Performance of Plasma Biomarkers and Diagnostic Panels for Nonalcoholic Steatohepatitis and Advanced Fibrosis in Patients With Type 2 Diabetes

Bril, Fernando; McPhaul, Michael J.; Caulfield, Michael P.; Clark, Virginia; Soldevilla-Pico, Consuelo; Firpi-Morell, Roberto J.; Lai, Jinping; Shiffman, Dov; Rowland, Charles M.; Cusi, Kenneth

doi:10.2337/dc19-1071

Cited by 131 publications

(178 citation statements)

References 30 publications

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“…This nding is possibly related to increasing BMI among some individuals. However, plasma ALT and AST concentrations are still regarded as better clinical indicators than other noninvasive biomarkers/scores for de nitive diagnosis of nonalcoholic steatohepatitis (NASH) and/or advanced brosis in patients with T2DM [24]. Consistently, we observed a signi cant reduction in ALT and AST levels in all participants after the intervention, which was more marked in the CIMWM than TMWM group at the end of the study period.…”

Section: Discussionsupporting

confidence: 78%

Companion-Intensive Multi-aspect Weight Management in Chinese Adults with Obesity: A Six-Month Multicenter Randomized Clinical Trial

Jiang

Huang

et al. 2020

Preprint

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Background Obesity is a globally increasing health epidemic requiring early lifestyle intervention. Our main objective was to examine the effectiveness of companion-intensive multi-aspect weight management (CIMWM) for Chinese adults with obesity. Methods In this 6-month, prospective, open-label, multicenter, randomized controlled clinical trial, we included 272 obese adults aged 18–50 years with a body mass index (BMI) ≥ 28.0 kg/m2 and capable of using smartphones. CIMWM (n = 136) offered both daily online instructions and monthly face-to-face guidance by physicians, dietitians, and health managers along with the provision of meal replacements in the first 3 months. Traditional multi-aspect weight management (TMWM, n = 136) provided monthly face-to-face guidance by the above-mentioned professionals and required daily self-monitoring. Measurements of body composition and metabolic parameters were assessed face-to-face at baseline, 1, 2, 3, and 6 months by physicians. Primary outcomes were the changes in BMI and body composition. Results All participants showed significantly reduced BMI, body fat mass (BFM), visceral fat area (VFA), and HOMA-IR (P < 0.05). CIMWM was shown to be superior to TMWM in the improvement of BMI, alanine aminotransferase (ALT), and the body composition parameters BFM and VFA (P < 0.05). The relationship of baseline non-alcoholic fatty liver disease score (NFS) was positively related to the skeletal muscle mass-to-visceral fat area ratio (S/V). Additionally, the weight management program was beneficial in lowering the NFS among subjects with levels in the highest tertile (P < 0.05). Metabolic memory in terms of the continuous reduction of BMI, VFA, and ALT was retained up to 6 months in spite of participants transferring to self-monitored assessment in the final 3 months. Conclusions The CIMWM strategy in obese Chinese adults proved to be more effective than TMWM, and motivates greater adherence to intervention and lifestyle reprogramming. Trial registration: ChiCTR1800017463, Registered 31 July 2018, retrospectively registry. http://www.chictr.org.cn/showproj.aspx?proj=29649

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Section: Discussionsupporting

confidence: 78%

Companion-Intensive Multi-aspect Weight Management in Chinese Adults with Obesity: A Six-Month Multicenter Randomized Clinical Trial

Jiang

Huang

et al. 2020

Preprint

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“…| 85 CUSI recruited from hepatology clinics. 26 None of the diagnostic tests for NASH were better than plasma ALT (AUC: 0.78) (e.g. NashTest 2, HAIR,…”

Section: The Challeng E Of D Iag Nos Ing Na S H In Patients With T2dmmentioning

confidence: 99%

“…This is also our own personal experience in patients recruited in diabetes clinics. [23][24][25][26] A recent study compared several plasma biomarkers and diagnostic panels in 213 patients with T2DM not TA B L E 1 Potential mechanisms by which chronic hyperglycemia may play a role in NASH • Hepatic inflammation and oxidative stress with formation of hydrogen peroxide/hydroxyl radicals leading to hepatocyte lipid peroxidation. • Accelerate the production of advanced glycosylation endproducts (AGEs) and development of inflammation in Kupffer and hepatic stellate cells (both have receptors for AGE).…”

Section: The Challeng E Of D Iag Nos Ing Na S H In Patients With T2dmmentioning

confidence: 99%

A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions

Cusi

2020

Liver International

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There is a close link between steatohepatitis (NASH) and Type 2 diabetes (T2DM). Recently, the American Diabetes Association (ADA) recommended screening for NASH and advanced fibrosis in patients with diabetes and hepatic steatosis or elevated plasma alanine aminotransferase (ALT). This is because as many as ~30% to 40% may have NASH and ~10% to 15% advanced fibrosis. The role of hyperglycemia and the natural history of NASH in diabetes remain poorly understood, as well as which diagnostic algorithm or interventions are most cost‐effective. There is significant clinical inertia and most patients today are still not receiving adequate lifestyle intervention or pharmacological treatment with diabetes agents known to be effective against NASH. Lifestyle intervention improves steatohepatitis in proportion to the magnitude of weight loss, but this trend is not as consistent for regression of fibrosis. This limited success supports the need for concomitant pharmacological therapy. Pioglitazone has been shown to consistently induce resolution of NASH in both patients with or without diabetes in a total of 498 participants in five randomized controlled trials (RCTs), but with modest effects on liver fibrosis. Proof‐of‐concept studies suggest a potential role for GLP‐1RAs and SGLT2 inhibitors. Combination therapy is on the horizon. Treating diabetes and NASH with a combination of pioglitazone, GLP‐1RAs or SGLT2i, could be a cost‐effective strategy to treat both diseases while reducing their high cardiovascular risk. Future combination therapies will likely combine existing diabetes agents with novel NASH‐spechfic drugs under development. This review highlights current knowledge gaps and proposes future directions for the treatment of NASH in diabetes.

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“…In addition, it has been suggested that serum biomarkers of fibrosis, which were developed and validated in non-diabetic cohorts, underperform when applied to diabetic patients. 28 Also, the use of FIB-4 or NFS may lead to a higher proportion of patients in the intermediate category. 25 Thus, the direct use of a more specific test seems more suited to this setting ( Figure 2B).…”

Section: Diabetes Clinicsmentioning

confidence: 99%

Non‐invasive tests for liver fibrosis in NAFLD: Creating pathways between primary healthcare and liver clinics

Castéra

2020

Liver International

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Despite affecting around one‐fourth of the general population worldwide, non‐alcoholic fatty liver disease (NAFLD) remains a largely under‐recognized disease in primary healthcare, with not more than 10% of patients diagnosed with NAFLD referred to specialists. The main challenge in clinical practice is the identification of those with advanced liver fibrosis or cirrhosis, as they are at the greatest risk of developing complications. Liver biopsy appears to be an unrealistic and unsuitable option because of the large number of high‐risk patients and the well‐known limitations of this technique. This has favoured the development of non‐invasive tests, which have been an area of intensive research in the past decade. Transient elastography, FIB‐4 and the NAFLD fibrosis score are the most extensively used and best validated tests, with summary AUROC values for detecting advanced fibrosis in NAFLD patients of 0.88, 0.84 and 0.84 respectively. Although much work remains to be done to establish cost‐effective strategies for the screening for advanced fibrosis, the sequential use of non‐invasive tests (serum biomarkers, then measurement of liver stiffness using transient elastography) appears to be the most promising strategy. The next step is to establish effective pathways in primary healthcare and/or diabetes clinics where most NAFLD patients are seen, to identify those who need to be referred to liver clinics for further assessment.

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Performance of Plasma Biomarkers and Diagnostic Panels for Nonalcoholic Steatohepatitis and Advanced Fibrosis in Patients With Type 2 Diabetes

Cited by 131 publications

References 30 publications

Companion-Intensive Multi-aspect Weight Management in Chinese Adults with Obesity: A Six-Month Multicenter Randomized Clinical Trial

Companion-Intensive Multi-aspect Weight Management in Chinese Adults with Obesity: A Six-Month Multicenter Randomized Clinical Trial

A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions

Non‐invasive tests for liver fibrosis in NAFLD: Creating pathways between primary healthcare and liver clinics

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