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 LIMITATIONS1-6
Only analyzes 1/50,000 of the liver and interpretation may differ between pathologists, therefore serial biopsies may provide inconsistent findings2-4,6
Costly procedure2 which may require additional cost and time of an interventional radiologist5
Invasive procedure with a risk of rare but life- threatening complications, not ideal for monitoring patients over time2,6,7
Patient concerns related to the invasive nature of biopsy, as well as the potential for pain, discomfort, and complications6,7
According to claims data, ~7% of patients newly diagnosed with NASH (without cirrhosis) received a liver biopsy in the prior 12 months8*
A differential approach for patients with suspected NASH†:
Raised liver enzymes may trigger the initial suspicion of NASH9,10
Patient
presents
with abnormal
liver
biochemistry11-13
Assess
presence of fat
in the liver12,14
Exclude
other liver
diseases11-13,15
Consider
comorbidities
that may raise
suspicion of
NASH11,12,15
Assess
patient for
presence
of Advanced
Fibrosis11,12
Patient presents
with abnormal liver
biochemistry11-13
Raised liver enzymes may be a clinical indicator for liver conditions, triggering the need for additional investigation13
An elevated ALT may be the first clinical indicator of NASH and/or Advanced Fibrosis9,10
Considerations are not listed in chronological order and will vary between healthcare providers.
Assess presence
of fat in the liver12,14
Increased hepatic echogenicity visualized by ultrasound is an indicator of the presence of steatosis12,16†
A higher steatosis grade may be more likely to be associated with definitive NASH vs no NASH17‡
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
diseases11-13,15
Alcoholic liver
disease18
Hemachromatosis18
HBV,
HCV18
Autoimmune
disease18
An example of the disease spectrum in Swedish patients referred for elevated ALT levels18
After other liver diseases have been excluded, further investigation is needed to identify patients with NASH vs NAFL19
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.18
List of liver diseases to exclude is not exhaustive.
Other defined as unspecific histopathological findings.
Alcoholic liver diseases: ASH, alcoholic steatohepatitis/AFLD, alcoholic fatty liver disease = 10%; ALD, alcoholic liver disease = 4%; NALD, nonalcoholic fatty liver disease.
Consider
comorbidities that
may raise suspicion
of NASH11,12,15
Assess patients for comorbidities common among patients with NASH
66%NASH patients with hypertension20
83%NASH patients have hyperlipidemia/
dyslipidemia20
71%NASH patients have metabolic syndrome20
80%NASH patients are obese
(BMI ≥30 kg/m2)20
54%NASH patients have type 2 diabetes20†
Considerations are not listed in chronological order and will vary between healthcare providers.
Based on a meta-analysis of 85 studies across 22 countries with a total sample size of 8,515,431 patients aimed to estimate prevalence, incidence, progression and outcomes of NAFLD and NASH; prevalence estimates based on patients with NASH in North America.20
Assess patient for
presence of
Advanced Fibrosis11,12
In 2 studies of NAFLD patients, 85% and 94% of those with F3 fibrosis also had NASH17,21†‡
There is a clear collinearity between NASH and higher stages of fibrosis17,21
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.17
Based on a retrospective, cohort study of 646 patients with biopsy-proven NAFLD. Patients were followed for an average of 20 years, equivalent to 139,163 person-years.21
References: 1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. 2. 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. 3. 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. 4. 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. 5. Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med. 2017;23;377(21):2063-2072. 6. 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. 7. 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. 8. Data on File [US-NAS-MED-00826]. 9. 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. 10. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112:18-35. 11. 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. 12. 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. 13. 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. 14. Byrne CD, Patel J, Scorletti E, Targher G. Tests for diagnosing and monitoring non-alcoholic fatty liver disease in adults. BMJ. 2018;362:k2734. 15. Stengel JZ, Harrison SA. Nonalcoholic steatohepatitis: clinical presentation, diagnosis, and treatment. Gastroenterol Hepatol (NY). 2006;2(6):440-449. 16. Zhang YN, Fowler KJ, Hamilton G, et al. Liver fat imaging—a clinical overview of ultrasound, CT, and MR imaging. Br J Radiol. 2018;91(1089):20170959. 17. 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. 18. 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. 19. 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. 20. 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. 21. Hagström H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017;67(6):1265-1273.