Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Patients
2.2. Clinical Evaluation and Follow-Up
2.3. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Serum Myostatin Levels as an Independent Prognostic Factor for the Development of Hepatocellular Carcinoma within 5 Years
3.3. The Prognostic Performance of Serum Myostatin to Predict HCC Risk in Different Risk Groups According to the Toronto HCC Risk Index
3.4. Subgroup Analyses According to Age, Sex, and Child–Pugh Class
3.5. The Prognostic Performance of Serum Myostatin Levels to Predict HCC Risk According to Residual Functional Reserves and Hepatic Fibrosis
3.6. Correlation between Serum Myostatin Levels and Hepatic Fibrosis
3.7. Distant Metastasis, Serum α-Fetoprotein, and Serum Myostatin Levels
3.8. Risk Assessments for Developing Hepatic Decompensation and Liver-Related Death According to Serum Myostatin Levels
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ALC | alcoholic liver cirrhosis |
CI | confidence interval |
CP | Child–Pugh |
HCC | hepatocellular carcinoma |
HR | hazard ratio |
MELD | model for end-stage liver disease |
THRI | Toronto hepatocellular carcinoma risk index |
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Variables | Total (n = 1077) | No HCC (n = 998) | HCC (n = 79) | p-Value a | Low Myostatin (n = 781) | High Myostatin (n = 296) | p-Value a |
---|---|---|---|---|---|---|---|
Age, years | 55 (47, 62) | 55 (47, 61) | 57 (55, 63) | 0.003 | 55 (46, 62) | 55 (49, 59) | 0.73 |
Male, n (%) | 895 (83.1) | 820 (82.2) | 75 (94.9) | 0.002 | 615 (78.7) | 279 (94.3) | <0.001 |
Body mass index, kg/m2 | 23.0 (20.8, 25.3) | 22.9 (20.8, 25.2) | 24.1 (22.0, 26.9) | 0.009 | 22.9 (20.8, 24.9) | 23.7 (21.4, 26.2) | <0.001 |
Diabetes mellitus, n (%) | 247 (22.9) | 223 (22.3) | 24 (30.4) | 0.13 | 185 (23.7) | 62 (20.9) | 0.34 |
AST, IU/L | 53 (38, 84) | 53 (38, 85) | 62 (37, 78) | 0.60 | 53 (37, 88) | 53 (38, 78) | 0.97 |
ALT, IU/L | 22 (13, 37) | 22 (13, 37) | 23 (16, 34) | 0.43 | 23 (14, 39) | 21 (12, 34) | 0.02 |
Total bilirubin, mg/dL | 1.7 (0.9, 3.6) | 1.7 (0.9, 3.5) | 1.9 (1.2, 3.1) | 0.70 | 1.6 (0.8, 3.5) | 1.9 (1.1, 4.0) | 0.005 |
INR | 1.3 (1.2, 1.7) | 1.3 (1.2, 1.6) | 1.4 (1.2, 1.6) | 0.90 | 1.3 (1.1, 1.6) | 1.4 (1.3, 1.7) | <0.001 |
Creatinine, mg/dL | 0.9 (0.8, 1.2) | 0.9 (0.7, 1.2) | 0.9 (0.7, 1.1) | 0.10 | 0.9 (0.7, 1.2) | 1.0 (0.8, 1.2) | 0.006 |
Platelets, × 109/L | 105 (71, 168) | 107 (73, 174) | 93 (69, 137) | 0.03 | 113 (75, 183) | 94 (63, 125) | <0.001 |
Albumin, g/dL | 3.1 (2.6, 3.6) | 3.1 (2.6, 3.6) | 3.0 (2.6, 3.6) | 0.998 | 3.1 (2.7, 3.7) | 2.9 (2.6, 3.4) | <0.001 |
Toronto HCC risk index | 236 (186, 255) | 236 (186, 255) | 255 (205, 286) | <0.001 | 225 (166, 255) | 236 (205, 255) | <0.001 |
Low risk | 88 (8.2) | 86 (8.6) | 2 (2.5) | <0.001 | 84 (10.8) | 4 (1.4) | <0.001 |
Intermediate risk | 650 (60.4) | 613 (61.4) | 37 (46.8) | 489 (62.6) | 161 (54.4) | ||
High risk | 339 (31.5) | 299 (30.0) | 40 (50.6) | 208 (26.6) | 131 (44.3) | ||
FIB-4 index | 6.5 (3.7, 11.3) | 6.4 (3.6, 11.1) | 8.0 (4.3, 11.8) | 0.04 | 6.0 (3.2, 10.4) | 7.6 (4.9, 12.3) | <0.001 |
MELD score | 13.2 (9.5, 18.2) | 13.3 (9.5, 18.6) | 12.6 (10.2, 17.6) | 0.29 | 12.7 (9.0, 17.7) | 14.5 (11.0, 19.3) | <0.001 |
Child–Pugh class | |||||||
A, n (%) | 343 (31.8) | 318 (31.9) | 25 (31.6) | 0.53 | 274 (35.1) | 69 (23.3) | 0.001 |
B, n (%) | 464 (43.1) | 426 (42.7) | 38 (48.1) | 322 (41.2) | 142 (48.0) | ||
C, n (%) | 270 (25.1) | 254 (25.5) | 16 (20.3) | 185 (23.7) | 85 (28.7) | ||
α-fetoprotein | 4.2 (2.8, 6.7) | 4.2 (2.8, 6.7) | 5.4 (3.5, 7.0) | 0.053 | 4.1 (2.7, 6.5) | 4.8 (3.1, 7.4) | 0.003 |
Myostatin, ng/mL | 3.3 (2.1, 5.2) | 3.2 (2.0, 4.9) | 6.1 (4.0, 8.9) | <0.001 | 2.6 (1.8, 3.6) | 7.2 (6.0, 9.5) | <0.001 |
Variables | Univariable | Multivariable | ||
---|---|---|---|---|
HR (95% CI) | p-Value a | HR (95% CI) | p-Value a | |
Age (per year increase) | 1.04 (1.01–1.06) | <0.001 | 1.03 (1.01–1.06) | 0.004 |
Gender (male vs. female) | 4.05 (1.48–11.07) | 0.006 | 2.79 (1.01–7.75) | 0.04 |
Body mass index, kg/m2 | 1.08 (1.02–1.13) | 0.006 | 1.05 (0.98–1.12) | 0.12 |
Diabetes mellitus (yes vs. no) | 1.42 (0.88–2.29) | 0.16 | ||
AST (per IU/L) | 0.999 (0.996–1.001) | 0.34 | ||
ALT (per IU/L) | 0.995 (0.988–1.003) | 0.20 | ||
Total bilirubin (per mg/dL) | 0.97 (0.91–1.04) | 0.39 | ||
Albumin (per g/dL) | 0.60 (0.43–0.84) | 0.003 | 0.73 (0.50–1.10) | 0.09 |
Platelets (per × 109/L) | 0.993 (0.989–0.996) | <0.001 | 0.996 (0.992–0.999) | 0.03 |
INR | 0.99 (0.89–1.11) | 0.90 | ||
Creatinine (per mg/dL) | 0.90 (0.51–1.56) | 0.69 | ||
Child–Pugh score | 1.09 (0.99–1.21) | 0.09 | ||
FIB-4 | 1.01 (0.99–1.03) | 0.18 | ||
MELD score | 1.02 (0.98–1.10) | 0.37 | ||
Myostatin (per ng/mL) | 1.24 (1.19–1.30) | <0.001 | 1.18 (1.12–1.24) | <0.001 |
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Kim, J.H.; Kang, S.H.; Lee, M.; Youn, G.S.; Kim, T.S.; Jun, B.G.; Kim, M.Y.; Kim, Y.D.; Cheon, G.J.; Kim, D.J.; et al. Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study. Cancers 2020, 12, 3347. https://doi.org/10.3390/cancers12113347
Kim JH, Kang SH, Lee M, Youn GS, Kim TS, Jun BG, Kim MY, Kim YD, Cheon GJ, Kim DJ, et al. Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study. Cancers. 2020; 12(11):3347. https://doi.org/10.3390/cancers12113347
Chicago/Turabian StyleKim, Ji Hyun, Seong Hee Kang, Minjong Lee, Gi Soo Youn, Tae Suk Kim, Baek Gyu Jun, Moon Young Kim, Young Don Kim, Gab Jin Cheon, Dong Joon Kim, and et al. 2020. "Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study" Cancers 12, no. 11: 3347. https://doi.org/10.3390/cancers12113347