Patient POV: New and Emerging Approaches in the Management of Non-Alcoholic Steatohepatitis. Program link:

1. Provided by
Patient POV: New and Emerging
Approaches in the Management
of Non-Alcoholic Steatohepatitis
Chair
Zobair M. Younossi, MD, MPH, FACP, FAASLD, AGAF, FACG
Chairman, Department of Medicine, Inova Fairfax Medical Campus
Professor of Medicine, University of Virginia – Inova Campus
Patient Advocate
Tony Villiotti
Founder and Board Chair
NASH kNOWledge

2. Disclosures
 Zobair M. Younossi, MD, MPH, FACP, FAASLD, AGAF,
FACG, discloses the following commercial
relationships:
 Consulting: AstraZeneca, Boehringer Ingelheim, Bristol Myers
Squibb, Cymabay, GlaxoSmithKline, Intercept, Novo Nordisk,
Siemens
 Research: Bristol Myers Squibb, Intercept, Madrigal, Merck,
Siemens
 Tony Villiotti discloses the following commercial
relationships:
 Grants: Eisai, Inventiva, Madrigal, PPD, Regeneron

3. Learning Objectives
After participating in all modules, learners will be
able to:
 Identify methods for timely NASH diagnosis
 Assess emerging non-invasive methods for NASH
diagnosis
 Review current guidelines for NASH management
 Evaluate efficacy and safety data of emerging NASH
therapies

4. Introduction and Background
Patient POV: New and Emerging Approaches in the
Management of Non-Alcoholic Steatohepatitis

5. Global Prevalence of NAFLD and NASH
MENA, Middle East and North Africa; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.
Younossi et al, 2019; Younossi, Golabi et al, 2023.
(1990-2019)

6. Global Prevalence of NAFLD and NASH (cont.)
T2DM, type 2 diabetes mellitus.
Younossi et al, 2019; Younossi, Golabi et al, 2023.
Global Rates of NAFLD Increasing Over Time

7. Long-Term Outcomes of NAFLD: Mortality
17.15
8.3
10.3
7.7
5.64
4.1
1.65
0
2
4
6
8
10
12
14
16
18
20
Overall NAFLD US Gen Pop(1) US Gen Pop(2) Global Gen Pop(1) CVD-NAFLD ExtraHepatic
Cancer-NAFLD
Liver-NAFLD
Per
1,000
person-years
accounted for 66.4% of all deaths among NAFLD
 The pooled mortality rate among NAFLD (N=7) was 17.2 per 1,000 PY (9.02-32.37)
 The top three leading causes of death: CVD (5.64 per 1,000 PY [1.70-5.64]), extra-hepatic
cancer (4.10 per 1,000 PY [0.97-4.10]), and liver complications (1.65 per 1,000 PY [0.00-1.65])
CVD, cardiovascular disease; PY, person-years.
Younossi, Golabi et al, 2023.

8. Poll Question 1
 Which patients with NAFLD are at highest risk for
adverse outcomes?
a) Patients with type 2 diabetes
b) Patients with stage 2 or higher fibrosis
c) Patients with hypertension
d) a & b

9. Poll Question 1 - Rationale
The correct answer is d.
 The most important clinical predictor of mortality among patients with
NAFLD is presence of T2D. In fact, the increasing number of components
of metabolic syndrome, increases the risk of mortality.
 In addition to clinical predictor mortality, stage of fibrosis has important
prognostic implications. Patients with stage 2 or higher are at risk for
mortality.

10. High-Risk Groups: Clinical and Histologic Risks
All-Cause Mortality
Systematic Review and Meta-Analysis of 13 Studies
4,428 NAFLD Patients (2,875 with Histological NASH)
Liver-Related Mortality
0
0.1
0.2
0.3
DM HTN DM+HTN DM + HTN + Visceral obesity*)
%
with
moderate
to
severe
fibrosis
Positive
Negative
7.2
8.3
1.1 0.7
0
1
2
3
4
5
6
7
8
9
NASH CRN fibrosis stage Ishak fibrosis stage
No fibrosis
regression
Fibrosis
regression
69/957 69/834
2/176
2/300
Liver
related
events
(%)
HR 0.16 (95% CI: 0.04, 0.65)
p=0.0104
HR 0.08 (95% CI: 0.02, 0.32)
p=0.0004
Increasing Number of Metabolic Risks are Associated with Advanced Fibrosis
Fibrosis Regression and Liver-Related Events in NASH
Cirrhosis
Increasing Number of Metabolic Risks Are Associated with Mortality
CI, confidence interval; CRN, Clinical Research Network; DM, diabetes mellitus; HR, hazard ratio; HTN, hypertension; MS, metabolic syndrome.
Hossein et al, 2009; Taylor et al, 2020; Golabi et al, 2018; Sanyal et al, 2021.

11. Diagnosis
Patient POV: New and Emerging Approaches in the
Management of Non-Alcoholic Steatohepatitis

12. Poll Question 2
 Which non-invasive test is included as the first step in
risk stratification algorithms for patients with NAFLD?
a) MR elastography
b) Liver fibrosis
c) Aminotransferases
d) FIB-4

13. Poll Question 2 - Rationale
The correct answer is d
 Fib-4 is a simple test that has been used as the first test to risk stratify
patients with NAFLD
 In general, Fib-4 performs well for excluding patients at risk for cirrhosis
 There are some caveats to consider. These include higher threshold
should be used for older patients.

14. Case Discussion
 A 65-year-old man is referred by his family physician for
evaluation of “elevated liver enzymes”
 He has had mild aminotransferase elevation (ALT in the 50s) for
20 years, but his recent labs show persistent elevation of
aminotransferases (despite a 2-month statin holiday)
 AST 170
 ALT 92
 Albumin 4.0
 Bilirubin and alkaline
phosphatase are normal
 Platelets 210
 HbA1c 6.2%
 Ultrasound 3 years ago
showed fatty liver
 Medications: amlodipine,
atorvastatin, enalapril,
metformin, omeprazole
 PMH: hypertension, T2DM,
elevated LDL, GERD, anxiety
 Drinks 1 beer per day
 BMI 35
 Waist circumference 125 cm
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; GERD, gastroesophageal reflux disease;
LDL, low-density-lipoprotein; PMH, past medical history; T2DM, type 2 diabetes mellitus.

15. Case Discussion (cont.)
 Ultrasound shows:
 ”Increased echogenicity of
the liver parenchyma,
likely consistent with
hepatic steatosis
 No other hepatic
abnormalities
 No splenomegaly
 Labs
 HCV & HBV negative
 ASMA: 1:20, ANA: 1:80
 Iron profile
 Ferritin 640
 Iron saturation 65%
 A1AT: normal
A1AT, alpha-1 antitrypsin; ANA, antinuclear antibodies; ASMA, antismooth muscle antibodies; HBV/HCV, hepatitis B/C virus.

16. How to Identify High-Risk NAFLD Without Liver Biopsy
Non-invasive Tests (NITs): Serum Biomarkers and Clinical Decision Tools
APRI, AST(aspartate transferase)-to-platelet ratio; CAP, controlled attenuation parameter; CK-18, cytokeratin 18; MR-PDFF, magnetic resonance-proton
density fat fraction; MRE, magnetic resonance elastography; NPV, negative predictive value; PPV, positive predictive value TE, transient elastography.
Younossi, Alkhouri et al, 2023.

17. How to Identify High-Risk NAFLD Without Liver Biopsy
Non-invasive Tests (NITs): Radiologic Tests
kPa, kilopascals; LSM, liver stiffness measure; US, ultrasound.
Younossi, Alkhouri et al, 2023.

18. Non-Invasive Tests: Predicting Outcomes
 Longitudinal cohort study of 20,433 patients to evaluate the
association of 12-month changes in FIB-4 with risk of
developing severe NASH-related clinical events
 UK Clinical Practice Research Datalink linked with Hospital
Episodes Statistics and Office for National Statistics data (2001–
2020)
Change in FIB-4 calculated from baseline to 12 mos
 894 patients with biopsy-proven NAFLD in the NASH CRN
NAFLD Database 2 and 3 studies with ≥2 LSM readings from
2014 to 2022 were included
 LSM cirrhosis: LSM >14.9 kPa in those without cirrhosis on
initial VCTE
 Composite outcome, ≥1 of:
1) Death 2) Decompensation 3) HCC 4) MELD >15
Time to composite clinical outcomes in progressors to
LSM-defined cirrhosis vs non-progressors
HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease.
Anstee et al, 2022; Gawrieh et al, 2022.

19. Guidelines Are Being Developed to Identify High-Risk NAFLD
Algorithm to be included in the January 2023 American Diabetes Association
Standards of Care
Gastroenterology, 2021
J Hepatol. 2016;64:1388–402.
Kanwal et al, 2021; EASL, EASD & EASO, 2016; Lomanaco et al, 2021; ADA, 2019; Draznin et al, 2022; Cusi et al, 2022.

20. Fibrosis Risk Stratification
AACE 2022 Guidelines: Cirrhosis Prevention in NAFLD
Prediabetes
or
T2D
Obesity
and/or
≥2 cardiometabolic
risk factors
Steatosis (on imaging)
or
↑ AST or ALT
High-risk groups
for NAFLD
FIB-4 Index
Liver Stiffness Measurement (LSM)
by Elastography
or ELF Blood Test
Indeterminate Risk
Low
Risk
High
Risk
Low Risk
FIB-4 <1.3 or LSM <8 kPa or ELF <7.7
(or if liver biopsy was performed
fibrosis stage is F0-F1)
Indeterminate Risk
FIB-4 1.3–2.67 or LSM 8–12 kPa
or ELF 7.7–9.8
(liver specialist to consider need for biopsy)
High Risk
FIB-4 ≥2.67 or LSM ≥12 kPa or ELF ≥9.8
(or if liver biopsy was performed
fibrosis stage is F2-F4)
Cirrhosis risk higher if:
• T2D (or prediabetes)
• Age >50
• Higher BMI (40 kg/m2)
• More metabolic risk
factors
• Genetic factors (eg,
PNLPA3)
• Managed by primary care team, endocrinologist, other
• Focus care on obesity management & CVD prevention
• Referral to liver specialist for additional proprietary biomarkers or imaging (eg, MRE,
cT1)
• Multidisciplinary team to prevent cirrhosis and CVD
NAFLD
AACE, American Association of Clinical Endocrinology; BMI, body mass index; CVD, cardiovascular disease; ELF, Enhanced Liver Fibrosis.
Cusi et al, 2022.

21. AASLD 2023 NAFLD Guidelines
Rinella et al, 2023.

22. Case Discussion (cont.)
FIB-4 > 3.25 would have a 97%
specificity and positive predictive
value of 65% for advanced fibrosis.
APRI > 1.0 had a sensitivity of 76% and
specificity of 72% for predicting cirrhosis.
NFS
NFS score between
-1.455 – 0.675

23. Case Discussion (cont.)
• Non-invasive calculators have limitations
• However, they are inexpensive and easy to calculate with platelets, AST,
ALT, and albumin (and age, BMI, & presence of impaired fasting glucose or
diabetes for NFS)
Score Suggested Fibrosis Stage
APRI 0.95 3 or 4
FIB-4 2.4 2 or 3
NFS 0.08 > 2?

24. Case Discussion (cont.)

25. Case Discussion (cont.)
Score Suggested Fibrosis Stage
APRI 0.95 3 or 4
FIB-4 2.4 2 or 3
NFS 0.08 > 2?
Fibroscan 16.0 kPa 3 or 4

26. Case Discussion (cont.)
 Liver biopsy (N): steatohepatitis, nonalcoholic by history,
with bridging fibrosis
 Microscopic description
 The sections obtained after processing show three needle cores
with aggregate length of 35 mm, embedded in two blocks. More
than eleven portal tracts are present. The biopsy shows steatosis,
with lobular and portal inflammation, as well as hepatocellular
ballooning and a number of Mallory bodies, indicating an active
steatohepatitis. The trichrome stain shows centrilobular pericellular
fibrosis and periportal fibrosis with extensive bridging fibrosis but
not cirrhosis
 Special stains
 The Masson trichrome stain shows bridging fibrosis. Control
sections are appropriately positive
 Iron studies shows minimal staining

27. Treatment
Patient POV: New and Emerging Approaches in the
Management of Non-Alcoholic Steatohepatitis

28. Poll Question 3
 What are the first steps that must be implemented in
patients with NAFLD?
a) Lifestyle change in diet and exercise
b) Anti-obesity medication
c) Metformin
d) Bariatric endoscopy

29. Poll Question 3 - Rationale
The correct answer is a
 All patients with NAFLD should have a serious attempt with lifestyle
modification. This should be delivered by a multi-disciplinary team to
assure that weight loss and physical activity is sustained through
adopting healthy nutrition and activity/exercise. All other options are
secondarily considered in some patients with NAFLD or NASH.

30. Addressing the Main Risks of NAFLD: Obesity and T2D
>2 cups of coffee/d
Caloric intake reduction Weight loss No heavy alcohol
Exercise
• N=293 NASH patients
encouraged to adopt lifestyle
changes for weight loss over
52 weeks
Weight Loss with
Lifestyle Intervention
Intermittent (5:2) Diet
vs LCHF Diet
• Open-label RCT in 74
subjects with NAFLD in 2
diets and SOC
MRS
LCHF, low-carb high-fat; MRS, magnetic resonance spectroscopy; SOC, standard of care.
Vilar-Gomez et al, 2015; Holmer et al, 2021.

31. Addressing the Main Risks of NAFLD: Obesity and T2D (cont.)
Diet and
Exercise
Weight Loss with
Bariatric Surgery
• Mortality risk of bariatric surgery
in CC to be slightly higher than
without cirrhosis (0.9% vs 0.3%)
but significantly higher in DCC
(16.3%)
• Alcohol use disorder may be an
issue
CC, compensated cirrhosis; DCC, decompensated cirrhosis; DYSL, dyslipidemia; FU, follow up; MED, Mediterranean diet; PA, physical activity.
Lassailly et al, 2020; Patton et al, 2021; Gepner et al, 2018.
• Severely obese patients with
biopsy-proven NASH with 5
years of FU (N=180)
• RCT of 278 sedentary adults with obesity (75%) or DYSL randomized to 18 wks of
isocaloric low-fat or Mediterranean/low-carbohydrate diet +28g walnuts/day ±
moderate PA (80% aerobic)

32. Addressing Risks Using Available Medications:
PPAR Agonist Pioglitazone
• N=101 NASH with pre-DM or DM
• All participants were placed on a 500 kcal/d deficit diet and
randomized to placebo or pioglitazone 30 mg/day (titrated
to 45 mg/d after 2 months) for 18 months
DM, diabetes mellitus; NAS, non-alcoholic fatty liver disease activity score.
Cusi et al, 2016; Musso et al, 2017.

33. Addressing Risks Using Available Medications:
GLP-1 Agonist Semaglutide
BL, baseline; SEMA, semaglutide; VLDL, very-low-density lipoprotein.
Newsome et al, 2020; Newsome et al, 2021.
Resolution of steatohepatitis
without worsening fibrosis
 SEMA 0.4 mg resulted in increased HDL cholesterol and decreased free fatty acids,
triglycerides and VLDL cholesterol versus placebo
 Overall AE profile excellent - major AEs were nausea, constipation, and vomiting, but
these did not result in study drug discontinuation
Inclusion criteria:
 Biopsy confirmed
NASH
 NAS ≥4
 Fibrosis stage 1, 2
or 3
 BMI >25 kg/m2
 HbA1c ≤10%
Primary endpoint:
 Resolution of steatohepatitis and no worsening in liver fibrosis
Confirmatory secondary endpoint:
 Improvement in liver fibrosis and no worsening in steatohepatitis
Improvement in liver fibrosis
without worsening steatohepatitis
NASH resolution without fibrosis worsening with SEM 0.4 mg vs placebo,
according to BL subgroups

34. Future NASH Treatment:
Potential Therapeutic Targets
DAMP, danger-associated molecular patterns; ECM, extracellular matrix; IL-1β, interleukin-1beta; MoA, mechanism of action; PAMP,
pathogen-associated molecular patterns; PDGF, platelet-derived growth factor; TGF-β, transforming growth factor beta; TNF, tumor
necrosis factor; TNF-β, tumor necrosis factor-beta.
Benedict et al, 2017; Bedossa, 2017; Younossi et al, 2011.
Bacterial
translocation
(endotoxins)
DAMPs
Kupffer cells
Inflammatory
macrophages
PAMPs
Secondary
Inflammatio
n and Injury
IL-1ß
TNF
Inflammatory
monocytes
Maturation
Oxidative
Stress
Inflammatory Mechanisms
ECM
deposition
(collagen
formation)
Activation/
trans-
differentiation
Hepatic
stellate
cells
Activated
myofibroblast
Activated
myofibroblasts
Scar
formation/
Fibrosis
TGF-ß
PDGF Proliferatio
n
Fibrosis
Endothelial Cell
Dysfunction
Fat accumulation
drives injury
Hepatocyte
Visceral Adiposity
Insulin Resistance
Dysbiosis
Obesity
Wt loss procedure
Bariatric surgery
App Suppressors
Duodenal Muc Res
Naltre-Buprop
Phent-Topiramte
Lorcaserin
Liraglutide
Semaglutide
SGLT2i
Dysbiosis
Growth hormone
Tesamorelin
GH-axis
estosterone
Androgenic
Endocrinopathies
FGF 19/21 agonists
THR B agonists
FXR agonists FASNi
SCD1 inhibition
ACC inhibitors
Pegbelfermin
Resmetirom
aldafermin
PF-05221304
Gramchol
ASC40
Fircostat
Obeticholic acid
Cilofexor
Tropifexor PF-05221304
VK2809
EDP305
Lipotoxicity
Mito Dysfunction
ER stress
PPAR agonists
THR B agonists
Resmetirom
VK2809
Pioglitazone
Seladelpar
Lanifibranor
Saroglitazar
FXR agonists
Obeticholic acid
Cilofexor
Tropifexor
EDP305
VAP-1
TERN 201
PXS 4728
Inflammation
Metabolic
Multifunctional
Multiple MoAs
Simtuzumab
CCR2/5
BMS 986263
Fibrosis
Efinopegdutide

35. New Potential NASH Regimen: PPAR Agonist Lanifibranor
APO-A1/APO-B, apolipoprotein A1/B; HDL-C, high-density lipoprotein cholesterol; HS-CRP, high-sensitivity C-reactive protein; MMRM, mixed model for
repeated measures; SE, standard error; TG, triglyceride; TIMP1/MMP2, tissue inhibitors of metalloproteinase-2/matrix metalloproteinase-2.
Francque et al, 2020; Cooreman et al, 2021; Francque et al, 2021.
Placebo
Lanifibranor 1200 mg QD
Lanifibranor 800 mg QD
Screening
Liver biopsy
End of treatment
Liver biopsy
Randomization 1:1:1
Stratification on T2DM
Phase 2b
24-week treatment + 4-week follow-up
Double-blind, randomized, placebo-controlled
PAN PPAR (PPARa/d/g) agonist (N=247)
Once daily oral
administration
n=83
 Increase in HDL-C at Week 4 and decrease in triglycerides at Week 14
 No change in LDL-cholesterol
 Decrease of HbA1c
Mean ±SE (P-
value vs PBOa) Lanifibranor 800 mg Lanifibranor 1200 mg Lanifibranor pooled Placebo
APO-B/APO-A1 −0.09 ±0.02 (0.001) −0.07 ±0.02 (0.01) −0.08 ±0.01 (0.001) 0.01 ±0.02
Hs-CRP (mg/L) −2.01 ±0.50 (0.02) −1.00 ±0.52 (0.31) −1.53 ±0.36 (0.053) −0.23 ±0.55
MACK-3 −0.32 ±0.03 (<0.001) −0.28 ±0.03 (<0.001) −0.30 ±0.02 (<0.001) −0.01 ±0.03
TIMP1/MMP2 −0.79 ±0.10 (<0.001) −0.88 ±0.10 (<0.001) −0.83 ±0.07 (<0.001) −0.07 ±0.11
aFrom MMRM including absolute change from BL as endpoint, time, treatment, BL diabetic status,
interaction treatment*time and BL value as fixed effects, time repeated effect within each subject
340
320
300
Mean
CAP,
db.m-1
(95%CI)
 Data suggest that LAN reduced hepatic steatosis, assessed
using histologically and with CAP
 Fall in CAP correlated with HBA1c and TG drop

36. New Potential NASH Regimen: Thyroid Receptor β Agonist
Resmetirom
Key inclusion criteria
• ≥3 metabolic risk factors
• FibroScan VCTE ≥8.5 kPa
• NASH on biopsy: NAS ≥4
(with ≥1 in each component)
• Fibrosis stage F1B, F2, or F3
• ≥8% hepatic fat by MRI-PDF
Dual primary endpoint at Week 52:
• NASH resolution (ballooning score=0, inflammation
score=0/1 and a ≥2-point reduction in NAS) with no
worsening of fibrosis
• ≥1-stage improvement in fibrosis with no
worsening of NAS
n (%) Placebo
Resmetirom
80 mg
Resmetirom
100 mg
Headache 27 (8) 30 (9) 24 (7)
Vomiting 17 (5) 28 (9) 35 (11)
T2DM 25 (8) 25 (8) 27 (8)
Abdominal
pain
18 (6) 27 (8) 30 (9)
Constipation 18 (6) 21 (7) 27 (8)
Muscle spasms 21 (7) 14 (4) 22 (7)
Hypertension 25 (8) 16 (5) 13 (4)
Dizziness 11 (3) 21 (7) 19 (6)
n (%) Placebo
Resmetirom
80 mg
Resmetirom
100 mg
Diarrhea 50 (16) 89 (28) 109 (34)
COVID-19 68 (21) 78 (24) 56 (17)
Nausea 40 (13) 70 (22) 62 (19)
Arthralgia 40 (13) 46 (14) 34 (11)
Back pain 38 (12) 36 (11) 27 (8)
UTI 29 (9) 33 (10) 26 (8)
Fatigue 27 (9) 32 (10) 26 (8)
Pruritus 22 (7) 26 (8) 37 (12)
Abdominal
pain upper
29 (9) 25 (8) 27 (8)
MRI-PDF, magnetic resonance imaging proton density fat fraction; UTI, urinary tract infection.
Harrison et al, 2023.

37. New Potential NASH Regimen: FXR Agonist Obeticholic Acid
Primary Endpoint (ITT): Fibrosis
Improvement by ≥1 Stage
With No Worsening of NASH
Placebo OCA 10 mg OCA 25 mg
0
10
20
30
40
%
Patients
17.6%
23.1%
(n=311) (n=308)
*p=0.0002
11.9%
p=0.04
(n=312)
d/c, discontinuation; ITT, intent-to-treat; OCA, obeticholic acid; TEAE, treatment-emergent adverse event.
Younossi et al, 2019; Sanyal et al, 2019; Sanyal et al, 2022.
Placebo OCA 10 mg OCA 25 mg
0
10
20
30
40
%
Patients
11.2% 11.7%
(n=311) (n=308)
p=0.13
8.0%
p=0.18
(n=312)
Primary Endpoint (ITT): NASH Resolution
With No Worsening of Fibrosis
 End of Study analyses
 Progression to cirrhosis
 Complications secondary to
cirrhosis
 Liver transplant
 All-cause mortality
 ~7.5 years in total study duration
 Minimum 4 years follow-up
Primary Endpoint of Re-analysis
Using Consensus Panel
n (%)
Placebo
n=825
OCA
10 mg
n=825
OCA
25 mg
n=827
Deaths 8 (1.0) 9 (1.1) 10 (1.2)
TEAEs 766 (92.8) 795 (96.4) 807 (97.6)
Serious TEAEs 181 (21.9) 204 (12.4) 216 (26.1)
TEAEs leading to
discontinuation
93 (11.3) 102 (33.2) 179 (21.6)
Most frequent TEAE:
pruritus
200 (24.2) 274 (33.2) 453 (54.8)
Most frequent TEAE
leading to
discontinuation
8 (1.0) 14 (1.7) 93 (11.2)
Neoplasms benign,
malignant, and
unspecified
84 (10.2) 91 (11.0) 76 (9.2)
• Safety population, N=2477
• 8000+ total pt yrs of exposure
• ~1000 subjects received OCA for ≥4 yrs

38. New Potential NASH Regimen: GLP-1/Glucagon Receptor Co-
Agonist Efinopegdutide
LFC, liver fat content.
Romero-Gómez et al, 2023.

39. Conclusion & Key Takeaways
 NASH and its complications are growing
 NASH + T2DM and those with stage >2 are
especially at high risk
 NIT algorithms can be used to risk stratify patients
with NAFLD/NASH
 Management requires multidisciplinary team to
address driver of progressive NAFLD (T2D and
obesity) through
 Lifestyle intervention for all (diet & exercise)
 Bariatric experts (endoscopic, surg)
 Medical treatment of T2D and obesity
 A large number of drugs are in phase 2 with a few in
phase 3 clinical trials
 Combination of regimens, personalized medicine,
and induction and maintenance may be the future
Development of Care Pathway
Core Team
(Hepatology
Diabetologists,
Obesity Medicine
Bariatric (Surgical
and Endoscopic)
Nutritio
n
Experts
Primary Care
Exercise
Specialists
Behavioral
Health

40. Thank You for Joining Us!
 We are excited to see the impact of this educational
activity on patient care in NASH!
 In 4 weeks, you will receive a follow-up survey to see if
you’ve been able to implement any of your intended
changes as a result of what you learned
 Keep an eye out for the survey and feel free to send us
an email if you have any questions:
contact@cmespark.com

41. References
 American Diabetes Association (2019). 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of
Medical Care in Diabetes-2019. Diabetes Care. 42(Suppl 1):S34-S45. DOI:10.2337/dc19-S004
 Anstee QM, Berentzen TL, Nitze LM, et al (2022). Change in Fibrosis-4 index (FIB4) over time is associated with subsequent risk
of liver events, cardiovascular events, and all-cause mortality in patients with obesity and/or type 2 diabetes (T2D). Presented
at: AASLD The Liver Meeting 2022. Abstract 5049.
 Bedossa P (2017). Pathology of non-alcoholic fatty liver disease. Liver Int. 37(Suppl 1):85-89. DOI:10.1111/liv.13301
 Benedict M & Zhang X (2017). Non-alcoholic fatty liver disease: an expanded review. World J Hepatol. 9(16):715-32.
DOI:10.4254/wjh.v9.i16.715
 Cooreman M (2020). Lanifibranor treatment improves hepatic steatosis in patients with NASH, evaluated
 by histological grading and Controlled Attenuation Parameter (CAP). Presented at: AASLD The Liver Meeting.
 Abstract P1921.
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