Myostatin is associated with the presence and development of acute-on-chronic liver failure
Astrid Ruiz-Margáin,
Alessandra Pohlmann,
Silke Lanzerath,
Melanie Langheinrich,
Alejandro Campos-Murguía,
Berenice M. Román-Calleja,
Robert Schierwagen,
Sabine Klein,
Frank Erhard Uschner,
Maximilian Joseph Brol,
Aldo Torre-Delgadillo,
Nayelli C. Flores-García,
Michael Praktiknjo,
Ricardo U. Macías Rodríguez,
Jonel Trebicka
Affiliations
Astrid Ruiz-Margáin
Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico; Liver Fibrosis and Nutrition Lab (LFN-Lab), Mexico; MICTLÁN Network: Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases-research Network, Mexico
Alessandra Pohlmann
Department of Internal Medicine I, University of Bonn, Bonn, Germany
Silke Lanzerath
Department of Internal Medicine I, University of Bonn, Bonn, Germany
Melanie Langheinrich
Department of Surgery, University of Greifswald, Greifswald, Germany
Alejandro Campos-Murguía
Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
Berenice M. Román-Calleja
Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico; Liver Fibrosis and Nutrition Lab (LFN-Lab), Mexico; MICTLÁN Network: Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases-research Network, Mexico
Robert Schierwagen
Department of Internal Medicine B, University of Münster, Münster, Germany
Sabine Klein
Department of Internal Medicine B, University of Münster, Münster, Germany
Frank Erhard Uschner
Department of Internal Medicine B, University of Münster, Münster, Germany
Maximilian Joseph Brol
Department of Internal Medicine B, University of Münster, Münster, Germany
Aldo Torre-Delgadillo
Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
Nayelli C. Flores-García
Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
Michael Praktiknjo
Department of Internal Medicine B, University of Münster, Münster, Germany; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
Ricardo U. Macías Rodríguez
Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico; Liver Fibrosis and Nutrition Lab (LFN-Lab), Mexico; MICTLÁN Network: Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases-research Network, Mexico
Jonel Trebicka
Department of Internal Medicine B, University of Münster, Münster, Germany; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain; Corresponding author. Address: Department of Internal Medicine B (Gastroenterology, Hepatology, Endocrinology, Infectious Diseases), University Clinic Münster, University of Münster (WWU), Albert-Schweitzer-Campus 1, 48149, Münster, Germany. Tel.: +49 251 83 59689/57562; fax: +49 251 83 47570.
Background & Aims: Acute-on-chronic liver failure (ACLF) has been linked to different pathophysiological mechanisms, including systemic inflammation and mitochondrial dysfunction. Sarcopenia has also been proposed as a potential mechanism; myostatin is a key factor inducing sarcopenia. Therefore, this study aimed to evaluate the association of myostatin levels with the development of ACLF and mortality in patients with cirrhosis. Methods: We performed a prospective cohort study, including both outpatient and hospitalized patients with cirrhosis. Clinical, biochemical, and nutritional parameters were evaluated, and the development of acute decompensation (AD) or ACLF during follow-up was recorded. ACLF was defined according to the EASL-CLIF criteria. Receiver-operating characteristic, Kaplan-Meier and Cox regression analyses were performed. Results: A total of 186 patients with the whole spectrum of cirrhosis were included; mean age was 53.4 ± 14 years, mean Child-Pugh score was 8 ± 2.5 and mean MELD score was 15 ± 8. There was a stepwise decrease in myostatin levels from a compensated stage to AD and ACLF. Myostatin correlated positively with nutritional markers and negatively with severity scores. The prevalence of sarcopenia was 73.6%. During follow-up, 27.9% of patients developed AD and 25.8% developed ACLF. Most episodes were grade 2-3, mainly (62.5%) precipitated by infections. The most common organ failures observed were in the liver (63.3%) and the kidney (64.6%). Receiver-operating characteristic analysis yielded <1,280 pg/ml as the best serum myostatin cut-off for the prediction of ACLF. In Kaplan-Meier curves and multivariate analysis, myostatin levels remained independently associated with the incidence of ACLF and survival. Conclusions: There is a progressive decrease in myostatin levels as cirrhosis progresses, demonstrating an association of sarcopenia with the development of ACLF and increased mortality. Impact and implications: Myostatin is a muscle hormone, it is decreased in patients with muscle loss and is a marker of impaired muscle function. In this study we show that myostatin levels are decreased in patients with cirrhosis, with lower levels in patients with acute decompensation and acute-on chronic liver failure (ACLF). Low myostatin levels in cirrhosis predict the development of ACLF and mortality independently of liver disease severity and sex.
