Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies

Stefan, Norbert; Häring, Hans‐Ulrich; Cusi, Kenneth

doi:10.1016/s2213-8587(18)30154-2

Cited by 651 publications

(661 citation statements)

References 123 publications

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“…However, improvement of fibrosis was only reported in some of the studies . We refer readers to recent in‐depth reviews on the overall safety and efficacy of pioglitazone in NASH . Unfortunately, confusion between rosiglitazone and pioglitazone (e.g.…”

Section: The Future Of Treating Nash 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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Section: The Future Of Treating Nash 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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“…Early diagnosis, assessment and intervention are important to stop the progression of NAFLD, because no pharmacotherapies are currently approved by the US Food and Drug Administration for the treatment of the more advanced stage NASH . Glucose‐lowering agents have been shown to improve NAFLD, but their direct, long‐term impact remains to be fully explored . Pioglitazone has demonstrated reductions in fatty liver content and has provided some resolution of NASH in patients with type 2 diabetes, but with the side effect of significant weight gain .…”

Section: Introductionmentioning

confidence: 99%

Exenatide and dapagliflozin combination improves markers of liver steatosis and fibrosis in patients with type 2 diabetes

Gastaldelli

Repetto

Guja

et al. 2019

Diabetes Obesity Metabolism

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Aim To assess the efficacy of exenatide (EXE) once weekly + dapagliflozin once daily (DAPA) versus each drug alone in reducing biomarkers of fatty liver/steatosis and fibrosis in a post hoc analysis of DURATION‐8, a 104‐week study in 695 patients with type 2 diabetes uncontrolled by metformin monotherapy. Materials and methods We evaluated the impact of the study treatments on non‐invasive markers of hepatic steatosis (fatty liver index [FLI] and non‐alcoholic fatty liver disease [NAFLD] liver fat score), fibrosis (fibrosis‐4 index [FIB‐4]) and severe fibrosis (NAFLD fibrosis score), along with liver enzymes and insulin resistance, at weeks 28 and 52. All outcomes in this analysis were exploratory, with nominal P values reported. Results At week 28, biomarkers of fatty liver/steatosis and fibrosis were reduced from baseline in all treatment groups. At week 28, EXE once weekly + DAPA effects for decrease in FLI were stronger than those of EXE once weekly + placebo (PLB; −2.92, 95% confidence interval [CI] −5.11, −0.73; P = 0.0092) or DAPA+PLB (−2.77 [95% CI −4.93, −0.62]; P = 0.0119), and stronger than those of EXE once weekly + PLB at week 52 (−3.23 [95% CI −5.79, −0.68]; P = 0.0134). FIB‐4 showed reduction versus baseline only in the EXE once weekly + DAPA group at both week 28 (−0.06 [95% CI −0.11, −0.01]; P = 0.0135) and week 52 (−0.05 [95% CI −0.09, −0.004]; P = 0.0308). Conclusions The EXE once weekly + DAPA combination showed stronger effects than EXE once weekly + PLB or DAPA + PLB in ameliorating markers of hepatic steatosis and fibrosis in patients with type 2 diabetes. Prospective trials are needed to validate these findings.

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“…In this context, environmental, genetic and host factors have been implicated as the potential risk factors influencing the progression of NASH. In fact, the ethnic background of the patient has been implicated as an important host factor and genome‐wide association studies have revealed a linkage between development of NASH, advanced fibrosis and Patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) genotype in the Hispanic patients with NAFLD . In contrast, this association was not present among the Asian Americans .…”

Section: Introductionmentioning

confidence: 99%

Prevalence and outcomes of non‐alcoholic fatty liver disease (NAFLD) among Asian American adults in the United States

Golabi

Paik

Hwang

et al. 2019

Liver International

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Background & Aims Non‐alcoholic fatty liver disease (NAFLD) affects about 25% of the general population worldwide. Although epidemiology of NAFLD is well studied in the United States, there is paucity of data for the Asian Americans. Our aim was to assess the prevalence and risk factors for NAFLD among Asian Americans. Methods We utilized NHANES data for 2011‐2016. We defined NAFLD using recently derived US‐FLI. Relative risks (RRs) and population attributable fractions (PAFs) of metabolic components on atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis were calculated for Asian Americans, and these rates were compared to non‐Hispanic whites. Results NAFLD prevalence was 18.3% among Asian Americans and 28.4% among non‐Hispanic whites. Asian Americans with NAFLD had lower BMI and waist circumference than non‐Hispanic whites with NAFLD and were less likely to have metabolic syndrome, cardiovascular disease (CVD), chronic obstructive pulmonary disease, cancer and incident ASCVD (P < 0.05). Hyperlipidaemia had the highest attributable fraction (76.6%) for risk of ASCVD among Asian Americans with NAFLD, followed by diabetes (24.0%), current smoking (9.2%), and obesity (3.7%). Advanced fibrosis in Asian American with NAFLD was independently associated with presence of type 2 diabetes (RR = 2.70, 95% CI: 1.00‐7.27). Conclusions Asian Americans have lower prevalence of NAFLD than non‐Hispanic whites. However, Asian Americans with NAFLD have similar risk factors for advanced fibrosis and ASCVD than non‐Hispanic Whites.

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Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies

Cited by 651 publications

References 123 publications

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

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

Exenatide and dapagliflozin combination improves markers of liver steatosis and fibrosis in patients with type 2 diabetes

Prevalence and outcomes of non‐alcoholic fatty liver disease (NAFLD) among Asian American adults in the United States

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