Browsing by Subject "Hepatocellular carcinoma (HCC)"

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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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    A National Survey of Hepatocellular Carcinoma Surveillance Practices Following Liver Transplantation
    (Wolters Kluwer, 2020-12-08) Aggarwal, Avin; Te, Helen S.; Verna, Elizabeth C.; Desai, Archita P.; Medicine, School of Medicine
    Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT. Methods: We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries. Results: Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific "cutoff" values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol. Conclusions: Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.
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    Racial Disparities in Liver Transplantation for Hepatocellular Carcinoma Are Not Explained by Differences in Comorbidities, Liver Disease Severity, or Tumor Burden
    (Wiley, 2018-12-03) Dakhoul, Lara; Gawrieh, Samer; Jones, Keaton R.; Ghabril, Marwan; McShane, Chelsey; Orman, Eric; Vilar‐Gomez, Eduardo; Chalasani, Naga; Nephew, Lauren; Medicine, School of Medicine
    Black patients have higher mortality and are less likely to receive liver transplantation for hepatocellular carcinoma (HCC) than white patients. Reasons for these disparities have not been fully elucidated. Comorbid disease, liver disease severity, cirrhosis etiologies, and tumor characteristics were compared between black and white patients with HCC seen at the Indiana University Academic Medical Center from January 2000 to June 2014. Logistic regression was used to investigate the primary outcome, which was liver transplantation. Log-rank testing was used to compare survival between the two groups. Subgroup analysis explored reasons for failure to undergo liver transplantation in patients within Milan criteria. The cohort included 1,032 (86%) white and 164 (14%) black patients. Black and white patients had similar Model for End-Stage Liver Disease (MELD) and Child-Pugh scores (CPSs). There was a trend toward larger tumor size (5.3 cm versus 4.7 cm; P = 0.05) in black patients; however, Barcelona Clinic Liver Cancer (BCLC) staging and Milan criteria were similar. Black patients were less likely to undergo liver transplantation than white patients; this was a disparity that was not attenuated (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21-0.90) on multivariable analysis. Substance abuse was more frequently cited as the reason black patients within Milan criteria failed to undergo transplantation compared to white patients. Survival was similar between the two groups. Conclusion: Racial differences in patient and tumor characteristics were small and did not explain the disparity in liver transplantation. Higher rates of substance abuse in black patients within Milan criteria who failed to undergo transplantation suggest social factors contribute to this disparity in this cohort.