Tricyclic antidepressant use and the risk of fibrosis progression in hepatitis C‐infected persons: Results from ERCHIVES

Abstract

Recent preclinical studies have suggested an antifibrotic role for tricyclic antidepressants (TCA). Using the Electronically Retrieved Cohort of hepatitis C virus (HCV) Infected Veterans, we aimed to evaluate the impact of TCA use on fibrosis progression and development of hepatocellular carcinoma (HCC) among HCV-infected persons. Subjects were categorized according to use of TCAs, selective serotonin reuptake inhibitors (SSRI) or no antidepressants. TCAs or selective serotonin uptake inhibitors use was defined according to cumulative defined daily dose (cDDD), and categories were mutually exclusive. Subjects with HIV coinfection, hepatitis B surface antigen (HbsAg) positivity, cirrhosis or HCC at baseline were excluded. Outcomes were liver fibrosis progression measured by APRI scores and incident HCC. We utilized Cox proportional hazards regression to determine predictors of cirrhosis, defined as APRI > 2, and incident hepatocellular carcinoma (iHCC). Among 128 201 eligible HCV+ persons, 4% received TCAs, 43% received selective serotonin uptake inhibitors, and 53% received no antidepressants. Fewer TCAs users had drug abuse (34% and 43%) and alcohol abuse (32% vs 42%) compared to selective serotonin uptake inhibitor users. After adjusting for age, baseline APRI score, diabetes, hypertension, alcohol use, drug abuse and HCV RNA levels, TCAs use was associated with decreased risk of cirrhosis (hazard ratio [HR] = 0.77, 95% CI = 0.60, 0.99) and delayed time to development of cirrhosis, but not with decreased iHCC. In conclusion among a large cohort of HCV-positive Veterans, TCAs use was associated with decreased fibrosis progression and lower risk of developing cirrhosis. These data provide supportive evidence for the beneficial effects of TCAs on progression of liver fibrosis in patients with chronic HCV infection.

Impact of major depression and antidepressant use on alcoholic and non‐alcoholic fatty liver disease: A population‐based study

“…Multiple studies have shown that antidepressants may have a protective effect in undifferentiated populations of patients with diverse causes of CLDs. 8,38,39 Nonetheless, such effects were not observed for antidepressants among our specific NAFLD and ALD cohorts in our adjusted analysis with the exception of mirtazapine.…”

Social vulnerability in persons with chronic hepatitis C virus infection is associated with a higher risk of prescription opioid use

“…We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) as the data source for this analysis. ERCHIVES is well defined in numerous previous publications [24][25][26][27][28][29] . Briefly, all persons with HCV infection in the Department of Veterans Affairs healthcare system (VA) diagnosed after October 1, 2001 are identified based on a positive HCV antibody test.…”

Natural history of hepatitis C virus infection in a large national seroconversion cohort in the direct‐acting antiviral agent era: Results from ERCHIVES

“…We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well‐established and regularly updated national database of HCV infected Veterans and uninfected controls for the current study. ERCHIVES has been described in numerous published studies 2,5,13‐16 . Briefly, all Veterans in care at any of the Veterans Health Affairs (VA) facilities with a positive HCV antibody test from 2001 onwards are included in the database.…”