The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.
Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver-related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.
AIM: To evaluate the correlation between liver stiffness measurement (LSM) by real-time shear wave elastography (SWE) and liver fibrosis stage and the accuracy of LSM for predicting significant and advanced fibrosis, in comparison with serum markers. METHODS: We consecutively analyzed 70 patients with various chronic liver diseases. Liver fibrosis was staged from F0 to F4 according to the Batts and Ludwig scoring system. Significant and advanced fibrosis was defined as stage F ≥ 2 and F ≥ 3, respectively. The accuracy of prediction for fibrosis was analyzed using receiver operating characteristic curves. RESULTS: Seventy patients, 15 were belonged to F0-F1 stage, 20 F2, 13 F3 and 22 F4. LSM was increased with progression of fibrosis stage (F0-F1: 6.77 ± 1.72, F2: 9.98 ± 3.99, F3: 15.80 ± 7.73, and F4: 22.09 ± 10.09, P < 0.001). Diagnostic accuracies of LSM for prediction of F ≥ 2 and F ≥ 3 were 0.915 (95%CI: 0.824-0.968, P < 0.001) and 0.913 (95%CI: 0.821-0.967, P < 0.001), respectively. The cut-off values of LSM for prediction of F ≥ 2 and F ≥ 3 were 8.6 kPa with 78.2% sensitivity and 93.3% specificity and 10.46 kPa with 88.6% sensitivity and 80.0% specificity, respectively. However, there were no significant differences between LSM and serum hyaluronic acid and type IV collagen in diagnostic accuracy. CONCLUSION: SWE showed a significant correlation with the severity of liver fibrosis and was useful and accurate to predict significant and advanced fibrosis, comparable with serum markers.