Compound Sarcopenia in Hospitalized Patients with Cirrhosis Worsens Outcomes with Increasing Age

Abstract

Background: There are limited data on outcomes of older patients with chronic diseases. Skeletal muscle loss of aging (primary sarcopenia) has been extensively studied but the impact of secondary sarcopenia of chronic disease is not as well evaluated. Older patients with chronic diseases have both primary and secondary sarcopenia that we term compound sarcopenia. We evaluated the clinical impact of compound sarcopenia in hospitalized patients with cirrhosis given the increasing number of patients and high prevalence of sarcopenia in these patients. Design: The Nationwide Inpatients Sample (NIS) database (years 2010–2014) was analyzed to study older patients with cirrhosis. Since there is no universal hospital diagnosis code for “muscle loss”, we used a comprehensive array of codes for “muscle loss phenotype” in the international classification of diseases-9 (ICD-9). A randomly selected 2% sample of hospitalized general medical population (GMP) and inpatients with cirrhosis were stratified into 3 age groups based on age-related changes in muscle mass. In-hospital mortality, length of stay (LoS), cost of hospitalization (CoH), comorbidities and discharge disposition were analyzed. Results. Of 517,605 hospitalizations for GMP and 106,835 hospitalizations for treatment of cirrhosis or a cirrhosis-related complication, 207,266 (40.4%) GMP and 29,018 (27.7%) patients with cirrhosis were >65 years old, respectively. Muscle loss phenotype in both GMP and inpatients with cirrhosis 51–65 years old and >65 years old was significantly (p < 0.001 for all) associated with higher mortality, LoS, and CoH compared to those ≤50 years old. Patients >65 years old with cirrhosis and muscle loss phenotype had higher mortality (adjusted OR: 1.06, 95% CI [1.04, 1.08] and CoH (adjusted odds ratio (OR): 1.10, 95% confidence interval (CI) [1.04, 1.08])) when compared to >65 years old GMP with muscle loss phenotype. Muscle loss in younger patients with cirrhosis (≤50 years old) was associated with worse outcomes compared to GMP >65 years old. Non-home discharges (nursing, skilled, long-term care) were more frequent with increasing age to a greater extent in patients with cirrhosis with muscle loss phenotype for each age stratum. Conclusion: Muscle loss is more frequent in older patients with cirrhosis than younger patients with cirrhosis and older GMP. Younger patients with cirrhosis had clinical outcomes similar to those of older GMP, suggesting an accelerated senescence in cirrhosis. Compound sarcopenia in older patients with cirrhosis is associated with higher inpatient mortality, increased LoS, and CoH compared to GMP with sarcopenia.

Integrated multiomics analysis identifies molecular landscape perturbations during hyperammonemia in skeletal muscle and myotubes

“…An alternative explanation is that even if chromatin access changes drive RNA-Seq, other upstream events and their effects can mediate these differential responses. The canonical pathways enriched in both the late change ATAC-Seq and late change RNA-Seq clusters included those previously reported to be altered during hyperammonemia (HIF1α stabilization ( 27 ); mitochondrial oxidative dysfunction ( 15 ), and others, including the senescence genes ( 35 ), consistent with our recent clinical observations supporting an accelerated aging in muscle phenotype in cirrhosis ( 36 ) ( Fig. 4 H )).…”

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases

“…72 In older adults with cirrhosis, a combination of primary (aging-related) and secondary (chronic disease-related) sarcopenia occurs simultaneously and has been referred to as compound sarcopenia. 73 In hospitalized patients, compound sarcopenia was associated with higher odds of death (odds ratio [OR], 1.06; 95% CI, 1.04-1.08) and greater resource utilization (OR, 1.10; 95% CI, 1.04-1.08) than patients with cirrhosis but without compound sarcopenia. 73…”

“…73 In hospitalized patients, compound sarcopenia was associated with higher odds of death (odds ratio [OR], 1.06; 95% CI, 1.04-1.08) and greater resource utilization (OR, 1.10; 95% CI, 1.04-1.08) than patients with cirrhosis but without compound sarcopenia. 73…”

“…Sarcopenia has been shown to be a robust predictor of a wide spectrum of outcomes in adults with cirrhosis both with and without HCC. 70,73,131,142,147,151,154,[157][158][159][160][161][162][163][164][165] These outcomes have included not only mortality both before and after liver transplantation 131,160,161 but also hepatic decompensation, 166 reduced quality of life, 167 increased risk for infection, 157 and prolonged hospitalization. 44,73,168 In a metaanalysis of 3,803 liver transplant candidates across 19 studies in partly overlapping cohorts published between 2000 and 2015, "sarcopenia," as defined by a wide range of CT-assessed skeletal muscle mass cut-…”

“…( 70,73,131,142,147,151,154,157‐165 ) These outcomes have included not only mortality both before and after liver transplantation ( 131,160,161 ) but also hepatic decompensation, ( 166 ) reduced quality of life, ( 167 ) increased risk of infection, ( 157 ) and prolonged hospitalization. ( 44,73,168 ) In a meta‐analysis of 3,803 liver transplant candidates across 19 studies in partly overlapping cohorts published between 2000 and 2015, “sarcopenia,” as defined by a wide range of CT‐assessed skeletal muscle mass cut‐points, was associated with a pooled HR of 1.72 (95% CI, 0.99‐3.00) for waitlist mortality and 1.84 (95% CI, 1.11‐3.05) for posttransplant mortality. ( 159 ) A separate North American multicenter cohort of nearly 400 patients with cirrhosis listed for liver transplantation identified SMI cut‐points to predict waitlist mortality: < 39 cm 2 /m 2 in women and < 50 cm 2 /m 2 in men.…”