Assessment of mental health in patients with chronic liver disease

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INTRODUCTION

Depression and anxiety are prevalent in cirrhosis, portending a worse prognosis if left untreated, leading to a marked reduction in quality of life (QoL), increased symptom and hospitalization burden, increased waitlist and post‐liver transplantation (LT) mortality, and worse psychiatric outcomes. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ Effective recognition and treatment of depression has been shown to improve risk of decompensation and mortality in primary biliary cholangitis and may reduce the incidence of acute cellular rejection and post‐LT mortality. ⁷ , ⁸ , ⁹ , ¹⁰

APPROACH TO SCREENING TOOLS FOR MENTAL ILLNESS

The U.S. Preventive Services Task Force recommends screening for depression, regardless of risk factors, in all adults of 18 years or older. ¹¹ Despite these recommendations, screening for depression occurs infrequently in the primary care setting. ¹² The frequency of mental illness screening among hepatology practitioners is unknown.

Screening tools may be administered by a clinician, patient, reported via surveys or structured interviews with health professionals, or elicited via collateral report. ¹³ Any positive screen should be followed up with appropriate care, including a confirmation of diagnosis and linkage to treatment with a mental health provider. ¹¹ , ¹⁴ Well‐validated and well‐constructed tools for the detection of mental illness for patients with cirrhosis are lacking. ³ We review various psychological screening and evaluation tools, their validation in other disease states, and how they have been used to further understand mental illness in patients with liver disease.

AVAILABLE TOOLS

Structured diagnostic interview tools

The Mini International Neuropsychiatric Interview (MINI) is a structured diagnostic interview for the assessment of major psychiatric disorders. ¹⁵ Its shorter length allows for administration in the clinical setting as a follow‐up to a positive result of a screening tool. ¹⁵ In other studies of depression screening tools, the MINI has been used as the diagnostic gold standard to assess the validity of the tools’ results in various patient populations. ¹⁶ , ¹⁷ In a study that examined patient and providers’ experience with the MINI, both patients and providers viewed it favorably, finding that the questions were comprehensive, helped patients to better understand their mental illness, and allowed for the detection of other psychiatric comorbidities. ¹⁸

Patient self‐report tools

The Beck Depression Inventory (BDI) is a screening tool for depression that relies upon patient self‐report. ¹⁹ , ²⁰ It includes questions regarding somatic symptoms, such as insomnia, poor appetite, and fatigue in addition to depression. ²¹ , ²² Due to overlap of somatic symptoms of both depression and cirrhosis, the prevalence in studies that use the BDI‐II may be falsely elevated. ¹⁰ One study found that a more accurate measure of depression in patients with hepatitis C virus (HCV) infection could be obtained through the BDI‐II if analysis if the Cognitive‐Affective items were done separately from the Somatic subscale items (Table 1). ²²

TABLE 1.

Screening tool characteristics

Screening tool	Mental illness	Administered by	Time to administer	Number of questions	Screen for somatic symptoms	How to obtain
BDI‐II	Depression	Patient	5–10 min	21	Yes	Purchase
PHQ‐2	Depression	Patient	<2 min	2	No	Free online
PHQ‐9	Depression	Patient	5 min	9	Yes	Free online
HADS	Anxiety, depression	Patient	2–5 min	14	No	Purchase
HAM‐A	Anxiety	Provider, patient	–	14	Yes	Free online
GAD‐7	Anxiety	Patent	2–5 min	7	No	Free online
MINI	Anxiety, depression, and more	Provider	15–30 min	–	–	Purchase
BAI	Anxiety	Patient	–	21	Yes	Purchase
HDRS	Depression	Provider	20–30 min	17	Yes	Free online

Abbreviations: BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; GAD‐7, Generalized anxiety disorder; HADS, Hospital anxiety depression scale; HAM‐A, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; MINI, Mini International Neuropsychiatric Interview; PHQ‐9, Patient Health Questionnaire; SIPAT, Stanford Integrated Psychosocial Assessment for Transplantation; STAI; State‐Trait Anxiety Index.

The Patient Health Questionnaire‐9 (PHQ‐9) is a widely used questionnaire that allows for the detection of depression and assessment of its severity in the clinical setting. ¹⁴ It has been validated in a wide variety of patient populations, and its diagnostic accuracy of the PHQ‐9 was excellent, particularly with a score cutoff of 10 or greater. ²³ The Patient Health Questionnaire‐2 (PHQ‐2) is a shorter version of this and includes two questions regarding the presence of depressed mood and anhedonia. A positive screen then can be followed by the more in‐depth PHQ‐9. A patient‐administered version, where the patient rates depression and anhedonia on a scale of 0 to 3, demonstrates a sensitivity of 83% and specificity of 92% for a score of 3 or greater. ²⁵

The Hamilton Depression Rating Scale (HDRS) was once considered the gold standard tool for depression screening. Initially developed for the administration by physicians to hospitalized patients, it includes several questions related to somatic symptoms, such as insomnia, loss of appetite, and diarrhea symptoms, which frequently trouble patients with chronic liver disease. The tool can also be used to assess response to treatment for depression. ²⁶ The length of time to administer (20–30 min) and the fact that it must be physician administered is a significant limitation to this tool. ²⁷

The Hospital Anxiety and Depression scale (HADS) is a validated tool which produces a score for both anxiety (HADS‐A) and depression (HADS‐D). ²⁸ The HADS tool is unique in that it excludes somatic symptoms of depression or anxiety, such as insomnia, fatigue, headaches, and dizziness, as it is intended to identify mental illness in patients who also have physical illness. ²⁸ In one review of 747 studies, the HADS‐D and HADS‐A had a medium to strong correlation when compared to other tools such as the BDI. ²⁹ The HADS may be a more appropriate tool for those with lower level of education achieved and a high burden of somatic symptoms. ³⁰ Sensitivity and specificity of this tool using 8 as a cutoff score are around 80 and 90 percent, respectively. ³¹

The Generalized Anxiety Disorder (GAD)‐7 scale is a self‐administered questionnaire that is commonly used in the primary care setting. ³² It does not screen for the presence of nonspecific somatic symptoms but includes questions pertaining to patients’ thoughts and worries. A higher score is indicative of a greater degree of functional impairment due to GAD, and a cutoff of 10 allows for adequate sensitivity and specificity. ³³ , ³⁴ It is well‐validated in various patient populations. ³⁵ , ³⁶ , ³⁷ An abbreviated version that could be used as a preliminary assessment to the GAD‐7 is the GAD‐2, which also is designed to screen for the aforementioned disorders. It has a similar sensitivity and specificity for GAD detection as the GAD‐7 tool (86% and 83% respectively). ³⁸

The Beck Anxiety Inventory (BAI) is a self‐assessment tool for anxiety that effectively differentiates between anxiety and depression symptoms. The BAI has been suggested to have superior ability to identify those with panic disorder. ³⁹ It includes questions regarding somatic manifestations of anxiety, including difficulty relaxing and dizziness. Because of its emphasis on somatic symptoms, its discriminant validity is diminished when used in healthier patient populations. ³¹ Using a score of 8 as a cutoff in one study, the BAI sensitivity approached 89% and its specificity was 97%. ³⁹

The Hamilton anxiety rating scale (HAM‐A) is a widely used tool for the measurement of severity of anxiety symptoms. Initially developed for clinician administration, the tool is now available for patients to self‐administer. However, it is mainly used in the clinical research setting. In addition to eliciting psychological symptoms of anxiety, the survey includes somatic questions, including difficulty concentrating, fatigability, and insomnia. ⁴⁰

Several studies have included a variety of these screening tools to determine the prevalence of anxiety and depression in patients with chronic liver disease (CLD) (see Table 2). While there is heterogeneity with respect to the screening tools used, these studies demonstrate a high prevalence of depression and anxiety in the liver disease patient population. Patients with depression report poorer health‐related QoL (HRQoL) and higher rates of fatigue. ⁴¹ , ⁴² , ⁴³ The presence of mental illness complicates post‐LT recovery, leading to a higher prevalence of graft failure and a poorer post‐LT recovery. ⁴⁴ , ⁴⁵ Notably, there are no studies that validate these tools and their ability to accurately screen for mental illness in the liver disease patient population. Because there are insufficient data to recommend one tool over another when screening for mental illness in patients with CLD, further studies are needed to validate these tools in the chronic liver disease patient population.

TABLE 2.

Recent studies of mental health issues in patients with liver disease and liver transplantation recipients

Authors	Screening tool	Mental illness	Patients	Findings
Buganza‐Torio (2018) 43	MINI	Depression	305 patients with CLD	‐Depression prevalence 18% ‐Depressed patients were frailer, had lower HRQoL
	HADS
Corruble (2011) 44	BDI short form	Depression	339 LT and KT candidates	‐Depression prevalence >50% ‐LT graft failure within 18 months more common in patients with depression
Lee (2013) 48	PHQ‐9	Depression	10,231 patients with CLD	‐Those with HCV‐related liver disease most likely to have depression and MDD compared to other etiologies of liver disease
Hernaez (2021) 48	PHQ‐9	Depression/anxiety	1021 patients with CLD	‐Prevalence of moderately severe to severe depression was 15.6% ‐Widowed state, fear of HCC, poor self‐reported health associated with more severe depression ‐Prevalence of moderate to severe anxiety>40%
Telles‐Correia (2011) 49	HADS	Depression	84 LT recipients	‐Pre‐LT depression did not predict post‐LT mortality
Kalaitzakis (2012) 42	HADS	Depression/anxiety	108 LT candidates	‐Prevalence of anxiety/depression 23% ‐Psychological distress predicted presence of fatigue
Miller (2013) 45	HADS	Depression	82 LT recipients	‐More severe depression in pre and post‐LT evaluation predicted poorer self‐reported 6‐month recovery ‐Those with persistent fatigue after LT more frequently had pre‐LT depression
Youssef et al (2013) 50	HADS	Depression/anxiety	567 patients with biopsy‐proven NASH	‐Prevalence of subclinical depression 53%, depression 14% ‐Prevalence of subclinical anxiety 45%, anxiety 25% ‐Depression significantly associated with hepatocyte ballooning
Janik et al (2019) 51	PHQ‐9, GAD‐7, MINI	Depression/anxiety	14 patients with AIH	‐Prevalence of depression 60% ‐Prevalence of anxiety/stress‐related disorder 20%
Schramm et al (2014) 52	PHQ‐9	Depression/anxiety	103 patients with AIH	‐Prevalence of depression 10.8% ‐Rate of severe symptoms of anxiety exceeded that of general population
	GAD‐7

Abbreviations: AIH, autoimmune hepatitis; GAD‐7, Generalized anxiety disorder; HADS, hospital anxiety depression scale; HRQoL, health‐related quality of life; LT, liver transplant; MINI, Mini International Neuropsychiatric Interview; NASH, nonalcoholic steatohepatitis; PHQ‐9, Patient Health Questionnaire; STAI; State‐Trait Anxiety Index.

CONSIDERATIONS FOR HEPATOLOGISTS

Given the high prevalence of mental illness among patients with CLD, the use of screening tools in clinic may identify those at greatest need of attention from a mental health provider (MHP). Given the high degree of somatic symptoms associated with chronic liver disease, the use of the HADS‐D and HADS‐A screening tools may be best suited to discriminate between mental illness and liver‐related symptoms. Given their brevity and ease of administration, the PHQ‐2 and GAD‐2 may be used as pre‐screening tools as well. The integration of mental health screening tools into intake forms is feasible and could facilitate the identification of patients with possible underlying mental illness. A positive screen could then be reviewed by a hepatologist who could then gauge the severity of symptoms and determine need for referral/triage to dedicated MHPs. Because several of these tools also assess for suicidality, it would be of utmost importance to ensure that positive screens for such would trigger further evaluation and safety planning with linkage to appropriate care. The integration of MHPs within a hepatology clinic has been demonstrated to improve adherence and outcomes among patients with chronic HCV infection. ⁴⁶ Verma et al demonstrated that, when MHPs are embedded within hepatology clinics to deliver point‐of‐care assessment and treatment for hepatology patients with positive mental illness screens during intake, there is a significant improvement in QoL of patients over time. ⁴⁷ If it is not possible to imbed a provider within clinic, then ensuring easy linkage to mental health care following a positive screen is necessary.

CONCLUSION

Addressing the mental health of patients with liver disease is essential to providing holistic, comprehensive care. Anxiety and depression are prevalent and possibly underrecognized and underdiagnosed in this patient population. The variety of clinical tools available for the detection of symptoms of anxiety and depression are not well‐validated in patients with liver disease, but their use may be helpful in identifying patients in need of mental health care.

CONFLICT OF INTEREST

M.S. consults for Gilead, Inc.

Whitsett MP, Goswami Banerjee A, Serper M. Assessment of mental health in patients with chronic liver disease. Clin. Liver Dis. 2022;20:52–56. 10.1002/cld.1214