The complex relationship between pain, mental health, and quality-of-life in patients with cirrhosis undergoing liver transplant evaluation

Abstract

Goals and Background:

Patients with cirrhosis undergoing liver transplant evaluation have high rates of pain and mental health comorbidities; both may significantly impair health-related quality of life (HRQL). We investigated the association between pain, anxiety/depression, and HRQL in this population.

Study:

In 62 patients with cirrhosis undergoing liver transplant evaluation, we performed four validated assessments to characterize: pain (Brief Pain Inventory-Short Form, BPI-SF), anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-8), and liver-specific HRQL (Chronic Liver Disease Questionnaire). Presence of pain was determined using the BPI-SF screening question. Linear regression was used to identify demographic/clinical factors predictive of pain severity (PS) and interference (PI), and to evaluate the association between pain, anxiety/depression, and HRQL.

Results:

71% of patients reported pain, 26% had clinical depression, and 24% had moderate-severe anxiety. Neither liver disease severity, nor its complications were associated with pain (PS or PI), but anxiety and depression were predictors of pain on bivariate analysis. Only depression remained a significant predictor of PS (b=0.28, P<0.05) and PI (b=0.30, P<0.05) in multivariable models. HRQL was inversely associated with PS, PI, depression, and anxiety, but only anxiety (b=−0.14, P=0.003) remained associated with HRQL in the adjusted model.

Conclusions:

Pain is present in over 70% of patients with cirrhosis undergoing liver transplant evaluation. Anxiety and depression were highly correlated with pain and appeared to be key drivers in predicting poor HRQL. Evaluating and managing mental health comorbidities should be explored as a strategy to improve HRQL in patients with cirrhosis and pain.

Introduction

Chronic pain is increasingly common and has been identified as a global public health research priority.¹ Patients with cirrhosis are disproportionately affected by pain, which is reported by up to 80% of this population.^2–4 The multidimensional nature of pain makes it difficult to manage even in the general population. These challenges are magnified in patients with cirrhosis due impaired hepatic metabolism and renal excretion, as well as provider concerns about analgesic-related adverse effects (e.g. renal failure, gastrointestinal bleed, and hepatic encephalopathy) and potential for misuse and abuse in this population.^5–7 As a result, patients with cirrhosis are at particularly high risk for undertreatment of pain, which can profoundly impair their quality of life.

The impact of pain on patients’ lives has been well-reported in the literature. In both the general population and in those with other chronic diseases, pain is associated with poor quality of life.^8,9 This may be explained in part by the effect of pain on mental health. The relationship between pain and mental health is well-established in the general population, as individuals with persistent pain are four times more likely to suffer from depression and anxiety.¹⁰

Irrespective of pain, patients with cirrhosis have lower quality of life than the general population, as well as high rates of mental health comorbidities, including depression, anxiety and substance use disorders.^11–16 Moreover, the liver transplant process has been found to independently affect mental health, which can adversely impact outcomes before and after liver transplantation.^16–21 The presence of pain in this population, which can lead to further impairment in mental health and quality of life, may be particularly detrimental. Yet the relationship between pain, mental health, and quality of life in cirrhosis patients has been largely understudied.

In patients with other chronic diseases, pain, mental health, and quality of life have been connected using biopsychosocial models to understand and manage pain.^22–24 These data suggest an interplay between pathologic processes and psychosocial contributors in the experience of chronic pain, which strongly influences quality of life. However, the biopsychosocial model has not yet been applied to understanding or managing pain in patients with cirrhosis. The objective of this study is to assess the relationships between pain, anxiety, depression, and quality of life in a cohort of patients with cirrhosis undergoing liver transplant evaluation, with the ultimate goal of developing targeted interventions to improve quality of life and outcomes in this population.

Materials and Methods

Participants

Patients with cirrhosis who were seen in the outpatient UCSF Liver Transplant Clinic from September 29, 2022 to March 13, 2023 were eligible to participate in this cross-sectional study. Patients who did not speak English were excluded due to the unavailability of the questionnaires in other languages. This study was conducted as a part of the Functional Assessment in Liver Transplantation (FrAILT) Study, the methods of which have been previously described.^25,26 This study was approved by the IRB.

Study procedures

At a single visit during the pre-transplant evaluation, patients underwent four assessments to evaluate pain, anxiety, depression, and health-related quality of life:

1. Brief Pain Inventory-Short Form (BPI-SF)²⁷

The Brief Pain Inventory is a self-administered questionnaire that provides information about the intensity, location, and quality of pain. Numeric scales (range 0 to 10) indicate the intensity of pain. A figure representing the body is provided for the patient to shade the area corresponding to pain. Specific BPI-SF questions assess patients’ pain severity (PS) and the remaining questions assess pain interference (PI), or the degree to which pain interferes with function, mood, and enjoyment of life. We calculated PS and PI scores as the average ratings across items in the respective subscales. For our binary categorization of patients as having vs not having pain, we used patients’ answer to question 1: “Throughout our lives, most of us have had pain from time to time (such as minor headaches, sprains, and toothaches). Have you had pain other than these everyday kinds of pain today?” This survey has been well-validated to assess and characterize pain in many patient populations.^28–30

2. Generalized Anxiety Disorder-7 (GAD-7)³¹

The GAD-7 is the most commonly used anxiety survey. It is a brief self-report scale of general anxiety consisting of 7 items asking the patient how much they were bothered by each symptom in the last two weeks. The response options were “not at all,” “several days,” “more than half the days,” and “nearly every day,” scored as 0, 1, 2, and 3 respectively. The total score is calculated as the sum of the seven responses, with a higher score indicating a higher level of anxiety. A sum of 10–14 is consistent with moderate anxiety, and a sum of 15–21 is consistent with severe anxiety.

3. Patient Health Questionnaire-8 (PHQ-8)³²

This instrument is a brief self-report scale of depression consisting of 8 items asking the patient how much they were bothered by each symptom in the last two weeks. The response options were “not at all,” “several days,” “more than half the days,” and “nearly every day,” scored as 0, 1, 2, and 3 respectively. The total score is calculated as the sum of the eight item scores, with a higher score indicating a higher level of depression. A total score of 10 or higher on the PHQ-8 is consistent with depression. The PHQ-8 was chosen instead of the PHQ-9, which includes a question about suicidality. Prior studies have found that there is no difference between the two in detecting depression.^33,34

4. Chronic Liver Disease Questionnaire (CLDQ)³⁵

This disease-specific instrument was designed for patients with chronic liver disease, and has been validated among patients with different cirrhosis etiologies.^35–38 It is a 29-item self-reported questionnaire (each response ranging from 1 to 7), which provides a composite health-related quality of life, as well as specific quality of life scores across six domains (abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry).

Covariables

Covariables, including gender, race, ethnicity, education, marital status, Body Mass Index (BMI), comorbidities, presence of hepatocellular carcinoma (HCC), cirrhosis etiology, Model for End-Stage Liver Disease (MELD), Liver Frailty Index (LFI), and history of ascites and hepatic encephalopathy were collected as part of the FrAILT study through chart review.

Statistical Analysis

Survey measures, demographic variables, and clinical characteristics were described using frequencies and percentages for categorical variables, and medians and interquartile ranges (IQR) for continuous variables. Correlations between variables were assessed with Pearson’s correlation coefficients (r).

We performed simple and multiple regression models to determine associations between the clinical and mental health characteristics and pain (pain severity score and interference score, from the BPI) and Quality of Life (CLDQ total score) outcomes. For the multiple regression models, we selected covariates a priori, based on their clinical importance and potential association with the outcome in the population. All model assumptions were tested and satisfied. Statistical tests were two-sided and Bonferroni adjustments were made to account for multiple comparisons with the simple regression models. Inferences in these models were held to an alpha-level of 0.003. Multiple regression models used a standard alpha=0.05 since there was only one such model per outcome. We assessed multicollinearity by looking at variance inflation factors (VIF) and comparing coefficient estimates and adjusted R² for models with and without one or both highly correlated variables.

Data was mostly complete (95–100%). Missing data was excluded case-wise from regression models. Statistical analyses were performed using R-Studio (Posit team, 2022) and R Statistical Software v4.2.2 (R Core Team, 2022).

Results:

Baseline characteristics

Baseline characteristics of this cohort of patients with cirrhosis undergoing liver transplant evaluation (N=62) are shown in Table 1. Median age was 54, 53% were White, 44% were female, and 65% were in a committed partnership. Median MELD-Na was 16, 65% had a history of ascites, and 53% had a history of hepatic encephalopathy.

Table 1:

Demographic and clinical characteristics of patients undergoing liver transplant evaluation (N=62)

Demographic characteristics
Age (Median, IQR)	54 (45–63)
Gender
Male	35 (56.5)
Female	27 (43.5)
Race/Ethnicity
Asian	5 (8.0)
Black or African American	6 (9.7)
Latinx	18 (29.0)
White, non-Hispanic	33 (53.2)
Education
High school or less	29 (46.8)
Any college or higher	32 (51.6)
Missing	1 (1.6)
Marital Status
Committed Partnership	40 (64.5)
Other	20 (32.3)
Missing	2 (3.2)
Clinical characteristics
Body Mass Index (Median, IQR)	28.3 (24.6–32.2)
Comorbidities
Hypertension	28 (45.2)
Diabetes	16 (25.8)
Hepatocellular carcinoma	14 (22.6)
Cirrhosis Etiology
Alcohol	28 (45.2)
Hepatitis B	0
Hepatitis C	7 (11.3)
NASH	16 (25.8)
Autoimmune	2 (3.2)
Other	8 (12.9)
Unknown	1 (1.6)
MELD score (Median, IQR)	16 (12–19.5)
Liver Frailty Index	3.8 (3.2–4.1)
Complications
History of Ascites
None	22 (35.5)
Non-refractory	24 (38.7)
Refractory	16 (25.8)
History of hepatic encephalopathy	33 (53.2)

^*All variables are reported as n (%) unless otherwise specified.

Characterization of pain, depression, and anxiety in cohort

In this cohort, 71% of the patients experienced pain (answered “yes” to question 1) at the time of their evaluation, and 60% had experienced moderate or severe pain in the preceding 24 hours (Table 2). Additionally, 26% were depressed (PHQ-8≥10) and 24% had moderate-severe anxiety (GAD-7≥10). Among those who experienced pain, the median “worst pain in the last 24 hours” was 8 (out of 10, IQR 6–10) and the median “average pain in the last 24 hours” was 5 (IQR 4–7). The most common pain location was lower limb (57%), followed by back (46%). 32% reported abdominal pain. 52% experienced pain in more than one location.

Table 2:

Pain, mental health and quality-of-life survey results for cohort

	Full cohort (N=62)		Patients with Pain* (N=44)
	Min-Max	Median (IQR) / N (%)	Min-Max	Median (IQR) / N (%)
Pain (BPI Short-form)
Pain Severity	0–10	3.5 (1.1–5.6)	0.75–10	4.3 (3.3–6.3)
Pain Interference	0–10	1.4 (0.0–5.5)	0–10	3.9 (1.0–6.3)
Pain Severity Items
Item 3 “Worst Pain in last 24h”	0–10	5.0 (2.0–7.0)	1–10	8.0 (6.0–10.0)
Item 4 “Least Pain in last 24h”	0–10	1.0 (0.0–3.0)	0–10	2.0 (0.0–5.0)
Item 5 “Average Pain in last 24h”	0–10	4.0 (1.0–6.0)	0–10	5.0 (3.8–7.0)
Item 6 “Current Pain”	0–10	2.0 (0.0–5.0)	0–10	3.5 (1.0–7.0)
Item 3: Worst Pain in last 24 hours
Absence (0)		13 (21%)
Mild (1–4)		12 (19%)		8 (18%)
Moderate (5–6)		14 (23%)		13 (30%)
Severe (7–10)		23 (37%)		23 (52%)
Item 2: Pain Location (can mark >1 location)
Head or neck		8 (13%)		7 (16%)
Back		23 (37%)		20 (46%)
Abdominal		16 (26%)		14 (32%)
Upper Limb		16 (26%)		15 (34%)
Lower Limb		26 (42%)		25 (57%)
Depression (PHQ-8)
Total Score	0–24	5.0 (2.0–9.8)	0–24	6.0 (3.0–11.3)
Diagnostic cut-off
Clinically depressed (≥10)		16 (26%)		14 (32%)
Not depressed (<10)		46 (74%)		30 (68%)
Anxiety (GAD7)
Total Score	0–21	3.5 (1.0–8.8)	0–21	4.0 (2.0–10.0)
Diagnostic cut-off
Generalized Anxiety (≥8)		19 (31%)		17 (39%)
Not generalized anxiety (<8)		43 (69%)		27 (61%)
Severity classification
Minimal (0–4)		39 (63%)		23 (52%)
Mild (5–9)		8 (13%)		8 (18%)
Moderate (10–14)		10 (16%)		9 (21%)
Severe (15–21)		5 (8%)		4 (9%)
Quality of Life (Chronic Liver Disease Questionnaire)
Total score	1–7	4.9 (3.4–5.9)	1–6.6	4.5 (3.4–5.6)
Abdominal symptoms	1–7	5.0 (3.3–6.5)	1–7	4.8 (3.3–6.0)
Fatigue	1–7	5.0 (2.8–6.0)	1–7	4.6 (2.5–5.4)
Systemic symptoms	1–7	5.2 (3.8–5.8)	1–6.8	4.8 (3.6–5.8)
Activity	1–7	5.7 (3.9–6.7)	1–7	5.2 (3.3–6.4)
Emotional function	1–7	5.3 (3.6–6.4)	1–7	4.9 (3.1–6.1)
Worry	1–7	4.4 (3.0–5.4)	1–6.6	4.1 (2.9–5.3)

^*Pain defined as “yes” response for BPI item 1.

Patients who reported pain also reported that pain interfered with their daily activities, with a median pain interference score of 3.9 (out of 10, IQR 1.0–6.3). In addition, many of the patients with pain suffered from depression and anxiety: 32% met criteria for clinical depression and 39% met criteria for generalized anxiety.

Predictors of pain severity

Differences in pain severity (PS) by key clinical demographic and clinical characteristics are shown in Table 3 and Figure 1A. On simple linear regression, depression and anxiety were significantly associated with PS: higher depression or anxiety was associated with more severe pain (b=0.2, P<0.001 for both). No other demographic or clinical characteristics were associated with pain severity. In the adjusted multiple regression model, depression and history of ascites each independently predicted pain severity (b=0.3, P=0.01 and b=−2.3, P=0.02, respectively). On average, higher depression scores were associated with an increase in severity whereas a history of ascites was associated with lower pain severity. Notably, anxiety was not a significant predictor of pain severity after controlling for depression and the other covariates.

Table 3.

Associations between demographic and clinical characteristics and pain severity/interference (N=62)

	Pain Severity						Pain Interference
	Crude estimates			Adjusted estimates			Crude estimates			Adjusted estimates
Demographic characteristics	b	se	p-value 1	b	se	p-value	b	se	p-value 1	b	se	p-value
Intercept	-	-	-	5.3	1.2	-	-	-	-	5.4	1.22	-
Age	−0.07	0.03	0.01	−0.003	0.03	0.9	−0.1	0.03	0.008	0.03	0.04	0.5
Female gender	1.1	0.67	0.1	0.3	0.69	0.7	0.6	0.84	0.5	−0.3	0.73	0.7
Race ethnicity
Asian	−1.8	1.26	0.2	−1.6	1.12	0.2	−2.4	1.47	0.1	−2.0	1.15	0.09
Black	−0.2	1.16	0.9	−1.1	1.05	0.3	−0.7	1.47	0.6	−2.5	1.16	0.04
Latinx	1.0	0.77	0.2	1.3	0.87	0.1	1.2	0.91	0.2	0.6	0.91	0.5
White (reference)	-	-	-	-	-	-	-	-	-	-	-	-
Married	−1.8	0.70	0.01	−0.7	0.79	0.4	−1.4	0.86	0.1	−0.6	0.85	0.5
College education or higher	−1.5	0.66	0.03	−0.5	0.72	0.5	−2.2	0.79	0.008	−0.5	0.77	0.5
Clinical characteristics
BMI	0.00	0.05	0.9	−0.1	0.05	0.07	0.00	0.07	0.9	−0.1	0.05	0.2
Diabetes	−0.6	0.77	0.4	0.2	0.74	0.7	−1.3	0.91	0.1	−1.1	0.76	0.2
Hepatocellular Carcinoma	−0.8	0.81	0.3	−1.4	1.07	0.2	−1.9	0.97	0.06	−1.7	1.11	0.1
Alcohol Etiology	1.2	0.67	0.09	1.9	0.97	0.1	1.9	0.80	0.02	1.5	1.00	0.2
MELD score	−0.02	0.06	0.8	−0.1	0.07	0.1	0.04	0.07	0.6	−0.08	0.07	0.2
History of ascites	0.3	0.71	0.7	−2.3	0.91	0.02	1.2	0.85	0.2	−0.8	0.95	0.4
History of HE	0.4	0.68	0.6	−0.7	0.84	0.4	0.6	0.82	0.5	−1.8	0.89	0.05
Predictors of Interest
Depression (PHQ-8)	0.2	0.05	<0.001	0.3	0.11	0.01	0.4	0.05	<0.001	0.3	0.12	0.01
Anxiety (GAD-7)	0.2	0.05	<0.001	−0.03	0.12	0.8	0.4	0.05	<0.001	0.1	0.12	0.3

^*Continuous predictors were all mean centered.

^1.Crude estimate p-values were compared to a Bonferroni correction, alpha=0.05/15 comparisons = 0.003

Figure 1.

Pain severity and pain interference among cirrhosis patients by clinical characteristics.

Predictors of pain interference

Differences in pain interference (PI) by key demographic and clinical characteristics are shown in Table 3 and Figure 1B. Looking at simple regression models predicting PI, we again found that depression and anxiety were the only significant predictors at the $\alpha =0.003$ level. Higher depression or anxiety was associated with higher pain interference scores (b=0.4, P<0.001 for both). In the multiple regression model, Black race (vs. White) and depression independently predicted pain interference after controlling for demographic and clinical characteristics. On average, patients with higher depression reported higher pain interference scores (b=0.3, P=0.01). Patients who identified as Black reported lower pain interference scores compared to White patients (b=−2.5, P=0.04), after controlling for the other variables in the model.

The relationship between depression, anxiety, and pain

Depression (as measured by PHQ-8) and anxiety (as measured by GAD-7) are highly correlated constructs (r=0.84, Table S1). Depression alone and anxiety alone are each a strong predictor of BPI Pain Severity and BPI Pain Interference. However, when both variables are included in the model, depression remained a significant predictor of pain severity (b=0.3, P=0.01) and pain interference (b=0.3, P=0.01), while anxiety was no longer a significant predictor (Table S2).

Predictors of quality of life

As shown in Table 4, we found significant associations between quality of life and a history of ascites, mental health (depression and anxiety) and pain (both PS and PI) with simple regression models. Patients with a history of ascites reported lower quality of life compared to those without ascites (b=−1.3, P=0.002). Quality of life was also inversely associated with depression (b=−0.2, P=<0.001), anxiety (b=−0.2, P=<0.001), pain severity (b=−0.2, P=0.002), and pain interference (b=−0.3, P=<0.001). In the adjusted multiple regression model, alcohol-related etiology (b=1.0, P=0.02) and anxiety (b=−0.2, P=0.002) independently predicted quality of life. The adjusted effects of pain, anxiety, and depression on quality-of-life for a representative patient are shown in Figure 2.

Table 4.

Associations between demographic and clinical characteristics and Quality of Life (CLDQ Total Score) (N=62)

	Crude estimates			Adjusted estimates
Demographic characteristics	b	se	p-value	b	se	p-value
Intercept	-		-	3.9	0.50	-
Age	0.04	0.02	0.02	0.01	0.02	0.6
Female gender	−0.4	0.41	0.3	−0.1	0.30	0.7
Race ethnicity
Asian	0.8	0.75	0.3	0.2	0.47	0.7
Black	−0.5	0.70	0.4	0.6	0.49	0.2
Latinx	−0.8	0.46	0.1	0.6	0.39	0.2
White (reference)	-	-	-	-	-	-
Married	0.6	0.43	0.2	0.4	0.34	0.2
College or higher education	1.1	0.39	0.006	0.7	0.32	0.047
Clinical characteristics
BMI	−0.01	0.03	0.7	0.0	0.02	0.9
Diabetes	0.2	0.47	0.7	0.4	0.31	0.2
Hepatocellular Carcinoma	1.2	0.48	0.02	−0.2	0.47	0.7
Alcohol-related cirrhosis etiology	−0.6	0.41	0.1	1.0	0.42	0.02
MELD score	−0.04	0.03	0.2	−0.006	0.02	0.8
History of hepatic encephalopathy	−0.9	0.39	0.02	−0.4	0.37	0.3
History of ascites	−1.3	0.40	0.002	−0.7	0.42	0.1
PHQ-8 total score (Depression)	−0.2	0.02	<0.001	−0.1	0.05	0.1
GAD-7 total score (Anxiety)	−0.2	0.02	<0.001	−0.2	0.05	0.002
BPI Pain Severity	−0.2	0.07	0.002	0.1	0.07	0.2
BPI Pain Interference	−0.3	0.05	<0.001	−0.06	0.07	0.4

^*Continuous predictors were all mean centered.

^1.Crude beta estimate p-values were compared to a Bonferroni correction, alpha=0.05/17 comparisons = 0.003

Figure 2.

Adjusted quality of life by severity of pain, anxiety, and depression severity for a representative patient with the following characteristics: White, 54-years-old, married male with non-alcohol related cirrhosis, less than college education, BMI 28, no comorbidities, no cirrhosis complications, MELD 16.

Discussion

In this cross-sectional study of 62 patients with cirrhosis undergoing evaluation for liver transplantation, over 70% reported pain at the time of their evaluation. Depression was the strongest predictor of pain in this cohort. Interestingly, neither cirrhosis severity nor cirrhosis-specific complications were associated with higher pain severity or interference. While pain was independently associated with quality of life on simple regression, on multivariable analysis it appeared that mental health comorbidities, and specifically anxiety, were the primary drivers of quality of life even after adjusting for all demographic and clinical characteristics.

Why might anxiety and depression be such strong predictors of pain and poor quality of life? The relationship between these factors has previously been described in the chronic pain literature through the biopsychosocial model of pain, which considers the pathology of the pain, the patient’s experience of the pain, and the functional limitations and distress.²³ Patients with anxiety or depression are more likely to have higher perceived stress, more negative affect, and poorer adherence to treatment.^39,40 Additionally, depression and pain share neurotransmitter pathways. Serotonin and norepinephrine—neurotransmitters which are dysregulated in patients with depression—have been shown to dampen pain signals, altering individuals’ perception of pain.⁴⁰ Therefore, depression can lead to increased sensation of pain and thus poor quality of life, since pain can directly limit an individual’s ability to perform activities of daily living, take part in social activities, and gain satisfaction from their roles and responsibilities— all factors that have been found to lead to a decline in one’s quality of life.⁸

The findings of this study have important implications for the care of patients with cirrhosis, in whom pain is common but difficult to treat. Analgesics are thought to pose significant risks to this population, due to decreased hepatic metabolism, increased risk for adverse effects, and concurrent comorbidities, such as renal impairment and substance use disorders.^5–7 As a result, many patients with cirrhosis report that their pain is not adequately relieved.² Our findings suggest that acknowledging and leveraging the relationship between pain and mental health may help improve analgesia and quality of life in cirrhosis patients. Exploring such relationships, through the biopsychosocial model, in other populations has helped providers to better understand their patients’ pain and ultimately led to improved pain control.⁴¹ Given the challenges of managing pain in the cirrhosis population, this study highlights management of mental health comorbidities (through pharmacotherapy, psychotherapy, or other nonpharmacologic therapies) as an area that can be further studied to improve the experience of pain and quality of life in patients with cirrhosis (Figure 3).

Figure 3.

Proposed biopsychosocial model which can inform management of pain in patients with cirrhosis

This study has some limitations. First, the cross-sectional study design can only identify the associations between pain, mental health, and quality of life, but cannot prove causality. It also does not explore changes in pain over time in this population. However, prior literature on patients with other chronic diseases has pointed to a multidirectional relationship between these experiences.^23,39,40 Therefore, it is hypothesized that this would also be the case in patients with cirrhosis. Second, this study is also limited by its relatively small sample size at a single transplant center, so the results may not be generalizable. Additionally, pain is a subjective experience that may be under- or overreported, making its variability challenging to control for. Finally, there are likely other confounding variables that explain this complex relationship, which are not accounted for in this analysis. However, while our covariates only explained 46–66% of the variation in our PS and PI models, they explained 82% of the variation in our quality-of-life model (Table S2).

Despite these limitations, this study is one of the first to evaluate pain and its relationship with mental health disorders and health-related quality of life specifically in the cirrhosis population. The strong association between pain, mental health, and quality of life highlights the potential of depression and anxiety treatment as an effective pain management target for cirrhosis patients that may significantly improve their quality of life.