b0b8f09ea5a7d86cef936befa8a0f236 pmc_35054000.pdf 9329354cd56321205de2176ea4fad44448737276 pmc_35054000.pdf 7c194ee2b8b7466ca7dc38b5bad9b52af39334348c2888fd434ec89ad8aaa85c pmc_35054000.pdf Title: Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change Subject: Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 109 cells/L vs. 170 105 cells/L) in both groups. The T cells percentage was lower (80.3 5.6% vs. 77 7%; p = 0.03) and the NK cells percentage was higher (9.7 5% vs. 13 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = -0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression. Keywords: alcohol liver disease; FIB-4 score; lymphocyte population Author: Paola Zuluaga, Aina Teniente-Serra, Daniel Fuster, Bibiana Quirant-Sánchez, Anna Hernandez-Rubio, Eva Martínez-Cáceres and Roberto Muga Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Jan 8 10:52:58 2022 CET ModDate: Sat Jan 8 10:58:59 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1020321 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 LEVXPH+EURM10 Type 1 Builtin yes yes no 15 0 CLKAFP+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 SPDFKJ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 KZSTGQ+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 KDVHRI+CMSY10 Type 1 Builtin yes yes no 32 0 SSNIUI+VnURWPalladioL-Bold Type 1 Custom yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 44 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 48 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 52 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 64 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 67 0 WAXMEH+CMEX10 Type 1 Builtin yes yes no 89 0 WCFTGI+CMR10 Type 1 Builtin yes yes no 93 0 OPPCNO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 109 0 OPPCPA+PalatinoLinotype TrueType WinAnsi yes yes no 112 0 OPPCPC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 115 0 OPPCNO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 131 0 OPPCPA+PalatinoLinotype TrueType WinAnsi yes yes no 134 0 OPPCPC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 137 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 144 0 OPPCNO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 163 0 OPPCOP+PalatinoLinotype CID TrueType Identity-H yes yes yes 166 0 OPPCPA+PalatinoLinotype TrueType WinAnsi yes yes no 172 0 OPPCPC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 175 0 OPPCNO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 188 0 OPPCOP+PalatinoLinotype CID TrueType Identity-H yes yes yes 191 0 OPPCPA+PalatinoLinotype TrueType WinAnsi yes yes no 197 0 OPPCPC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 200 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-02-28 02:23:02 CET RepresentationInformation: pmc_35054000.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-01-31 03:37:43 CET Size: 1020321 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 355 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Flow Cytometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Patients Details Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Count and Distribution of Lymphocyte Subpopulations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Correlation between NK Cells and Lymphocyte Subpopulations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change Author: Paola Zuluaga, Aina Teniente-Serra, Daniel Fuster, Bibiana Quirant-Sánchez, Anna Hernandez-Rubio, Eva Martínez-Cáceres and Roberto Muga Subject: Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 109 cells/L vs. 170 105 cells/L) in both groups. The T cells percentage was lower (80.3 5.6% vs. 77 7%; p = 0.03) and the NK cells percentage was higher (9.7 5% vs. 13 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r =  0.65, p < 0.01) and with ALF (r = -0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression. 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