We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.