. The explanations for these differences are unknown, but they may result from interactions among behavioral, social and biological factors.[41]

Geographic distribution of different SEN virus variants was also noted. Previous studies have shown that SEN virus-D is the predominant genotype in Japan and Greece,[42,43] whereas SEN virus-H genotype is predominant in the United States and Taiwan.[1,8] Our results indicated that SEN virus-D is more prevalent than SEN virus-H among Egyptian patients and healthy controls. This variability in the prevalence of different genotypes may be attributed to different exposure rates or routes of infection or to differing rates of spontaneous clearance between these two strains.[33] Whether differences in SEN virus variants affect the heterogeneity in clinical outcome or response to antiviral therapy in patients with chronic SEN virus infection requires further study.

Previous studies strongly suggest that SEN virus is transmitted through blood transfusion.[1,14,44] However, our results indicate that SEN virus was not absolutely associated with a history of blood transfusion or duration of hemodialysis. In addition, no statistically significant differences were observed for the distribution of HCV or hepatitis B virus (well-known blood-borne viruses) between SEN virus-infected and noninfected hemodialysis patients. A possible explanation is that SEN virus can be transmitted through not only parenteral but also nonparenteral routes. This possibility is supported by the finding that TTV, which is distantly related to SEN virus, can also be transmitted through the fecal-oral route.[45] Recent data suggest that vertical transmission of SEN virus does occur, presumably at delivery, but that it may not induce persistent viremia.[46] Further epidemiologic studies on larger groups of SEN virus-infected patients are recommended.

In conclusion, SEN virus does not seem to be a common infection in Egyptian patients. It has no apparent influence on the severity of coexistent HCV-related chronic liver disease, but it may have a role in the development of hepatocellular carcinoma in these patients. SEN virus is probably transmitted via parenteral and nonparenteral routes. Further studies are needed to define the pathogenic and clinical importance of SEN virus infection.

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