Fallon, Michael B.

ABSTRACT Background and Aim Significant health disparities persist in alcohol‐associated liver disease (ALD), largely driven by social determinants of health (SDOH). However, the influence of neighbourhood‐level SDOH on ALD outcomes remains underexplored. In this study, we aimed to evaluate how neighbourhood‐level SDOH are associated with disease burden, comorbid conditions, and mortality in individuals with ALD. Methods We conducted a retrospective cohort study of patients with ALD in the Banner Health System, representing hospitals across Arizona, California, Nevada, Wyoming and Colorado, from January 2012 to October 2024 using ICD codes. Neighbourhood‐level SDOH were quantified using the Social Deprivation Index (SDI). Patients were stratified into quartiles based on SDI score, with Quartile 4 representing the most socioeconomically disadvantaged neighbourhoods. Primary outcomes included incidence of mortality, cirrhosis, major adverse liver outcome (MALO), Type 2 diabetes mellitus, any cancer, and major adverse cardiovascular events (MACE). A multivariable competing risk analysis was performed adjusting for age, sex, race/ethnicity, insurance type, primary language, smoking status, Type 2 diabetes mellitus, hypertension, hyperlipidemia, aspirin use, statin use, alcohol use disorder and a composite mental‐health/substance‐use disorder variable encompassing depression, anxiety disorders, post‐traumatic stress disorder, bipolar disorder, schizophrenia, and non‐alcohol substance use disorders. Results Among 11,394 patients with ALD and available SDI data, 6747 had ≥ 365 days of follow‐up. The average age was 51 years and 65.6% were female; 68.8% were non‐Hispanic White, 19.7% Hispanic, 5.9% Native American/Alaskan Native (NA), 3.2% Black, and 0.4% Asian/Pacific Islanders. Patients residing in the most disadvantaged neighbourhoods (Quartile 4) were significantly younger, more likely to be female, had a higher median BMI, and more frequently reported a non‐English primary language compared with those in the least disadvantaged areas (Quartile 1). Patients in the most deprived neighbourhoods were more likely to be Hispanic, Black, or Native American/Alaska Native and to be uninsured or on Medicaid, whereas those in the least disadvantaged neighbourhoods predominantly had private insurance. Individuals in Quartile 4 had increased mortality (adjusted hazard ratio [aHR]: 1.48, 95% Confidence Interval [CI]: 1.09–2.01) compared with individuals in Quartile 1. Conclusions In this large and demographically diverse ALD cohort, residing in socioeconomically disadvantaged neighbourhoods was associated with increased risk of mortality. These findings support the need for contextually tailored clinical interventions and broader treatment strategies that target upstream sociocultural and environmental factors that are associated with health outcomes. Addressing neighbourhood‐level SDOH through community engagement, policy reform, and cross‐sector partnerships to improve collaborative care efforts is needed to reduce health disparities in ALD.

ABSTRACT In normal health, the liver and lungs enjoy a close anatomic, physiologic, and functional relationship. In the context of pulmonary vascular disease, however, there is accumulating evidence that the interplay between the gut microbiome, hepatic system, and pulmonary vasculature (so‐called “gut‐liver‐lung” axis) plays an important role in driving disease pathogenesis and determining clinical outcomes. Despite recognizing the importance of the gut‐liver‐lung axis in pulmonary vascular disease however, little is known about the clinical characteristics, circulating factors, and physiologic pathways that mediate this important axis of communication. In this clinical and translationally focused review, we provide an overview of liver‐lung communication in normal physiology, and contrast this with gut‐liver‐lung derangements in pulmonary arterial hypertension, portopulmonary hypertension, and hepatopulmonary syndrome. We conclude with identifying key gaps in knowledge that will need to be addressed in order to manipulate the gut‐liver‐lung axis to prevent worsening pulmonary vascular disease, develop novel therapeutics, and improve patient outcomes.

Background and Aims: Liver transplant is a specialized treatment for a spectrum of indications that use a scarce resource. Transplant is guided by principles of justice, equity, and benefit, with a constant conflict between competing interests. Organs are a national resource with a goal of equitable distribution across sites. An AASLD guideline for the evaluation and selection of appropriate candidates for transplant has been available since 2005. Methods: A multidisciplinary writing group of liver transplant experts and a librarian convened over 24 months. The writing group reviewed the literature, generated guideline recommendations, and rated the level of evidence for each recommendation based on the Oxford Center for Evidence-Based Medicine. The group categorized the strength of recommendations based on the level of evidence, risk-benefit ratio, and patient preferences. Conclusions: Liver transplant is a lifesaving procedure that should be offered to selected patients with clear indications and a reasonable prospect of benefit. The evaluation is designed to identify those in need, to outline hurdles to a successful outcome, and to develop an effective transplant plan. The goal of this document is to provide a template for this process.

Backgrounds and Aims: HBV-related liver disease ranks as the seventh leading cause of mortality. Despite advances in prevention and treatment, global disparities in the burden of primary liver cancer (PLC) persist. We evaluate global trends in the prevalence, incidence, and death of HBV-related liver disease. Approach and Results: Data from the Global Burden of Disease Study 2021 evaluated acute HBV infection, HBV-related cirrhosis, and HBV-related liver cancer prevalence, incidence, and death. In 2021, there were 7.30 million cases of acute HBV, 283.64 million cases of HBV-related cirrhosis, and 288,110 cases of HBV-related PLC. HBV-related PLC accounted for 39% of the global incidence of PLC; Western Pacific had the highest rates for HBV-related PLC, with an incidence of 5.24 and a death rate of 4.38 per 100,000 population. Between 2000 and 2021, age-standardized incidence, prevalence, and death rates from HBV-related liver disease decreased; however, the incidence of HBV-related PLC rose in 65 countries from 2000 to 2021. In parallel, age-standardized prevalent rates from HBV-related PLC increased in Europe (annual percent change: 0.77%, 95% CI: 0.72%–0.81%) and the Americas (annual percent change: 1.05%, 95% CI: 1.00%–1.10%). Conclusions: From 2000 to 2021, decreases in HBV-related liver disease incidence and prevalence were observed; however, more than one-third of countries showed an increase in the incidence of HBV-related PLC. These findings highlight the need for strengthened HBV treatment efforts to reduce the risk of liver cancer.

Portopulmonary hypertension (POPH), a form of pulmonary artery hypertension, occurs because of portal hypertension. Pulmonary hemodynamics and right heart function are key entities that are considered when diagnosing and treating POPH. Medical management, combined with liver transplantation, offers a unique opportunity for POPH “cure”; however, transplant risk can be significant as it relates to the severity of POPH. In addition to recent POPH practice guidelines, continued efforts can be suggested to improve our understanding of prognostic factors, investigate newer medical treatments, and improve outcomes of POPH. Herein, we identify specific “unmet needs” that focus on expanding and complementing current POPH practice guidelines.

Patients with chronic liver disease commonly have abnormal lung function; however, the impact of smoking on outcomes in these patients is unknown. We hypothesized current or past smoking would be associated with worse survival in patients with advanced liver disease. The Pulmonary Vascular Complications in Liver Disease Study 2 (PVCLD2) was a prospective cohort of patients with advanced liver disease undergoing evaluation for liver transplantation (LT). Patients were classified by self-report as a “non-smoker,” “past smoker,” or “current smoker.” We used Cox proportional hazards models and Fine-Gray models with LT as a competing risk. Models were adjusted for age, sex, body mass index, race, family income, liver disease etiology, and Model for End-Stage Liver Disease-Sodium score. Of the 410 patients included, most (65%) were male and the mean age at enrollment was 56.5 years. One hundred sixty (39%) patients were nonsmokers, 183 (45%) were past smokers, and 67 (16%) were current smokers. In total, 151 (37%) patients received an LT, and 88 (20%) patients died. When compared to nonsmokers, current smokers had a 2.17-fold increase in risk of death overall (95% CI: 1.12–4.18, p = 0.02). There was a 7% increase in overall risk of death for every 5 pack-years increase (95% CI: 1.01–1.13, p = 0.02). With LT as a competing risk, the subdistributional HR of current smokers versus nonsmokers for death was 2.45 (95% CI: 1.31–4.60, p = 0.005). In this model, past smokers displayed a nonsignificant increase in the risk of death compared to nonsmokers (subdistributional HR: 1.58, 95% CI: 0.91–2.72, p = 0.10). Patients with advanced liver disease undergoing evaluation for LT who smoke have an increased risk of death. Smoking cessation could lead to improved overall survival with or without LT.

Background Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. Objective We aimed to assess the global, regional and national burden of gastrointestinal cancers. Designs Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). Results In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. Conclusions Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers—most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.

AbstractBackground and AimEarly‐onset colorectal cancer (CRC) is a growing global health concern, especially in the Asia‐Pacific region. However, comprehensive research on this topic from the region is lacking. Our study aims to investigate trends in early‐onset CRC in Asia over 10 years, filling this research gap.MethodsThis study utilized data from the Global Burden of Disease Study 2019 to assess temporal trends in early‐onset CRC in the Asia‐Pacific. The analysis included estimating annual frequencies and age‐standardized rates (ASRs) of early‐onset CRC incidence, death, and disability‐adjusted life‐years (DALYs) by gender.ResultsThe incidence of early‐onset CRC significantly increased in both regions with higher increase and in the Western Pacific region. Notable increases were observed among males in the Western Pacific and females in Southeast Asia (SEA). Mortality rates remained stable in the Western Pacific but increased by 10.6% in SEA, especially among females. DALYs due to CRC also increased significantly in SEA, with a greater rise among females. The Western Pacific had the highest CRC incidence, and in SEA, the mortality rate was higher in females than males.ConclusionsOur study reveals a substantial increase in early‐onset CRC in the Asia‐Pacific underscoring the urgency for effective interventions. Thus, a comprehensive approach comprising controlled risk reduction, health promotion to heightened disease awareness, and implementation of effective screening strategies should be executed timely to mitigate the burden of early‐onset CRC.

Background and Aims: Hepatopulmonary syndrome (HPS) and a hyperdynamic circulation are common complications of advanced liver disease, but the relationship between HPS and cardiac index (CI) is poorly understood. We sought to compare CI in patients with and without HPS and to assess the relationship between CI and symptoms, quality of life, gas exchange, and exercise capacity among liver transplantation (LT) candidates. We performed a cross-sectional analysis within the Pulmonary Vascular Complications of Liver Disease 2 study, a multicenter prospective cohort study of patients being evaluated for LT. We excluded patients with obstructive or restrictive lung disease, intracardiac shunting, and portopulmonary hypertension. We included 214 patients (81 with HPS and 133 controls without HPS). Compared with controls, patients with HPS had a higher CI (least square mean 3.2 L/min/m2, 95% CI 3.1–3.4 vs. 2.8 L/min/m2, 95% CI 2.7–3.0, p < 0.001) after adjustment for age, sex, Model for End-stage Liver Disease-Sodium (MELD-Na) score and beta-blocker use, and a lower systemic vascular resistance. Among all LT candidates, CI was correlated with oxygenation (Alveolar-arterial oxygen gradient r=0.27, p< 0.001), intrapulmonary vasodilatation severity (p < 0.001), and biomarkers of angiogenesis. Higher CI was independently associated with dyspnea and worse functional class and physical quality of life after adjusting for age, sex, MELD-Na, beta-blocker use, and HPS status. HPS was associated with a higher CI among LT candidates. Independent of HPS, higher CI was associated with increased dyspnea and worse functional class, quality of life, and arterial oxygenation.