BOSTON, MA—Use of tricyclic antidepressants (TCAs) is associated with decreased liver fibrosis progression and delayed time to cirrhosis development, according to a large cohort of veterans with hepatitis C virus (HCV), presented at The Liver Meeting® 2016.

“These data provide supportive evidence for the beneficial effects of TCAs on disease progression in patients with HCV,” noted study coauthor Jennifer Y. Chen, MD, Gastroenterology/Hepatology, Massachusetts General Hospital, in Boston. “Further evaluation of the basis for TCA’s effects on liver fibrosis is warranted.”

Preclinical findings have indicated that TCAs might have antifibrotic activity, but details have been lacking. The drug amitriptyline, a TCA, has also been shown to decrease the development of fibrosis in vivo. The research team therefore sought to evaluate the effects of TCAs on fibrosis progression and hepatocellular carcinoma (HCC) development in veterans with HCV between 2001 and 2015, using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES).  

Records for patients who had received TCAs, selective serotonin reuptake inhibitors (SSRIs), or those who had not taken antidepressant medications were used to define cumulative defined daily dose (cDDD), liver fibrosis progression (measured by APRI scores), and incidence HCC (iHCC). Patients with HIV co-infection or HBsAg positivity at any time, no baseline APRI available, or with cirrhosis or HCC at baseline, were excluded from analysis Dr. Chen noted.

Cirrhosis was defined as any follow-up APRI score >2 during study observation period in patients with baseline APRI score <2. TCA use was defined as TCA ≥180 cDDD yearly without SSRI use; SSRI use was defined as ≥180 cDDD yearly without TCA use. 

Of 128,201 eligible HCV+ persons, 4% were determined to have received TCAs and 43% had received SSRIs. Another 53% had received no antidepressants.

“TCA users were more likely to have hypertension (52%, 45%, and 48% respectively) and less likely to have diabetes (6%, 40%, and 54% respectively) compared to SSRI users and those receiving no antidepressants,” Dr. Chen reported. “Fewer TCA users had histories of alcohol abuse (32% vs. 42%) and drug abuse (34% vs. 43%) compared to SSRI users.”

TCA was associated with decreased cirrhosis development (hazard ratio [HR] 0.77, 95% CI: 0.60, 0.99; P=0.04 in multivariate analyses that controlled for clinical factors like age, baseline APRI score, diabetes, hypertension, alcohol use, alcohol dependence, and HCV RNA. TCA use however, was not associated with a decreased risk of iHCC incidence (HR 0.40, 95% CI: 0.06, 2.84; P=0.36) according to bivariate or multivariable analyses. 

Average APRI scores were lower among patients taking TCA users than SSRI and those receiving no antidepressants, Dr. Chen reported.

Study coauthors disclosed research support from Gilead, Mass Biologics, AbbVie, Merck, and BMS.