Authors: Derek D. Satre (1Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, CA USA.; 2Kaiser Permanente Northern California, Division of Research, Pleasanton, CA USA.), Dhweeja Dasarathy (3Vanderbilt School of Medicine, Nashville, TN USA.), Steven L. Batki (1Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, CA USA.; 4Mental Health Service, Veterans Affairs San Francisco Health Care System, San Francisco, CA USA.), Michael J. Ostacher (5Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA USA.; 6Department of Psychiatry, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA USA.), Hannah R. Snyder (7Department of Family and Community Medicine, University of California, San Francisco, CA USA. University of California, San Francisco, Department of Psychiatry and Behavioral Sciences, San Francisco, CA USA.), William Hua (1Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, CA USA.; 4Mental Health Service, Veterans Affairs San Francisco Health Care System, San Francisco, CA USA.), Priti Parekh (8Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA USA.), Amy M. Shui (9Department of Epidemiology and Biostatistics, University of California, San Francisco, CA USA.), Ramsey Cheung (8Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA USA.; 10Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA USA.), Alexander Monto (11Division of Gastroenterology and Hepatology, Veterans Affairs San Francisco Health Care System, San Francisco, CA USA.), Robert J. Wong (8Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA USA.; 10Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA USA.), Jennifer Y. Chen (12Division of Gastroenterology and Hepatology, Zuckerberg San Francisco General, San Francisco, CA USA.; 13Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, CA USA.), Meimei Liao (8Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA USA.), Michele Tana (12Division of Gastroenterology and Hepatology, Zuckerberg San Francisco General, San Francisco, CA USA.; 13Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, CA USA.; 15University of California San Francisco Liver Center, San Francisco, CA USA), Po-Hung Chen (14Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD USA), Christina G. Haight (11Division of Gastroenterology and Hepatology, Veterans Affairs San Francisco Health Care System, San Francisco, CA USA.), Taylor Fakadej (12Division of Gastroenterology and Hepatology, Zuckerberg San Francisco General, San Francisco, CA USA.; 13Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, CA USA.), Mandana Khalili (12Division of Gastroenterology and Hepatology, Zuckerberg San Francisco General, San Francisco, CA USA.; 13Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, CA USA.; 15University of California San Francisco Liver Center, San Francisco, CA USA)
Categories: Article, cirrhosis, alcohol, depression, metabolic-associated steatohepatitis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, COVID-19
Source: Alimentary pharmacology & therapeutics
Doi: 10.1111/apt.18387
Authors: Derek D. Satre, Dhweeja Dasarathy, Steven L. Batki, Michael J. Ostacher, Hannah R. Snyder, William Hua, Priti Parekh, Amy M. Shui, Ramsey Cheung, Alexander Monto, Robert J. Wong, Jennifer Y. Chen, Meimei Liao, Michele Tana, Po-Hung Chen, Christina G. Haight, Taylor Fakadej, Mandana Khalili
Alcohol use is prevalent among hepatology clinic patients with chronic liver disease (CLD). We explored factors associated with the importance and confidence dimensions of motivation to reduce drinking.
Participants (N=121) with unhealthy alcohol use (i.e., over NIH guidelines) receiving care in hepatology clinics from a safety-net hospital (SN, N=54) and two Veterans Affairs Healthcare Systems (VA, N=67) were enrolled in an alcohol intervention trial from March 2022 through October 2023. Baseline assessments included Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-8), Alcohol Use Disorders Identification Test (AUDIT), COVID-19 stress; and measures of importance and confidence to decrease alcohol use (readiness rulers, scales of 1–10). Liver disease etiology and severity were extracted from electronic health records. We performed multivariable linear regression models with forward selection to assess pre-specified variables’ associations with importance and confidence.
The sample was 84% male, 40% Latino, 31% White, 18% Black, and 11% other races; median age was 61 years. Median (Q1–Q3) AUDIT score was 16 (12–24), importance was 9 (6–10), and confidence was 8 (5–9). On multivariable analysis, VA site (vs. SN) participants had a 0.97-point lower importance score (p=0.02); higher symptoms of depression (PHQ-8 score ≥10 vs. <10) and AUDIT scores (for each point increase) were associated with higher importance score (estimates 1.2 and 0.08, p<0.05, respectively). Liver disease etiology and severity were not significantly associated with outcomes.
Depression, alcohol problem severity, and treatment site may influence motivation to reduce alcohol use and could inform future hepatology-based interventions.
Alcohol use is prevalent among patients with chronic liver disease (CLD) and occurs at a range of use levels and problem severity (1). Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide (1–3). Additionally, ALD prevalence has increased over the course of the COVID-19 pandemic, associated with higher levels of alcohol consumption (4).
Adverse health outcomes of alcohol use extend beyond organ damage. These include depression and anxiety, which is very prevalent among individuals with CLD and active alcohol use (5–9). In clinical settings that provide care for patients with CLD, alcohol use is also associated with worse liver disease quality of life in important domains, including cognition and health-related distress (10). Unfortunately, alcohol treatment is underutilized (11, 12), and some studies indicate that patients have misconceptions about treatment as well as a lack of understanding about the serious consequences of continuing alcohol use (13, 14). The readiness of patients with CLD to reduce alcohol use is inconsistent, based on a limited number of studies (15, 16) that have examined motivation to reduce drinking.
There is substantial variability in patients’ recognition of the importance of alcohol use reduction and confidence in their ability to do so, among those with unhealthy alcohol use identified in other medical settings such as HIV care (17). These dimensions of motivation have been associated with subsequent drinking behaviors and alcohol use treatment response (18, 19). Individuals with greater recognition of problems related to drinking and self-reported importance of alcohol use reduction have better alcohol treatment outcomes and are more likely to change their alcohol use behavior (15, 18). However, these measures have not been well studied in patients with CLD. Motivation could also vary across healthcare systems, e.g., due to differing approaches to treatment for chronic conditions, as multidisciplinary teams are available in some systems while other settings may have fewer resources (20). Better understanding of factors contributing to self-reported motivation to reduce alcohol use, including importance and confidence to do so, can help tailor interventions to increase alcohol treatment engagement and efficacy. Indeed, measures of motivation to reduce alcohol use (referred to as readiness rulers) are often included as part of cohort descriptive characteristics in alcohol intervention trials(18, 19).
We therefore used baseline assessments obtained as part of an ongoing alcohol intervention clinical trial (NCT05191446) among individuals with CLD and unhealthy alcohol use to describe two important dimensions of motivation to reduce alcohol use (importance and confidence). The clinical trial was conducted in hepatology clinics across three sites and two different healthcare systems. We also explored clinical, social determinants of health, and psychosocial factors associated with the importance and confidence domains of motivation.
In the clinical trial used for this analysis, CLD patients with unhealthy alcohol use receiving care in hepatology clinics were enrolled from three medical centers in Northern California: Palo Alto Veterans Affairs Health Care System (PAVA), San Francisco Veterans Affairs Health Care System (SFVA), and Zuckerberg San Francisco General Hospital (ZSFG), a hospital affiliated with the San Francisco safety-net health system. Following enrollment, patients completed detailed demographic, clinical, social determinant of health, alcohol use, and motivation to reduce alcohol use measures at baseline (see Baseline Measures). These baseline measures were used for this analysis.
Eligibility criteria included age 18 years or greater, English- or Spanish-speaking, having a clinical diagnosis of CLD, self-reported unhealthy alcohol use within the prior 30 days based on National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria [defined as on average more than 1 drink per day (7 drinks per week) for women and more than 2 drinks per day (14 drinks per week) for men, or at least one heavy drinking day (4+ drinks in a day for women and 5+ drinks in a day for men) in the last 30 days (a standard drink defined as ~14 g of alcohol)], and ability to access a telephone or a digital device (i.e., computer, tablet or smartphone).
Participants with severe medical or psychiatric conditions that investigators thought could impact participation in the study or those with evidence of acute alcohol intoxication were excluded. Additionally, individuals with active pharmacotherapy for alcohol use disorder (AUD) or current formal AUD treatment (excluding self or mutual-help groups [i.e., Alcoholics Anonymous]) and women who were pregnant or breastfeeding or actively trying to become pregnant were excluded.
Recruitment and assessment interviews with Spanish-speaking participants were assisted by certified medical interpreters on an as-needed basis. This study was approved by the Institutional Review Boards of the University of California, San Francisco, and Stanford University, and by local review committees at PAVA, SFVA, and ZSFG; and is registered as a clinical trial (NCT05191446).
Hepatology practices at all three sites routinely screen participants for alcohol use as part of standard care. Potentially eligible participants were identified using the electronic medical record (EMR) and, following permission from their provider, were contacted via mail, telephone, and in-person during clinic visits regarding the study. Participants were also referred directly by providers. Interested participants who met eligibility criteria were consented to participate in the study. Following enrollment, participants were randomly assigned to a) a stepped-care alcohol treatment intervention developed for patients with CLD (three sessions of motivational interviewing followed by addiction medicine referral if needed (21, 22)), or b) standard hepatology care. Clinical and questionnaire assessments were conducted at baseline, 3-, 6-, and 12-month; participants received 100 for the 12-month visit. Baseline enrollment data were used for the current analysis, and subsequent randomization, treatment received, or follow-up data were not included.
Participants self-reported their age, sex at birth, race/ethnicity, household size, annual household income, education level, employment status, marital status, born inside or outside of the US, and English fluency.
The Generalized Anxiety Disorder-7 (GAD-7) (23) and Patient Health Questionnaire-8 (PHQ-8) (24) were used to measure current symptoms of anxiety and depression respectively, with a score of 10 or higher used to indicate probable generalized anxiety disorder and probable depressive disorder (23, 25).
COVID-19 pandemic-related stress was measured using an item from the Pandemic Stress Index: “How much is/did COVID-19 (coronavirus) impact your day-to-day life?” (26) Participants rated the impact of COVID-19 on a Likert response scale that ranged from 1 (not at all) to 5 (extremely). A higher rating indicated higher pandemic-related stress (10).
The alcohol importance and confidence ruler scales ask participants to rate how important it is to cut down or stop drinking and how confident they are that they could cut down or stop drinking, with scores ranging from 1 (not at all important/confident) to 10 (extremely important/confident) (27). The importance ruler has been validated against measures of stages of change to determine how ready primary care participants are to reduce drinking (27). Higher scores on the importance and confidence rulers are both associated with better alcohol use reduction outcomes (18).
The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organization as a screening and assessment tool for alcohol use disorders in primary care (28). A cutoff of 8 or above is a well-established clinical threshold that indicates hazardous or harmful alcohol use (29) and was used to categorize participants into two AUDIT < 8 and AUDIT ≥ 8.
Liver disease etiology was determined from EMR chart review of hepatology clinic notes and laboratory data using standardized procedures. Clinical diagnosis of cirrhosis was determined based on review of hepatology clinic notes. Decompensated cirrhosis was defined by presence or history of ascites, variceal bleeding, encephalopathy, or Child-Pugh Class B or C (30). The Model for End-Stage Liver Disease-Sodium (MELD-Na) score was calculated based on laboratory measures obtained within the prior 6 months (31).
We developed a self-report questionnaire capturing any alcohol use treatment utilization (ever and also in the past 12 months), including inpatient and outpatient services, medications, and self-help groups such as Alcoholics Anonymous, using the validated Treatment Services Review instrument (32).
Demographic and baseline clinical characteristics were described by site using summary statistics and frequencies. Comparisons between groups were analyzed using chi-square tests for categorical variables and Kruskal-Wallis tests for continuous variables. If 20% or more of the cross-tabulated cells had expected counts below 5, then Fisher’s exact tests were used instead of chi-square.
Multivariable linear regression models were developed to assess the association between the two outcome measures (importance score and confidence score) and the binary site variable (VA vs. non-VA safety net), along with other a priori factors potentially associated with these outcomes. These factors included age, race/ethnicity, paid employment, high school education, married/partnered, annual household income, number of people in household, mean alcohol consumption per day, tobacco use in the past 30 days, GAD-7 score, PHQ-8 score, non-ALD vs ALD, presence of cirrhosis, MELD-Na score, self-help for alcohol management, and impact of COVID-19 on daily life and were pre-specified based on clinical knowledge and prior literature. Linear regression assumptions were evaluated using quantile-quantile and residual plots. For continuous pre-specified factors, quadratic terms were included in regression models to test for the presence of nonlinearity. The final multivariable model was determined by forward stepwise selection with an entry criterion of p<0.1 for candidate factors and p<0.05 criterion to stay in the model. Selection of variables to include in the modeling was based on input by clinician experts on the team. Linear regression and Pearson correlation were used to assess the association between the importance and confidence measures.
Three sensitivity analysis models were performed, each adding one covariate to the final multivariable 1) Final model + MELD-Na, 2) Final model + cirrhosis status, 3) Final model + confidence score.
Significance tests were two-sided, and the threshold was set to 0.05. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA).
The final sample included 121 participants enrolled between March 2022 through October 2023 from ZSFG (N=54), VASF (N = 32), and PAVA (N=35). The median (Q1–Q3) participant age was 61 (50–68), 84% were male, 40% Latino, 31% White, 18% Black, and 11% other races; and the median score on the AUDIT was 16 (12–24).
Participants from ZSFG were younger (median age 51.9) compared to other sites (median age 66.1 at VA 62.9 at PAVA and 69.6 at SFVA) and had a higher proportion of Latino participants (59% vs. 24% at VA 26% at PAVA and 23% at SFVA) (Table 1). The cohort at the VA sites was >90% male vs. 67% male at ZSFG. Participant education and income differed across sites, with ZSFG having the highest proportion with less than high school education (31%) and less than $30,000 annual household income (79%). Participants at PAVA had the highest median AUDIT scores (21 vs. 14 at SFVA and 16 at ZSFG). (Table 1).
The majority of participants at all sites had a diagnosis of ALD (82%). Other etiologies included chronic hepatitis B (3%), metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) (23%), other (8%). Overall, 63% of participants had cirrhosis. However, the two VA sites had a higher proportion of participants with cirrhosis but a lower proportion with current or prior history of decompensated cirrhosis compared to ZSFG participants. MELD-Na scores were not significantly different across sites (Table 1).
Overall, median (Q1, Q3) importance score was 9 (6, 10), and median confidence score was 8 (5, 9). The importance and confidence scores were significantly correlated (Figure 1; r=0.29 (95% CI 0.12–0.46), p=0.001).
Univariable analyses identified several factors associated with importance of alcohol use reduction, including site, probable generalized anxiety disorder, probable depressive disorder, and ever having accessed self-help groups to reduce drinking. Participants from the two VA sites had a 0.95 point lower importance score compared to ZSFG participants (p=0.04). Moreover, participants with probable generalized anxiety disorder (vs. without) had a 1.26 point higher importance score (p=0.01), and participants with probable depressive disorder (vs. without) had a 1.8 point higher importance score (p<0.001). Finally, participants who had a history of alcohol self-help had a 1.35 point higher importance score as compared to those with no self-help history (p=0.004). There were no statistically significant factors associated with confidence score (Table 2).
Single factor models that adjusted for site found that higher AUDIT score, anxiety score, depression score, and history of self-help were each associated with higher importance score. A one-point increase in AUDIT score was associated with a 0.11 point increase in importance score (95% CI 0.05, 0.16, p<0.001). Participants with probable generalized anxiety disorder (vs. not) had a 1.2 point higher importance score (95% CI 0.27, 2.2, p=0.01), participants with probable depressive disorder (vs. not) had a 1.8 point higher importance score (95% CI 0.87, 2.7, p<0.001), and participants histories of self-help for alcohol management (vs. never) had a 1.3 point higher importance score (95% CI 0.45, 2.2, p=0.004). In each of the above models, VA site (vs. ZSFG) participants had a one-point lower importance score, with estimates ranging from −0.84 to −1.07.
After completing the forward selection process, the final multivariable model included site, AUDIT score, and probable depressive disorder (not shown on tables). Results showed that VA site (vs. ZSFG) participants had a 0.97 point lower importance score (95% CI −1.8, −0.15, p=0.02), and participants with probable depressive disorder (vs. not) had a 1.2 point higher important score (95% CI 0.30, 2.18, p=0.01). Finally, a one-point increase in AUDIT score was associated with a 0.08 point increase in importance score (95% CI 0.03, 0.14, p=0.006). To further explore the potential role of liver disease severity, we conducted sensitivity analyses that include MELD-Na score and cirrhosis status in the multivariable model assessing the “importance” outcome. MELD-Na score was added to the final multivariable model in one analysis and cirrhosis status was added to the final multivariable model in another analysis. Adding either MELD-Na or cirrhosis status to the multivariable model did not alter the significance or direction of estimates of the variables from the original multivariable model, and the magnitude of estimates remained similar (Supplemental Table 1). Neither of the added variables were statistically significant (MELD-Na per point estimate = 0.02 (95% CI −0.06, 0.11), p=0.59; and cirrhosis estimate = 0.02 (95%CI −0.84, 0.88), p =0.96).
To account for the observed correlation between importance and confidence scores, we performed a sensitivity analysis by adding confidence score to the final multivariable model. Addition of the confidence score did not change the significance or direction of estimates of the variables from the original multivariable model, and the magnitude of estimates remained similar (Supplemental Table 1).
In this study of hepatology clinic patients with CLD and unhealthy alcohol use who were enrolled in an alcohol use reduction intervention trial, factors associated with higher self-reported importance of alcohol use reduction included alcohol problem severity and depression, as well as health system effects based on where participants received care. However, none of the factors examined were significantly associated with confidence in ability to reduce drinking. Notably, liver disease etiology and severity were not associated with either of the alcohol use reduction motivation measures.
Research examining alcohol use treatment barriers or factors associated with the acknowledgement of the importance to reduce alcohol use among people with CLD is lacking (13, 33). Studies in HIV treatment settings (17), mental health (34), and other clinically important populations (35, 36) observed that higher depression and greater alcohol-related problems on standard symptom scales were associated with higher patient-acknowledged importance to reduce alcohol use, and therefore potentially greater readiness to change alcohol use behavior. These relationships may be present in patients with liver disease as well (15). However, it remains possible that depression could have a negative impact on behavior-focused treatment adherence (37, 38). Our findings suggest that patients with CLD who report psychological distress are important to assist, and for whom integrated behavioral interventions may be more effective than addressing alcohol use alone (39, 40).
In addition to providing integrated mental health and alcohol treatment in hepatology (9, 41), awareness of individual, patient-level factors associated with importance of alcohol use reduction is key to tailoring motivational interventions. Linking the values expressed by patients to importance of alcohol use reduction in the context of a dialogue between patients and providers is a core mechanism of facilitating behavior change (42). Alcohol use reduction is likely to lead to improvements in mood symptoms (43). Based on our findings regarding the link between depression symptoms and importance of alcohol reduction, exploration of the role of emotional distress in motivating alcohol use reduction could be a valuable counseling approach to assisting the ALD patient population and should be explored in future research.
We also observed significant differences in outcomes by site, which were not explained by measured social determinants of health, such as demographic factors and socioeconomic status. However, unmeasured population characteristics such as cultural factors, stigma, or differences in the prevalence of marginally housed or justice system-involved individuals between safety net systems and the VA could potentially impact perceptions regarding alcohol use (44). Moreover, reporting biases such as social desirability may have influenced the reported scores (45). Alternatively, health system differences (e.g., greater availability and ease of accessing a range of primary and specialty care services, including behavioral and pharmacological alcohol and drug treatment services within the VA) may have been associated with a lower sense of urgency to reduce alcohol use in this portion of our sample.
We had anticipated that ALD liver disease etiology or severity of liver disease could influence motivation to reduce alcohol use. While there is evidence that reducing unhealthy alcohol use (i.e., harm reduction) may prevent the development of ALD (46), in patients with ALD, complete abstinence from alcohol use is recommended in clinical settings (47). However, our results did not show a significant relationship between importance and confidence measures and ALD etiology vs. CLD with unhealthy alcohol use, nor with presence of cirrhosis or MELD-Na scores. It is possible that presence of any liver disease in and of itself and alcohol’s impact on disease progression, presence of other comorbidities (e.g., mental health), or unmeasured factors (e.g., stigma, beliefs) previously shown to influence lifestyle modification in the context of CLD (37), are drivers of motivation for harm reduction.
Although alcohol use reduction importance and confidence scale scores were statistically correlated, this correlation was modest (r=0.29) and none of the factors we examined were significantly associated with confidence as an outcome. Moreover, on sensitivity analysis, the relationships between factors associated with importance remained significant despite addition of confidence as a variable to the model. Nevertheless, prior research has identified factors associated with lower confidence, such as race/ethnicity and use of other substances in addition to alcohol (17), and associations on some similar factors such as sex and current smoking status approached significance in our study. Enhancing patients’ confidence in their ability to reduce hazardous drinking is a valuable target of behavioral interventions and is associated with better alcohol use outcomes over time (18, 48), and further investigation into factors associated with confidence should be considered.
Inclusion of participants across three clinical sites, including VA and safety-net contributes to diversity of study population. However, the sample was primarily male and was drawn from a regional population of participants with CLD in the San Francisco Bay Area and thus may not necessarily be generalizable to women or to other geographic settings (e.g., more rural locations). Individuals who declined to participate in the intervention trial may have different motivational factors compared with those who enrolled, although recruitment staff emphasized that patients did not need to be ready to stop drinking in order to enroll. Nevertheless, selection bias within the context of any clinical trial limits generalizability. In the multivariable analysis, unmeasured patient factors (e.g., understanding of alcohol effects on CLD) could have contributed to site differences, and reasons for our findings regarding site effects deserve further examination. We also did not assess relationships between importance and confidence ruler scores at baseline and subsequent alcohol use outcomes, but these will be reported along with other results of the clinical trial once completed.
The number of people living with CLD has increased in the US in tandem with increasing unhealthy alcohol use, and this population is especially vulnerable to serious adverse effects of drinking. In a sample of participants with CLD in hepatology care who were also enrolled in an alcohol use intervention study, we identified site differences as well as individual factors associated with motivation to reduce alcohol use such as depression symptoms and alcohol problem severity, which could be integrated into the development of effective alcohol interventions in the future.