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Monday, March 26, 2018

Editorial: diabetes, obesity and clinical inertia—the recipe for advanced NASH

We should screen patients with diabetes for “diabetic hepatopathy” (NAFLD), in the same way, we do today for diabetic retinopathy or nephropathy, considering NASH as the “new” complication of T2DM. Earlier treatment will likely benefit patients as evidence shows that the majority of patients that lose ≥8%‐10% of body weight,1 or about two‐thirds of prediabetics/diabetics treated with pioglitazone,8 experience resolution of NASH. Breaking clinical inertia by targeting obese patients with T2DM is a reasonable first step to curb the looming epidemic of NASH‐cirrhosis among us.

Editorial: diabetes, obesity and clinical inertia—the recipe for advanced NASH

J. Leey K. Cusi
First published: 25 March 2018
https://doi.org/10.1111/apt.14473

Linked content
This article is linked to Patel et al and Patel and Hunt papers. To view these article visit https://doi.org/10.1111/apt.14411 and https://doi.org/10.1111/apt.14505.

The prevalence of NAFLD continues to rise, with T2DM and obesity being major risk factors for advanced NASH, cirrhosis and HCC.1 The prevalence of diabetes in adults ≥18 years in the USA is 12.2%, but doubles to 25.2% in those aged ≥65 (CDC, July 2017). This epidemic is particularly concerning at the Veterans Health Administration (VHA) that looks after an ageing population. At our Veterans Administration Medical Center (Gainesville, Florida), the prevalence of diabetes in 2016 among primary care clinics was 29%. Obesity is also a problem: 41% of all veterans are obese.2 Calls to systematically screen obese patients with T2DM are gaining traction.3 Despite veterans being a high‐risk population, and NAFLD being identified as a significant problem,4 a cohesive early screening/treatment strategy is still lacking within the VHA and at a national level.

In a recent issue, Patel5 makes an even stronger case for action. They examine risk factors for advanced NASH in 399 patients identified with a liver biopsy between 2005 and 2015. The strength of the study was the large sample size with patients divided into well‐defined categories across the spectrum of NAFLD. Shortcomings were the lack of centralised pathology reading and inclusion of few females. However, the study had two important take home messages: the relevance of T2DM as the major risk factor for advanced NASH and the need to reverse clinical inertia. Both diabetes and clinical inertia, combined with obesity, appeared to be the perfect mix for disease progression, cirrhosis and even HCC. For instance, while 37% of patients with NAFL steatosis had T2DM, this climbed to 66% and 80% with NASH‐fibrosis and NASH‐cirrhosis respectively. Relative to controls, diabetics had a 4‐fold increase in the odds of being in the group of NASH‐without‐fibrosis, but eightfold in the NASH‐fibrosis and 12‐fold in the NASH‐cirrhosis groups. No other risk factor was as significant as diabetes; although most patients were obese and obesity‐related metabolic defects and “lipotoxicity”6 contributed to advanced NASH. Of note, 68% of women and 56% of men with T2DM in the VHA are obese.2 The study5 also highlights the need to educate healthcare providers about NAFLD. Even for a study between 2005 and 2015, lifestyle or pharmacological interventions were unacceptably low. The value of weight loss for NASH is well‐established,1 but only 12.3%‐19.5% of patients were offered diet/exercise and ≤2.6% had bariatric surgery. Considering ~30%‐40% of veterans have obesity/T2DM, still today few are offered the VHA behavioural modification programme and weight loss medications remain restricted. Medications proven to be effective for NASH, such as pioglitazone or vitamin E,1 were rarely prescribed (≤10%) in the study.5 The thiazolidinedione has been reported to be safe and effective in RCTs in NASH since 2006,7 including patients with7, 8 and without T2DM.1, 4 Pioglitazone may benefit even patients with advanced NASH‐fibrosis.9

In summary, Patel's work5 makes the case for screening obese patients with T2DM. It is ill‐advised to wait on long‐term outcome studies before supporting such a strategy as ~70% of obese patients with T2DM have NAFLD, and ~20% moderate‐to‐severe NASH‐fibrosis.4 We should screen patients with diabetes for “diabetic hepatopathy” (NAFLD), in the same way, we do today for diabetic retinopathy or nephropathy, considering NASH as the “new” complication of T2DM.10 Earlier treatment will likely benefit patients as evidence shows that the majority of patients that lose ≥8%‐10% of body weight,1 or about two‐thirds of prediabetics/diabetics treated with pioglitazone,8 experience resolution of NASH. Breaking clinical inertia by targeting obese patients with T2DM is a reasonable first step to curb the looming epidemic of NASH‐cirrhosis among us.

Alimentary Pharmacology & Therapeutics


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