title: Inflammation, psychiatric symptoms, and opioid use are associated with pain and disability in patients with cirrhosis.
abstract: OBJECTIVE
  Cirrhosis is associated with significant pain and disability, the etiologies of which are poorly understood. We investigated whether the pain and disability in patients with cirrhosis are associated with systemic inflammation and psychiatric symptoms.
  
  
  METHODS
  In a prospective study, we recruited 193 patients with cirrhosis caused by hepatitis C virus infection, nonalcoholic steatohepatitis, or alcohol from the hepatology clinic at the University of Pittsburgh. Patients were assessed using the McGill Pain Questionnaire, the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Pain Disability Index. Serum samples were collected and markers of inflammation were measured using standardized Luminex assays (Milipore, St. Charles, MO). We evaluated factors associated with pain, pain-related disability, and chronic opioid use by using multivariable regression models.
  
  
  RESULTS
  Pain was reported by 79% of patients, pain-related disability was reported by 75%, and depression and/or anxiety was reported by 47%; the average Model for End-Stage Liver Disease score was 12 ± 5. Serum samples from 58% percent of patients had increased levels of C-reactive protein. Opioids were prescribed for 30% of patients with pain. In multivariate analysis, factors significantly associated with pain included younger age (odds ratio [OR]/y, 0.93; 95% confidence interval [CI], 0.90-0.99), serum level of interleukin 6 (OR per pg/L, 1.63; 95% CI, 1.09-2.58), Hospital Anxiety and Depression Scale score (OR/point, 1.14; 95% CI, 1.07-1.24), and etiology (hepatitis C virus infection vs alcohol: OR, 3.70; 95% CI, 1.27-11.11). Disability scores were related significantly to psychiatric symptoms (incidence rate ratio [IRR]/point, 1.04; 95% CI, 1.02-1.05), prescription opioid use (IRR, 1.49; 95% CI, 1.14-1.94), Model for End-Stage Liver Disease score (IRR/point, 1.02; 95% CI, 1.0001-1.05), level of C-reactive protein (IRR per mg/dL, 1.13; 95% CI, 1.02-1.24), and pain severity (IRR/point, 1.19; 95% CI, 1.08-1.32).
  
  
  CONCLUSIONS
  Pain and disability are common among patients with cirrhosis, and are associated with inflammation, psychiatric symptoms, and opioid use, which potentially are modifiable. Although opioids are used commonly to treat pain, psychiatric symptoms and inflammation also might be treatment targets in this population.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Health Equity Research and Promotion, Veterans Affairs Healthcare System, Pittsburgh, Pennsylvania. Electronic address: shari.rogal@gmail.com.
authors.forename: Shari S
authors.initials: SS
authors.lastname: Rogal
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bielefeldt
authors.affiliation: Department of Anesthesia, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Wasan
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.affiliation: Center for Health Equity Research and Promotion, Veterans Affairs Healthcare System, Pittsburgh, Pennsylvania; Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Susan
authors.initials: S
authors.lastname: Zickmund
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Eva
authors.initials: E
authors.lastname: Szigethy
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Andrea F
authors.initials: AF
authors.lastname: DiMartini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D006233:Persons with Disabilities / Q000523:psychology*; D004363:Drug Utilization; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000453:epidemiology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D008108:Liver Diseases, Alcoholic / Q000150:complications; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology* / Q000473:pathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications; D010146:Pain / Q000188:drug therapy / Q000523:psychology*; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid
keywords: CRP; Cirrhosis; Hepatitis C; IL6; Opioid Use; Pain Management