Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution

OBJECTIVES: HIV-related enhancement of gut microbial translocation is associated with progression of hepatic fibrosis. Although hepatic macrophages (Kupffer cells) clear most microbial translocation products and can be infected by HIV, their fate in HIV progression has not been carefully investigated. METHODS: We studied Kupffer cell density (KCD) in 76 HIV-hepatitis C virus coinfected patients investigated at various stages of liver disease and CD4 lymphocyte depletion (and restoration). RESULTS: KCD averaged 23 cells per high-powered field (range 4.4-52.2) and was highest in portal and periportal regions as compared with centrilobular regions (P < 0.001). No differences were detected in KCD by age, liver fibrosis stage, or hepatic inflammatory score. Compared with individuals without apparent HIV-related immunosuppression, however, KCD was substantially lower in persons with lower peripheral blood CD4 lymphocyte counts (P = 0.027) and lowest among those with deepest CD4 lymphocyte nadir (P = 0.006). After the initial liver biopsy, eight patients began antiretroviral therapy and had immune restoration (≥2-fold increase in peripheral CD4 lymphocyte count) and a second histologic evaluation with a median of 36.8 months later (range 28.1-58.4 months); KCD increased in all (P = 0.007). CONCLUSION: Given the central role of Kupffer cells in controlling microbial translocation, these data suggest Kupffer cell loss needs to be considered in the pathogenesis of liver fibrosis in HIV-hepatitis C virus coinfected persons. The abundance of portal and periportal Kupffer cells is suggestive of their contribution to fibrosis in periportal regions in chronic viral hepatitis.