Depressive Symptoms Linked to Severity of Primary Biliary Cholangitis

Credit: Adobe Stock/ Gregory Miller

A new study found depressive symptoms are linked to the severity of primary biliary cholangitis (PBC).¹

“Elevated HAMD-17 score was a discriminating factor for high risk of cirrhosis in Lasso-logistic regression and CART models,” wrote investigators, led by Simin Zhou Jiwen Li, from the department of gastroenterology and hepatology at Tianjin Medical University in China.

Approximately 30% to 40% of patients with PBC do not respond well to ursodeoxycholic acid (UDCA), the first-line therapy for PBC. This lack of response not only puts patients at risk of progressing to liver cirrhosis or liver failure but also increases the burden of symptoms that impact quality of life, including depression, anxiety, insomnia, fatigue, and poor overall health.

Patients with PBC frequency experience depressive symptoms, which have been shown to correlate with poorer clinical outcomes in chronic liver diseases. A previous study found those diagnosed with depression had lower survival rates following liver transplantation.²

Limited research has addressed the impact of depressive symptoms on disease progression and clinical outcomes in patients with PBC. A study had found 40% of patients with PBC would progress to cirrhosis within 10 years, and another study showed cirrhotic patients had a high prevalence of depressive symptoms.³

Investigators sought to assess the influence of depressive symptoms on disease severity among patients with PBC aged > 18 years.¹ The team also evaluated the potential association between HLA-DRB1 alleles and cirrhosis. To better understand the role of depressive symptoms on cirrhosis, investigators developed a reliable risk model for cirrhosis that considered depressive symptoms and HLA-DRB1 alleles.

The study included 162 patients with PBC who visited the team’s hepatology clinics from December 2017 to December 2020 as the training group and 54 patients with PBC recruited from January 2021 to January 2023 as the validation group. All participants had been on UDCA monotherapy for > 1 year but < 2 years to prevent illness duration from affecting depressive symptoms.

Investigators assessed depression symptoms using the 17-item Hamilton Depression Rating Scale (HAMD-17). The team collected data on liver pathology, diagnostic imaging reports, and laboratory parameters use to diagnose cirrhosis. All patients were also recruited for HLA-DRB1 genotyping.

The team divided participants into the groups: PBC with depressive symptoms (n = 85) and PBC without depressive symptoms (n = 77). Investigators observed that the rate of depressive symptoms in patients with PBC (52.5%) was more than three times greater than in healthy controls (16.1%) (P < .001). Compared to patients with PBC without depressive symptoms, those with depressive symptoms showed poorer responses to UDCA treatment (79.2% vs 55.3%; P = .001).

Furthermore, the levels of ALP (P = .022) GGT, (P = .006) and IgM (P = .049) were statistically greater in PBC patients with depressive symptoms than in those without.

Additionally, the HAMD-17 score was negatively linked to C4 levels (P = .039) and positively linked to levels of alkaline phosphatase (P = .12), y-glutamyl transpeptidase (P < .001), total bilirubin (P = .010), immunoglobin G (P = .020), and immunoglobin M (P < .001).

Lasso-logistic regression analysis demostrated the HAMD-17 score (OR, 1.087; 95% CI, 1.021 – 1.157; P = .009), human leukocyte antigen (HLA)-DRB1*03:01 allele (OR, 7.353; 95% CI, 2.271 – 23.809; P = .001), age (OR, 1.075; 95% CI, 1.028 – 1.124; p = .001), alkaline phosphate levels (OR, 1.009; 95% CI, 1.003 –1.015; P = .004), and immunoglobin M levels (OR, 1.005; 95% CI, 1.001 – 1.009; P= .020) were independent risk factors for cirrhosis. Additionally, an increased HAMD-17 score was a discriminating risk factor for a high risk of cirrhosis in patients with PBC in the decision tree model.

“The construction of the risk models could facilitate identification of cirrhosis and contribute to timely intervention in patients with PBC,” investigators wrote. “Our findings indicated the considerable impact of depressive symptoms on the risks of cirrhosis, providing valuable insights into the clinical significance of the prompt identification and proper management of depressive symptoms in patients with PBC.”

References

1. ^{Zhou S, Li J, Liu J, et al. Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models. Brain Behav. 2024;14(8):e3639. doi:10.1002/brb3.3639}
2. ^{Rogal SS, Mankaney G, Udawatta V, et al. Pre-Transplant Depression Is Associated with Length of Hospitalization, Discharge Disposition, and Survival after Liver Transplantation. PLoS One. 2016;11(11):e0165517. Published 2016 Nov 7. doi:10.1371/journal.pone.0165517}
3. ^{Harms MH, de Veer RC, Lammers WJ, et al. Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis. Gut. 2020;69(8):1502-1509. doi:10.1136/gutjnl-2019-319057}