NASH and diabetes: the importance of collaboration between liver and diabetes specialists
People with type 2 diabetes mellitus (T2DM) are at greater risk of developing nonalcoholic fatty liver disease (NAFLD) and subsequently progressing to nonalcoholic steatohepatitis (NASH). Typically, NASH is only diagnosed late by a liver specialist, when the patient already has liver fibrosis; however, with the development of simple tools, such as the Fibrosis-4 (FIB-4) index, diabetes specialists are starting to play a greater role in identifying high-risk patients and facilitating appropriate follow-up.
Dr Kenneth Cusi, Chief of the Division of Endocrinology and Diabetes at the University of Florida in the United States, and Dr Salvador Augustin, Consultant Hepatologist at the University of Barcelona in Spain, discuss the importance of collaboration between diabetes and liver specialists when it comes to the identification, diagnosis and management of NAFLD.
Diabetes and liver health
Liver health can sometimes be overlooked in people with obesity and diabetes, where managing cardiovascular and endocrine complications takes priority. However, individuals with obesity, type 2 diabetes mellitus (T2DM) and insulin resistance are at greatest risk of developing NAFLD and NASH.1,2
“The typical situation that I find myself in [as a diabetologist], is that the patient has obesity, diabetes, and now advanced fibrosis.”
– Dr Cusi
Dr Augustin noted that, from his own studies and experience, approximately 10% of patients in a diabetes clinic are likely to have advanced fibrosis due to NASH.
“In the last decade, we've been experiencing an explosion of cases of advanced fibrosis related to fatty liver disease in the context of metabolic diseases and most especially diabetes.”
– Dr Augustin
Identifying advanced fibrosis in people with diabetes
Monitoring and assessment of NAFLD and NASH in the T2DM population is important. At present, a diagnosis of advanced fibrosis due to NASH is usually confirmed by liver specialists. However, because up to 65% people with T2DM are estimated to have NAFLD,1 screening should play a role in the diabetes clinic as well.
“We have good tools to make the diagnosis of NASH with fibrosis outside of the liver clinics.”
– Dr Augustin
Liver fibrosis can lead to measureable changes in many serum biomarkers, including the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Therefore, as a first step, people with suspected NAFLD are often assessed for abnormal liver enzyme levels and fibrosis serum biomarkers.3 However, reviewing serum transaminase levels alone can be misleading:
“40% of our patients with advanced fibrosis do have normal transaminases. On the other hand, 70% of our patients, or patients in your clinics, with high liver enzymes probably won’t have fibrosis”
– Dr Augustin
To help ensure patients at greatest risk of advanced fibrosis are being identified, there are a number of easy-to-calculate and readily available screening tools, such as the Fibrosis-4 (FIB-4) index. The FIB-4 index is a simple algorithm shown to have high accuracy for assessing risk of advanced fibrosis (F3/F4).4,5 More information on the FIB-4 algorithm, and an online FIB-4 calculator can be found here.
However, FIB-4 and other indexes have some limitations, meaning that another test should be used in combination to rule-in fibrosis, explains Dr Augustin:
“FIB-4 is excellent for screening, it has a very high negative predictive value, but it has a lot of false positives. With FIB-4 and Fibroscan together, we can make a final assessment of the risk of fibrosis and decide on the follow-up.”
From guidelines to the future
Discussing American clinical guidelines on diabetes,8 Dr Cusi acknowledges that:
“A big game changer has been that the American Diabetes Association recommends diabetologists to begin thinking about NASH and fibrosis if a patient has elevated liver enzymes or steatosis.”
Likewise, the European guidelines for liver specialists place importance on the diabetes patient population,3 adds Dr Augustin:
“Liver guidelines in Europe recommend assessing for fibrosis in high-risk populations with the type 2 diabetes population being on the top of that list.”
Concluding their interview, Dr Cusi and Dr Augustin agree that the field would see significant changes in the near future with the increased role of NAFLD assessment within the diabetes clinics, as summarised by Dr Augustin:
“I’m pretty sure that, in the next 5−10 years, liver issues will be incorporated into the galaxy of complications of diabetes and managed accordingly within hospitals and primary care.”
“In 2019, diabetologists need to think liver and, from there, discuss it with the patients because early intervention will prevent cirrhosis and other problems.”
– Dr Cusi
- Targher G, et al. Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients. Diabetes Care 2007;30:1212–1218.
- Sung KC, et al. Predicting incident fatty liver using simple cardio-metabolic risk factors at baseline. BMC Gastroenterol 2012;12:84.
- European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Obes Facts 2016;9:65–90.
- McPherson S, et al. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic liver disease. Gut 2010;59:1265–1269.
- Sterling R, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006;43:1317–1325.
- Afdhal N. Fibroscan (Transient Elastography) for the measurement of liver fibrosis. Gastroenterol Hepatol 2012;8:605–607.
- Memorial Sloan Kettering Cancer Center. Understanding your FibroScan® Results 2018. Available at: https://www.mskcc.org/cancer-care/patient-education/understanding-your-fibroscan-results (last accessed January 2019).
- American Diabetes Association. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019;42(Suppl 1):S34–45.
Job code: LID/IHQ/19-11//1090 Date of Preparation: November 2019