High Prevalence of NASH and Advanced Fibrosis in Type 2 Diabetes: A Prospective Study of 330 Outpatients Undergoing Liver Biopsies for Elevated ALT, Using a Low Threshold

Abstract

OBJECTIVE Most people with type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH) or advanced fibrosis (AF) remain undiagnosed, resulting in missed opportunities for early intervention. This multicenter, prospective study assessed the yield of using routinely available data to identify these patients. RESEARCH DESIGN AND METHODS A total of 713 outpatients with T2DM, screened in four diabetology clinics for nonalcoholic fatty liver disease according to American Diabetes Association criteria, were referred to hepatologists for further work-up (Fibrosis-4 and vibration-controlled transient elastography [VCTE]). A liver biopsy was proposed when ALT levels were persistently >20 IU/L in female patients or >30 IU/L in male patients, in the absence of other liver disease. RESULTS Liver biopsies were performed in 360 patients and considered adequate for reading after central review for 330 specimens (median patient age, 59 years; male patients, 63%; median BMI and HbA1C values, 32 and 7.5%, respectively). Prevalence of NASH, AF, and cirrhosis were 58%, 38%, and 10%, respectively. Liver lesions were independently associated with the components of metabolic syndrome but not with the micro- and macrovascular complications of T2DM. Models based on routinely available data with or without VCTE had good accuracy to predict AF (respectively: area under the receiver operating characteristic curve [AUROC], 0.84 and 0.77; and correctly classified 59% and 45%) and NASH (respectively: AUROC, 0.82 and 0.81; 44% and 42%). CONCLUSIONS Despite the use of a low ALT threshold, prevalence of NASH (58%) or AF (38%) was high. Routinely available data had a high yield in identifying patients with T2DM with AF and/or NASH requiring further liver assessment.

Diabetes and cirrhosis: Current concepts on diagnosis and management

“…It should be stressed that with the exception of one study,7 liver biopsies were rarely performed to confirm the presence of advanced fibrosis. More recently, in a cohort of 713 outpatients with T2DM systematically screened for NAFLD referred to a hepatologist, of whom 330 underwent a liver biopsy, bridging fibrosis and cirrhosis were found in 28% and 10%, respectively, despite mild liver test abnormalities 6. Liver lesions were independently associated with metabolic syndrome.…”

“…However, cirrhosis is often diagnosed at a late stage, that is when complications occur 5. Early cirrhosis remains undiagnosed in most patients with T2DM because of low awareness regarding CLDs among general practitioners and the lack of a clear referral pathway between clinicians in primary care or diabetes clinics and liver specialists 6. However, this is rapidly changing based on an increased awareness brought about by recent studies showing a high prevalence of NAFLD and advanced liver disease in people with obesity and T2DM in primary care and diabetes clinics,7–10 combined with recent multidisciplinary consensus statements and clinical practice guidelines that have simplified the referral strategy 11–13.…”

Prospective direct comparison of non‐invasive liver tests in outpatients with type 2 diabetes using intention‐to‐diagnose analysis

“…The methods details were already described in previous publications, the validation of the Nash-FibroTest (a panel including FibroTest, SteatoTest and NashTest), 16,18 and the assessment of MASH prevalence and advanced fibrosis in in the first 330 participants with T2D. 24 A total of 713 outpatients with T2D, systematically screened for MASLD, were referred to hepatologists for further work-up.…”

“…Clinical assessment, diabetes complications and NITs assessment were detailed elsewhere. 24 In summary, for each patient, a 12 h fasting blood sample was collected and tested locally for laboratory parameters using the standard formula for FIB4 and the manufacturers' recommendations. 5,6 VCTE-CAP and liver stiffness measurements were performed by trained nurses or physicians, certified by the manufacturer and blinded to the patient's histological evaluation using a VCTE (FibroScan 502 Touch model; Echosens) equipped with both M and XL probes.…”

“…For stiffness, missing data could be due to <10 stiffness measures or unreliable result due to an interquartile range (IQR)/median ≥ 30%. 22,24 For VCTE-CAP, at the time of protocol construction, only examinations with ≥10 valid individual measurements were deemed reliable, without exclusion criteria due to the CAP IQR/ median ratio in the absence of consensual guidelines. 25,26 A recent study validated the reliability of the VCTE-CAP when the IQR/median ratio was <0.30.…”