Editor's Note: From June 5-8, 2024, the European Association for the Study of the Liver (EASL) Annual Meeting took place in the beautiful city of Milan, Italy. Over 7,000 liver disease experts from around the world attended this top-tier academic event. The conference covered a range of diseases including viral hepatitis, metabolic associated fatty liver disease, cirrhosis, liver cancer, and liver failure, presenting the latest clinical research findings in the field. Among the participants, Professor Rui Huang's team from Peking University People's Hospital had two studies accepted for presentation as poster sessions. Their research found that the ratio of visceral fat area to subcutaneous fat area (VSR), sarcopenia, and muscle fat infiltration are independent predictors of liver-related mortality in cirrhosis patients. Additionally, loss of skeletal muscle mass is crucial in predicting liver-related mortality in cirrhosis patients. These findings suggest that actively managing body composition, particularly skeletal muscle mass and visceral and subcutaneous fat content, can help improve prognosis in cirrhosis patients.

Study 1: CT-Based Body Composition Assessment Predicts Mortality Risk in Cirrhosis Patients

Researchers: Wenhui Ren, Jiarui Zheng, Rui Huang

Protein-calorie malnutrition and muscle mass loss are very common among cirrhosis patients. Abnormal body compositions, such as sarcopenia, muscle fat infiltration, and sarcopenic obesity, are often closely associated with adverse outcomes in cirrhosis patients. Sarcopenia, the degenerative loss of muscle mass, strength, and function, affects a significant proportion (20%-70%) of cirrhosis patients. Sarcopenic obesity, describing the coexistence of sarcopenia and obesity, is present in 20%-35% of cirrhosis patients. Patients diagnosed with muscle fat infiltration show pathological fat deposition in skeletal muscle, which may or may not coexist with sarcopenia.

Previous studies have demonstrated that changes in body composition, muscle mass, or sarcopenia are associated with increased risks of complications (such as hepatic encephalopathy) and mortality in cirrhosis patients both in China and globally. However, there is a lack of research on the dynamic changes in body composition among Chinese cirrhosis patients. Professor Rui Huang’s team conducted a study to analyze the potential correlation between changes in body composition over time and prognosis in cirrhosis patients.

This single-center, retrospective study included patients diagnosed with cirrhosis who were hospitalized at Peking University People’s Hospital from 2018 to 2023. CT scans at the third lumbar vertebra (L3) level were used to obtain body composition information, including skeletal muscle area (SMA), subcutaneous adipose tissue area (SATA), and visceral adipose tissue area (VATA). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were calculated by dividing SMA, VATA, and SATA values by height squared (m²), respectively. The visceral to subcutaneous fat area ratio (VSR) was calculated by dividing VATI by SATI. Average skeletal muscle density (SMD) was defined as the average density of SMA at the L3 level. Sarcopenia was defined as SMI < 38 cm²/m² for females and SMI < 42 cm²/m² for males. Sarcopenic obesity was diagnosed based on the coexistence of sarcopenia and VATA > 100 cm². Muscle fat infiltration was defined using SMD with cutoff values < 41 HU for patients with BMI < 25 kg/m² and < 33 HU for patients with BMI ≥ 25 kg/m². Visceral obesity was defined as VATA ≥ 100 cm².

The study included 158 patients diagnosed with cirrhosis, with a mean age of 57.1 ± 12.6 years. Among them, 60 patients (37.97%) were overweight, 96 patients (60.76%) were male, and 54 patients were diagnosed with alcoholic cirrhosis. Analysis of L3 CT images showed that 85 patients had sarcopenia, 22 patients had sarcopenic obesity, 66 patients had visceral obesity, and 68 patients had muscle fat infiltration. Statistical analysis revealed that age, L3 SMD, and L3 VATA were significantly associated with these abnormal body composition states (P < 0.05). The prevalence of visceral obesity was significantly higher in patients with sarcopenic obesity and muscle fat infiltration than in those with sarcopenia alone (all P < 0.05). Additionally, sarcopenia was significantly associated with lower BMI, female gender, and ascites, while muscle fat infiltration was significantly associated with higher BMI and male gender (P < 0.05). A history of hypertension was significantly different between patients with and without sarcopenic obesity (P = 0.020).

Researchers observed dynamic changes in body composition in individual patients through repeated CT scans. The number of individuals in each state was 48 (normal state), 38 (sarcopenia only), 37 (muscle fat infiltration only), and 35 (combined state). Kaplan-Meier curves showed that patients with sarcopenia alone had higher mortality rates compared to those with normal body composition (Gray’s test, P = 0.006). Additionally, cumulative mortality rates were higher in patients diagnosed with muscle fat infiltration or both sarcopenia and muscle fat infiltration, although these differences were not statistically significant (Gray’s test, P = 0.076; P = 0.140).

Multivariate analysis revealed that history of ascites (HR = 2.99, 95% CI: 1.30-6.86; P = 0.010), MELD score (HR = 1.10, 95% CI: 1.03-1.18; P = 0.006), and VSR (HR = 1.32, 95% CI: 1.04-1.24; P = 0.007) were significant predictors of survival. Notably, sarcopenia (HR = 3.18, 95% CI: 1.37-7.41; P = 0.007) and muscle fat infiltration (HR = 2.38, 95% CI: 1.10-5.16; P = 0.028) were significant predictors of liver-related mortality.

In conclusion, this study suggests that changes in body composition are related to liver-related mortality in cirrhosis patients, indicating that managing skeletal muscle mass and visceral and subcutaneous fat content may help improve patient prognosis.

Original Article Link: Jiarui Zheng, Wenhui Ren, Shuo Yang, et al. The Relationship Between Abnormal Body Composition by Computed Tomography Imaging and Long-term Mortality in Patients with Cirrhosis. EASL 2024 Abstract FRI-127

Study 2: Dynamic Changes in Muscle Mass Predict Long-term Liver-related Mortality in Cirrhosis Patients

Researchers: Jiarui Zheng, Shuo Yang, Rui Huang

Sarcopenia is a degenerative musculoskeletal disease characterized by rapid loss of muscle mass and function, leading to increased negative outcomes such as falls, functional decline, frailty, and mortality. It is also associated with infections, ascites, hepatic encephalopathy, and portal hypertension. The incidence of muscle wasting in cirrhosis patients ranges from 40% to 70%, and the presence of sarcopenia is independently associated with increased mortality risk in these patients. These findings suggest that effective management of cirrhosis patients requires not only liver function assessment but also sarcopenia diagnosis.

Chronic liver disease often leads to loss of skeletal muscle mass (LSMM), making it one of the most common complications associated with cirrhosis. LSMM is linked to increased all-cause mortality risk in patients diagnosed with hepatocellular carcinoma (HCC) or non-alcoholic fatty liver disease (NAFLD). However, the impact of LSMM on cirrhosis patients remains unclear. This retrospective study aimed to investigate whether changes in skeletal muscle mass could predict prognosis in cirrhosis patients.

This single-center, retrospective study included patients diagnosed with cirrhosis who were hospitalized at Peking University People’s Hospital from 2018 to 2023. CT scans at the third lumbar vertebra (L3) level were used to obtain body composition information. Tissue classification was based on Hounsfield unit (HU) thresholds: the HU range for the skeletal muscle area (SMA) at the L3 level was -29 to 150 HU. The L3 skeletal muscle index (SMI, cm²/m²) was calculated by dividing the SMA by height squared (m²). For liver disease patients, sarcopenia was defined using the following SMI cutoff values: females < 38 cm²/m², males < 42 cm²/m². The annual change in skeletal muscle index (ΔSMI/y) was calculated as follows: ΔSMI/y (%) = [(SMI at the second CT scan – SMI at the baseline CT scan) / SMI at the baseline CT scan / CT scan interval (years)] × 100%. Loss of skeletal muscle mass (LSMM) was defined as ΔSMI/y < 0.

The study included 158 patients diagnosed with cirrhosis (mean age 57.1 ± 12.6 years). The mean MELD score was 9.5 ± 4.6, with 24.1% having HCC, but there was no statistically significant difference between the groups. Imaging parameters showed significant differences, with males having higher SMI (44.1 ± 9.2 vs. 37.1 ± 5.3, P < 0.001) and less sarcopenia (39.6% vs. 56.5%, P = 0.038). Among all patients, the median ΔSMA/y% was -0.9 (IQR: -3.8, 1.6), with no significant difference between the groups.

Out of all patients, 95 (60.1%) were diagnosed with LSMM. LSMM patients were older (58.8 ± 12.5 vs. 54.6 ± 12.3, P = 0.001) and had a higher prevalence of chronic kidney disease (11.6% vs. 1.6%, P = 0.028). CT images showed that a patient initially diagnosed with cirrhosis developed sarcopenia during follow-up. Univariate analysis indicated that LSMM patients were more likely to have hypertension, diabetes, chronic kidney disease, HCC, and hepatic encephalopathy, although only chronic kidney disease showed statistical significance (OR = 8.12, 95% CI: 1.02-64.5; P = 0.048).

During a median follow-up of 68.1 (IQR: 43.5, 105.0) months, 61 cirrhosis patients died, with 57 deaths due to liver-related diseases. Univariate analysis showed that ascites, bacterial peritonitis, hepatic encephalopathy, MELD score, L3 SMI, and LSMM were significantly associated with liver-related mortality risk. Multivariate analysis revealed that ascites (HR = 3.28, 95% CI: 1.68-6.38; P < 0.001) and LSMM (HR = 1.86, 95% CI: 1.01-3.44; P = 0.047) were independently associated with liver-related mortality. Patients with LSMM showed significantly lower cumulative survival rates compared to non-LSMM patients (P = 0.004). The 1-year, 3-year, and 5-year survival rates for non-LSMM patients were 96.8%, 81.0%, and 65.1%, respectively, compared to 97.9%, 80.0%, and 56.8% for LSMM patients.

In conclusion, the study results indicate that evaluating the loss of muscle mass in cirrhosis patients is crucial for predicting liver-related mortality. Focusing on skeletal muscle management may help improve the prognosis of cirrhosis patients.

Original Article Link: Jiarui Zheng, Shuo Yang, Wenhui Ren, et al. Independent Association of Loss of Skeletal Muscle Mass with Long-term Liver-related Mortality in Cirrhotic Patients. EASL 2024 Abstract FRI-118

Expert Profile

Rui Huang

• Doctor of Medicine from Peking University
• Associate Chief Physician, Department of Hepatology, Peking University People’s Hospital, and Peking University Liver Research Institute
• Participated in over 20 national/provincial research projects and global/national multi-center clinical trials
• Principal Investigator for one research and development fund at Peking University People’s Hospital
• First/corresponding author of over ten SCI papers
• Invited speaker and poster presenter at AASLD, EASL, and APASL annual meetings
• Recipient of the third prize in the 2023 Chinese Medical Science and Technology Award, second prize in the 2022 Beijing Science and Technology Award, and the 2019 EASL Young Investigator Award
• Youth Editorial Board Member of GUT (Chinese version) and peer reviewer for SCI journals such as Quality of Life Research, BMJ Open, Frontiers in Medicine, and Frontiers in Endocrinology