Poster Theater Flash Session
Aging and Chronic Disease
Antiretroviral therapy has increased life expectancy for HIV infected patients; however, this population is developing chronic illnesses associated with aging. Liver disease is a major cause of non-AIDS mortality, characterized by progressive fibrosis. Infection with HIV and with Hepatitis C Virus (HCV) promotes liver fibrogenesis. Tissue inhibitor of metalloproteinase-1 (TIMP1), inhibits fibrosis regression and is profibrogenic. Association between TIMP1 and liver disease progression in an aging population of HIV/HCV co-infected, HIV mono-infected, HCV mono-infected, and healthy groups from the Miami Adult Studies on HIV (MASH) cohort in Miami, Florida, was investigated.
Methods : Serum TIMP1 levels were determined by ELISA. A non-invasive estimate of liver fibrosis, FIB-4 score was calculated. Liver fibrosis was defined as FIB-4: Low < 1.45, intermediate1.45< =FIB-4< =3.25, High >3.25. ANOVA with Tukey’s test assessed the mean differences of FIB-4 score and TIMP1 level between groups, TIMP1 levels between 3 FIB-4 categories, and the effect of age on FIB-4 and TIMP1. Linear regression predicted the association of FIB-4 score and TIMP-1 level.
Results : Mean age of the cohort was 54.3±8.1 years with no difference between groups. Mean FIB-4 for HIV/HCV co-infected group was the highest among the 4 groups (p< 0.05). Mean TIMP1 for HIV/HCV co-infected group was also the highest among the 4 groups (p< 0.05). FIB-4 and TIMP1 were associated and remained so (β=0.01, SE=0.002, p< 0.001) after adjusting for age. Mean TIMP1 for the high FIB-4 category was the highest among the 3 FIB-4 categories (p< 0.05). There was a direct effect of TIMP1 levels on FIB-4 category (p< 0.001). After adjusting for HIV/HCV co-infection (p< 0.001), HIV infection (p < 0.0001), HCV infection (p< 0.002), non-infection (p< 0.001) and age, the relationship between TIMP1 and FIB-4 remained significant. The adjusted TIMP1 mean for HIV/HCV co-infected group was significantly higher compared to HIV infected (p < 0.0001), HCV infected (p< 0.002), and healthy groups (p < 0.0001), regardless of age.
Age is a significant factor of liver diseases progression. Our findings of the highest levels of TIMP1 in HIV/HCV co-infected group, which had the highest liver fibrosis regardless of age, supports the role of TIMP1 as a regulator in the progression of hepatic fibrosis.
Funding Sources : National Institutes on Drug Abuse #5UO1DA040381