Screening for social determinants of health among populations at risk for MASLD: a scoping review.

Background: Social determinants of health (SDoH) have been associated with disparate outcomes among those with metabolic dysfunction-associated steatotic liver disease (MASLD) and its risk factors. To address SDoH among this population, real-time SDoH screening in clinical settings is required, yet optimal screening methods are unclear. We performed a scoping review to describe the current literature on SDoH screening conducted in the clinical setting among individuals with MASLD and MASLD risk factors. Methods: Through a systematic literature search of MEDLINE, Embase, and CINAHL Complete databases through 7/2023, we identified studies with clinic-based SDoH screening among individuals with or at risk for MASLD that reported pertinent clinical outcomes including change in MASLD risk factors like diabetes and hypertension. Results: Ten studies (8 manuscripts, 2 abstracts) met inclusion criteria involving 148,151 patients: 89,408 with diabetes and 25,539 with hypertension. Screening was primarily completed in primary care clinics, and a variety of screening tools were used. The most commonly collected SDoH were financial stability, healthcare access, food insecurity and transportation. Associations between clinical outcomes and SDoH varied; overall, higher SDoH burden was associated with poorer outcomes including elevated blood pressure and hemoglobin A1c. Conclusion: Despite numerous epidemiologic studies showing associations between clinical outcomes and SDoH, and guidelines recommending SDoH screening, few studies describe in-clinic SDoH screening among individuals with MASLD risk factors and none among patients with MASLD. Future research should prioritize real-time, comprehensive assessments of SDoH, particularly among patients at risk for and with MASLD, to mitigate disease progression and reduce MASLD health disparities.

Staff-Facilitated Telemedicine Care Delivery for Treatment of Hepatitis C Infection among People Who Inject Drugs.

BACKGROUND: Telemedicine offers the opportunity to provide clinical services remotely, thereby bridging geographic distances for people engaged in the medical system. Following the COVID-19 pandemic, the widespread adoption of telemedicine in clinical practices has persisted, highlighting its continued relevance for post-pandemic healthcare. Little is known about telemedicine use among people from socially marginalized groups. METHODS: The No One Waits (NOW) Study is a single-arm clinical trial measuring the acceptability, feasibility, and safety of an urban point-of-diagnosis hepatitis C (HCV) treatment initiation model delivered in a non-clinical community setting. Participants enrolled in the NOW Study are recruited via street outreach targeting people experiencing homelessness and injecting drugs. Throughout the NOW Study, clinical care is delivered through a novel staff-facilitated telemedicine model that not only addresses geographic and transportation barriers, but also technology and medical mistrust, barriers often unique to this population. While clinicians provide high-quality specialty practice-based care via telemedicine, on-site staff provide technical support, aid in communication and rapport, and review the clinicians' instructions and next steps with participants following the visits. Research questionnaires collect information on participants' experience with and perceptions of telemedicine (a) prior to treatment initiation and (b) at treatment completion. DISCUSSION: For people from socially marginalized groups with HCV infection, creative person-centered care approaches are necessary to diagnose, treat, and cure HCV. Although non-clinical, community-based staff-facilitated telemedicine requires additional resources compared to standard-of-care telemedicine, it could expand the reach and offer a valuable entrance into technology-delivered care for socially marginalized groups. TRIAL REGISTRATION: NCT03987503.

Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. AIMS: We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. METHODS: Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. RESULTS: From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1-0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04-0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07-0.9, p = 0.03 and OR 0.2, 95% CI 0.04-0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. CONCLUSIONS: Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients' experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care.

Cross-sectional study on stigma and motivation to adhere to lifestyle modification among vulnerable populations with fatty liver disease.

Objectives: Adherence to lifestyle modification (diet, exercise, and alcohol cessation) for fatty liver disease (FLD) management remains challenging. The study examined stigma, barriers, and factors associated with motivation to adhere to lifestyle modification in a diverse and vulnerable population with FLD. Methods: From 2/19/2020 to 2/28/2022, 249 FLD patients within San Francisco safety-net hepatology clinics were surveyed along with clinical data taken from medical records. Multivariable modeling assessed factors associated with motivation to adhere to lifestyle modification in a cross-sectional study. Results: Median age was 53 years, 59% female, 59% Hispanic, 25% Asian/Pacific Islander, 9% White, and 2% Black, 79% were non-English speakers, 64% had ≤ high school education, and 82% reported <$30,000 annual income. Common comorbidities included hyperlipidemia (47%), hypertension (42%), diabetes (39%), and heavy alcohol use (22%). Majority (78%) reported experiencing stigma, 41% reported extreme motivation, and 58% reported ≥ two barriers. When controlling for age, sex, Hispanic ethnicity, alcohol consumption, BMI, >high school (coef 1.41, 95% CI 0.34-2.48), stigma (coef 0.34, 95% CI 0.07-0.62), and depression (coef -1.52, 95% CI -2.79 to -0.26) were associated with motivation. Conclusions: Stigma is commonly reported among FLD patients. Interventions to enhance patient education and mental health support are critical to FLD management, especially in vulnerable populations.

A pilot study to understand and respond to loss, theft, and misplacement of hepatitis C treatment medication for people who inject drugs.

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Undiagnosed abnormal alanine transaminase levels in vulnerable populations: Impact of sex, race/ethnicity, and body mass.

Background: Liver disease is a leading cause of death in the United States and is often initially detected incidentally on lab tests ordered by general practitioners. Alanine transaminase (ALT), a marker of liver inflammation, is commonly ordered and may be abnormal in the setting of elevated body mass index, diabetes and dyslipidemia. Data regarding ALT testing within vulnerable populations are limited. Therefore, the prevalence of ALT testing and abnormal ALT in the absence of known chronic liver disease (CLD) among a safety-net population were assessed and factors associated with these outcomes were identified. Methods: In this retrospective longitudinal study of 92,997 patients seen between 01/2017-01/2019 within San Francisco's Safety-Net Healthcare System, electronic medical records were used to abstract data back to 04/1997. Descriptive analyses and multivariable modeling were performed. Results: Overall, 59,323 (69%) without known CLD received an ALT test. Age, Black race, Latinx ethnicity, and metabolic factors were associated with higher odds of ALT testing, (p < 0.01). Among those with an abnormal ALT (44%) without known CLD: median age 53 years, 41% male, 19% White, 11% Black, 40% Latinx, 29% Asian/Pacific Islander (API), and 84% overweight/obese. On multivariable analysis, female sex (OR 2.7), Latinx ethnicity (OR 2.6), API race (OR 1.3), overweight/obesity (OR 1.8, OR 2.6), and dyslipidemia (OR 1.3) were associated with abnormal ALT, (p ≤ 0.001). Conclusions: In the absence of known CLD, women, Latinx, API and persons with excess body weight were associated with greater odds of abnormal ALT. Future longitudinal studies are needed to confirm these differences and to determine if adequate work up for CLD is performed for abnormal ALT levels among at-risk populations.

Racial/ethnic differences in fibrosis prevalence and progression in biopsy-proven steatosis: A focus on the Asian American population.

Fatty liver disease (FLD) is a leading cause of chronic liver disease (CLD) globally, and vulnerable populations are disproportionately affected. Prior studies have suggested racial/ethnic differences in FLD prevalence and severity; however, these studies often excluded Asian Americans. This study aims to evaluate racial/ethnic differences in the prevalence of, and predictors associated with steatohepatitis, advanced fibrosis, and fibrosis progression over time within a diverse population. Using descriptive analyses and multivariable modeling, we performed a longitudinal evaluation of 648 patients with histologic evidence of FLD (steatosis or steatohepatitis) from August 2009 to February 2020 within San Francisco's safety-net health care system. Overall demographics were median age of 53 years, 54% male, and 38% Asian (40% Hispanic, 14% White). On histology, 61% had steatohepatitis and 30% had advanced fibrosis (≥F3). The comparison between steatosis and steatohepatitis groups showed differences in sex, race/ethnicity, metabolic risk factors, and co-existing CLD (predominantly viral hepatitis); patients with steatosis were more likely to be Asian (50%), and those with steatohepatitis were more likely to be Hispanic (51%). On multivariable modeling, while Asian race (vs. non-Asian) was not associated with steatohepatitis or advanced fibrosis when models included all relevant clinical predictors, Asian race was associated with higher relative risk of fibrosis progression as defined by change in Fibrosis-4 category over time (relative risk ratio = 1.9; p = 0.047). Conclusion: In this vulnerable population with a large proportion of Asian Americans, Asian race was associated with progression of fibrosis. Given the relative paucity of data in this high-risk group, future studies should confirm these findings.

Noninvasive Fibrosis Screening in Fatty Liver Disease Among Vulnerable Populations: Impact of Diabetes and Obesity on FIB-4 Score Accuracy.

OBJECTIVE: Fatty liver disease (FLD) is prevalent in diabetes, and both disproportionately affect vulnerable populations. The FIB-4 index is recommended to screen for advanced liver fibrosis. Limited data have suggested that diabetes may impact FIB-4. RESEARCH DESIGN AND METHODS: We evaluated FIB-4 accuracy for advanced fibrosis compared with liver biopsy in the presence of diabetes and obesity. RESULTS: Among 363 FLD patients receiving care in San Francisco's safety net health care system from August 2009 to February 2020, characteristics were as follows: median age 51 years, 46% male, 59% Hispanic, 68% obese, 33% with diabetes, and 31% with advanced fibrosis on histology. Overall, the c-statistic for FIB-4 was 0.79, but was worse in patients with diabetes, 0.68, than without, 0.85 (P = 0.003). Accuracy also varied by weight, at 0.65, 0.85, and 0.75 for normal weight, overweight, and obese, respectively, although not significantly (P = 0.24). CONCLUSIONS: The findings highlight limitations of FIB-4 in screening for advanced liver fibrosis, particularly in individuals with diabetes.

Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals.

BACKGROUND: Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV. METHODS: One hundred fifty-three nondiabetic Latino individuals (60 HCV+, 93 HCV-) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow-up of 1.5 years. Peripheral IR and hepatic IR were measured via steady-state plasma glucose (SSPG) and endogenous glucose production during a two-step, 240-min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time. RESULTS: Overall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 µU-mg/kg-min-ml, p = 0.04) and HCV status (coef 4.4 µU-mg/kg-min-ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow-up (coef 5.8 µU-mg/kg-min-ml, p = 0.03). CONCLUSIONS: In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti-HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.

Fatty Liver and the Coronavirus Disease 2019 Pandemic: Health Behaviors, Social Factors, and Telemedicine Satisfaction in Vulnerable Populations.

The coronavirus disease 2019 (COVID-19) pandemic has impacted health-related behaviors that influence fatty liver disease (FLD) management. We evaluated the impact of the pandemic on FLD management and satisfaction with care delivery in this population. In the San Francisco safety-net hepatology clinics, we evaluated health-related behaviors and factors associated with self-reported weight gain during the COVID-19 pandemic as well as satisfaction with telemedicine in adults with FLD by using multivariable modeling. From June 1, 2020, to May 5, 2021, 111 participants were enrolled. Median age was 52 years, 30% were men, 63% were Hispanic, 21% were Asian/Pacific Islander, and 9% were White. Eating habits were unchanged or healthier for 80%, physical activity decreased in 51%, 34% reported weight gain, and 5% reported increased alcohol intake. Forty-five percent had severe depressive symptoms, 38% in those without diagnosed depression and 60% of individuals with heavy alcohol use. On multivariable analysis, decreased physical activity (odds ratio [OR], 4.8) and heavy alcohol use (OR, 3.4) were associated with weight gain (all P < 0.05). Among those with telemedicine visits (n = 66), 62% reported being very satisfied. Hispanic ethnicity was associated with a 0.8-unit decrease in the telemedicine satisfaction score (P = 0.048) when adjusting for sex, age, and pandemic duration. Conclusion: During the pandemic, decreased physical activity and heavy alcohol use were most influential on self-reported weight gain in FLD. Maintenance of healthy eating and increased physical activity, alcohol cessation counseling, and mental health services are critical in preventing poor FLD-associated outcomes during the pandemic recovery. Dissatisfaction with telemedicine should be explored further to ensure equitable care, especially among the vulnerable Hispanic population.

TRP53 Mutants Drive Neuroendocrine Lung Cancer Through Loss-of-Function Mechanisms with Gain-of-Function Effects on Chemotherapy Response.

Lung cancer is the leading cause of cancer-related deaths with small-cell lung cancer (SCLC) as the most aggressive subtype. Preferential occurrence of TP53 missense mutations rather than loss implicates a selective advantage for TP53-mutant expression in SCLC pathogenesis. We show that lung epithelial expression of R270H and R172H (R273H and R175H in humans), common TRP53 mutants in lung cancer, combined with RB1 loss selectively results in two subtypes of neuroendocrine carcinoma, SCLC and large cell neuroendocrine carcinoma (LCNEC). Tumor initiation and progression occur in a remarkably consistent time frame with short latency and uniform progression to lethal metastatic disease by 7 months. R270H or R172H expression and TRP53 loss result in similar phenotypes demonstrating that TRP53 mutants promote lung carcinogenesis through loss-of-function and not gain-of-function mechanisms. Tumor responses to targeted and cytotoxic therapeutics were discordant in mice and corresponding tumor cell cultures demonstrating need to assess therapeutic response at the organismal level. Rapamycin did not have therapeutic efficacy in the mouse model despite inhibiting mTOR signaling and markedly suppressing tumor cell growth in culture. In contrast, cisplatin/etoposide treatment using a patient regimen prolonged survival with development of chemoresistance recapitulating human responses. R270H, but not R172H, expression conferred gain-of-function activity in attenuating chemotherapeutic efficacy. These data demonstrate a causative role for TRP53 mutants in development of chemoresistant lung cancer, and provide tractable preclinical models to test novel therapeutics for refractory disease. Mol Cancer Ther; 16(12); 2913-26. ©2017 AACR.

Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Statins have been variably shown to decrease risk and complications of chronic liver diseases (CLDs). We performed a systematic review and meta-analysis to evaluate the association between statins and risk of cirrhosis and related complications in patients with CLDs. METHODS: Through a systematic literature search up to March 2017, we identified 13 studies (3 randomized trials, 10 cohort studies) in adults with CLDs, reporting the association between statin use and risk of development of cirrhosis, decompensated cirrhosis, improvements in portal hypertension, or mortality. Pooled relative risk (RR) estimates with 95% confidence interval (CIs) were calculated using random effects model. Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess quality of evidence. RESULTS: Among 121,058 patients with CLDs (84.5% with hepatitis C), 46% were exposed to statins. In patients with cirrhosis, statin use was associated with 46% lower risk of hepatic decompensation (4 studies; RR, 0.54; 95% CI, 0.46-0.62; I2 = 0%; moderate-quality evidence), and 46% lower mortality (5 studies; RR, 0.54; 95% CI, 0.47-0.61; I2 = 10%; moderate-quality evidence). In patients with CLD without cirrhosis, statin use was associated with a nonsignificant (58% lower) risk of development of cirrhosis or fibrosis progression (5 studies; RR, 0.42; 95% CI, 0.16-1.11; I2 = 99%; very-low-quality evidence). In 3 randomized controlled trials, statin use was associated with 27% lower risk of variceal bleeding or progression of portal hypertension (hazard ratio, 0.73; 95% CI, 0.59-0.91; I2 = 0%; moderate-quality evidence). CONCLUSIONS: Based on a systematic review and meta-analysis, statin use is probably associated with lower risk of hepatic decompensation and mortality, and might reduce portal hypertension, in patients with CLDs. Prospective observational studies and randomized controlled trials are needed to confirm this observation.