Abstract
Simple SummarySarcopenia is prevalent in patients with liver cirrhosis. It has been well-known that cirrhotic patients with sarcopenia had poorer survival as compared to those without it, and expression of serum myostatin is associated with sarcopenia. In this study, we aimed to evaluate whether serum myostatin is associated with hepatocellular carcinoma development in patients with alcoholic cirrhosis or not. We found that serum myostatin is associated with hepatocellular carcinoma development in a large cohort of patients with alcoholic cirrhosis. Among patients with similar residual liver function or similar risk of developing hepatocellular carcinoma using other models, higher serum myostatin was significantly associated with a higher risk of developing hepatocellular carcinoma. In addition, patients with more advanced hepatic fibrosis had significantly higher serum myostatin than those with less advanced hepatic fibrosis. Thus, serum myostatin as a prognostic marker can be useful to identify high-risk patients who need stringent surveillance for hepatocellular carcinoma.Background and Aim: Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC). Methods: This retrospective, multicenter study assessed 1077 Asian ALC patients enrolled from 2007 to 2017. The primary endpoint was the development of HCC within 5 years. Cox proportional hazards model analyses were used to assess the association of serum myostatin levels and HCC development. The time-dependent areas under the receiver operating characteristic curve (AUROC) of serum myostatin for 5-year HCC development were calculated. Serum myostatin levels were measured using an enzyme-linked immunosorbent assay with samples collected on the index date. Results: During a median follow-up of 2.5 years, 5-year cumulative HCC incidence rates were 6.7% in the total population. The median level of serum myostatin was 3.3 ng/mL (interquartile, 2.1–5.2 ng/mL). The AUROC of serum myostatin for 5-year HCC development was 0.78 (95% confidence interval [CI], 0.76–0.81). In Cox proportional hazards model analyses, age, gender, platelet counts, and serum myostatin levels were independent risk factors for HCC development (adjusted hazard ratios [HRs] of age, male gender, platelet counts, and serum myostatin: 1.03, 2.79, 0.996, 1.18, respectively; all p < 0.05). Patients with high myostatin levels had a significantly higher risk of 5-year HCC development than those with low myostatin levels (HR 7.53, p < 0.001). Conclusion: Higher serum myostatin levels were significantly associated with a higher risk of developing HCC in ALC patients, which could identify high-risk patients who need stringent surveillance.
Highlights
Sarcopenia is a syndrome characterized by age-related skeletal muscle loss, which is prevalent in adults with cancer and chronic comorbidities such as liver cirrhosis [1,2,3]
For the multivariate Cox analyses, age, gender, platelet counts, and serum myostatin levels were found to be independent risk factors for hepatocellular carcinoma (HCC) development (HR for age 1.03, 95% Confidence intervals (CI) 1.01–1.06, p = 0.004; HR for gender 2.79, 95% CI 1.01–7.75, p = 0.04; HR for platelet counts 0.996, 95% CI 0.992–0.999, p = 0.03; and HR for serum myostatin 1.18, 95% CI 1.12–1.24, p < 0.001; Table 2)
We evaluated the correlation between serum myostatin levels and hepatic fibrosis using the FIB-4 scores [31]
Summary
Sarcopenia is a syndrome characterized by age-related skeletal muscle loss, which is prevalent in adults with cancer and chronic comorbidities such as liver cirrhosis [1,2,3]. Several studies have reported that sarcopenia is associated with the development and recurrence of hepatocellular carcinoma (HCC) [6,7]. It was reported that higher serum myostatin levels were significantly correlated with muscle mass loss, hyperammonemia, and impaired protein synthesis in cirrhotic patients [8,9]. Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC)
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