Impact of Human Immunodeficiency Infection on Incidence of Autoimmmune Hemolytic Anemia (AIHA) in Patients with Hepatitis C; Correlation the Genotype of Hepatitis C Virus and AIHA
Authors: Patsiornik Yelena , Nesa Mushammat , Foss Scott , Bernstein Michael , Burton Jack 
Published: April 2020

Abstract
Background: Autoimmune hematologic abnormalities are frequent among patients with chronic hepatitis C, possibly related to the lymphotropic nature of hepatitis C virus (HCV). It is generally accepted that B-cells infected with HCV clonally expand and produce autoantibodies, which can explain the high prevalence of serological markers of autoimmunity in patients with chronic HCV infection. We recently reported significantly higher incidence of autoantibodies to RBCs and autoimmune hemolytic anemia (AIHA) in patients with HCV as compared to healthy blood donors. Human immunodeficiency virus (HIV) infection is associated with numerous hematologic manifestations. A review of current literature review indicates that a positive direct antiglobulin test (DAT) has been observed in 20% to 40% patients with clinical AIDS. Overt AIHA in patients with AIDS is rare, but can be lethal due to the lack of adequate bone marrow reserve. Many of these patients are also co-infected with HCV, which tends to make immunologic dysregulation more pronounced. Our current analysis of 68 patients, who are positive for both HIV and HCV showed a higher incidence of RBC autoantibodies and clinical AIHA, compared with patients with hepatitis C or HIV/AIDS only. We hypothesized that patients with coinfection with hepatitis C and HIV with anemia would have a higher incidence of AIHA and, thus, would benefit from DAT testing at baseline to detect potentially severe AIHA.
Patients and Method: To test this hypothesis, we conducted a retrospective study to confirm that HCV infection in patients with HIV significantly increases the risk of AIHA. A group of 1056 patients with hepatitis C from our hospital’s database from July 2004 to December 2007 was studied. Of this group, 99 patients were co-infected with HCV and HIV. We also looked for an association, if any, of HCV genotype and clinically significant AIHA.
Result: Our data showed that AIHA was diagnosed in 9/1056 patients with hepatitis C. Out of this group 6 (0.57%) patients had hepatitis C infection only and 3 (0.3%) patients had co-infection with HCV and HIV. The Z-test was applied to these data from the two groups (HCV+ and HCV+/HIV+) to determine if they were significantly different from one another. The Z-value was determined to be 2.064, with 1-tail confidence level of 98% and 2-tail confidence level of 96.1%, which gives a P value of 0.039 and 0.02, respectively, for the HepC/HIV co-infected group compared with the group of patients infected with HepC only. However, no association between AIHA and particular HCV genotype was noted.
Conclusions: Our results indicate that patients with hepatitis C have a relatively high incidence of AIHA, which is even higher in patients concurrently infected with HIV. No particular genotype of HCV was associated with AIHA. In a view of the potential clinical severity of this condition, there needs to be a high degree of clinical suspicion for possible AIHA in patients with co-infection with hepatitis C and HIV.