Intended for US healthcare professionals only.
Intended for US healthcare professionals only.
Intended for US healthcare professionals only.
Intended for US healthcare professionals only.
BIOPSY HAS TRADITIONALLY BEEN USED FOR IDENTIFICATION OF NASH BUT IS ASSOCIATED With NUMEROUS LIMITATIONS1-5
Only analyzes 1/50,000 of the liver and interpretation may differ between pathologists, therefore serial biopsies may provide inconsistent findings1-3,5
Costly procedure1 which may require additional cost and time of an interventional radiologist4
Invasive procedure with a risk of rare but life- threatening complications, not ideal for monitoring patients over time1,5,6
Patient concerns related to the invasive nature of biopsy, as well as the potential for pain, discomfort, and complications5,6
CONSIDERATIONS FOR A ROUTINE WORK-UP OF PATIENTS WITH
SUSPECTED NASH7-11*
Patient
presents
with abnormal
liver
biochemistry
Assess
presence of fat
in the liver
Exclude
other liver
diseases†
Consider
comorbidities
that may raise
suspicion of
NASH
Assess
patient for
presence
of Advanced
Fibrosis
Patient presents
with abnormal liver
biochemistry
Raised liver enzymes may be a clinical indicator for liver conditions, triggering the need for additional investigation9
An elevated ALT may be the first clinical indicator of NASH and/or Advanced Fibrosis12,13
Considerations are not listed in chronological order and will vary between healthcare providers.
Assess presence
of fat in the liver
Ultrasound is often utilized to assess the presence of fat in the liver11‡
A higher steatosis grade may be more likely to be associated with definitive NASH vs no NASH14§
Considerations are not listed in chronological order and will vary between healthcare providers.
Other methods of identifying fat in the liver, e.g. computed tomography (CT) or magnetic resonance imaging (MRI), are available, but not widely used at this stage.
Biopsies and data from 976 adults in NASH CRN studies were evaluated, to compare demographic and clinical characteristics across NASH diagnostic categories.
Exclude other liver
diseases†
Alcoholic liver
disease
Hepatocellular
carcinoma
HBV,
HCV
Autoimmune
disease
Diagnosis based on biopsy of individuals referred for appraisal due to asymptomatic elevation of serum levels of ALT15‡
After other liver diseases have been excluded, further investigation is needed to identify patients with NASH vs bland steatosis16
Considerations are not listed in chronological order and will vary between healthcare providers.
List of other liver diseases is not exhaustive.
Based on liver biopsy of 256 Swedish individuals referred for appraisal because of asymptomatic elevation of serum levels of ALT. Inclusion criteria = persistently elevated levels of aspartate aminotransferase and alanine aminotransferase for longer than 6 months. For illustrative purposes only and not intended to inform management decisions. This population may not be representative of the US population.
Alcoholic liver diseases: ASH, alcoholic steatohepatitis/AFLD, alcoholic fatty liver disease = 10%; ALD, alcoholic liver disease = 4%.
Consider
comorbidities that
may raise suspicion
of NASH
Assess patients for comorbidities common among patients with NASH
68%NASH patients with hypertension17
72%NASH patients have hyperlipidemia/
dyslipidemia17
71%NASH patients have metabolic syndrome17
82%NASH patients are obese
(BMI ≥30 kg/m2)17
Considerations are not listed in chronological order and will vary between healthcare providers.
Assess patient for
presence of
Advanced Fibrosis
In a study of NAFLD patients with biopsy-confirmed steatosis, 85% of those with F3 fibrosis also had definitive NASH14‡
Considerations are not listed in chronological order and will vary between healthcare providers.
In a study of patients with a histologic diagnosis of NAFLD of the dataset from the NASH CRN including biopsies from adult patients
enrolled in either the Database study or pretreatment biopsies from the adult treatment trial (PIVENS). Assignment of a diagnostic
category of definitive NASH, borderline NASH or no NASH was based on consensus recognition of the distinctive features of SH. Biopsies
classified as cirrhosis were excluded as it is well recognized that the active lesions of steatohepatitis may not be retained in cirrhosis.
References: 1. European Association for Study of Liver. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237-264. 2. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD; American Association for the Study of Liver Diseases. Liver biopsy. Hepatology. 2009;49(3):1017-1044. 3. Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20(2):475-485. 4. Diehl AM, Day C. Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis. N Engl J Med 2017;23;377(21):2063-2072. 5. Anstee QM, Lawitz EJ, Alkhouri N, et al. Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials. Hepatology. 2019;70(5):1521-1530. 6. Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World J Gastroenterol. 2018;24(30):3361-3373. 7. Jennison E, Patel J, Scorletti E, Byrne CD. Diagnosis and management of non-alcoholic fatty liver disease. Postgrad Med J. 2019;95(1124):314-322. 8. Byrne CD, Patel J, Scorletti E, Targher G. Tests for diagnosing and monitoring non-alcoholic fatty liver disease in adults. BMJ. 2018;362:k2734. 9. Tsochatzis EA, Newsome PN. Non-alcoholic fatty liver disease and the interface between primary and secondary care. Lancet Gastroenterol Hepatol. 2018;3(7):509-517. 10. Stengel JZ, Harrison SA. Nonalcoholic Steatohepatitis: Clinical Presentation, Diagnosis, and Treatment. Gastroenterol Hepatol (NY). 2006;2(6):440-449. 11. Dyson JK, Anstee QM, McPherson S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Frontline Gastroenterol. 2014;5(3):211-218. 12. Verma S, Jensen D, Hart J, Mohanty SR. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Liver Int. 2013;33(9):1398-1405. 13. Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol. 2017;112:18-35. 14. Brunt E, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53(3):810-820. 15. Söderberg C, Stal P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51:595-602. 16. Spengler EK, Loomba R. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Mayo Clin Proc. 2015;90(9):1233-1246. 17. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.