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

doi:10.1016/j.jhepr.2023.100761

Myostatin is associated with the presence and development of acute-on-chronic liver failure

JHEP Rep. 2023 Apr 14;5(8):100761. doi: 10.1016/j.jhepr.2023.100761. eCollection 2023 Aug.

Authors

Astrid Ruiz-Margáin^{1

2

3}, Alessandra Pohlmann⁴, Silke Lanzerath⁴, Melanie Langheinrich⁵, Alejandro Campos-Murguía¹, Berenice M Román-Calleja^{1

2

3}, Robert Schierwagen⁶, Sabine Klein⁶, Frank Erhard Uschner⁶, Maximilian Joseph Brol⁶, Aldo Torre-Delgadillo¹, Nayelli C Flores-García¹, Michael Praktiknjo^{6

7}, Ricardo U Macías Rodríguez^{1

2

3}, Jonel Trebicka^{6

7}

Affiliations

¹ Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico.
² Liver Fibrosis and Nutrition Lab (LFN-Lab), Mexico.
³ MICTLÁN Network: Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases-research Network, Mexico.
⁴ Department of Internal Medicine I, University of Bonn, Bonn, Germany.
⁵ Department of Surgery, University of Greifswald, Greifswald, Germany.
⁶ Department of Internal Medicine B, University of Münster, Münster, Germany.
⁷ European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.

Abstract

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.

Keywords: ACLF; cirrhosis; liver failure; malnutrition; myostatin; sarcopenia.