Inflammation, psychiatric symptoms, and opioid use are associated with pain and disability in patients with cirrhosis

Abstract

Background & aims: 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.

Keywords: CRP; Cirrhosis; Hepatitis C; IL6; Opioid Use; Pain Management.

Figure 1

Subject Enrollment

Figure 2

Symptom Clustering

Figure 3

Distribution of Pain: the percentage of participants selecting various regions of pain on the MPQ is denoted with color coding