Wegermann, Kara

ABSTRACT Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with heart failure (HF), independent of shared risk factors. Our aim was to describe the incidence of HF in patients with biopsy-proven MASLD. Methods and results We followed patients with biopsy-proven MASLD from the prospective Duke NAFLD Biorepository and Clinical Database from liver biopsy (2007–2013) until death or 5 January 2023. Clinical and echocardiographic data were abstracted via manual chart review. Incident HF was defined as one of the following: (1) hospitalization for HF, (2) medical record diagnosis of HF, (3) ≥1 sign/symptom of HF and elevated natriuretic peptide, or (4) diastolic dysfunction on transthoracic echocardiography with ≥1 sign/symptom of HF. Univariable and multivariable logistic regression models were evaluated. Overall, 570 patients with biopsy-proven MASLD were included. The mean age was 49.5 years, 42.5% were male and 87.0% were non-Hispanic White. Ten patients (1.8%) had baseline HF, leaving 560 patients to assess for incident HF. Over a median follow up of 4009 days (11.0 years) (interquartile range 2270–4672 days), 100 (17.9%) patients developed incident HF while 268 (47.9%) met criteria for HF suspicion. In a multivariable model, increasing age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.08, p < 0.001) and female sex (OR 1.85, 95% CI 1.12–3.04, p = 0.02) were associated with incident HF. Conclusions We found a high incidence of HF in patients with biopsy-proven MASLD. Despite nearly half of patients having suspected HF, very few carried a chart diagnosis. Screening for HF in high-risk patients and establishment of formal care pathways to address early HF may reduce morbidity and mortality.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with heart failure with preserved ejection fraction (HFpEF), independent of shared risk factors. The aim of this study was to determine the prevalence, clinical, and echocardiographic (TTE) features of HFpEF in patients with biopsy-proven NAFLD. Methods: We performed a retrospective single-center cohort study of patients with biopsy-proven NAFLD in the Duke NAFLD Biorepository and Clinical Database. Study entry was at the time of liver biopsy and patients were followed until death or 5/1/2023. Clinical and echocardiographic data were abstracted via manual chart review. HFpEF was defined as: at least one TTE characteristic (left atrial volume index ≥ 29 ml/m 2 , septal wall thickness ≥ 1 cm, or evidence of diastolic dysfunction) and signs or symptoms of heart failure (diagnosis of heart failure on problem list, hospitalization for heart failure, elevated NT pro-BNP level, jugular venous distention, use of loop diuretics, pulmonary or peripheral edema, fatigue, or exertional symptoms). Descriptive statistics were evaluated. Results: A total of 742 patients were included in the study. The mean age of the cohort was 50 +/- 12 years, and 83% were White. 95 (13%) had TTE both prior to study entry and during follow up, while 279 patients (38%) had TTE only during follow up. A total of 185 patients met criteria for HFpEF during follow up. After removing patients with TTE evidence of HFpEF prior to study entry, there were 132 cases of incident HFpEF over a mean follow up of 9.1 years, representing 47% of those with TTE after liver biopsy, and 18% of the overall cohort. Considering only TTE criteria, 142 patients had incident HFpEF. During follow up, 12 patients were hospitalized for heart failure. Conclusions: HFpEF is common in patients with NAFLD and a small percentage of patients do not have a chart diagnosis despite meeting echocardiographic criteria, suggesting that HFpEF may be under-recognized. Screening for HFpEF and/or formal care pathways to address early heart failure will be important to prevent morbidity and mortality in this population.

INTRODUCTION: Hospitalized patients with cirrhosis can develop respiratory failure (RF), which is associated with a poor prognosis, but predisposing factors are unclear. METHODS: We prospectively enrolled a multicenter North American cirrhosis inpatient cohort and collected admission and in-hospital data (grading per European Association for the Study of Liver-Chronic Liver Failure scoring system, acute kidney injury [AKI], infections [admission/nosocomial], and albumin use) in an era when terlipressin was not available in North America. Multivariable regression to predict RF was performed using only admission day and in-hospital events occurring before RF. RESULTS: A total of 511 patients from 14 sites (median age 57 years, admission model for end-stage liver disease [MELD]-Na 23) were enrolled: RF developed in 15%; AKI occurred in 24%; and 11% developed nosocomial infections (NI). At admission, patients who developed RF had higher MELD-Na, gastrointestinal (GI) bleeding/AKI-related admission, and prior infections/ascites. During hospitalization, RF developers had higher NI (especially respiratory), albumin use, and other organ failures. RF was higher in patients receiving albumin (83% vs 59%, P < 0.0001) with increasing doses (269.5 ± 210.5 vs 208.6 ± 186.1 g, P = 0.01) regardless of indication. Admission for AKI, GI bleeding, and high MELD-Na predicted RF. Using all variables, NI (odds ratio [OR] = 4.02, P = 0.0004), GI bleeding (OR = 3.1, P = 0.002), albumin use (OR = 2.93, P = 0.01), AKI (OR = 3.26, P = 0.008), and circulatory failure (OR = 3.73, P = 0.002) were associated with RF risk. DISCUSSION: In a multicenter inpatient cirrhosis study of patients not exposed to terlipressin, 15% of patients developed RF. RF risk was highest in those admitted with AKI, those who had GI bleeding on admission, and those who developed NI and other organ failures or received albumin during their hospital course. Careful volume monitoring and preventing nosocomial respiratory infections and renal or circulatory failures could reduce this risk.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to define serum metabolites associated with HFpEF in a cohort of patients with biopsy‐proven NAFLD to identify common mechanisms. Methods and Results We performed a retrospective, single‐center study of 89 adult patients with biopsy‐proven NAFLD who had transthoracic echocardiography performed for any indication. Metabolomic analysis was performed on serum using ultrahigh performance liquid and gas chromatography/tandem mass spectrometry. HFpEF was defined as ejection fraction >50% plus at least 1 echocardiographic feature of HFpEF (diastolic dysfunction, abnormal left atrial size) and at least 1 heart failure sign or symptom. We performed generalized linear models to evaluate associations between individual metabolites, NAFLD, and HFpEF. Thirty‐seven out of 89 (41.6%) patients met criteria for HFpEF. A total of 1151 metabolites were detected; 656 were analyzed after exclusion of unnamed metabolites and those with >30% missing values. Fifty‐three metabolites were associated with the presence of HFpEF with unadjusted P value <0.05; none met statistical significance after adjustment for multiple comparisons. The majority (39/53, 73.6%) were lipid metabolites, and levels were generally increased. Two cysteine metabolites (cysteine s‐sulfate and s‐methylcysteine) were present at significantly lower levels in patients with HFpEF. Conclusions We identified serum metabolites associated with HFpEF in patients with biopsy‐proven NAFLD, with increased levels of multiple lipid metabolites. Lipid metabolism could be an important pathway linking HFpEF to NAFLD.

Background: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. Methods: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19. Results: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31–462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n=1332), patients with CLD with COVID-19 had worse long-term survival [p<0.001; hazards ratio (HR): 1.69; 95% CI: 1.19–2.41] and higher rate of hospitalization (p<0.001, HR: 2.00, 1.62–2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p=0.05, HR: 2.45, 1.01–2.11), Hispanic ethnicity (p=0.003, HR: 1.94, 1.26–2.99), and severe COVID-19 requiring mechanical ventilation (p=0.028, HR: 1.74, 1.06–2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n=470) of patients with CLD and history of COVID-19, of whom, 70% (n=326) had received the COVID-19 vaccine. Conclusions: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems.