Response to Pioglitazone in Patients With Nonalcoholic Steatohepatitis With vs Without Type 2 Diabetes

Bril, Fernando; Kalavalapalli, Srilaxmi; Clark, Virginia; Lomonaco, Romina; Soldevila-Pico, Consuelo; Liu, I-Chia; Orsak, Beverly; Tio, Fermin O.; Cusi, Kenneth

doi:10.1016/j.cgh.2017.12.001

Cited by 176 publications

(130 citation statements)

References 23 publications

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“…On the other hand, diabetes itself appears to accelerate steatohepatitis and the progression of fibrosis to cirrhosis, although there are few controlled prospective studies to date. In a recent small head‐to‐head analysis more significant fibrosis progression was found in 18 months in patients with diabetes than in those without.…”

Section: The Link Between Diabetes and Nash: Knowledge Gaps And Futurmentioning

confidence: 91%

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 Link Between Diabetes and Nash: Knowledge Gaps And Futurmentioning

confidence: 91%

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

Cusi

2020

Liver International

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“…In addition to worse disease reported in many crosssectional studies in patients with T2DM, recent longitudinal studies have suggested a faster progression of fibrosis among patients with NASH and T2DM. 2,6 Moreover, hepatocellular carcinoma happens more commonly in such patients compared with those without diabetes. 7 Finally, recent data by our group show that pioglitazone is safe and effective to halt the natural history of the disease and reverse NASH in patients with prediabetes or T2DM.…”

Section: Introductionmentioning

confidence: 99%

Use of a metabolomic approach to non‐invasively diagnose non‐alcoholic fatty liver disease in patients with type 2 diabetes mellitus

Bril

Millán

Kalavalapalli

et al. 2018

Diabetes Obesity Metabolism

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“…Certain subgroups of NASH patients have been shown to respond better to vitamin E, and individualized therapy may be a possible strategy . Pioglitazone has been shown to benefit NASH patients without diabetes, prediabetes or overt diabetes . This agent improves insulin sensitivity and enhances adipocyte fat storage.…”

Section: Targeting Downstream Pathways In Nashmentioning

confidence: 99%

“…Pioglitazone has been shown to improve steatohepatitis, disease activity scores and possibly fibrosis in non‐diabetic patients. A recent trial has also demonstrated histological benefits in NASH patients with type 2 diabetes . However, these results must be balanced against the weight gain, fluid retention and possible worsening of heart failure associated with this drug.…”

Section: Managing Diabetes In Patients With Nashmentioning

confidence: 99%

“…12 Pioglitazone has been shown to benefit NASH patients without diabetes, prediabetes or overt diabetes. 10,13 This agent improves insulin sensitivity and enhances adipocyte fat storage. Pioglitazone causes weight gain, which discourages patients who are already struggling to adhere to weight loss interventions.…”

Section: Targ E Ting Down S Tre Am Pathways In Na S Hmentioning

confidence: 99%

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Current management of non‐alcoholic steatohepatitis

Muthiah

Sanyal

2020

Liver International

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Non‐alcoholic steatohepatitis (NASH) is the most common cause of liver disease in Western populations, and its prevalence is increasing rapidly. It is part of a multisystem disease affecting other organs such as the kidneys, heart and blood vessels, and is closely associated with the components of the metabolic syndrome. Physicians managing patients with NASH should not only focus on the management of NASH, but also on associated comorbidities in individual patients. The approaches to treatment of NASH include either limiting energy surplus alone, or in combination with targeting of downstream pathways of inflammation and fibrosis. In this mini‐review, we discuss the currently available treatment options for NASH, as well as those in late‐stage clinical trials. We discuss the challenges of managing these patients with a limited number of approved therapies, as well as managing advanced‐stage patients with NASH and cirrhosis. We also discuss the specific management of comorbidities in NASH patients, in particular diabetes, hypertension, dyslipidaemia and cardiovascular diseases. Finally, we present the screening protocols for both hepatocellular carcinoma and extrahepatic malignancies in these patients.

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Response to Pioglitazone in Patients With Nonalcoholic Steatohepatitis With vs Without Type 2 Diabetes

Cited by 176 publications

References 23 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

Use of a metabolomic approach to non‐invasively diagnose non‐alcoholic fatty liver disease in patients with type 2 diabetes mellitus

Current management of non‐alcoholic steatohepatitis

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