title: Effects of Sex, Drinking History, and Omega-3 and Omega-6 Fatty Acids Dysregulation on the Onset of Liver Injury in Very Heavy Drinking Alcohol-Dependent Patients.
abstract: Heavy alcohol consumption frequently causes liver inflammation/injury, and certain fatty acids (FAs) may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking and the changes in the FA levels involved in the ω-6 (pro-inflammatory) and ω-3 (anti-inflammatory) state in alcohol-dependent (AD) patients who had no clinical manifestations of liver injury. We aimed to identify sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking.
  
  
  
  A total of 114 heavy drinking AD female and male patients aged 21 to 65 years without clinical manifestations of liver injury, who were admitted to an alcohol dependence treatment program, were grouped by the alanine aminotransferase (ALT) levels: ≤40 IU/l, as no liver injury (GR.1), and >40 IU/l, as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic panel, comprehensive FA panel, and drinking history data were evaluated.
  
  
  
  Elevated ALT and aspartate aminotransferase (AST) showed close association with markers of heavy alcohol intake. In the patients with mild biochemical liver injury (GR.2), females showed significantly higher AST level than males. Significant association of AST and total drinks in past 90 days (TD90) in females, and AST and heavy drinking days in past 90 days (HDD90) in males was observed. The ω-6:ω-3 ratio showed a significant pro-inflammatory response only in females with mild liver injury (GR.2) when adjusted by drinking history marker, TD90. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased in males with liver injury, while females did not show any comparable rise in EPA; and DHA levels were lower.
  
  
  
  Measures of heavy drinking, TD90 and HDD90, predicted changes in liver injury. Changes in the ω-3 and ω-6 FA levels and the ω-6:ω-3 ratio showed a pro-inflammatory shift in patients with biochemical liver injury with a significant effect in females. Changes in FAs involved in the inflammatory state may represent one mechanism for liver inflammation/injury in response to heavy alcohol drinking.
authors: Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky. vatsalya.vatsalya@louisville.edu.|Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky. vatsalya.vatsalya@louisville.edu.|Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. vatsalya.vatsalya@louisville.edu.
authors: Vatsalya
authors: 0000-0001-6764-6891
authors: V
authors: Vatsalya
authors: Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky.
authors: Ming
authors: M
authors: Song
authors: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
authors: Melanie L
authors: ML
authors: Schwandt
authors: Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky.|Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.
authors: Matthew C
authors: MC
authors: Cave
authors: Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.
authors: Shirish S
authors: SS
authors: Barve
authors: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
authors: David T
authors: DT
authors: George
authors: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
authors: Vijay A
authors: VA
authors: Ramchandani
authors: Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky.|Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.
authors: Craig J
authors: CJ
authors: McClain
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000097:blood*; D000437:Alcoholism / Q000097:blood* / Q000150:complications; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004281:Docosahexaenoic Acids / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D043371:Fatty Acids, Omega-6 / Q000097:blood*; D005260:Female; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D062706:Prodromal Symptoms; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Alcohol; Fatty Acids; Heavy Drinking Markers; Liver Injury; Sex