1. NAFLD and NASH: The Not-So-New Kids on the Block
Mary E. Rinella, MD
Associate Professor of Medicine
Feinberg School of Medicine
Northwestern University
Chicago, Illinois
This program is supported by an educational grant from Intercept Pharmaceuticals, Inc.

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3. Faculty Disclosures
Quentin M. Anstee, BSc, MB BS, PhD, MRCP(UK), FRCP, has disclosed that he has received consulting fees paid to his institution from Acuitas Medical, Eli Lilly, Genfit, Intercept, Inventiva, Janssen, NewGene, Pfizer, Raptor Pharmaceuticals, and Tobira and funds for research support paid to his institution from AbbVie and GlaxoSmithKline. Stephen A. Harrison, MD, COL (Ret.), FAASLD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, the Chronic Liver Disease Foundation, FibroGen, Genfit, Intercept, Medivation, Merck, NGM Biopharmaceuticals, and Pfizer; speaker fees from AbbVie, Alexion, Gilead Sciences, and Merck; and funds for research support paid to his institution from Bristol-Myers Squibb, Conatus, Galectin, Galmed, Gilead Sciences, Immuron, Intercept, Madrigal, Merck, NGM Biopharmaceuticals, and Tobira. Mary E. Rinella, MD, has disclosed that she has received consulting fees from Amarin, BioPharma, Echosens, Enanta, Immuron, Intercept, NGM Biopharmaceuticals, and NuSirt.
This slide lists the disclosure information of the faculty and staff involved in the development of these slides.

4. Change in Etiology From 2002-2014 (%) NASH and Cryptogenic Cirrhosis
NASH: Number One Indication for Liver Transplant in Pts Aged < 50 Yrs
In 2015 registry of pts listed for liver transplant, NASH surpassed HCV infection
Etiology Among Pts Listed for Liver Transplant
NASH and cryptogenic cirrhosis
P < .0001
HCV infection
150
194
200
124
100
160
148 50
120 25
Pts Aged Yrs
Change in Etiology From (%) 80
HCV, hepatitis C virus; NASH, nonalcoholic steatohepatitis.
-25 40
-50
-100
NASH and Cryptogenic Cirrhosis
HCV Infection
-78
-150
Slide credit: clinicaloptions.com
Banini BA, et al. ACG Abstract 46.

5. Patient Case: 25-Yr-Old Hispanic Male With Obesity, T2DM, and ALT Elevation
Referred by PCP for mild ALT/AST elevation (70/63)
Other liver chemistries normal over past yr
Ferritin 500 ng/mL
No current meds
Past medical history: dyslipidemia, type 2 diabetes
Family history:
Mother: diabetes, hypothyroid
Father: alcohol-related cirrhosis
Physical exam
BP 130/85
BMI 32, central obesity
Acanthosis nigricans
No stigmata of cirrhosis, liver 3 cm below costal margin
Normal cardiopulmonary exam
No splenomegaly
Normal skin and nails
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BP, blood pressure, PCP, primary care provider; T2DM, type 2 diabetes mellitus.
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6. Goals Exclude other etiologies Identify risk factors for NASH
Assess and quantify fibrosis
Serum and imaging biomarkers
Role of liver biopsy
NASH, nonalcoholic steatohepatitis.

7. What Diseases Need to Be Excluded in This Patient?
Alcoholism
Common,
father with alcoholism
Autoimmune
liver disease
Mother
with hypothyroidism
Wilson disease
Age, devastating
if not treated
Viral hepatitis, hemochromatosis
Risk factors,
can’t miss this
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8. Rule Out Other Causes of Hepatic Steatosis
Examples of other causes of fatty liver
Excessive alcohol consumption
Malnutrition
Examples of other liver diseases that can present with steatosis
Hepatitis C, acute hepatitis D
Wilson disease
Hemachromatosis
Medications
Parenteral nutrition
Lipodystrophy
Lysosomal acid lipase deficiency
Angulo P, et al. Hepatology. 2007;45:
Brunt EM, et al. Nat Rev Dis Primers. 2015;1:15080.
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9. Patient Case: Ultrasound Findings
Bright liver
Echotexture increased vs kidney
Vascular blurring
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10. How Reliable Is Ultrasound in Diagnosis of NAFLD?
Considerations:
Changes consistent with NAFLD may not be detected if < 20% to 30% of liver contains fat
Ultrasound findings for fatty liver cannot be distinguished from those of early cirrhosis
NAFLD, nonalcoholic fatty liver disease.
Hernaez R, et al. Hepatology. 2011;54:
Dasarathy S, et al. J Hepatol. 2009;51:
Hannah WN Jr, Harrison SA. Hepatology. 2016;[Epub ahead of print].
Slide credit: clinicaloptions.com

11. Mortality in Patients With NAFLD
Patients with NAFLD (N = 420) matched by age and sex to general population in Minnesota, followed for 7.6 ± 4.0 yrs
100
General population
Patients with NAFLD 80
P = .03 60
Top 3 Causes of Death in NAFLD, %
Patients
(n = 53)
Malignancy 28
Ischemic heart disease 25
Liver disease 13
Survival (%) 40
Survival at 10 Yrs
General population: 87%
Patients with NAFLD: 77%
Log-rank P < .005
NAFLD, nonalcoholic fatty liver disease. 20 2 4 6 8 10 12 14 16
Yrs
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Adams LA, et al. Gastroenterology. 2005;129:

12. Mortality Due to NASH Among Patients With NAFLD
Patients with NAFLD (N = 129) matched by age and sex within same county in Sweden and followed for 13.7 yrs (SD: 1.3 yrs)
Nonalcoholic Liver Steatosis ±
Nonspecific Inflammation
NASH
100
100 80 80 60 60
General population
Patients with nonalcoholic steatosis ± unspecific inflammation
P = NS
Survival (%)
General population
Patients with NASH
P = .01
Survival (%) 40
NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NS, not significant; SD, standard deviation. 40 20 20 5 10 15 20 5 10 15 20
Yrs
Yrs
Slide credit: clinicaloptions.com
Ekstedt M, et al. Hepatology. 2006;44:

13. Goals Exclude other etiologies Identify risk factors for NASH
Assess and quantify fibrosis
Serum and imaging biomarkers
Role of liver biopsy
NASH, nonalcoholic steatohepatitis.

14. Association Between NAFLD/NASH and Diabetes Mellitus Is Bidirectional
Patients with NAFLD/NASH have:
Increased risk of developing diabetes[1,2]
Synergistic increase in risk of diabetes when combined with obesity or insulin resistance[3]
Patients with obesity, NAFLD, or insulin resistance each have x the risk of diabetes, but patients with all 3 have 14 x risk of diabetes
High prevalence of diabetes[4]
Patients with diabetes have:
Increased risk of NASH with family history of diabetes[5]
Increased risk of dying from cirrhosis[6,7]
Up to 3-fold increased risk of dying from chronic liver disease, mostly attributable to NAFLD[8]
Increased risk of chronic liver disease[9]
NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
References
1. Kasturiratne A, et al. J Gastroenterol Hepatol. 2013;28:
2. Shibata M, et al. Diabetes Care. 2007;30:
3. Sung KC, et al. Diabetes Care. 2012;35:
4. Ortiz-Lopez C, et al. Diabetes Care. 2012;35:
5. Loomba R, et al. Hepatology. 2012;56:
6. de Marco R, et al. Diabetes Care. 1999;22:
7. Campbell PT, et al. Diabetes Care. 2012;35:
8. Zoppini G, et al. Am J Gastroenterol. 2014;109:
9. El-Serag HB, et al. Gastroenterology. 2004;126:
Slide credit: clinicaloptions.com
References in slidenotes.

15. Clinical Predictors of NASH in Patients With NAFLD
Characteristic
Outcome
Advanced age[1]
Greater duration of disease
Sex[2]
Postmenopausal women experience accelerated disease
Race[3]
↑ Prevalence, severity in Hispanic, Asian patients;
↓ Prevalence, severity in black patients
HTN, central obesity, dyslipidemia (↑ TG, ↓ HDL), insulin resistance/diabetes[4]
Risk increases with metabolic syndrome,* 66% prevalence of bridging fibrosis if older than 50 yrs of age and obese or diabetic[5,6]
AST/ALT ratio > 1,[7] low platelets[8]
Indicators of NASH cirrhosis
Persistently elevated ALT[9]
Can be associated with greater risk of disease progression
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATP, Adult Treatment Panel; HDL, high density lipoprotein; HTN, hypertension; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; TG, triglycerides.
References
1. McPherson S, et al. Am J Gastroenterol. 2016;[Epub ahead of print].
2. Yang JD, et al. Hepatology. 2014;59:
3. Pan JJ, Fallon MB. World J Hepatol. 2014;6:
4. Younossi, Z M, et al. Hepatology. 2016;64:73–84.
5. Ratziu V, et al. Gastroenterology. 2000;118:
6. Angulo P, et al. Hepatology. 1999;30:
7. Neuschwander-Tetri BA, et al. Hepatology. 2010;52:
8. McPherson S, et al. Gut. 2010;59:
9. Ekstedt M, et al. Hepatology. 2006;44:
*Based on ATP III criteria.
Slide credit: clinicaloptions.com
References in slidenotes.

16. Goals Exclude other etiologies Identify risk factors for NASH
Assess and quantify fibrosis
Serum and imaging biomarkers
Role of liver biopsy
NASH, nonalcoholic steatohepatitis.

17. Histological Subtypes[1,2]
NAFLD Disease Progression
Histological Subtypes[1,2]
Change in Fibrosis*[3,4]
NAFLD
70% to 75%
25% to 30%
Regression: 18%-22%
Stable: 40%-43%
Progression: 34-42%
Isolated steatosis
Steatosis with mild inflammation
NASH
Cirrhosis
Fibrosis
NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
*N = 108 pts with NAFL/NASH and median 6.6 yrs follow-up (data from serial biopsies).
1. Ludwig J, et al. Mayo Clin Proc. 1980;55(7): Kleiner DE, et al. Hepatology. 2005;41(6): McPherson S, et al. J Hepatol. 2015;62: Singh S, et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):643-54
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18. Normal ALT Does Not Rule Out Progressive Disease in NAFLD or NASH
Persistently elevated ALT can be associated with disease progression[1]
Patients with normal ALT levels can also develop progressive disease[2-4]
Up to 80% of NAFLD patients can have normal ALT[5]
No designated ALT cutoff for prediction of NASH or advanced fibrosis in NAFLD pts[6]
ALT, alanine aminotransferase; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
1. Ekstedt M, et al. Hepatology. 2006;44: Maximos M, et al. Hepatology. 2015;61: Mofrad P, et al. Hepatology. 2003;37: Amarapurkar DN, Patel ND. Trop Gastroenterol. 2004;25: Dyson JK, et al. Frontline Gastroenterol. 2014;5: Verma S, et al. Liver Int. 2013;33:
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19. Tools for Diagnosis of NAFLD
Method
Sensitivity
Specificity
Comments
Liver enzymes
GGT[1]
63%
65%
Not reliable for diagnosis
Ultrasound[2]
Any degree[3]
Cutoff ≥ 20%[3]
CT without contrast[4]
Cutoff > 30%
MRI[5]
Cutoff PDFF 6.4%, gr ≥ 1
Cutoff PDFF 17.4%, gr ≥ 2
MRS[6]
Cutoff ≥ 5%
Cutoff > 33%
85%
61%
100%
79%
86%
64%
90-96%
92-100%
94%
90%
97%
83%
96%
87-100%
92-97%
Inexpensive and accessible, but cannot distinguish fibrosis/steatosis
Better in morbid obesity, but affected by iron, fibrosis, and less accurate with less steatosis
Detects mild steatosis, quantifies hepatic fat most accurately
Liver biopsy
Gold standard, but invasive and subject to sampling error
CT, computed tomography; GGT, gamma-glutamyl transferase; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NAFLD, nonalcoholic fatty liver disease; PDFF, proton density fat fraction.
References
1. Alam S, et al. BSMMU J. 2015;8:61-67.
2. Hernaez R, et al. Hepatology. 2011;54:
3. Dasarathy S, et al. J Hepatol. 2009;51:
4. Rogier J, et al. Liver Transpl. 2015;21:
5. Tang A, et al. Radiology. 2015;274:
6. McPherson S, et al. J Hepatol. 2009;51:
Slide credit: clinicaloptions.com
References in slidenotes.

20. Limitations of Noninvasive Tests
Method
Sensitivity
Specificity
Comments
Liver enzymes
GGT[1]
63%
65%
Not reliable for diagnosis
Ultrasound[2]
Any degree[3]
Cutoff ≥ 20%[3]
CT without contrast[4]
Cutoff > 30%
MRI[5]
Cutoff PDFF 6.4%, gr ≥ 1
Cutoff PDFF 17.4%, gr ≥ 2
MRS[6]
Cutoff ≥ 5%
Cutoff > 33%
85%
61%
100%
79%
86%
64%
90-96%
92-100%
94%
90%
97%
83%
96%
87-100%
92-97%
Inexpensive and accessible, but cannot distinguish fibrosis/steatosis
Better in morbid obesity, but affected by iron, fibrosis, and less accurate with less steatosis
Detects mild steatosis, quantifies hepatic fat most accurately
Liver biopsy
Gold standard, but invasive and subject to sampling error
Liver enzymes and standard imaging modalities
cannot distinguish NASH from
non-NASH NAFLD
CT, computed tomography; GGT, gamma-glutamyl transferase; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PDFF, proton density fat fraction.
References
1. Alam S, et al. BSMMU J. 2015;8:61-67.
2. Hernaez R, et al. Hepatology. 2011;54:
3. Dasarathy S, et al. J Hepatol. 2009;51:
4. Rogier J, et al. Liver Transpl. 2015;21:
5. Tang A, et al. Radiology. 2015;274:
6. McPherson S, et al. J Hepatol. 2009;51:
Slide credit: clinicaloptions.com
References in slidenotes.

21. Imaging for Diagnosis of NASH
Prospective analysis of adults without liver disease or substantial alcohol use (N = 270 with results at interim analysis)
Cutoff for Detecting NASH, %
Sensitivity
Specificity
PPV
NPV
LIF score > 2 93 32 25 95
Transient elastography > 7 kPa 69 80 48 91
MR elastography > 3 kPa 33 98 83 85
LIF, Liver Inflammation and Fibrosis; MR, magnetic resonance; NASH, nonalcoholic steatohepatitis; NPV, negative predictive values; PPV, positive predictive values.
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Roberts KK, et al. AASLD Abstract 42.

22. How Reliable Is Noninvasive Assessment of Liver Fibrosis in NAFLD?
NAFLD, nonalcoholic fatty liver disease.

23. Fibrosis Staging in NASH
F1: Perisinusoidal
F2: Perisinusoidal + Portal
F3: Bridging Fibrosis
F4: Cirrhosis
NASH, nonalcoholic steatohepatitis.
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24. Noninvasive Diagnosis of Liver Fibrosis in NAFLD
Clinical or Laboratory Tests
Imaging
Simple
AST/platelet ratio index
FIB-4 index
NAFLD fibrosis score
BARD score
Complex
NASH FibroSure
ELF
HepaScore
Elastography
VCTE FibroScan
MR elastography
ARFI
AST, aspartate aminotransferase; ARFI, acoustic radiation force impulse; ELF, enhanced liver fibrosis; FIB-4, fibrosis-4 score; MR, magnetic resonance; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; VCTE, vibration-controlled transient elastography; BARD: body mass index, AST/ALT ratio, diabetes.
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25. Back to Our Case . . . NAFLD Fibrosis Score
Parameter
Our Patient
Age, yrs
AST
ALT
Platelet count, cells x 109
BMI
Albumin, g/L
Impaired fasting glucose/diabetes?
FIB-4 score:
NAFLD Fibrosis Score:
NAFLD Cutoff Value[1]
Stage
<
F0-F2
to 0.676
Indeterminate
> 0.676
F3-F4
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; FIB-4, fibrosis-4 score; NAFLD, nonalcoholic fatty liver disease.
FIB-4 Cutoff Value[2]
Stage
< 1.45
F0-F2
1.45 to 3.25
Indeterminate
> 3.25
F3-F4
1. Angulo P, et al. Hepatology. 2007;45: Sterling RK, et al. Hepatology. 2006;43:  
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26. Back to Our Case . . . NAFLD Fibrosis Score
Parameter
Our Patient
Age, yrs 25
AST 63
ALT 70
Platelet count, cells x 109
200
BMI 32
Albumin, g/L
4.0
Impaired fasting glucose/diabetes?
Yes
FIB-4 score: 0.94
NAFLD Fibrosis Score:
-0.96
NAFLD Cutoff Value[1]
Stage
<
F0-F2
to 0.676
Indeterminate
> 0.676
F3-F4
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; FIB-4, fibrosis-4 score; NAFLD, nonalcoholic fatty liver disease.
FIB-4 Cutoff Value[2]
Stage
< 1.45
F0-F2
1.45 to 3.25
Indeterminate
> 3.25
F3-F4
Cutoffs differ at age > 65 years[3]
1. Angulo P, et al. Hepatology. 2007;45: Sterling RK, et al. Hepatology. 2006;43:   3. McPherson S, et al. Am J Gastroenterol. 2016;[Epub ahead of print].
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27. Negative Predictive Value for F3-F4 (%)[1]
Can Noninvasive Clinical or Lab Tests Distinguish NASH Stages 0-2 vs 3-4?
100 80
Negative Predictive Value for F3-F4 (%)[1]
FIB4 score
AST/ALT
BARD
APRI
NAFLD 95 93 84 92 60
Sensitivity (%) 40 20 20 40 60 80
100
ALT, alanine aminotransferase; APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; FIB-4, fibrosis-4 score; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; BARD: body mass index, AST/ALT ratio, diabetes.
Specificity (%)
Strength of noninvasive fibrosis predictive tests is in their ability to exclude advanced disease (F3-F4)
Least accurate in identifying middle ranges of fibrosis
McPherson S, et al. Gut. 2010;59: McPherson S, et al. Am J Gastroenterol. 2016;[Epub ahead of print].
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28. How Reliable Is Noninvasive Imaging Assessment of Liver Fibrosis in NAFLD?
MRE, magnetic resonance elastography; NAFLD, nonalcoholic fatty liver disease; SWE, shear wave elastography; US, ultrasound.
Reprinted by permission from Macmillan Publishers Ltd: Brunt EM, et al. Nat Rev Dis Primers. 2015;1:15080, copyright (2015).
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29. Diagnostic Performance of Supersonic Shear Imaging, FibroScan, and ARFI
Fibrosis Stage
AUROC (95% CI)
Best Accuracy, % (n/N)
Supersonic shear imaging
≥ F2
≥ F3 F4
0.86 ( )
0.89 ( )
0.88 ( )
80 (185/232)
85 (196/232)
87 (202/232)
FibroScan (M probe only)
0.82 ( )
0.86 ( )
0.87 ( )
77 (172/223)
79 (175/223)
89 (198/223)
ARFI
0.77 ( )
0.84 ( )
74 (175/236)
79 (186/236)
84 (199/236)
ARFI, acoustic radiation force impulse; AUROC, area under receiver operating characteristic.
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Cassinotto C, et al. Hepatology. 2016;63:

30. Vibration-Controlled Transient Elastography: Cutoffs for Fibrosis
9.9
F0-F2 10
8.75
8.7
F2-F4
< 7.9 8
F3-F4
7.25
7.0 6
Cutoff, kPa 4 2
US[1]
Europe[2]
France and Hong Kong[3]
1. Tapper EB, et al. Am J Gastroenterol. 2016;111:
2. Petta S, et al. Aliment Pharmacol Ther. 2011;33:
3. Wong VW, et al. Hepatology. 2010;51:  
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31. Vibration-Controlled Transient Elastography: Known Confounders
Inflammation
Obesity
Nonfasting
Cholestasis
Alcohol use
Congestion
Operator inexperience
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Tapper EB, et al. Clin Gastroenterol Hepatol. 2015;13:27-36.

32. Magnetic Resonance Elastography
Stiffness[1]
High
Low
CPR, clinical prediction rule; NAFLD, nonalcoholic fatty liver disease.
References
1. Chen J, et al. Radiology. 2011;259:
2. Imajo K, et al. Gastroenterology. 2016;150:
3. Cui J, et al. Aliment Pharmacol Ther. 2015;41:
4. Loomba R, et al. Hepatology. 2014;60:
Simple Steatosis
Inflammation, But No Fibrosis
Fibrosis
In NAFLD, higher diagnostic accuracy for fibrosis vs transient elastography and CPRs,[2,3] can accurately predict advanced fibrosis[4]
Inflammation can increase stiffness values in the absence of fibrosis[1]
Reprinted, with permission, from Radiology 2011;259: ©RSNA. References in slidenotes.
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33. Management Strategies
Identification of the risk of NASH and disease progression is guided by:
Clinical risk factors (eg, metabolic, family history)
Noninvasive markers
Fairly accurate to diagnose advanced fibrosis
Know the confounders
Lesser cutoffs on imaging in combination with other factors can predict NASH with modest accuracy
Can reliably exclude advanced fibrosis but not NASH
NASH, nonalcoholic steatohepatitis.
Slide credit: clinicaloptions.com

34. Goals Exclude other etiologies Identify risk factors for NASH
Assess and quantify fibrosis
Serum and imaging biomarkers
Role of liver biopsy
NASH, nonalcoholic steatohepatitis.

35. Risk Stratification in Pts With Suspected NAFLD
Hepatic steatosis on imaging
± elevated serum ALT levels
Evaluate alcohol consumption
Confirm NAFLD
Exclude alternate causes of ↑ALT levels
Low-risk profile
BMI < 29.9
Age < 40 yrs
No T2DM or metabolic syndrome features
Noninvasive fibrosis estimation:
FIB-4 < 1.30
APRI < 0.5
NFS <
FibroScan < 5 kPa
Intermediate-risk profile
BMI > 29.9*
Age > 40 yrs
Multiple features of the metabolic syndrome*
Noninvasive fibrosis estimation:
FIB
APRI
NFS
FibroScan 6-11 kPa
High-risk profile
AST level > AST level
Platelets < 150,000
Noninvasive fibrosis estimation:
FIB-4 > 2.67
APRI > 1.5
NFS > 0.675
FibroScan > 11 kPa
ALT, alanine aminotransferase; APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; FIB-4, fibrosis-4 score; MRE, magnetic resonance elastography; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NFS, nonalcoholic fatty liver disease fibrosis score.
MR, magnetic resonance; VCTE, vibration-controlled transient elastography.
Consider liver biopsy or confirmatory testing for cirrhosis (eg, MRE)
Follow and reassess as risk factors evolve
Consider liver biopsy
*Risk factors in our patient.
Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol. 2016;13:
Reprinted by permission from Macmillan Publishers Ltd.
Slide credit: clinicaloptions.com

36. The Role of Liver Biopsy
Isolated Steatosis
Steatohepatitis/NASH
Make diagnosis of NASH (surrogates insufficient)[1]
Initiate drug therapy
Assess prognosis: liver, cardiovascular, etc
Stage fibrosis (if imaging or tests are indeterminate)[1]
Rule out concomitant liver disease[1]
Autoimmune, Wilson disease, DILI, iron overload (ferritin can be high in NAFLD in absence of iron overload[2])
DILI, drug-induced liver injury; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
1. Rinella ME, et al. Gastroenterol Hepatol (NY) ;10:
2. Camaschella C, Poggiali E. Haematologica. 2009;94:
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37. Noninvasive Assessment of Liver Fibrosis to Guide Treatment, Monitor Progression
British study comparing identification of advanced fibrosis in patients with NAFLD (N = 145)
No data using elastography to assess response to intervention
AUROC
FIB-4: 0.86
AST/ALT ratio: 0.83
NAFLD fibrosis score: 0.81
BARD: 0.77
APRI: 0.67
NPV, %
FIB-4: 95
BARD: 95
AST/ALT ratio: 93
NAFLD fibrosis score: 92
APRI: 84
PPV, %
NAFLD fibrosis score: 79
FIB-4: 75
AST/ALT ratio: 55
APRI: 37
BARD: 27
ALT, alanine aminotransferase; APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; FIB-4, fibrosis-4 score; NAFLD, nonalcoholic fatty liver disease; NPV, negative predictive value; PPV, positive predictive value; BARD: body mass index, AST/ALT ratio, diabetes.
Slide credit: clinicaloptions.com
McPherson S, et al. Gut. 2010;59:

38. Clinical Take-Home Points
Is this NAFLD or
something else?
It’s NAFLD, likely NASH
(exclude other diseases)
How to differentiate
NAFLD from NASH?
Use clinical predictors and
noninvasive tests to
guide decisions
Reliability of noninvasive
assessment of liver fibrosis
in NAFLD?
Reliable for exclusion,
very good for identification;
can’t differentiate NASH vs NAFLD
ALT, alanine aminotransferase; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
Is a liver biopsy
necessary?
Yes: risk factors for NASH
and progression;
persistently elevated ALT
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39. Go Online for More CCO Coverage of NASH!
Downloadable slidesets on diagnostic and treatment strategies for NASH CME-certified On-demand Webcast from the live symposium
clinicaloptions.com/hepatitis