In the present review, a meta-analysis was performed to identify and quantify the current evidence regarding the correlation between body composition parameters and HVPG. The pooled results indicated that there was no significant correlation between muscle or adipose quantity and the HVPG value, regardless of muscle index. The results of the secondary outcome were unstable due to different sarcopenia definitions. With consideration of the statistical significance and ethnicity-specific cut-off value of sarcopenia, the result appears to reveal that patients with lower muscle mass may have a higher HVPG value.
Body composition and HVPG are of paramount importance for patients with LC. Nevertheless, a knowledge gap remains in the correlation between them. To the best of the present authors’ knowledge, this meta-analysis is the first to quantitatively combine current data to assess the correlation between body composition parameters and HVPG.
In fact, limited LC-related studies have reported both composition parameters and HVPG values at the same time, seldom exploring the association between them. Specifically, CT-based quantitative analysis and invasive operation hamper the acquisition of data in clinical practice. Despite the fact that the limited evidence grade leads to a cautious interpretation of the results, the findings of this meta-analysis could help explore the impact of PH on body composition parameters and might be instrumental in refining a comprehensive evaluation algorithm of patients with LC.
In this meta-analysis, several points merit attention. First, the HVPG value was used to evaluate the PH instead of the portosystemic pressure gradient, largely because the portosystemic pressure gradient was commonly collected in the transjugular intrahepatic portosystemic shunt procedure with a limited clinical application prospect. Second, to reduce the bias derived from different global cut-off values of sarcopenia, only the muscle or adipose tissue quantity as the continuous variable normalized to height or height2 was extracted and comparable. In addition, other statistics would have been summarized if they could have been converted to the correlation coefficient using a validated statistical method, including the contingency coefficient and standardized beta value; however, such a study was not found in the study screening. Third, SMI is recognized as the gold standard for measuring muscle quantity in defining sarcopenia, and psoas-muscle-related parameters have been shown to be less strongly correlated with the total body protein or mortality risk compared with SMI.29,30 Therefore, of the five studies reporting the secondary outcome, 1 study reporting via PRI was not included in the meta-analysis. Last, all included studies were published in the past 5 years, thereby enabling a standard care for patients with LC.
Negative results of the primary outcome are partly explainable because of a considerable interindividual variation of the liver function reserve among the included patients. In the included studies, decompensated cirrhosis or clinical signs of PH, such as ascites, gastro-esophageal varices, and hepatic encephalopathy, were deemed indications of HVPG measurement. Among all the evaluable patients, the mean values of the MELD score were 9–13, the decompensation proportions were 54.8%–100%, and the baseline HVPG values were 14–19 mmHg. In fact, sarcopenia is relatively frequently found in advanced liver disease or the decompensated stage.31,32 Furthermore, some characteristics of patients with LC, including the cause of liver disease, decompensated cirrhosis, or oral beta‐blocker administration should have been used in the subgroup analyses with the aim of ruling out confounding factors and further identifying a potential association between the muscle quantity and the HVPG value in a certain subgroup of patients with LC. Likewise, adipose tissue change and re-distribution could be affected by BMI and sex.33Therefore, for the primary outcome of the adipose tissue, the non-significant summary result may indicate the likelihood of the correlation between adipose tissue indexes and HVPG depending on the baseline characteristics of the included patients.
In addition, the result of the secondary outcome was not robust. It is speculated that a lower cut-off value (42 cm2/m2 for men or <38 cm2/m2 for women) could identify more individuals with a low muscle quantity and further re-classify a proportion of patients as having sarcopenia; that is, a lower cut-off value of sarcopenia has more statistic power to differentiate patients with different PH stratifications. It is noted that all included studies on the secondary outcome were from Asian countries (Japan and the Republic of Korea). The Asian sarcopenia definition (42 cm2/m2 for men or <38 cm2/m2 for women) thus allows for better interpretability and practical applicability.9
As the present study is a pilot meta-analysis exploring the unknown relationship between two important characteristics of patients with LC, some limitations exist. First, a considerable interindividual variation of baseline characteristics among included patients, especially liver function status, leads to a cautious interpretation of the results. Second, some included studies only presented the effect size instead of analyzing it in the subgroups. The evidence grade is limited by the number of included studies and the data blank. Most importantly, the number of available studies that fulfilled the present study’s inclusion criteria is low, precluding meta-regression to further identify the potential confounding factors. Hence, a prospective study dedicated to recording relevant information is required in the future.
In conclusion, overall, this meta-analysis showed a non-significant correlation between body composition parameters, including muscle and adipose tissue quantity, and the HVPG value. However, its current clinical usefulness is uncertain due to a lack of universal definition and limited research.