The Progression of Liver Fibrosis is Associated with the Severity of the HIV Disease in HIV-HCV Co-infected Female Patients Mohammad K. Mohammad 1, Babu Sriram Maringanti 2, Amy Wilson 2, Martin Gnoni 2, Timothy Wiemken 2, Shirish Barve 1, Craig McClain 1, Paula Peyrani Division Gastroenterology and Hepatology and Nutrition, 2. Division of Infectious Diseases, University of Louisville. Louisville, KY ABSTRACT Background: At present, an estimated 40 million people are infected with HIV worldwide, and 180 million are HCV-infected. A third of HIV-infected individuals in Europe and the USA have HCV co-infection. As a result, HCV is now regarded as an opportunistic infection in people with HIV infection. HCV infection has been reported as the most common cause of death in HIV infected subjects which may be due to systemic inflammation enhancing HIV replication and CD4 cell depletion. The objective of our study was to define the severity of liver fibrosis in patients with HCV-HIV confection and evaluate if an association exists between the severities of HCV induced liver fibrosis and CD4+ cell count. Methods Age (year) X AST / Retrospectively, the study enrolled 145 female with HIV disease on care at the University of Louisville Wings Clinic, Of these a group of only 20 Patients were HCV positive. Liver fibrosis was defined using the Fib-4 score. The Fib-4 score was calculated as = Age (year) X AST / Platelet Count X ALT ½ Platelet Count X ALT ½. The severity of HIV infection was defined by the CD4+ cell count. A simple linear model was used to correlate Fib-4 with CD4+ cell count. Results The correlation between liver fibrosis and CD4+ cell count is depicted in the following figure. The linear model results are as follows: y= This indicates that for every 1 point increase in Fib-4, the CD4+ cell count decreases by 70 cells. Conclusions This study demonstrates that as the liver fibrosis increases, the CD4+ cell count of the patient deteriorates. HCV/HIV co- infection affects the immunocompetence of the patients. Also the systemic inflammatory response associated with increased liver fibrosis may acts as cofactor for HIV disease progression. Further studies confirming the role of systemic inflammatory responses induced by HCV as a cofactor for HIV disease progression may lead to the development of therapeutic strategies INTRODUCTION REFERENCES RESULTS (Cont’d)  The study demonstrates an inverse correlation between liver fibrosis and CD-4 cell count, for every 1 point increase in Fib-4, the CD4+ cell count decreases by 70 cells.  Future research should focus on the influence of HCV on natural history of HIV disease and the management of HCV co-infected patients for better clinical outcomes. Physicians should have a high suspicion of HCV co-infection in HIV patients because of increasing prevalence CONCLUSIONS Figure 1: shows the association between the absolute CD4+ cell count and the liver fibrosis score (FIB-4). Study design and study population:  Wings Clinic Women’s Cohort study is a retrospective observational study of HIV-infected female patients managed at the Wings Clinic in Louisville, KY from 2006 to Based on the results, patients were divided into two groups: those with HIV mono-infection and those with HIV/HCV co- infection.  We retrospectively studied the medical charts of the patients and collected data from for  HCV co-infection is common in human immunodeficiency virus seropositive patients due to shared route of viral transmission. Liver disease is currently the leading cause of non-AIDS related death among HCV/HIV co-infected patients.  There is clear cut evidence that HIV impacts HCV[5] but the impact of HCV co-infection on HIV is controversial.  The objective of this study was to examine the impact of HCV co-infection on HIV disease progression and to evaluate the association between indirect marker for the fibrosis and the severity of HIV disease. MATERIALS AND METHODS Statistical Analysis:  HIV disease progression was evaluated using CD4+ cell count  The assessment of the liver fibrosis is calculated using the Fib-4.  A simple linear model was used to correlate the fibrosis as Fib-4 with CD4+ cell count. A total of 20 female HIV-HCV patients were studied from Wings Clinic Cohort Study.  Patient characteristics are shown in table 1.  Table 2 shows the risk factors for Hepatitis C patients.  Figure 1 shows the association between the absolute CD4+ cell count and the liver fibrosis score. The linear model results are as follows: y= This indicates that for every 1 point increase in Fib-4, the CD4+ cell count decreases by 70 cells. 1.Expanded HIV testing and trends in diagnoses of HIV infection - District of Columbia, Risk factorsHCV patientsPercentage Heterosexual20100 Intravenous drug use325 Homosexual00 Transfusion related00 Table 2 Risk factors for Hepatitis C. Table 1.Patient characteristics. Patient CharacteristicNumberPercentage Age < > AST < ALT < Platelet < Fib-4 score < CD4 count < Study Definitions:  To classify patients into HIV/HCV co-infection group, we included patients with documented evidence of positive serology for HCV antibody and/or positive PCR for HCV RNA.  The Fib-4 indirect invasive marker of liver fibrosis was used for analysis. This measure can be calculated using readily available patient and laboratory data. Fib-4 Fib-4  Age (years)  AST is Aspartate amino transferase.  ALT is Alanine amino transferase.  Platelet count (10/ L)  The severity of HIV infection was defined by the CD4+ cell count.  Data on current alcohol usage, smoking and HIP-B infection was derived from patient’s charts. RESULTS RESULTS (Cont’d) Habits Alcohol < 2 drinks/week 2 10 Tobacco6 30 HIP B0 0 Table 3 Risk factors for liver fibrosis.