Elevated TGF‐β1 levels might protect HCV/ HIV‐coinfected patients from liver fibrosis

Abstract

HIV accelerates hepatitis C virus (HCV)-induced liver fibrosis by mechanisms not well understood. As HIV dysregulates transforming growth factor-β1 (TGF-β1) and T regulatory (Treg) cells, both of which are involved in hepatic fibrogenesis, herein we describe their influence on liver fibrosis staging in patients with chronic hepatitis C with and without HIV coinfection. Eighty-eight subjects (42 HIV/HCV co-infected patients, 20 HCV-monoinfected patients, and 26 healthy controls) were examined. Treg cells (CD4+Foxp3+) were measured in peripheral blood using flow cytometry. An enzyme immunoassay was used to measure TGF-β1 in plasma. Liver fibrosis staging was estimated using elastometry and advanced liver fibrosis was considered for ≥ 9·5 kPa (F3-F4 Metavir estimates). Treg cells were increased in HIV/HCV-coinfected patients compared with HCV-monoinfected patients (P = 0·004), whereas TGF-β1 levels were similar in both groups of patients. While Treg cells levels were similar in both null-mild and advanced liver fibrosis patients, a high level of TGF-β1 was found in patients with low levels of liver fibrosis compared with those with advanced liver fibrosis [14·9 ng mL(-1) (5·6-37·9) vs. 5·5 ng mL(-1) (1·9-7·9) respectively P = 0·007]. In a multivariate logistic regression model, elevated TGF-β1 levels were significantly associated with not having advanced liver fibrosis [OR: 0·13 (95% CI: 0·02-0·71), P = 0·019]. While Treg cells do not influence liver fibrosis staging, elevated TGF-β1, probably through its anti-inflammatory effects, might protect HCV/HIV-coinfected patients from liver fibrosis.