Browsing by Author "Chalasani, Sai"

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    Alcohol Abstinence Does Not Fully Reverse Abnormalities of Mucosal-Associated Invariant T Cells in the Blood of Patients With Alcoholic Hepatitis
    (Wolters Kluwer, 2019-06) Li, Wei; Lin, Edward L.; Liangpunsakul, Suthat; Lan, Jie; Chalasani, Sai; Rane, Sushmita; Puri, Puneet; Kamath, Patrick S.; Sanyal, Arun J.; Shah, Vijay H.; Radaeva, Svetlana; Crabb, David W.; Chalasani, Naga; Yu, Qigui; Microbiology & Immunology, IU School of Medicine
    OBJECTIVES: Alcoholic hepatitis (AH) develops in approximately 30% of chronic heavy drinkers. The immune system of patients with AH is hyperactivated, yet ineffective against infectious diseases. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are highly enriched in liver, mucosa, and peripheral blood and contribute to antimicrobial immunity. We aimed to determine whether MAIT cells were dysregulated in heavy drinkers with and without AH and the effects of alcohol abstinence on MAIT cell recovery. METHODS: MR1 tetramers loaded with a potent MAIT cell ligand 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil were used in multiparameter flow cytometry to analyze peripheral blood MAIT cells in 59 healthy controls (HC), 56 patients with AH, and 45 heavy drinkers without overt liver disease (HDC) at baseline and 6- and 12-month follow-ups. Multiplex immunoassays were used to quantify plasma levels of cytokines related to MAIT cell activation. Kinetic Turbidimetric Limulus Amebocyte Lysate Assay and ELISA were performed to measure circulating levels of 2 surrogate markers for bacterial translocation (lipopolysaccharide and CD14), respectively. RESULTS: At baseline, patients with AH had a significantly lower frequency of MAIT cells than HDC and HC. HDC also had less MAIT cells than HC (median 0.16% in AH, 0.56% in HDC, and 1.25% in HC). Further, the residual MAIT cells in patients with AH expressed higher levels of activation markers (CD69, CD38, and human leukocyte antigen [HLA]-DR), the effector molecule granzyme B, and the immune exhaustion molecule PD-1. Plasma levels of lipopolysaccharide and CD14 and several cytokines related to MAIT cell activation were elevated in patients with AH (interferon [IFN]-α, interleukin [IL]-7, IL-15, IL-17, IL-18, IL-23, IFN-γ, and tumor necrosis factor α). Decreased MAIT cell frequency and upregulated CD38, CD69, and HLA-DR correlated negatively and positively, respectively, with aspartate aminotransferase level. MAIT cell frequency negatively correlated with IL-18. HLA-DR and CD38 levels correlated with several cytokines. At follow-ups, abstinent patients with AH had increased MAIT cell frequency and decreased MAIT cell activation. However, MAIT cell frequency was not fully normalized in patients with AH (median 0.31%). DISCUSSION: We showed that HDC had a reduction of blood MAIT cells despite showing little evidence of immune activation, whereas patients with AH had a severe depletion of blood MAIT cells and the residual cells were highly activated. Alcohol abstinence partially reversed those abnormalities.
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    Hepatic steatosis is highly prevalent but is not correlated with stiffness in autoimmune hepatitis
    (Wolters Kluwer, 2020-10-16) Chalasani, Sai; Mathur, Karan; Shammas, Nicole; Orman, Eric; Vuppalanchi, Raj; Lammert, Craig; Medicine, School of Medicine
    The prevalence and impact of hepatic steatosis among patients with autoimmune hepatitis (AIH) is not well described. We conducted a cross-sectional study to determine the prevalence of hepatic steatosis in AIH patients and examined its relationship with hepatic fibrosis using vibration controlled transient elastography. Liver stiffness measurement (LSM), controlled attenuation parameter (CAP), gender, current age, and body mass index (BMI) were collected from 277 AIH patients. Hepatic steatosis was defined as CAP >263 db/m. The study participants were mostly female (82%) with an average age of 49 years and BMI 29.7 kg/m2. Mean LSM was 12.5 (standard deviation 13.5) kPa and CAP was 244 (standard deviation 63) db/m. The prevalence of coexisting steatosis was 33.2%, and steatosis did not correlate with LSM (r = 0.05, P = .46). In this study, only gender (females with 31% lower LSM on average compared to males, P = .001) and BMI (each unit increase of BMI resulted in a 1.48% increase on average LSM, P = .01) correlated with LSM. Male gender had significant association with increased LSM, after controlling for age, BMI, and CAP (P = .001). This exploratory study using noninvasive vibration controlled transient elastography revealed hepatic steatosis is highly prevalent in patients with AIH but not associated with liver fibrosis.
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    Utilization and Impact of Complementary and Alternative Medicines in Symptomatic Autoimmune Hepatitis Patients
    (Springer, 2022) Gelow, Kayla; Chalasani, Sai; Green, Kelsey; Lammert, Craig; Medicine, School of Medicine
    Background: Complementary and alternative medicine (CAM) use has become increasingly common. It is also prevalent in patients with chronic liver disease, but the scope, depth, and safety of use is not well known. Aims: This study aimed to evaluate the prevalence and patterns of CAM use in autoimmune hepatitis (AIH) patients. Methods: Electronic invitation to complete a 22 item CAM-specific questionnaire was posted weekly to well-established AIH Facebook communities (combined membership of 4700 individuals) during a 6-week study period. Age ≥ 18 years and AIH diagnosis made by a treating physician were the eligibility criteria. Results: The prevalence of ever CAM use among participants was 56.4%, and nearly 42% used CAM after AIH diagnosis. Among those reporting CAM use after diagnosis, 53.7% (51/95) indicated CAM was used to mitigate AIH-related phenomenon, most often targeting liver inflammation/fibrosis (67.7%), fatigue (51%), joint pain (47.1%), and sleep issues (45.1%). Most frequent physical CAM strategies were exercise (49.5%) and yoga (34%), whereas most frequent consumable CAM included healthier eating (45.3%), cannabidiol preparations (45.3%), and probiotics (44.3%). Seventy-five percent reported that CAM improved AIH symptoms and no severe adverse events were reported. Conclusions: CAM use in AIH patients is prevalent, yet providers have historically failed to document their patient's CAM strategies. Beyond inherent drug-induced liver injury risk, drug-drug interactions remain a concern and could alter baseline immunosuppression levels in AIH. Despite a majority found CAM approaches that improved targeted symptoms, all were unable to alter the course of chronically prescribed medications by physicians.