Management of Nonalcoholic Steatohepatitis: An Evidence-Based Approach
Introduction
Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), are an increasingly common cause of chronic liver disease in the developed world, with NASH projected to be the leading cause of liver transplantation in the United States by 2020.1 The aim of treatment in NASH is to reduce progression to advanced fibrosis, cirrhosis, and its sequelae. However, the optimal treatment remains uncertain because of the perceived futility of lifestyle modification, adverse effects of drug therapies, and the narrow selection criteria, suboptimal availability, and costs of bariatric surgery. Effective therapies for NASH are a research priority not only to reduce the projected burden of liver disease but also because of emerging evidence that NASH is associated with incident cardiovascular disease independent of traditional risk factors.2
This review addresses current data from the perspective of levels of evidence3 for the various therapeutic options in NASH, including lifestyle modification, drug therapies, and bariatric surgery. Such an approach has not previously been taken, including in the published guidelines by the American Association for the Study of Liver Diseases,4 the European Association for the Study of the Liver,5 and the Asian Pacific Association for the Study of the Liver,6 and is therefore timely. In particular, behavioral therapies to assist patients in adopting lifestyle changes are highlighted and a research agenda for future NASH management is presented.
Section snippets
Lifestyle modification
Lifestyle modification remains the standard of care for patients with NASH. By definition, it is a tripartite and holistic approach incorporating dietary, exercise, and behavioral changes. However, there is little robust evidence to support these recommendations, with minimal trial-based data and the relevant observational studies at high risk of multiple biases. The lack of adequate methodology led to the publication of a position paper that addresses desirable aspects of study design for
Pharmacologic therapies for NASH
While lifestyle modification should remain the initial therapeutic approach for people with NASH, it will not be successful in a significant proportion and thus may not be sufficient to control disease progression. However, there is no consensus on the indications for pharmacologic treatment in NASH and when to initiate it, the clinical outcomes that should be achieved, and when treatment can be safely stopped. Current therapeutic options include insulin sensitizers, antioxidants, and a range
Bariatric surgery for NASH
Surgical treatment of obesity is attractive because of its ability to achieve a more sustained weight loss compared with medical therapy, but the selection criteria are narrow.101 Bariatric surgery includes restrictive procedures (laparoscopic adjustable gastric banding [LAGB]) and malabsorptive procedures (Roux-en-Y gastric bypass, biliopancreatic diversion), and is indicated for morbid obesity (body mass index >40 or >35 kg/m2) if associated with comorbidities such as insulin resistance,
NASH management: a future research agenda
A summary of the various treatment approaches for people with NASH, along with the associated level of evidence, is presented in Table 1. From this table it is clear that several areas remain a research priority if patients with NASH are to be treated effectively. Patient-related outcomes have not been well studied, and preferences for different treatment approaches in NASH are unknown. This information is needed to improve adherence to treatment, and to this end quality-of-life data should be
Summary
This review of the current evidence base for NASH management highlights the paucity of data relative to the high prevalence of the disease. In hepatology, this is all the more apparent given the major advances in the treatment of other liver disorders such as viral hepatitis and hepatocellular carcinoma. Current practice comprises a mixture of lifestyle modification with nutraceutical and potential pharmacologic treatments, without a high level of evidence that any of these approaches improves
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Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice
2020, Toxicology and Applied PharmacologyCitation Excerpt :It is proposed that approximately ¼ of the US adult population have abnormal liver enzymes - a surrogate marker for NAFLD/NASH. Indeed, NASH has been projected to be the leading cause of liver transplantation in the United States by 2020 (Mahady and George, 2012). NAFLD progression is enhanced in patients with features of the metabolic syndrome, such as insulin resistance, type II diabetes, and dyslipidemia (Bechmann et al., 2012).
Genetic and hormonal control of hepatic steatosis in female and male mice
2017, Journal of Lipid ResearchEstimated time from clinical presentation to the development of cirrhosis in non-cirrhotic adult patients with non-alcoholic fatty liver disease
2016, Annals of HepatologyCitation Excerpt :The findings also do not account for patients presenting at different stages in the course of their disease. Although therapeutic interventions that might alter the course of NAFLD (vitamin E or thiazolidinediones) were limited to less than 5% of the study population, the effects of dieting and other life style changes that were advocated could not be ascertained.4 Finally, although commonly employed as a non-invasive marker of progression to advanced fibrosis/cirrhosis, the ALT/AST ratio has limitations with respect to sensitivity and specificity.5,6
C/EBP homologous protein modulates liraglutide-mediated attenuation of non-alcoholic steatohepatitis
2016, Laboratory InvestigationThe molecular mechanisms between metabolic syndrome and breast cancer
2016, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The effect of MMP-9 on the malignant progression of invasive BC promoted by membrane progesterone receptorα (mPRα) has been widely investigated, and it is recently reported that mPRα was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt in the invasive BC [45]. NAFLD, which has become the most common cause of chronic liver disease in the developed world, is projected to become the leading cause of liver transplantation in the USA by 2020 [46]. Selective estrogen receptor modulator (SERM)-associated NAFLD might be related to treatment efficacy in patients with BC because of circulating estrogen antagonism.
Disclosures: None.