Liver Fibrosis and Steatosis in HIV-Infected Patients: Impact of Race/Ethnicity, Gender, BMI, and ART

BACKGROUND: The advent of antiretroviral therapy (ART) led to a decline in morbidity and mortality related to AIDS and its related complications. With this decline, an increasing proportion of morbidity and mortality in people living with HIV (PLWH) is secondary to liver and cardiovascular disease. Previous studies have shown that PLWH have traditional risk factors for these diseases, such as obesity, as well as risk factors that are unique to their population, including direct metabolic effects of HIV and ART. Several factors, such as race, ethnicity, gender, and BMI, have been shown to have an impact on the course of liver steatosis and fibrosis in general population. The impact of these factors on the course of liver steatosis and fibrosis in the setting of hepatitis B and C co-infections in PLWH have been studied, but there is a paucity of literature detailing the impact in the absence of viral hepatitis co-infection. NAFLD, APRI, and FIB-4 scores have been shown to be effective noninvasive markers for clinically significant liver steatosis and fibrosis. However, these non-invasive markers have not been validated for use in patients without viral hepatitis co-infection. This study aims to determine if race, ethnicity, gender, BMI, and the specific ART regimen have a differential impact on non-invasive markers of liver steatosis and fibrosis in PLWH. OBJECTIVE: Determine if race, ethnicity, gender, BMI, and specific ART regimen will modulate changes in non-invasive markers of liver steatosis and fibrosis. METHODS: All patients initiating ART at the Parkland Memorial Hospital HIV clinic from 2009-2017 were analyzed. Exposure to ART was defined as concurrent receipt of at least two nucleoside reverse transcriptase inhibitor (NRTI) drugs plus at least one protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or integrase inhibitor (INSTI). The existing patient database includes demographics (notably, gender, race, and ethnicity), CD4 and HIV RNA levels, co-morbidities, laboratory values (most notably, liver function tests), ART regimen, and body mass index (BMI). An analysis of yearly changes in BMI was calculated based on specific ART drugs, and differences between groups stratified by gender or race/ethnicity were compared. For subjects who meet certain pre-determined liver function test minimums, non-invasive markers for liver fibrosis (APRI, NAFLD, and FIB-4 scores) will be utilized and trended over time. Manual chart extraction will be examined for patients with clinically-indicated imaging (abdominal ultrasound, computed tomography, or magnetic resonance imaging) to estimate the incidence and prevalence of liver fibrosis or steatosis in this population and to determine whether race/ethnicity or gender modifies these risks. RESULTS: The difference in yearly BMI change was statistically significant for the INSTI dolutegravir (DTG; p=<0.01) between Blacks and non-Hispanic whites (NHW) but not for any other ART drugs tested. The difference in yearly BMI change showed a trend for statistical significance for DTG (p=0.06) between Hispanics and NHW but not for any other ART drugs tested. The difference in yearly BMI change by ART drug in men versus women was statistically significant for atazanavir (ATV; p=0.03), darunavir (DRV;p=<0.01), lopinavir (LPV; p=0.03), and dolutegravir (DTG; p=<0.01) but not with elvitegravir (EVG; p=0.72). CONCLUSIONS AND NEXT STEPS: Our preliminary results indicate that particular ART drugs, principally the INSTI DTG, appear to be associated with greater BMI gains than other agents. Additionally, in PLWH on ART, women demonstrated greater BMI gains than men, and Blacks and Hispanics demonstrated greater BMI gains than NHW in our cohort. The next steps will be to analyze the trends of APRI, FIB-4, and NAFLD scores over time in our cohort as non-invasive markers of liver fibrosis and to determine the demographic, HIV, and ART-related factors associated with higher rates of liver fibrosis. We will also conduct a review of clinically-indicated abdominal imaging for evidence of hepatic fibrosis in a subset of our cohort to validate the use of these non-invasive markers in PLWH without viral hepatitis. Given that HIV has been transformed into a chronic disease and that PLWH are now living decades on these ART regimens, it is of paramount importance to determine the long-term metabolic and hepatic consequences of these medications to better inform patient care and practice guidelines. We believe that our large cohort of demographically diverse PLWH on contemporary ART regimens and with detailed clinical follow-up data offers an important population to further our understanding of these critical issues.