Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions

Anstee, Quentin M.; Hallsworth, Kate; Lynch, Niall; Hauvespre, Adrien; Mansour, Eid; Kozma, Sam; Marino, John-Paul; Bottomley, J. M.; Piercy, James; Higgins, Victoria

doi:10.1016/j.jhepr.2021.100411

Cited by 35 publications

(32 citation statements)

References 37 publications

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“…Practices related to referral, use of NITs, monitoring, and implementation of nonpharmacological interventions are largely suboptimal and often at odds with current evidence‐based recommendations, as also recently highlighted. [ 25 ] Some differences between surveyed countries are useful for tailoring recommendations to specific national health care systems or physician practices. Finally, there is a strong expectation among SPs for effective pharmacological therapies in most patients with fibrotic steatohepatitis, while current difficulties in implementing the necessary dietary and lifestyle changes at the NAFLD practitioner level should not be neglected.…”

Section: Discussionmentioning

confidence: 99%

An international survey on patterns of practice in NAFLD and expectations for therapies—The POP‐NEXT project

et al. 2022

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Background and Aims Differences between countries in NAFLD patient care pathways and management need to be understood prior to defining supranational guidelines. Approach and Results We conducted an anonymous survey in France, Germany, Hong Kong, Italy, Romania, Spain, the United Kingdom, and the United States among physicians providing specialist care for patients with NAFLD. Modalities of patient referral, patterns of practice (diagnosis, staging, monitoring, and indications for liver biopsy), therapeutic management, and expectations for future NASH pharmacotherapies were assessed, with 664 physicians completing the survey. Referral to surveyed physicians (SPs) mostly came from primary care. Prior to referral, NAFLD was rarely diagnosed, and noninvasive tests were not performed. Screening for comorbidities by SPs was incomplete and cardiovascular risk not calculated. Elastometry in combination with a serum biomarker was the most common first‐line method for fibrosis staging. Liver biopsy, when performed, was often delayed by at least 1 year after diagnosis. It was, however, recommended even if noninvasive methods indicated advanced fibrosis. Frequent, biannual monitoring was conducted, including HCC surveillance in Stage 3 fibrosis. SPs rarely implemented and followed dietary and lifestyle changes themselves, and local availability of such programs was highly heterogenous. SPs favored pharmacotherapy based on mechanism of action adapted to the stage of the disease, including for early stages such as steatohepatitis with mild fibrosis. Conclusions This international survey revealed major deficiencies and delays in referral pathways, suboptimal screening for comorbidities or managing of lifestyle modifications by SPs, and limited local availability for nonpharmacological interventions. Monitoring practices are not aligned with current guidelines.

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Section: Discussionmentioning

confidence: 99%

An international survey on patterns of practice in NAFLD and expectations for therapies—The POP‐NEXT project

et al. 2022

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“…In this regard, several outstanding medical associations initiated a "Call to Action" to issue guiding strategies for the management of NASH 8,13 due to its increasing impact on global public health and substantial socioeconomic burden. 10,40 Until that, PE appears to be the gold-standard preventive and/or therapeutic nonpharmacological strategy against several negative consequences of many obesity-associated metabolic dysfunctions. 5,14,18,41,42 In accordance with the histological score from Kleiner et al, 32 our results showed that sedentary animals fed with HFD have the typical hepatic injury induced by NASH in humans, such as steatosis, hepatocellular ballooning, and hepatic inflammation (as expected 43 ).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, there are substantial management gaps between clinical guidelines and clinical practice in what concerns NASH patients. In this regard, several outstanding medical associations initiated a “Call to Action” to issue guiding strategies for the management of NASH 8,13 due to its increasing impact on global public health and substantial socioeconomic burden 10,40 . Until that, PE appears to be the gold‐standard preventive and/or therapeutic nonpharmacological strategy against several negative consequences of many obesity‐associated metabolic dysfunctions 5,14,18,41,42 …”

Section: Discussionmentioning

confidence: 99%

Physical exercise positively modulates nonalcoholic steatohepatitis‐related hepatic endoplasmic reticulum stress

Passos

Pereira

Gonçalves

et al. 2022

J of Cellular Biochemistry

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Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic‐based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER‐related proapoptotic signaling, and oxidative stress in an animal model of high‐fat diet (HFD)‐induced NASH. Adult male Sprague–Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD [SS], voluntarily physically active animals with access to SCLD [SV], and endurance‐trained animals with access to SCLD [ST] in the former and sedentary animals with access to liquid HFD [HS], voluntarily physically active animals with access to liquid HFD [HV], and endurance‐trained animals with access to liquid HFD [HT] in the latter, respectively). Hepatic ER stress and ER‐related proapoptotic signaling were evaluated by Western blot and reverse transcriptase‐polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD‐treated animals, VPA significantly decreased eukaryotic initiation factor‐2 alpha (eIF2α). In HFD‐treated animals, VPA significantly decreased eIF2α and phospho‐inositol requiring enzyme‐1 alpha (IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X‐box binding protein 1 (sXBP1) and unspliced X‐box binding protein 1; a significant increase of phosphorylated‐eIF2α (p‐eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p‐eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH‐related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α–X‐box binding protein 1 pathway.

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“…42,56 In Europe, Canada and the Middle East, although physicians advocate dietary modification and physical activity, only about half of the NAFLD patients receive support to make lifestyle changes or are referred to a dietitian. 57 Liaison with dietitians, physical activity trainers and behaviourists will improve the successful implementation of lifestyle changes. In addition, maintenance of weight reduction is often the hardest part, and long-term follow-up is required in most patients.…”

Section: Life S T Yle Interventi Onmentioning

confidence: 99%

“…The vast majority of adults with NAFLD in usual clinical practice do not meet with a dietitian or attend weight loss programmes 42,56 . In Europe, Canada and the Middle East, although physicians advocate dietary modification and physical activity, only about half of the NAFLD patients receive support to make lifestyle changes or are referred to a dietitian 57 . Liaison with dietitians, physical activity trainers and behaviourists will improve the successful implementation of lifestyle changes.…”

Section: Lifestyle Interventionmentioning

confidence: 99%

Management of NAFLD in primary care settings

Wong

Zelber‐Sagi

Cusi

et al. 2022

Liver International

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Non-alcoholic fatty liver disease (NAFLD) affects at least 25% of the general population and is an increasingly important cause of cirrhosis and hepatocellular carcinoma.Although it is the research focus of the hepatology field, it is clear that primary care physicians are seeing the majority of NAFLD patients and are in a pivotal position to provide quality care. In this article, we review the role of primary care in the management of NAFLD. NAFLD is common in patients with diabetes, obesity and other metabolic risk factors. Abdominal ultrasonography is the most commonly used method to diagnose fatty liver. Simple fibrosis scores have high negative predictive values in excluding advanced liver fibrosis and future liver-related events and can be used in primary care as initial evaluation. An abnormal result should be followed by subsequent workup or specialist referral. Primary care is the ideal setting to institute multidisciplinary care, especially the involvement of dietitians and physical activity trainers in lifestyle intervention, as well as initiating the discussion of bariatric surgery in patients with severe obesity. Although specific drug treatment for steatohepatitis would require a more precise diagnosis, metabolic drugs that improve both steatohepatitis and cardiovascular outcomes (e.g. glucagon-like peptide-1 receptor agonists) may be considered in patients with NAFLD.

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Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions

Cited by 35 publications

References 37 publications

An international survey on patterns of practice in NAFLD and expectations for therapies—The POP‐NEXT project

An international survey on patterns of practice in NAFLD and expectations for therapies—The POP‐NEXT project

Physical exercise positively modulates nonalcoholic steatohepatitis‐related hepatic endoplasmic reticulum stress

Management of NAFLD in primary care settings

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