Welch, Nicole

Background & Aims: The clinical course and outcomes of alcohol-associated hepatitis (AH) remain poorly understood. Major adverse liver outcomes do not capture the added risk of return to drinking. We examined the natural history of AH and developed a composite endpoint using a contemporary observational cohort of AH. Approach & Results: A cohort of 1127 participants: 712 AH patients, 256 heavy drinking controls without clinically evident liver disease, and 159 healthy controls, were prospectively followed for 6 months at 8 United States centers as part of the Alcoholic Hepatitis Network (AlcHepNet) consortium. Outcomes included mortality and a composite endpoint (AlcHepNet composite index) that included death, liver transplantation, hepatic decompensation (new onset/worsening ascites, HE, variceal bleeding), liver-related hospital admission, MELD increase ≥5, and return to drinking. Of 712 AH patients (age 45±10.7 y; 59.1% male), 558 (79.0%) had severe and 148 (21.0%) had moderate AH, 232 (32.5%) died, and 86 (12.1%) underwent liver transplantation. Mortality rates in moderate AH and severe AH were 0.7% versus 17.2% (30 d), 3.4% versus 26.5% (90 d), and 8.8% versus 30.5% (180 d), respectively (all p <0.001). Composite liver/alcohol use events were noted in 459 (64.5%) AH patients. Higher MELD score, lower mean arterial pressure, and baseline leukocytosis were associated with higher 90-day mortality in AH (all p <0.05). College education and higher ALP were associated with lower mortality. Heavy drinking controls had low mortality (n=3; 1.2%). Conclusions: This large observational study showed a high incidence of composite liver and alcohol-use events within 6 months, reiterating the need for early interventions.

Abstract Background. Sarcopenia (i.e. skeletal muscle loss) and physical frailty are significant contributors to adverse clinical outcomes in lung cancer patients. Nutritional intake and physical activity influence skeletal muscle mass and strength. We determined the impact of lung cancer on clinical outcomes in hospitalized patients with sarcopenia, frailty, or sarcopenia+frailty. Design. The Nationwide Inpatient Sample (NIS) (years 2018-2020) from the United States was analyzed to study adult hospitalized patients with a diagnosis of lung cancer. Sarcopenia and frailty were defined by ICD10 codes that have been previously validated. Multivariate regression models were generated to determine the clinical impact of sarcopenia, frailty, or sarcopenia+frailty in patients with a diagnosis of lung cancer as compared to a general medical population (GMP) without lung cancer. Age was restricted to &gt;40 years old for both cohorts because lung cancer is rare in those less than 40 years old. Models were adjusted for age, race, sex, and comorbidities (cardiovascular disease, anemia, coagulopathy, HIV, depression, diabetes mellitus, and COPD). Results. Compared to the GMP (n=126,099), patients with lung cancer (n=241,913) were older (mean+SD age: 69.6+10.0 vs. 67.6+13.3 years, p&lt;0.001), and had a higher prevalence of sarcopenia (22.5% vs 9.0%, p&lt;0.001), frailty (53.4% versus 49.8%, p&lt;0.001), and sarcopenia+frailty (15.3% versus 6.8%, p&lt;0.001). COPD was common and found in 52.3% of lung cancer patients and 20.2% of the GMP. In lung cancer patients, the most common medical reasons for admission were sepsis, pneumonia, and COPD exacerbation. In GMP patients, the most common medical reasons for admission were sepsis, congestive heart failure, and acute kidney injury. In lung cancer patients, frailty had the greatest association with mortality (unadj OR 3.12, 95% CI: 3.02-3.23; adj OR 3.04, 95% CI: 2.91-3.17). Sarcopenia+frailty was most associated with greater healthcare utilization including greater healthcare cost (unadj OR 1.31, 95% CI: 1.29-1.32; adj OR 1.28, 95% CI: 1.26-1.30) and length of stay (unadj OR 1.57, 95% CI: 1.55-1.58; adj OR 1.50, 95% CI: 1.48-1.52). Sarcopenia+frailty were more likely to require additional healthcare facilities upon discharge and were the least likely to be discharged to home (unadj OR 0.32, 95% CI: 0.32-0.33; adj OR 0.35, 95% CI: 0.33-0.36). (see Table 1). Conclusion. While frailty was most associated with in-hospital mortality in lung cancer patients, sarcopenia+frailty was most associated with greater healthcare utilization. Our findings highlight the need to develop targeted interventions to improve clinical outcomes in lung cancer patients with sarcopenia and/or frailty.

Abstract Background. Sarcopenia (i.e. skeletal muscle loss) is a significant contributor to adverse clinical outcomes in patients with COPD. Nutritional intake and physical activity influence sarcopenia and frailty. There is increasing recognition that social determinants of health (SDOH) play critical roles in nutritional status. We evaluated the impact of SDOH on clinical outcomes in hospitalized patients with COPD and sarcopenia and/or frailty. Design. The Nationwide Inpatient Sample (NIS) (years 2018-2020) was analyzed to study adult hospitalized patients with a primary diagnosis of COPD (J43, J44). SDOH was defined by ICD-10 Z-codes as a composite sum of problems related to housing and economic status, unemployment, occupation, psychosocial, family, and healthcare access. Sarcopenia and frailty were defined by a composite of ICD10 codes that have been previously validated in the literature. Multivariate regression models were generated to determine the impact of sarcopenia, frailty, and sarcopenia+frailty on clinical outcomes in COPD patients, which were adjusted for age, race, sex, SDOH, and comorbidities (cardiovascular disease, anemia, coagulopathy, HIV, depression, diabetes mellitus). Results. Of the 282,164 COPD patients that were analyzed, 7254 (2.6%) had codes related to SDOH, 21,035 (7.5%) had sarcopenia, 106,995 (37.9%) had frailty, and 11,293 (4%) had both sarcopenia and frailty. The predominant SDOH code was related to housing (70.9%) followed by social environment (11.5%). SDOH codes were more prevalent in patients with sarcopenia alone (3.6%), compared with frailty (2.5%) or sarcopenia+frailty (2.6%) (p&lt;0.001). When adjusted for demographics including age, race, and sex, SDOH was associated with greater odds of sarcopenia (adj OR 1.64, 95% CI: 1.51-1.79), frailty (adj OR 1.17, 95% CI: 1.11-1.24), and sarcopenia+frailty (adj OR 1.72; 95% CI: 1.54-1.90). COPD patients with sarcopenia+frailty had the greatest association with adverse clinical outcomes (i.e. in-hospital mortality, higher healthcare cost, and higher length of stay), followed by frailty alone, and sarcopenia alone (Table 1). Conclusion. In COPD patients, SDOH increased the odds for a diagnosis of sarcopenia, frailty, and sarcopenia+frailty. Sarcopenia+frailty had the greatest association with adverse outcomes in COPD patients, followed by frailty alone, and sarcopenia alone.

INTRODUCTION: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. METHODS: The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. RESULTS: The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified. DISCUSSION: The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion. REGISTRATION: NCT05740358.