Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening

Abstract

Objective: Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).

Research design and methods: A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m²; and HbA_1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.

Results: The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).

Conclusions: Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

Figure 1

A: Proportion of patients with T2DM screened in the outpatient clinical setting having liver steatosis (measured by CAP) and with liver fibrosis (LSM by VCTE). B: Proportion of patients with steatosis and fibrosis having plasma AST or ALT levels ≥40 units/L. Total number of patients: 561.

Figure 2

A: Severity of liver fibrosis (LSM) in patients with T2DM screened in the outpatient clinical setting, divided into four stages: mild (F1), moderate (F2), severe or precirrhosis (F3), and cirrhosis (F4). B: Proportion of patients with moderate-to-advanced fibrosis (≥F2) having elevated plasma AST or ALT levels. C: Proportion of patients with a low risk, indeterminate risk, or high risk of advanced liver fibrosis by the fibrosis diagnostic panel APRI score. Total number of patients: 561.

Figure 3

A: Severity of liver steatosis in patients with T2DM screened in the outpatient clinical setting divided into mild (S1), moderate (S2), and severe (S3). B: Proportion of patients with steatosis having elevated plasma AST or ALT levels. Total number of patients: 561.