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

Abstract

<b>Objective:</b> Assess the prevalence of NAFLD and of liver fibrosis associated with nonalcoholic steatohepatitis (NASH) in unselected patients with T2DM. <p><b>Research Design and Methods:</b> 561 patients with T2DM (age: 60±11; BMI: 33.4±6.2 kg/m<sup>2</sup>; HbA1c: 7.5±1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by CAP (≥274 dB/m) and LSM (≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as APRI and FIB-4, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.</p> <p><b>Results:</b> 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. Non-invasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 U/L were 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, APRI).</p> <p><b>Conclusions: </b>Moderate-to-advanced fibrosis (F≥2), an established risk factor for cirrhosis and overall mortality, affects at least one-out-of-six (15%) patients with T2DM. These results support the ADA guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.</p>

Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease

“…Patients with T2D: Many studies report a high prevalence of clinically significant fibrosis in patients with T2D, with as many as 20% of these patients affected in recent studies. 1,17 We recommend clinicians screen all patients with T2D. This approach has been demonstrated to be cost-effective.…”

“…The remaining 30%-40% of patients with an FIB-4 test would likely have values in the indeterminate range (ie, 1.3-2.67). 1 These patients should also undergo LSM, depending on the clinical setting (see Step 4), which can be done as a point-of-care test (if available) in the primary care or endocrinology clinic, ordered by the clinician as other imaging tests to be reviewed at the next visit or as part of a referral to hepatology.…”

“…However, recent studies have shown that the prevalence of advanced fibrosis (F3-F4) in primary care clinic populations of patients with risk factors for NAFLD (such as diabetes) is higher than previously believed, ranging from 9% to 15% in different studies. 1,2 Furthermore, most NITs have high negative predictive values at the low cutoffs and can reliably rule out clinically significant fibrosis. Indeed, this 2-tier, risk-stratification process is supported in part by a study of 759 patients with biopsy-proven NAFLD showing that using noninvasive fibrosis scores followed by LSM (with FibroScan) only for patients with indeterminate or high scores was most accurate for diagnosing advanced fibrosis.…”

“…Most patients screened in primary care will have a low risk of clinically significant liver fibrosis, defined as having a FIB-4 score <1.3, LSM <8.0 kPa by transient elastography, or a liver biopsy fibrosis stage of F0-F1 (Figure 3). 1,2,[50][51][52][53] We recommend therapeutic lifestyle interventions for these patients. Specific pharmacologic treatment targeting liver steatosis is not necessary in this lower-risk population.…”

“…A pproximately 37% of adults in the United States, and as many as 70% of individuals with type 2 diabetes (T2D), have nonalcoholic fatty liver disease (NAFLD). [1][2][3] Nonalcoholic steatohepatitis (NASH), a subtype of NAFLD characterized by inflammation, ballooning, and Mallory's hyaline on liver biopsy, can lead to hepatic fibrosis, cirrhosis, and hepatocellular cancer (HCC). Both NAFLD and NASH are also associated with an increased risk of cardiovascular disease, 4 cardiovascular and liver-related mortality, and impaired health-related quality of life.…”