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DEPRESSION AS A RISK FACTOR FOR CIRRHOSIS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: A DECISION TREE-BASED RETROSPECTIVE COHORT STUDY

Liping Guo 1, Simin Zhou 1, Lu Zhou 1

Affiliations

1 Tianjin Medical University General Hospital, Tianjin, China

Summary

AI Generated

Depression is common in primary biliary cholangitis patients (53.9%) and serves as a risk factor for cirrhosis alongside the HLA-DRB1*03:01 allele and other clinical parameters.

Depression was observed in 76 of 141 (53.9%) patients with PBC and was positively associated with serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, and immunoglobulin M.
The HLA-DRB1*03:01 allele was more common in PBC patients with depression and increased the risk of cirrhosis with an odds ratio of 5.676 (p<0.001).
Logistic regression identified PHQ-9 score, HLA-DRB1*03:01 allele, age, and alkaline phosphatase level as risk factors for cirrhosis, with elevated PHQ-9 score (≥3.5) serving as a discriminating factor in decision tree modeling.
Depressive symptoms were associated with poor treatment response in PBC patients, highlighting the clinical importance of identifying and managing depression in this population.

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Abstract

Introduction

Primary biliary cholangitis (PBC) is an immune-mediated cholestatic liver disease characterized by progressive destruction of the small intrahepatic bile ducts, leading to fibrosis and eventually cirrhosis. Previous studies demonstrated a high proportion of depression in patients with PBC. Accumulating evidences have shown that depression is associated with the severity of liver diseases and some extrahepatic autoimmune diseases (EHAIDs). Compared to general population, the prevalence of depressive symptoms in patients with cirrhosis is higher (18-58% vs. 10%). Moreover, cirrhotic patients with depression experience worse clinical outcomes. A diagnosis of depression before liver transplantation is related to reduced survival after transplantation. Antidepressant mirtazapine correlated with the reduced incidence of decompensated cirrhosis, liver transplantation and decreased mortality in patients with PBC. Therefore, it is important to screen for depression, and the effect of depression on patients with PBC remains to be fully elucidated.
Previous studies demonstrated that HLA alleles were closely related to PBC susceptibility. DRB1*08:03, DRB1*07:01, and DPB1*17:01 conferred an increased risk to PBC among Chinese populations. In another study, DRB1*07:01, 14:01 and 14:05 were the major predisposing alleles for PBC in China. Among Europeans, DRB1*08 was demonstrated to be a risk factor for PBC. HLA-DRB1 alleles were also associated with cirrhosis in patients with autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and chronic hepatitis C. However, DRB1*11 and DRB1*13 were associated with a reduced risk of developing PBC. DRB1*11:01 was also demonstrated to be protective in post-traumatic stress disorder, bipolar affective disorders, and depression of early undifferentiated arthritis. In summary, it is helpful to explore the effect of HLA-DRB1 alleles on depression and further cirrhosis in patients with PBC.

Aims & Methods

A comorbid depression is common in patients with primary biliary cholangitis (PBC), of which the role in disease progression remains unclear. Genetic predisposition such as human leukocyte antigen (HLA)-DRB1 alleles are reported to be linked with both depression and PBC. For better management of PBC, it is pivotal to establish a risk model for cirrhosis that takes depression and HLA-DRB1 alleles into account. In this study, patients with PBC and healthy controls were evaluated for depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Patients with PBC were divided into a model (n = 141) and validation cohort (n = 51). Further, we designed our study to determine the role of depression in treatment response, as well as the effect of depression and HLA-DRB1 alleles on cirrhosis.

Results

In detail, depression was observed to be a common phenomenon in patients with PBC (76/141, 53.9%), and positively associated with levels of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and Immunoglobulin (Ig)M in serum. HLA-DRB1*03:01 allele, which was more common in PBC patients with depression than those without, increased the risk of cirrhosis in patients with PBC (odds ratio [OR], 5.676; p < 0.001). Importantly, our study showed that PHQ-9 score, HLA-DRB1*03:01 allele, and other factors (age and level of ALP), were determined as risk factors for cirrhosis in patients with PBC by logistic analysis. Consistent with the logistic regression model, the elevated PHQ-9 score (>= 3.5) was calculated as a discriminating risk factor for cirrhosis in decision tree model.

Conclusion

In conclusion, the depressive symptom was associated with poor treatment response and was a risk factor for cirrhosis in patients with PBC. These results highlight the important clinical significance of the identification and management of depression in patients with PBC.

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

PP 07 Liver & biliary (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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PRIMARY PERCUTANEOUS STENTING VERSUS ENDOSCOPIC DRAINAGE FOR UNRESECTABLE MALIGNANT HILAR BILIARY OBSTRUCTION: A MULTICENTER RANDOMIZED CONTROLLED TRIAL, THE TESLA RCT

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PRIMARY PERCUTANEOUS STENTING VERSUS ENDOSCOPIC DRAINAGE FOR UNRESECTABLE MALIGNANT HILAR BILIARY OBSTRUCTION: A MULTICENTER RANDOMIZED CONTROLLED TRIAL, THE TESLA RCT

Merve Rousian 1, Jessica Holster 1, Victorien M. T. van Verschuer 2, Stijn Franssen 3, Andries E. Braat 2, Joep de Bruijne 3, Marc C. Burgmans 2, Otto M. van Delden 4, Maxime Dewulf 5, Joris I. Erdmann 6, Jeroen Hagendoorn 3, Akin Inderson 2, Christiaan van der Leij 5, Jan Werner Poley 5, Maarten L. J. Smits 3, Rogier P. Voermans 6, Ijsbrand A. J. Zijlstra 4, Bronno van der Holt 1, Diederik C. Bijdevaate 1, Behnam Mohseny 1, Lydi van Driel 7, Bas Groot Koerkamp 8

Affiliations

1 Erasmus MC Cancer Institute, Rotterdam, Netherlands

2 Leiden University Medical Center, Leiden, Netherlands

3 University Medical Center Utrecht, Utrecht, Netherlands

4 Academic Medical Center (AMC), Amsterdam, Netherlands

5 Maastricht University Medical Center, Maastricht, Netherlands

6 Amsterdam University Medical Center, Amsterdam, Netherlands

7 Erasmus Medical Center, Schiedam, Netherlands

8 Erasmus MC University Medical Center, Rotterdam, Netherlands