Prognostic impact of liver fibrosis and steatosis by transient elastography for cardiovascular and mortality outcomes in individuals with nonalcoholic fatty liver disease and type 2 diabetes: the Rio de Janeiro Cohort Study

Abstract

Background Liver stiffness measurement (LSM, which reflects fibrosis) and controlled attenuation parameter (CAP, which reflects steatosis), two parameters derived from hepatic transient elastography (TE), have scarcely been evaluated as predictors of cardiovascular complications and mortality in individuals with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Methods Four hundred type 2 diabetic patients with NAFLD had TE examination (by Fibroscan®) performed at baseline. Multivariate Cox analyses evaluated the associations between TE parameters and the occurrence of cardiovascular events (CVEs) and mortality. TE parameters were assessed as continuous variables and dichotomized at low/high values reflecting advanced liver fibrosis (LSM > 9.6 kPa) and severe steatosis (CAP > 296 or > 330 dB/m). Improvements in risk discrimination were assessed by C-statistic and by the relative Integrated Discrimination Improvement (IDI) index. Results During a median follow-up of 5.5 years, 85 patients died (40 from cardiovascular causes), and 69 had a CVE. As continuous variables, an increasing LSM was a risk marker for total CVEs (hazard ratio [HR]: 1.05; 95% CI: 1.01–1.08) and all-cause mortality (HR: 1.04; 95% CI: 1.01–1.07); whereas an increasing CAP was a protective factor for both outcomes (HR: 0.93; 95% CI: 0.89–0.98; and HR: 0.92; 95% CI: 0.88–0.97; respectively). As dichotomized variables, a high LSM remained a risk marker of adverse outcomes (with HRs ranging from 2.5 to 3.0) and a high CAP was protective (with HRs from 0.3 to 0.5). The subgroup of individuals with low-LSM/high-CAP had the lowest risks while the opposite subgroup with high-LSM/low-CAP had the highest risks. Both LSM and CAP improved risk discrimination, with increases in C-statistics up to 0.037 and IDIs up to 52%. Conclusions Measured by hepatic TE, advanced liver fibrosis is a risk marker and severe steatosis is a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD.

Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes

“…Moreover, low body weight and thus (assumed) low liver fat as well as ALT values in the lower normal range were previously reported to associate with worse cardiovascular outcomes and mortality 30 . Of interest, advanced liver fibrosis (as measured by transient elastography) was identified as a risk marker and severe steatosis as a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD, which would support the present results 31 …”

“…30 Of interest, advanced liver fibrosis (as measured by transient elastography) was identified as a risk marker and severe steatosis as a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD, which would support the present results. 31 The present analysis further suggests that study participants in all steatosis and fibrosis risk categories profit similarly in relative terms from empagliflozin treatment in regard to cardiorenal outcome and all-cause mortality. Similarly, former analyses of the EMPA-REG OUT-COME study reported that cardiorenal treatment benefits with empagliflozin are consistent across age groups as well as underlying cardiovascular and heart failure risk.…”

The association of fatty liver index and BARD score with all-cause and cause-specific mortality in patients with type 2 diabetes mellitus: a nationwide population-based study

“…Regarding the increased risk of CVD-related mortality, a recent study consistently revealed that advanced hepatic fibrosis was significantly associated with the risks of CVD events and mortality [ 36 ]. Advanced liver fibrosis, measured by hepatic transient elastography, was a risk marker while severe steatosis was a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD [ 37 ]. Collectively, these results suggest that advanced hepatic fibrosis is potentially useful as a screening tool for predicting both hepatic and extrahepatic adverse outcomes in patients with type 2 diabetes mellitus.…”

Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes

“…Within this category, TE is extensively available and can be used as a point-of-care test to estimate liver fibrosis by measuring liver stiffness and hepatic steatosis using controlled attenuation parameter (CAP) measurement [ 39 , 40 ]. The practice guidelines of the Brazilian Society of Hepatology and Brazilian College of Radiology have recently supported the use of elastography, among others, as a tool to assess fibrosis and steatosis in various chronic liver diseases, including NAFLD; due to its accuracy, elastography seems to be a non-invasive and cost-effective alternative to liver biopsy [ 41 ].…”