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Surveillance of the Liver in Type 2 Diabetes
abstract
This abstract is available on the publisher's site.
Access this abstract nowFatty liver plays a pivotal role in the pathogenesis of the metabolic syndrome and type 2 diabetes. According to an updated classification, any individual with liver steatosis and one or more features of the metabolic syndrome, without excess alcohol consumption or other known causes of steatosis, has metabolic dysfunction-associated steatotic liver disease (MASLD). Up to 60-70% of all individuals with type 2 diabetes have MASLD. However, the prevalence of advanced liver fibrosis in type 2 diabetes remains uncertain, with reported estimates of 10-20% relying on imaging tests and likely overestimating the true prevalence. All stages of MASLD impact prognosis but fibrosis is the best predictor of all-cause and liver-related mortality risk. People with type 2 diabetes face a two- to threefold increase in the risk of liver-related death and hepatocellular carcinoma, with 1.3% progressing to severe liver disease over 7.7 years. Because reliable methods for detecting steatosis are lacking, MASLD mostly remains an incidental finding on imaging. Regardless, several medical societies advocate for universal screening of individuals with type 2 diabetes for advanced fibrosis. Proposed screening pathways involve annual calculation of the Fibrosis-4 (FIB-4) index, followed by a secondary test such as transient elastography (TE) for intermediate-to-high-risk individuals. However, owing to unsatisfactory biomarker specificity, these pathways are expected to channel approximately 40% of all individuals with type 2 diabetes to TE and 20% to tertiary care, with a false discovery rate of up to 80%, raising concerns about feasibility. There is thus an urgent need to develop more effective strategies for surveying the liver in type 2 diabetes. Nonetheless, weight loss through lifestyle changes, pharmacotherapy or bariatric surgery remains the cornerstone of management, proving highly effective not only for metabolic comorbidities but also for MASLD. Emerging evidence suggests that fibrosis biomarkers may serve as tools for risk-based targeting of weight-loss interventions and potentially for monitoring response to therapy.
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Surveillance of the liver in type 2 diabetes: important but unfeasible?
Diabetologia 2024 Jun 01;67(6)961-973, S Qadri, H Yki-JärvinenFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Screening for liver steatotic fibrosis in diabetics
Up to 60% to 70% of patients with type 2 diabetes have metabolic dysfunction–associated steatotic liver disease (MASLD). Currently, four major societies from the fields of hepatology, endocrinology, diabetes, and gastroenterology recommend screening for liver fibrosis in individuals with type 2 diabetes due to the risk of cirrhosis in these patients. This paper argues that this recommendation should be re-evaluated.
The authors state that there are 30 million Americans with type 2 diabetes, and, if everyone followed these guidelines, 12 million with steatosis would require annual ultrasound elastography to check for fibrosis, resulting in a high amount of false-positive results. This would also lead to 5.5 million referrals to hepatologists, adding cost and worsening specialty access.
These guidelines would be useful if this intervention resulted in therapy that was not otherwise available. The authors state that lifestyle modification is highly effective at reversing metabolic dysfunction–associated steatosis across all stages of liver fibrosis, even cirrhosis. Prior research has revealed that greater than 10% weight loss over 52 weeks resulted in the resolution of steatosis in 90% of patients with metabolic dysfunction–associated steatohepatitis (MASH) and reversed fibrosis in 45%.1 The treatment is the same for type 2 diabetes and MASLD. If we are getting at the root of treating type 2 diabetes, we will also treat liver steatosis by encouraging healthy lifestyle through a high-fiber plant-based diet low in sugar, regular exercise, and striving towards optimal weight.
The paper provides some useful pearls in addressing steatosis in type 2 diabetes.
The FIB-4 calculation incorporates information on age, AST, ALT, and platelet counts. The main determinant is the platelet level, which decreases as the liver becomes more fibrotic. Once platelets go down, a large percentage of the liver is not functioning due to fibrosis. FIB-4 is a poor screening test and is not an early screening tool.
The take-home message from this paper is to aggressively treat both type 2 diabetes and liver steatosis as early as possible so we don’t have to worry about liver fibrosis progressing to cirrhosis. But if ALT/AST are elevated and there is steatosis on ultrasound, consider ordering an ultrasound elastrography to get baseline fibrosis scores. If the fibrosis is severe (F3–4), then that is the time to recruit the support of our liver specialist colleagues. But, hopefully, an early salutogenic approach focused on supporting healthy lifestyle behavior will reduce this demand.
Reference
Metabolic dysfunction–associated steatotic liver disease (MASLD; previously known as nonalcoholic fatty liver disease) is defined as hepatic fat accumulation in more than 5% of hepatocytes in association with one or more cardiometabolic risk factor (overweight/obesity, type 2 diabetes [T2DM], high blood pressure, dyslipidemia), without other discernible etiology to account for the increased hepatic steatosis in its entirety. MASLD has become one of the most common causes of chronic liver disease worldwide and a leading indication for liver transplantation. Fibrosis stage is the single greatest predictor for both hepatic and extrahepatic outcomes in individuals with MASLD. Over the past several years, recognition of the increased prevalence of MASLD and its more aggressive subtype, metabolic dysfunction–associated steatohepatitis (MASH; previously known as nonalcoholic steatohepatitis), appreciation of its close link with cardiometabolic risk factors (especially T2DM), identification of the prognostic value of fibrosis, and deployment of previously existing as well as recently developed noninvasive tests1 for screening have led various societies to propose screening pathways to help identify individuals with MASLD at high risk.
In this review, Qadri et al discuss the pathogenesis and prevalence of MASLD in the context of T2DM and discuss the feasibility and practical implications of recent guidelines recommending universal screening for MASLD in individuals with T2DM. The authors highlight the increased mortality risk in individuals with steatosis (even without fibrosis), albeit not reaching the mortality risk demonstrated by individuals with fibrosis, who demonstrate an increase in mortality in a stepwise fashion in correlation with fibrosis severity. By applying the proposed screening pathway advocated by several societies, including the American Diabetes Association, to a hypothetical cohort of 1000 patients with T2DM, the authors highlight the challenges associated with feasibility of the screening pathway, cost, and accessibility of noninvasive tests as well as hepatology expertise. This review emphasizes the need to develop better noninvasive tests, identifies several evidence gaps both for universal and targeted screening in high-risk populations, and proposes some strategies for targeted case-finding while several groups work to develop better screening methods and fill the evidence gaps.
Reference