The impact of cirrhosis on CD4⁺ T cell counts in HIV-seronegative patients

Background. Studies of the progression liver fibrosis in human immunodeficiency virus (HIV) and hepatitis C virus-coinfected patients suggest that cirrhosis is associated with immunosuppression, as measured by low absolute CD4⁺ T cell counts. However, we hypothesized that, in patients with advanced liver disease, low CD4⁺ T cell counts may occur secondary to portal hypertension and splenic sequestration, regardless of the presence or absence of HIV infection. Methods. Sixty HIV-seronegative outpatients with cirrhosis were enrolled during the period 2001-2003 in a prospective, cross-sectional study of the association between liver disease and CD4 ⁺ T cell counts and percentages. Demographic characteristics, liver disease-related characteristics, and laboratory results-including CD4 ⁺ T cell parameters-were collected. Results. A total of 39 patients (65%) had a low CD4⁺ T cell count; 26 patients (43%) and 4 patients (7%) had CD4⁺ T cell counts <350 and <200 cells/mm³, respectively. Abnormal CD4⁺ T cell counts were associated with splenomegaly (P = .03), thrombocytopenia (P = .002), and leukopenia (P < .001). The percentage of CD4⁺ T cells was normal in 95% of patients who had a low absolute CD4⁺ T cell count. CD4⁺ T cell counts were significantly lower among cirrhotic patients than among 7638 HIV-seronegative historic control subjects without liver disease. Conclusions. Cirrhosis is associated with low CD4⁺ T cell counts in the absence of HIV infection. Discordance between low absolute CD4⁺ T cell counts and normal CD4⁺ T cell percentages may be attributable to portal hypertension and splenic sequestration. Our findings have significant implications for the use and interpretation of absolute CD4⁺ T cell counts in HIV-infected patients with advanced liver disease.