Journal of Clinical Research & Bioethics

Evaluating Sarcopenia in Liver Disease: Assessment of Skeletal Muscle Mass by Computed Tomography is not Related to MASLD by Liver Biopsy

Carine Luíze Panke¹, Gabriela Perdomo Coral¹, Fábio Kunihiro Maeda², Eiji Suwa³, Angelo Alves de Mattos¹, Cristiane Valle Tovo¹ and Luis Fernando Ferreira^{1* 1}Post-graduation program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
²Nuclear Medicine Service, Santa Casa de Misericordia de Porto Alegre, RS, 90035-072, Brazil
³Department of Gastroenterology and Hepatology, Hospital Nossa Senhora da Conceição, Porto Alegre, RS, 91350-200, Brazil
^*Correspondence: Luis Fernando Ferreira, Post-graduation program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil, Email:

Received: 12-Nov-2023, Manuscript No. JCRB-23-23891; Editor assigned: 14-Nov-2023, Pre QC No. JCRB-23-23891 (PQ); Reviewed: 28-Nov-2023, QC No. JCRB-23-23891; Revised: 05-Dec-2023, Manuscript No. JCRB-23-23891 (R); Published: 14-Dec-2023, DOI: 10.35248/2155-9627.23.S17.003

Introduction

The relation between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and sarcopenia have been widely studied in the recent years [1]. They apparently share some physiological pathways, making possible to find a connection in the etiology for both conditions, such as the insulin resistance, the loss of skeletal muscle mass, and the fat accumulation in other tissues, as muscle and hepatocytes [2,3].

Although some consensuses to diagnose sarcopenia have emerged in the last years, the mostly of them are for older people, and not for patients of other conditions, such MASLD [4,5]. So, the main authors in the field are still conducting researches to find ways to diagnose sarcopenia in MASLD patients, that can relate with this specific condition, even trying to define the most appropriate cutoff points for this condition [6,7].

The objective of this study was to compare the results of Skeletal Muscle Mass (SMM) assessment by Computed Tomography (CT) with the MASLD degree evaluated by Liver Biopsy (LB).

Materials and Methods

Observational and prospective study, conducted according the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines [8]. Patients aged >18 years, diagnosed with MASLD by LB, treated on the Gastroenterology and Hepatology outpatient clinic at Irmandade Santa Casa de Misericordia de Porto Alegre (ISCMPA), a tertiary care hospital in southern Brazil, between 2017 and 2020, were included.

Were excluded patients with hepatitis B or hepatitis C virus; with significant alcohol consumption (>20 g/day for women and >30 g/day for men); with other causes of chronic liver disease; secondary causes of MASLD and; patients with Hepatocellular Carcinoma (HCC) [9].

Liver biopsy was indicated according to the guideline of the American Association for Study of Liver Disease. LB were analyzed by a professional with experience in liver pathology blinded for patient’s data, using the NAFLD Activity Score for histopathological analysis [10]. MASLD was defined according the new classification.

CT was performed to assess muscle mass, by analyzing the transverse area of the third lumbar vertebra (L3), using specific software [11]. For this quantification, L3 was identified, and the transverse area of the abdominal and paravertebral wall muscles involved at the height of L3 was measured. The value obtained in square centimeters was divided by the patient's height (in meters) squared, resulting in the Skeletal Muscle Mass Index (SMI).

Other indicators were also assessed, such as weight and height (calculating the body mass index by dividing weight by height square); clinical conditions, such as Systemic Arterial Hypertension (SAH), type 2 Diabetes Mellitus (DM2), and dyslipidemia; and blood tests as Total Cholesterol (TC), Low- Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) cholesterol, Triglycerides (TG), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total and direct bilirubin, prothrombin time, albumin, platelets, glucose, insulin, CReactive Protein (CRP) and ferritin. In addition, resistance to insulin action was estimated through Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) [12].

The Kolmogorov-Smirnov test was used to assess the normality. To compare continuous variables between groups, Independent sample Student’s T-Test was used. The analyzes were processed in the Statistical Package for the Social Sciences program (PASW Statistics for Windows, version 18.0. Chicago: SPSS Inc). The level of significance assumed was 5% and the Confidence Interval (CI) was 95%. The data were analyzed grouping the patients into two different groups: G1 being the patients with less liver impairment (F0, F1 and F2); and G2 the patients with advanced fibrosis (F3) and cirrhosis (F4).

The project was approved by the Research Ethics Committee of the Federal University of Health Sciences of Porto Alegre, under letter nº 57328416.8.0000.5335. Volunteers read and signed the Informed Consent Form. The entire research was conducted following Resolution 196/96 of the National Health Council (Brazil) and adhered to the principles of the Declaration of Helsinki for research involving human subjects. Data were processed in accordance with the General Data Protection Law (Brazilian Law nº 13.709/2018).

Results

The final sample consisted of 66 patients, being mostly women, as can be seen in Table 1. The sample characterization data, such as age, gender and BMI did not showed statistically significant difference. However, some discriminant data were different between the groups, being weight, height, abdominal circumference, AST, bilirubin, insulin and HOMA-IR means significantly higher in G2, as well the prevalence of DM were higher in this group; while total and LDL cholesterol, and platelets were significantly higher in G1.

Table 1: Sample Characteristics categorized by MASLD levels (n=66).

About the SMM, the mean was statistically higher in G2 than in G1. When divided by stages, is possible to see that the means are below the total mean for stages F0, F1 and F2 (46.62 ± 7.29; 46.31 ± 6.8; 45.34 ± 11.1 cm²/m², respectively), while F3 and F4 are above it (55.08 ± 15.98; 50.209.1 cm²/m², respectively).

Discussion

In this study, although there was a statistically significant difference in Skeletal Muscle Mass (SMM) between G1 and G2, the indices were higher in G2, precisely in those patients with greater hepatic impairment, in the opposite way to that would be expected. Most studies correlating hepatic diseases such as MASLD, fibrosis, and cirrhosis with sarcopenia have reported that muscle mass tends to decrease as liver impairment increases (an inverse correlation) [13,14]. This phenomenon is attributed to the shared physiological pathways between the two conditions. For instance, insulin resistance, closely linked to the onset of hepatic diseases, is also considered a risk factor for sarcopenia.

Apart from the shared physiological pathways, a direct relationship between sarcopenia and MASLD exists, who found that myostatin activation in SMM may be influenced by hepatic malfunction caused by fat accumulation in hepatocytes [15,16].

Additionally, various authors suggest that hepatic diseases decrease the macronutrient absorption rate, influencing protein synthesis in SMM and directly reducing the resynthesize phenomenon, as hepatocytes gradually lose the capacity for synthesis [17,18].

As reported, the reduction in SMM, beyond merely explaining hepatic impairment progression, may activate stellate cells with fibrogenic properties in the liver, thereby increasing the risk of fibrosis, cirrhosis, and hepatocellular carcinoma [19]. Thus, not only can low SMM levels explain advanced hepatic impairment, but greater hepatic impairment can also elucidate SMM reduction.

Considering the literature's solid evidence on the liver diseasesarcopenia relationship, it can be hypothesized that the discrepant result in this sample may be attributed not directly to the sample itself, but rather to the method of assessment employed for SMM quantification.

Although Computed Tomography (CT) is recommended for muscle mass evaluation by most sarcopenia consensuses, being a cheaper test than other options and offering lower radiation levels compared to Dual-Energy X-ray Absorptiometry (DXA) and Magnetic Resonance Imaging (MRI), CT has been discussed for its inherent errors [20].

Firstly, despite a correlation between SMM evaluation by DXA (the gold standard) and CT for elderly patients, this relationship has not been fully explored in patients with other pathologies that may directly affect specific muscle groups or alter the proportion of other body components, such as fluid accumulation (ascites, a common manifestation of hepatic diseases) and intramuscular lipid accumulation (also common in hepatic steatosis) [21].

In these cases, evidence points toward bio-impedance analysis and DXA as more suitable examinations, as they can detect the accumulation of other components in SMM and assess the entire body, unlike CT, which examines only a slice of muscle, generally assessed at the level of the third lumbar vertebra) [22].

CT may also face issues related to equipment calibration and evaluator analysis. Regarding equipment calibration, the assumption that the equipment returns a value of zero for water, expected for a well-calibrated scanner, can be misleading, increasing the risks of precision errors in muscle density determination [23]. Regarding the evaluator, it's important to note that, unlike DXA and Bioelectrical Impedance Analysis (BIA), CT-based SMM assessment is evaluator-dependent, as a professional need to delineate the contours of the muscle being evaluated. Thus, not only there is a possibility of evaluator bias, but the image quality, with shadows or undefined lines, can influence the final assessment result [24].

Conclusion

In conclusion, for this sample, a higher level of hepatic impairment is related with higher amount of SMM level assessed by CT, although there may be a strong influence of the assessment method on the presented results.

The major limitation of this study is that the evaluation of SMM by CT, as reported, may not be the best choice for assessing SMM in sarcopenic hepatic patients due to its significant margin of error and inherent biases in this assessment model. Furthermore, it is recommended that new studies with larger samples be conducted, comparing different methods of SMM evaluation in hepatic patients to validate methods and increase the security and efficacy of collected data.

Funding

This study was financed in part by the Coordenação de Aperfeiçoa-mento de Pessoal de Nível Superior-Brasil (CAPES)- Finance Code 001.

Conflict of Interests

The authors declare not have conflict of interest of any kind for the realization of this study.

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