Editor: Won Kim, Seoul National University College of Medicine, Korea
Sarcopenia negatively affects the prognosis of cirrhotic patients, but clinical implications of changes in muscle mass remain unclear. We aimed to elucidate its role in the prognosis of outpatients with cirrhosis.
Patients with cirrhosis who underwent annual abdominal computed tomography (CT) for hepatocellular carcinoma surveillance were included in the prospective cohort. The L3 skeletal muscle index (SMI) was adopted as a proxy for the amount of skeletal muscle, and the rate of SMI change between inclusion and after 1 year (ΔSMI/yr%) was calculated.
In total, 595 patients underwent a second CT after 1 year. Among them, 109 and 64 patients had sarcopenia and Child-Pugh class B/C decompensation at inclusion, which changed to 103 and 45 at the 1-year follow-up, respectively. During a median follow-up of 30.1 months after 1 year, 86 patients had at least one cirrhosis complication, and 18 died or received liver transplantation. In the development of cirrhosis complications, ΔSMI/yr% was independently associated, even after adjusting for the Child-Pugh and model for end stage liver disease (MELD)-Na scores. In addition, ΔSMI/yr% showed a good predictive performance for the development of cirrhosis complications within 6 months after 1-year follow-up in all subgroups, with a cut-off of -2.62 (sensitivity, 83.9%; specificity, 74.5%) in the overall population. SMI at 1-year and Child-Pugh score were independent factors associated with survival. In addition, changes in sarcopenia status significantly stratified survival.
ΔSMI/yr% was a good predictor of the development of cirrhosis complications in outpatients with cirrhosis, independent of Child-Pugh and MELD scores.
• Reduced muscle mass in patients with cirrhosis reflects a poor prognosis. However, the impact of change in muscle mass on prognosis is unclear.
• SMI and Child-Pugh score were the independent factors for LT-free survival.
• In a prospective cohort which involved regular CT scans, the changes in muscle mass were associated with development of cirrhosis complications and it was independent even after adjusting Child-Pugh and MELD-Na scores.
• We could select the high-risk group among cirrhotic patients by merging the change in muscle mass into Child-Pugh class.
Sarcopenia is characterized by reduced skeletal muscle mass, strength, or physical performance [
In particular, sarcopenia is closely related to chronic liver disease; therefore, guidelines for sarcopenia were presented by liver societies in various countries [
A recent meta-analysis suggested that sarcopenia and skeletal muscle index (SMI) are independently associated with the prognosis of patients with cirrhosis. Sarcopenia and a 1 cm2/m2 decrease in the third lumbar vertebra (L3)-SMI were associated with a 2.30- and 1.03-fold higher mortality risk, respectively [
However, muscle mass can change, and there is a limit to predict muscle mass at one time point for the long-term prognosis of patients. Most of sarcopenia-related studies involved a majority of patients with severe liver dysfunction and a poor prognosis and, accordingly investigated shortterm prognoses [
Herein, we aimed to investigate the impact of changes in muscle mass, including ∆SMI over 1 year, on the survival and development of complications in outpatients with cirrhosis using a prospective cohort whose members with a Child-Pugh score of 5‒10 underwent regular computed tomography (CT) scans.
We investigated a cohort of patients at the Korea University Ansan Hospital from a multicenter prospective study of hepatocellular carcinoma (HCC) surveillance using biomarkers (alpha-fetoprotein [AFP], AFP-L3, and PIVKA-II) and imaging tools in patients with cirrhosis. This prospective cohort enrolled outpatients with cirrhosis aged 19‒75 years from September 2016 to February 2020 at 15 tertiary medical centers in South Korea. Patients with serum creatinine >1.5 mg/dL or Child-Pugh scores >10 were excluded due to the nephrotoxicity of the contrast medium and the probability of early dropout. Patients with HCC, a history of liver or kidney transplantation, incurable malignancy, or any contraindication for enhanced CT scans were excluded. Additional details regarding this prospective study are described in the Supplementary Materials.
This prospective study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Board at the Korea University Ansan Hospital (IRB No. 2016AS0064). Written informed consent was obtained from all patients. Among them, we recruited and reviewed patients who were enrolled between July 2016 and February 2020 and underwent a 1-year CT scan before March 2021. Thus, we set the date taking the 1-year CT scan to the 1 year in this study. All authors accessed the study data, and reviewed and approved the final manuscript.
Following inclusion, patient’s demographic and clinical data, as well as the results of liver and kidney tests were collected, and the laboratory tests were repeated at least every 3 to 6 months, with ultrasound scans every 6 months and CT scans every year until HCC development. HCC was diagnosed according to the guidelines of the Korean Liver Cancer Association [
At inclusion and after 1 year, we measured the cross-sectional area of the skeletal muscles (cm2) on a CT scan at the caudal end at the level of the L3. In this study, in-house software was used to identify subcutaneous fat, visceral fat, and muscle (i.e., the psoas, paraspinal muscles, transversus abdominis, rectus abdominis, and internal and external obliques) in CT images for body composition analysis based on MATLAB version R2010a (Mathworks Inc., Natick, MA, USA). This open-source software (BMI_CT) is available at the following URL:
SMI (cm2/m2) was calculated by dividing the L3-skeletal muscle area (SMA) by the square of the height. Sarcopenia was defined as SMI <39 cm2/m2 in women and <50 cm2/m2 in men, according to the American Association for the Study of Liver Diseases guidelines [
We further defined the change in SMI within 1 year as “∆SMI/yr%” using the following formula: ∆SMI/yr% = (SMI after 1 year – SMI at inclusion) / SMI at inclusion × 100 (%).
The principal outcomes included death and liver transplantation (LT), and the development of cirrhosis complications, which included clinically apparent new-onset ascites, refractory ascites, spontaneous bacterial peritonitis (SBP), overt hepatic encephalopathy, or variceal bleeding [
Refractory ascites was defined as ascites that was uncontrollable even with high-dose diuretics or intractable owing to diuretic-induced complications, mandating repeated paracentesis. SBP was diagnosed when the ascitic polymorphonuclear leukocyte count was ≥250 cells/mm3 without evident intra-abdominal infection [
Statistical analysis was performed using R software (version 4.1.2;
We calculated the minimal sample size with an alpha-error of 0.05 and power of 0.8. Based on a study by Jeong et al. [
The probabilities of LT-free survival and the cumulative development of cirrhosis complications in 1 year were estimated using the Kaplan-Meier method, and the differences between the groups were assessed using the log-rank test. Patients who were lost to follow-up were censored based on the date of their last follow-up.
A Cox proportional hazard regression model was established to analyze the factors associated with the principal outcomes, and significant factors in the univariate analyses were subjected to multivariable analysis to determine the independent predictive factors. For the development of cirrhosis complications, we further performed the Fine and Gray regression with mortality and LT as competing events [
To evaluate predictive performance, receiver operating characteristic (ROC) curves were constructed, and the values of the area under the curve (AUC) were compared.
All tests were two-tailed, and
Among the 729 patients of the prospective cohort, 595 were included in this study (
The clinical characteristics of the enrolled patients at inclusion are shown in
The median duration from CT at the time of inclusion to the second CT was 12.1 months (11.7, 12.9). Sarcopenia was present in 109 patients at the time of inclusion, but it decreased to 103 patients after 1 year (
During the median follow-up period of 30.1 months (19.6, 39.2), 10 patients died, and eight patients received LT. The causes of death were infection (50%), hepatorenal syndrome (20%), variceal bleeding (20%), and stroke (10%).
In the Cox regression analyses, SMI at 1 year was independently associated with LT-free survival even after adjusting for Child-Pugh and MELD-Na scores (
Sarcopenia at 1 year was not significantly associated with LT-free survival (
Cirrhosis complications occurred in 34 patients within 6 months prior to the 1-year CT. ∆SMI/yr% was not significantly different according to the presence of previous cirrhosis complications (median [interquartile range], -1.0 [-3.0, 2.5] vs. -0.35 [-8.87, 3.62] in patients without and with previous cirrhosis complications;
After the 1-year CT, 86 patients experienced at least one cirrhosis complication. The first episode of complication was ascites (47.7%), including newly developed ascites (32.6%) and progression to refractory ascites (15.1%), varix bleeding (38.4%), and hepatic encephalopathy (13.9%). According to the presence of sarcopenia at 1 year and the change in sarcopenia status, the development of cirrhosis complications was not significantly different (
In contrast to LT-free survival, SMI at 1 year was not associated with the development of cirrhosis complications. In contrast, ∆SMI/yr% was an independent prognostic factor for the development of cirrhosis complications even after adjusting for the Child-Pugh and MELD-Na scores (
To investigate the predictive performance, ROC analysis was performed on the development of cirrhosis complications within 6 months after 1-year follow-up. Overall, the AUC of ∆SMI/yr% was 0.817 (95% confidence interval [CI], 0.729-0.905), and the optimal cut-off value was -2.62 with a sensitivity of 83.9% and specificity of 74.5% (
Based on these results, we classified patients into four groups as follows: group 1: patients with Child-Pugh class A and ∆SMI/yr% ≥-3.66 (n=445); group 2: those with ChildPugh class A and ∆SMI/yr% <-3.66 (n=105); group 3: those with Child-Pugh class B/C and ∆SMI/yr% ≥-2.62 (n=25); and group 4: those with Child-Pugh class B/C and ∆SMI/yr% <-2.62 (n=20).
The cumulative incidence of development of cirrhosis complications differed significantly among the four groups: the cumulative incidences of LC complications at 6, 12, 24, and 36 months were 0.7%, 2.6%, 6.8%, and 9.1%, respectively, in group 1; 9.8%, 15.9%, 18.6%, and 25.4%, respectively, in group 2; 16.0%, 36.3%, 55.1%, and 60.7%, respectively, in group 3; and 55.0%, 70.8%, 82.5%, and 82.5%, respectively, in group 4 (
Groups 1 and 2 showed significantly better LT-free survival than did groups 3 and 4 (
Many previous studies have shown that SMI and sarcopenia are independently associated with prognosis, including survival and the development of cirrhosis complications in patients with cirrhosis [
Previously, two studies by Hanai et al. [
This study showed that presence of sarcopenia and ∆SMI/ yr% did not significantly influence the survival of outpatients with cirrhosis (
In contrast, ∆SMI/yr% was independently associated with the development of cirrhosis complications, even after adjusting for Child-Pugh and MELD-Na scores. AUCs of ∆SMI/yr% for the development of cirrhosis complications within 6 months were >0.75 in overall and all subgroups analyses, suggesting the reliable predictive performance of ∆SMI/yr%. In addition, the optimal cut-off value of ∆SMI/yr% was -2.62 for the development of cirrhosis complications within 6 months, which is similar to -2.4%, the optimal cut-off value of ∆SMA/y for survival, as suggested by Jeong et al. [
Based on these findings, we created four new groups integrating ∆SMI/yr% and Child-Pugh class, which connote the presence of existing complications. The risk of complications was well stratified in the four new groups, and all comparisons between the groups showed a significant difference. Patients with Child-Pugh class B/C and severe muscle loss had a 26-fold higher risk of development of cirrhosis complications than those with Child-Pugh class A and less muscle loss. However, mortality was stratified entirely based on Child-Pugh class, not on ∆SMI/yr%.
It is not yet clear whether the change in muscle mass is a consequence of, or the cause of the development of cirrhosis complications. In this study, previously development of complications did not significantly affect ∆SMI/yr% (
This study had some limitations. First, because ∆SMI/yr% was required, patients who died or received a LT within 1 year were excluded. This might bring about selection bias and weaken the clinical impact of SMI and ∆SMI/yr%. However, it was unavoidable to use a cohort with regular CT follow-up. At present, CT is the most accurate and accessible method for diagnosing sarcopenia in cirrhosis patients, and it is difficult to perform CT scans at short intervals owing to the radiation risk and cost. Recently, to overcome this limitation, a model for predicting sarcopenia using blood test results in cirrhosis patients has been developed; however, further validation is still needed [
Applying our findings to clinical practice, patients who meet the group 4 requirement should be followed up for short-term observation and for prevention of aggravating factors. In addition, the results of Cox regression analysis in our cohort suggest that every 1-point increase in ∆SMI/yr% was associated with a 5.0% decrease in the risk of cirrhosis complications. Although further studies are needed, steady resistance training could increase muscle size and strength, even in patients with cirrhosis, as shown by Aamann et al. [
In conclusion, we demonstrated that changes in sarcopenia status and muscle mass are associated with greater mortality and the development of cirrhosis complications, respectively, in outpatients with cirrhosis. In particular, even after adjusting for the Child-Pugh and MELD-Na scores, change in muscle mass was an independent predictor of the development of complications. Simple classifications using these muscle mass changes could help stratify the prognosis of outpatients with cirrhosis. Additionally, this study warrants a prospective comparison in a study involving muscle mass change over a short period of time and with an exercise intervention.
Conception: YKJ, HJY; Study design: YKJ; Participation in patient management and data collection: YKJ, HJY, YSS, JHK, JEY, KSB; Contribution to data acquisition and blind measurements: JWB, YSL; Statistical analysis: THK; Writing the original draft: THK, YKJ; Writing, review, and editing: YKJ, HJY; Guarantor: YKJ; All authors have reviewed the paper and approved the final version.
The authors have no conflicts to disclose.
This clinical trial was registered in the ClinicalTrials.gov (NCT04414956). This study was supported by a Korea University Grant (K1512701). We would like to thank Editage (
Supplementary material is available at Clinical and Molecular Hepatology website (
Comparison of included and excluded participants
Characteristics of patients based on sarcopenia status at inclusion
Univariate and multivariate competing risk analyses for the development of LC complication after 1-year CT
Calibration plot of CLIF-SOFA scores. Diagonal line is the line of perfect calibration. Dots represent the intersects of observed and expected values for the risk of mortality, and bars represent the 95% confidence interval of the observed probability. Blue line indicates the calibration trend; since this line is close to the diagonal line, it indicates that the CLIF-SOFA fits the data well. CLIF-SOFA, Chronic Liver Failure-Sequential Organ Failure Assessment; ΔSMI/yr%, % change in SMI after 1 year.
Prevalence of sarcopenia according to various conditions at inclusion. ALD, alcoholic liver disease.
Change of SMI according to the presence of cirrhosis complications between 6‒12 months. The ΔSMI/yr% was not significantly different between patients with and without previous liver cirrhosis complications within 6 months prior to the 1 year (
Receiver operating characteristic curve of ΔSMI/yr% for development of cirrhosis complication within 6 months after the 1-year follow-up in eight subgroups. (A) In men, the AUROC of ΔSMI/yr% was 0.836, and the optimal cut-off was -5.74, with a sensitivity of 68.4% and specificity of 91.9%. (B) AUROCs, optimal cut-offs, sensitivities, and specificities were 0.783, -2.62, 83.3%, and 75.1% in women; (C) 0.807, -2.62, 83.3%, and 74.3% in non-sarcopenia at inclusion; (D) 0.856, -5.74, 85.7%, and 90.1% in sarcopenia at inclusion; (E) 0.767, -2.62, 80.0%, and 72.9% in non-alcoholic etiology; (F) 0.883, -2.82, 87.5%, and 83.2% in alcohol etiology; (G) 0.827, -2.74, 81.0%, and 77.8% in non-HBV etiology; and (H) 0.824, -2.62, 90.0%, and 73.6% in HBV etiology. ΔSMI/yr%, % change in skeletal muscle index after 1 year; AUROC, area under the receiver operating characteristic curve; HBV, hepatitis B virus.
alpha-fetoprotein
area under the curve
confidence interval
computed tomography
estimated glomerular filtration rate
hepatocellular carcinoma
liver transplantation
model for end-stage liver disease
non-sarcopenia to non-sarcopenia
non-sarcopenia to sarcopenia
receiver operating characteristic
spontaneous bacterial peritonitis
skeletal muscle area
skeletal muscle index
sarcopenia to non-sarcopenia
sarcopenia to sarcopenia
Flow diagram of patient inclusion. HCC, hepatocellular carcinoma; CT, computed tomography.
Kaplan-Meier plots for LT-free survival after 1-year CT. (A) LT-free survival was not significantly different between two groups with non-sarcopenia and sarcopenia at 1 year (
Kaplan-Meier plots for the development of cirrhosis complication after 1-year CT. The development of cirrhosis complication was not well-stratified by (A) the sarcopenia status and (B) sarcopenia status change (
Receiver operating characteristic curve of ΔSMI/yr% for development of cirrhosis complication within 6 months after 1-year CT. The AUCs of ΔSMI/yr% were (A) 0.817 in all, (B) 0.855 in patients with Child-Pugh class A, and (C) 0.754 in those with Child-Pugh classes B/C. ΔSMI/ yr%, % change in skeletal muscle index after 1 year; CT, computed tomography; AUC, area under curve.
Characteristics of patients based on sarcopenia at the 1-year follow-up
Variable | NN (n=471) | SN (n=21) | NS (n=15) | SS (n=88) | |
---|---|---|---|---|---|
Age (years) | 56.9 (51.2, 61.7) | 56.0 (48.6, 60.1) | 51.9 (49.1, 58.3) | 58.2 (51.3, 61.3) | 0.34 |
Male | 285 (60.5) | 16 (76.2) | 11 (73.3) | 69 (78.4) | <0.01 |
BMI (kg/m2) | 25.4 (23.7, 27.5) | 24.1 (21.7, 25.1) | 22.8 (21.7, 24.1) | 20.8 (19.7, 23.1) | <0.01 |
Hypertension | 116 (24.6) | 4 (19.1) | 1 (6.7) | 18 (20.5) | 0.34 |
Diabetes mellitus | 132 (28.0) | 8 (38.1) | 4 (26.7) | 19 (21.6) | 0.42 |
Alcohol-related | 99 (21.0) | 10 (47.6) | 3 (20.0) | 32 (36.4) | <0.01 |
Hepatitis B | 280 (59.5) | 10 (47.6) | 11 (73.3) | 56 (63.6) | 0.39 |
Hepatitis C | 39 (8.3) | 1 (4.8) | 0 (0.0) | 3 (3.4) | 0.26 |
Platelets (×103/mm3) | 127 (84, 172) | 131 (85, 155) | 139 (93, 163) | 138 (97, 168) | 0.90 |
Albumin (g/dL) | 4.5 (4.2, 4.7) | 4.5 (4.2, 4.7) | 4.6 (3.8, 4.8) | 4.4 (4.2, 4.7) | 0.99 |
AST (U/L) | 29 (24, 37) | 31 (20, 39) | 28 (26, 38) | 27 (23, 41) | 0.90 |
ALT (U/L) | 23 (17, 31) | 20 (15, 28) | 23 (17, 31) | 18 (13, 27) | <0.01 |
Bilirubin (mg/dL) | 0.84 (0.65, 1.25) | 0.90 (0.57, 1.15) | 1.00 (0.73, 1.64) | 0.85 (0.66, 1.32) | 0.57 |
Prothrombin time (INR) | 1.08 (1.04, 1.16) | 1.09 (1.03, 1.16) | 1.09 (1.04, 1.14) | 1.08 (1.03, 1.16) | 0.90 |
Creatinine (mg/dL) | 0.82 (0.70, 0.94) | 0.82 (0.72, 0.93) | 0.78 (0.72, 0.92) | 0.76 (0.66, 0.90) | 0.23 |
eGFR (mL/min/1.73 m2) | 89.2 (76.9, 102.6) | 90.5 (83.4, 107.3) | 92.0 (80.0, 108.2) | 96.7 (82.0, 114.0) | <0.01 |
Sodium (mmol/L) | 142 (140, 143) | 142 (141, 142) | 140 (139, 143) | 141 (140, 143) | 0.46 |
Ascites | 30 (6.4) | 0 (0.0) | 3 (20.0) | 6 (6.8) | 0.26 |
Overt encephalopathy | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (1.1) | 0.12 |
Child-Pugh score | 5 (5, 5) | 5 (5, 5) | 5 (5, 5) | 5 (5, 5) | 0.44 |
Child-Pugh class B/C | 34 (7.2) | 0 (0.0) | 1 (6.7) | 1 (1.1) | 0.14 |
MELD-Na score | 8 (7, 10) | 8 (7, 9) | 9 (8, 12) | 8 (7, 9) | 0.32 |
SMI (cm2/m2) | 55.7 (49.9, 62.0) | 51.0 (50, 52.2) | 48.1 (38.2, 48.7) | 43.7 (37.6, 46.7) | <0.01 |
∆SMI/yr% (%) | -0.13 (-2.77, 2.38) | 7.04 (4.34, 12.40) | -7.99 (-12.57, -3.90) | -0.40 (-4.03, 2.17) | <0.01 |
Values are expressed as number (%) or median (interquartile range).
NN, non-sarcopenia to non-sarcopenia; SN, sarcopenia to non-sarcopenia; NS, non-sarcopenia to sarcopenia; SS, sarcopenia to sarcopenia; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, international normalized ratio; eGFR, estimated glomerular filtration rate; MELD, model for end-stage liver disease; SMI, skeletal muscle index; ΔSMI/yr%, % change in SMI after 1 year.
Univariate and multivariable Cox regression analyses for LT-free survival after 1-year CT
Variable | Univariate |
Model 1 |
Model 2 |
Model 3 |
||||
---|---|---|---|---|---|---|---|---|
HR (95% CI) | aHR (95% CI) | aHR (95% CI) | aHR (95% CI) | |||||
Age (years) | 0.92 (0.85–1.00) | 0.06 | ||||||
Gender, male | 0.55 (0.16–1.89) | 0.34 | ||||||
BMI (kg/m2) | 1.04 (0.87–1.23) | 0.70 | ||||||
HTN | 2.09 (0.59–7.40) | 0.25 | ||||||
DM | 3.82 (1.08–13.55) | 0.04 | 2.58 (0.95–7.00) | 0.06 | 2.01 (0.73–5.50) | 0.17 | 2.55 (0.94–6.94) | 0.07 |
Alcohol-related | 1.35 (0.35–5.21) | 0.67 | ||||||
Hepatitis B | 0.07 (0.01–0.56) | 0.01 | 0.57 (0.20–1.62) | 0.29 | 0.44 (0.16–1.22) | 0.11 | 0.55 (0.19–1.59) | 0.27 |
Hepatitis C | 1.88 (0.12–6.62) | 0.98 | ||||||
Platelets (×109/L) | 0.99 (0.98–1.00) | 0.07 | 1.00 (0.99–1.01) | 0.42 | 0.99 (0.98–1.00) | 0.17 | 0.99 (0.99–1.00) | 0.31 |
Albumin (g/dL) | 0.12 (0.05–0.26) | <0.01 | 0.28 (0.08–1.02) | 0.05 | 0.28 (0.07–1.08) | 0.06 | ||
AST (U/L) | 1.01 (1.00–1.01) | 0.01 | 1.00 (0.99–1.01) | 0.33 | 1.00 (0.99–1.01) | 0.34 | 1.00 (0.99–1.01) | 0.32 |
ALT (U/L) | 0.99 (0.93–1.04) | 0.61 | ||||||
Bilirubin (mg/dL) | 2.00 (1.49–2.69) | <0.01 | 1.05 (0.63–1.75) | 0.85 | ||||
Prothrombin time (INR) | 65.06 (12.51–338.45) | <0.01 | 2.06 (0.14–30.31) | 0.60 | ||||
Creatinine (mg/dL) | 0.01 (0.01–0.79) | 0.04 | ||||||
eGFR (mL/min/1.73 m2) | 1.03 (1.01–1.05) | <0.01 | 1.01 (0.99–1.03) | 0.33 | 1.01 (0.99–1.03) | 0.25 | 1.01 (0.99–1.03) | 0.27 |
Sodium (mmol/L) | 0.88 (0.73–1.08) | 0.22 | ||||||
Ascites | 18.56 (5.34–64.51) | <0.01 | 1.74 (0.35–8.73) | 0.50 | 1.81 (0.36–9.02) | 0.47 | ||
Child-Pugh score | 1.90 (1.55–2.33) | <0.01 | 1.66 (1.34–2.07) | <0.01 | ||||
Child-Pugh class, B/C | 13.65 (6.19–30.10) | <0.01 | ||||||
MELD-Na score | 1.32 (1.18–1.47) | <0.01 | 1.03 (0.87–1.21) | 0.76 | ||||
Sarcopenia | 2.08 (0.54–8.06) | 0.29 | ||||||
SMI (cm2/m2) | 0.95 (0.90–1.00) | 0.04 | 0.94 (0.90–0.99) | 0.02 | 0.95 (0.90–0.99) | 0.02 | 0.95 (0.91–0.99) | 0.02 |
∆SMI/yr% (%) | 0.98 (0.90–1.07) | 0.72 |
The values of variables were derived by examinations at the 1-year follow-up.
Model 1, multivariable Cox regression analysis with DM, hepatitis B, platelet count, albumin, AST, bilirubin, INR, eGFR, presence of ascites, and SMI, which showed
LT, liver transplantation; CT, computed tomography; HR, hazard ratio; CI, confidence interval; aHR, adjusted hazard ratio; BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, international normalized ratio; eGFR, estimated glomerular filtration rate; MELD, model for end-stage liver disease; SMI, skeletal muscle index; ΔSMI/yr%, % change in SMI after 1 year.
Univariate and multivariable Cox regression analyses for the development of LC complication after 1-year CT
Variable | Univariate |
Model 1 |
Model 2 |
Model 3 |
||||
---|---|---|---|---|---|---|---|---|
HR (95% CI) | aHR (95% CI) | aHR (95% CI) | aHR (95% CI) | |||||
Age (years) | 1.02 (0.99–1.05) | 0.19 | ||||||
Gender, male | 1.06 (0.68–1.66) | 0.80 | ||||||
BMI (kg/m2) | 0.95 (0.89–1.02) | 0.13 | ||||||
HTN | 1.79 (1.15–2.79) | 0.01 | 2.07 (1.21–3.54) | <0.01 | 1.93 (1.16–3.21) | 0.01 | 2.03 (1.20–3.42) | <0.01 |
DM | 1.82 (1.18–2.80) | <0.01 | 1.17 (0.72–1.93) | 0.53 | 1.12 (0.69–1.82) | 0.65 | 1.23 (0.76–2.00) | 0.40 |
Alcohol-related | 4.48 (2.93–6.86) | <0.01 | 2.00 (1.22–3.28) | <0.01 | 2.22 (1.38–3.59) | <0.01 | 1.99 (1.22–3.24) | <0.01 |
Hepatitis B | 0.20 (0.13–0.33) | <0.01 | 0.37 (0.21–0.66) | <0.01 | 0.33 (0.19–0.58) | <0.01 | 0.38 (0.22–0.68) | <0.01 |
Hepatitis C | 0.48 (0.15–1.52) | 0.21 | ||||||
Platelets (×109/L) | 0.99 (0.98–0.99) | <0.01 | 1.00 (0.99–1.00) | 0.10 | 0.99 (0.98–1.00) | <0.01 | 1.00 (0.99–1.00) | 0.14 |
Albumin (g/dL) | 0.14 (0.10–0.19) | <0.01 | 0.33 (0.18–0.61) | <0.01 | 0.32 (0.17–0.60) | <0.01 | ||
AST (U/L) | 1.01 (1.00–1.01) | <0.01 | 1.01 (1.00–1.01) | <0.01 | 1.01 (1.00–1.02) | <0.01 | 1.01 (1.00–1.01) | <0.01 |
ALT (U/L) | 1.01 (1.00–1.01) | 0.01 | 0.99 (0.98–1.00) | 0.14 | 0.99 (0.98–1.00) | 0.12 | 0.99 (0.98–1.01) | 0.15 |
Bilirubin (mg/dL) | 1.67 (1.48–1.89) | <0.01 | 0.97 (0.74–1.27) | 0.83 | ||||
Prothrombin time (INR) | 17.85 (9.34–34.11) | <0.01 | 0.83 (0.22–3.11) | 0.78 | ||||
Creatinine (mg/dL) | 0.50 (0.14–1.76) | 0.28 | ||||||
eGFR (mL/min/1.73 m2) | 1.01 (1.00–1.03) | <0.01 | 1.00 (0.99–1.01) | 0.96 | 1.00 (0.99–1.01) | 0.70 | 1.00 (0.99–1.01) | 0.81 |
Sodium (mmol/L) | 0.81 (0.76–0.86) | <0.01 | 0.96 (0.89–1.04) | 0.35 | 0.92 (0.86–0.99) | 0.03 | ||
Ascites | 12.17 (7.64–19.38) | <0.01 | 1.96 (0.98–3.91) | 0.06 | 2.08 (1.04–4.14) | 0.04 | ||
Child-Pugh score | 1.77 (1.61–1.95) | <0.01 | 1.35 (1.19–1.54) | <0.01 | ||||
Child-Pugh class, B/C | 10.87 (6.94–17.02) | <0.01 | ||||||
MELD-Na score | 1.25 (1.20–1.31) | <0.01 | 0.99 (0.92–1.08) | 0.87 | ||||
Sarcopenia | 1.31 (0.78–2.21) | 0.30 | ||||||
SMI (cm2/m2) | 0.98 (0.96–1.01) | 0.12 | ||||||
∆SMI/yr% (%) | 0.95 (0.93–0.97) | <0.01 | 0.96 (0.93–0.98) | <0.01 | 0.96 (0.93–0.98) | <0.01 | 0.95 (0.93–0.98) | <0.01 |
The values of variables were derived by examinations at the 1-year follow-up.
Model 1, multivariable Cox regression analysis with HTN, DM, alcohol, hepatitis B, platelet count, albumin, AST, ALT, bilirubin, INR, sodium, presence of ascites, and ΔSMI/yr%, which showed
LC, liver cirrhosis; CT, computed tomography; HR, hazard ratio; CI, confidence interval; aHR, adjusted hazard ratio; BMI, body mass index; HTN, hypertension; DM, diabetes mellitus; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, international normalized ratio; eGFR, estimated glomerular filtration rate; MELD, model for end-stage liver disease; SMI, skeletal muscle index; ΔSMI/yr%, % change in SMI after 1 year.