Browsing by Subject "Hepatocellular carcinoma (HCC)"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Correlating genomic copy number alterations with clinicopathologic findings in 75 cases of hepatocellular carcinoma
    (Springer Nature, 2021-06-08) Peng, Gang; Chai, Hongyan; Ji, Weizhen; Lu, Yufei; Wu, Shengming; Zhao, Hongyu; Li, Peining; Hu, Qiping; Medical and Molecular Genetics, School of Medicine
    Background: Oligonucleotide array comparative genomic hybridization (aCGH) analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors. This study aimed to assess the clinical utility of aCGH for cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings. Methods: aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Survival outcomes from these cases were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means. Results: The survival outcomes indicated that BCLC stages and recurrence status could be predictors and E-S grades could be a modifier for HCC. The most common CNAs involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%), and losses of 8p and 13q (30%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated with good survival, while loss of 1p36.31p22.1 and gains of 2q11.2q21.2 and 20p13p11.1 seen in cases of stage C, grade III and recurrence were possibly correlated with worst prognosis. Conclusions: These results indicated that aCGH analysis could be used to detect recurrent CNAs and involved key genes and pathways in patients with HCC. Further analysis on a large case series to validate the correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    The impact of antibiotic use in gastrointestinal tumors treated with immune checkpoint inhibitors: systematic review and meta-analysis
    (Frontiers Media, 2024-06-03) Alotaibi, Faizah M.; Albalawi, Ibrahim Abdullah S.; Anis, Amna M.; Alotaibi, Hawazin; Khashwayn, Seham; Alshammari, Kanan; Al-Tawfiq, Jaffar A.; Medicine, School of Medicine
    Background: Immune checkpoint inhibitors (ICI) have improved overall survival in patients with different cancer types. However, treatment efficacy varies between patients depending on several factors. Recent research suggested that antibiotic-induced dysbiosis can impair ICI efficacy. Here we review the impact of antibiotic use in clinical outcome of patients with gastrointestinal cancer treated with ICI. Methods: This is a systematic review and utilized a thorough search of MEDLINE, Cochrane, Scopus, EB-SCO, Web of Science of studies published till September 2023. The aim of the study is to determine the association between antibiotic use and ICI treatment efficacy in patients with gastrointestinal cancers (GI). We utilized a meta-analysis of the association between the use of antibiotics and overall survival and progression-free survival. Results: Nine studies met the inclusion criteria with a total of 2,214 patients. The most common type of cancers was hepatocellular carcinoma (HCC). The majority of the studies were retrospective, and one was collective of clinical trials. The use of antibiotics was associated with decreased both overall survival [haz-ard ratio (HR) 1.92, 95% confidence interval (CI) 1.41, 2.63] and progression-free survival [HR 1.81, 95% CI 1.29, 2.54]. Conclusion: The use of antibiotics may affect clinical outcomes in patients with GI cancers treated with ICI. Further prospective studies are needed to improve the understanding of this phenomenon. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023462172.