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Associate Professor of Medicine
Division of Gastroenterology and Hepatology
Medical University of South Carolina
Division of Gastroenterology and Hepatology
Ralph H. Johnson VAMC
Charleston, South Carolina
Wing-Kin Syn, MBChB, PhD, FACP, FRCP, has disclosed that he has received funds for research support from Conatus, Enyo, Genfit, Hequant, Intercept, and Mallinckrodt; and has received consulting fees from Intercept, and Echosens.
Individuals with type 2 diabetes are among the highest-risk group for developing nonalcoholic steatohepatitis (NASH) and NASH fibrosis, and professional guidelines recommend that these patients should be further evaluated. But in these and other high-risk groups, such as those with obesity and metabolic syndrome, what is the best approach to screening?
A common question is whether we should we perform ultrasound for every patient?
This is a challenging question. Although ultrasound is readily available, in practice, I think it would place a large burden on healthcare systems to perform ultrasound imaging on every individual with type 2 diabetes or obesity.
In addition, ultrasound can identify steatosis only, and the degree of steatosis has not been shown to relate to or predict liver outcomes. A finding of mild vs severe hepatic steatosis would not influence your management.
By contrast, current data suggest that the degree of liver fibrosis is more prognostic. Significant liver fibrosis, meaning F2 or greater, is associated with overall mortality as well as liver morbidity and mortality. It is those patients with significant liver fibrosis whom we want to identify.
My First Step: Lab Scores
Personally, in a patient with type 2 diabetes or obesity, as a first step, I recommend the use of noninvasive laboratory tools such as the FIB‑4 or the nonalcoholic fatty liver disease (NAFLD) fibrosis score, which can help identify patients who are unlikely to have significant or advanced liver disease or fibrosis.
Of these 2 tests, in patients with type 2 diabetes, I prefer the FIB-4 as there is no additional weighting based on the presence of diabetes. By contrast, the NAFLD fibrosis score considers the presence or absence of diabetes, such that anyone with type 2 diabetes receives an indeterminate or high‑risk score, and I worry about the possibility of false positives.
Whichever of these noninvasive tests you use, both have excellent negative predictive value; we can use them to rule out risk in patients who have a low score, who can then be reassured and followed.
Low Score: Follow-up
If the FIB-4 or NAFLD fibrosis score is low, how often should such patients with low risk be followed? That is another challenging question with no clear recommendations. Some would propose annually: Individuals with type 2 diabetes usually have annual physical checks by primary care, so they will have all these routine labs done anyway, which will allow the FIB‑4 to be measured.
Personally, for a patient with type 2 diabetes and at low risk by FIB-4 or NAFLD fibrosis score, I think checking the FIB‑4 score every 2-3 years would be a reasonable timeframe.
High-Risk Score: Imaging
But what if the patient’s FIB-4 or NAFLD fibrosis score is indeterminate or is clearly high risk? In this case, I would recommend subsequent evaluation with a second modality to identify whether the patient is likely to have significant or advanced hepatic fibrosis. These could include imaging-based tests such as vibration‑controlled transient elastography (VCTE, or FibroScan), 2D shear wave elastography (acoustic radiation force impulse or SuperSonic Aixplorer), and MR elastography; or they could include complex noninvasive blood tests such as the enhanced liver fibrosis panel (when this becomes available).
The choice of this secondary screening modality will depend largely on which tests are available in your clinic.
At my institution, I typically forego the ultrasound in favor of VCTE. The VCTE measures liver stiffness, an indirect measure of fibrosis, but of importance, it can also provide an objective measure of liver fat (through the controlled attenuation parameter software, or “CAP”).
With these capabilities of VCTE, there is little need for an ultrasound scan unless the patient has significant disease, in which case an ultrasound is useful for hepatocellular carcinoma surveillance or to exclude other causes of liver dysfunction or to evaluate liver-associated symptoms.
Alanine Aminotransferase or Aspartate Aminotransferase
What about a patient with type 2 diabetes or obesity who has liver function tests that are normal? Should we screen for NAFLD/NASH?
Of importance, even in a patient with type 2 diabetes, obesity, or metabolic syndrome, having normal liver function tests, such as alanine aminotransferase does not preclude the possibility of having NAFLD. The vast majority of those with NAFLD will have liver enzymes in the normal range. So, if the patient has risk factors for NAFLD, I think it is still important to determine if the individual has significant liver fibrosis.
To summarize, when stratifying risk of NAFLD fibrosis, there have been many proposals about which tests to use and the best sequential use, but there is little agreement to date. I recommend starting with a simple noninvasive lab score such as the FIB‑4 or NAFLD fibrosis score and adding VCTE in combination if it is readily available in your practice. This approach is useful for all patients, including those with type 2 diabetes.
Which tools do you use to assess risk of NAFLD fibrosis in patients with type 2 diabetes? Answer the polling question and join the conversation by posting in the discussion section.