Experts vs AI: Who Is Better at Monitoring and Treating MASLD and MASH?
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Jun 07, 2024
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About This Presentation
Chair and Presenter Rohit Loomba, MD, MHSc, and Alina M. Allen, MD, MS, discuss metabolic dysfunction–associated steatohepatitis in this CME activity titled “Experts vs AI: Who Is Better at Monitoring and Treating MASLD and MASH?.” For the full presentation, downloadable Practice Aids, and com...
Slide Content
Experts vs Al
Who Is Better at Monitoring
and Treating MASLD and MASH?
Rohit Loomba, MD, MHSc Alina M. Allen, MD, MS
Professor of Medicine Associate Professor of Medicine
Chief, Division of Gastroenterology Director, MASLD Clinic
and Hepatology Division of Gastroenterology
Director, MASLD Research Center and Hepatology
Adjunct Professor, Division of Epidemiology Mayo Clinic
University of California at San Diego Rochester, Minnesota
La Jolla, California
Go online to access full CME information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Who Is Better at Monitoring
and Treating MASLD and MASH?
Rohit Loomba, MD, MHSc Alina M. Allen, MD, MS
Professor of Medicine Associate Professor of Medicine
Chief, Division of Gastroenterology Director, MASLD Clinic
and Hepatology Division of Gastroenterology
Director, MASLD Research Center and Hepatology
Adjunct Professor, Division of Epidemiology Mayo Clinic
University of California at San Diego Rochester, Minnesota
La Jolla, California
Go online to access full CME information, including faculty disclosures.
Copyright © 2000-2024, PeerView
Objectives for This Activity
Describe the disease pathways and mechanisms that define MASLD/MASH as serious,
chronic, and progressive metabolic diseases
Discuss the role of GLP-1 as a therapeutic target in MASLD/MASH and other
components of the metabolic syndrome
Explore the use of noninvasive tests and biomarkers to monitor MASLD/MASH
disease progression
Decide how to initiate early guideline-driven management with available and
emerging pharmacotherapies to delay MASLD/MASH progression and improve
outcomes for patients
PeerView.com/RNX827
Describe the disease pathways and mechanisms that define MASLD/MASH as serious,
chronic, and progressive metabolic diseases
Discuss the role of GLP-1 as a therapeutic target in MASLD/MASH and other
components of the metabolic syndrome
Explore the use of noninvasive tests and biomarkers to monitor MASLD/MASH
disease progression
Decide how to initiate early guideline-driven management with available and
emerging pharmacotherapies to delay MASLD/MASH progression and improve
outcomes for patients
PeerView.com/RNX827
What’s in a Name?
Level Setting the Conversation
Around MASLD and MASH
Rohit Loomba, MD, MHSc
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Director, MASLD Research Center
Adjunct Professor, Division of Epidemiology
University of California at San Diego
La Jolla, California
Copyright © 2000-2024, PeerView
Level Setting the Conversation
Around MASLD and MASH
Rohit Loomba, MD, MHSc
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Director, MASLD Research Center
Adjunct Professor, Division of Epidemiology
University of California at San Diego
La Jolla, California
Copyright © 2000-2024, PeerView
An Update in Nomenclature: NAFLD Is Now MASLD!
A name change
Metabolic dysfunction
associated steatotic liver
Nonalcoholic fatty liver
disease (NAFLD) disease (MASLD)
A definition change
Steatosis in the absence
of other etiologies Steatosis in the presence
of at least one
(eg, moderate or significant
alcohol use, viral hepatitis) metabolic comorbidity
1.Rinela ME eta. Ann Hepatol 2024:20:101133, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
A name change
Metabolic dysfunction
associated steatotic liver
Nonalcoholic fatty liver
disease (NAFLD) disease (MASLD)
A definition change
Steatosis in the absence
of other etiologies Steatosis in the presence
of at least one
(eg, moderate or significant
alcohol use, viral hepatitis) metabolic comorbidity
1.Rinela ME eta. Ann Hepatol 2024:20:101133, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
Factors Precipitating the Nomenclature Change’
Under SLD
three acronym choices
Final acronym for MASLD,
MASH, and MASLD plus.
Te flow carton te le rate the exciton in decson-makng as regards naming, whereas he one on height stats decision making a regars ef re
1. Rival ME et al, Ann Hepat, 2026.20:101133. RA = PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Under SLD
three acronym choices
Final acronym for MASLD,
MASH, and MASLD plus.
Te flow carton te le rate the exciton in decson-makng as regards naming, whereas he one on height stats decision making a regars ef re
1. Rival ME et al, Ann Hepat, 2026.20:101133. RA = PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
New Steatotic Liver Disease Classification’
Steatotic Liver Disease
(SLD)
MASLD and increased alcohol intake*
‘Alcohol-associa
(MetALD)
(alcohol-related)
ALD
dominant
280 350/420
Metabolic ve
function-associated
steatohepatitis,
ninant
50/60
Average daily alcohol intake, g
* Week intake 140-350 9 (women). 210-420 g (men): average daty 20-50 g (women), 30-60 (men). Including lysosomal aci lipase deficiency (LALO), Wison disease,
hypobetaipoproteinemia and inbom errors of metabolism, Including hepatis © vius (HCV), malnutrition, cei disease, and human immunodeficiency virus (HV).
1 Rinela ME et al. Ann Hopatol 2024,29:101133.
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Steatotic Liver Disease
(SLD)
MASLD and increased alcohol intake*
‘Alcohol-associa
(MetALD)
(alcohol-related)
ALD
dominant
280 350/420
Metabolic ve
function-associated
steatohepatitis,
ninant
50/60
Average daily alcohol intake, g
* Week intake 140-350 9 (women). 210-420 g (men): average daty 20-50 g (women), 30-60 (men). Including lysosomal aci lipase deficiency (LALO), Wison disease,
hypobetaipoproteinemia and inbom errors of metabolism, Including hepatis © vius (HCV), malnutrition, cei disease, and human immunodeficiency virus (HV).
1 Rinela ME et al. Ann Hopatol 2024,29:101133.
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Copyright © 2000-2024, PeerView
The Scope of MASLD and MASH as
Metabolic Diseases and Underlying Causes
Rohit Loomba, MD, MHSc
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Director, MASLD Research Center
Adjunct Professor, Division of Epidemiology
University of California at San Diego
La Jolla, California
E
3
Copyright © 2000-2024, PeerView
Metabolic Diseases and Underlying Causes
Rohit Loomba, MD, MHSc
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Director, MASLD Research Center
Adjunct Professor, Division of Epidemiology
University of California at San Diego
La Jolla, California
E
3
Copyright © 2000-2024, PeerView
What Is Metabolic Dysfunction-Associated Steatotic
Liver Disease (MASLD)?12
The term MASLD encompasses a spectrum ranging from histologic documentation
of “simple steatosis” (in >5% of hepatocytes; metabolic dysfunction-associated fatty liver, or MAFL) to metabolic
dysfunction-associated steatohepatitis (MASH), which is histologic evidence of hepatic steatosis, lobular
inflammation, hepatocyte ballooning with or without pericellular fibrosis, and/or Mallory-Denk bodies
MASH can progre:
to cirrhosis or
carcinoma (HC
and may r
ES
Normal Steatosis MASH MASH with
advanced fibrosis
1.Kabarra K et al. Endoer Connect. 2021:10:R240-R247. 2. Younassi ZM et al. Hepatology. 2018:68:349-360. PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Liver Disease (MASLD)?12
The term MASLD encompasses a spectrum ranging from histologic documentation
of “simple steatosis” (in >5% of hepatocytes; metabolic dysfunction-associated fatty liver, or MAFL) to metabolic
dysfunction-associated steatohepatitis (MASH), which is histologic evidence of hepatic steatosis, lobular
inflammation, hepatocyte ballooning with or without pericellular fibrosis, and/or Mallory-Denk bodies
MASH can progre:
to cirrhosis or
carcinoma (HC
and may r
ES
Normal Steatosis MASH MASH with
advanced fibrosis
1.Kabarra K et al. Endoer Connect. 2021:10:R240-R247. 2. Younassi ZM et al. Hepatology. 2018:68:349-360. PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Diagnosis of MASLD!
Steatotic Liver Disease
(Hepatic steatosis identified by imaging or bio;
the patient me
the cardiometabolic criteria?
Yes No
1. Rinela ME eta. Ann Hepat 2024:29:101133, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Steatotic Liver Disease
(Hepatic steatosis identified by imaging or bio;
the patient me
the cardiometabolic criteria?
Yes No
1. Rinela ME eta. Ann Hepat 2024:29:101133, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Cardiometabolic Criteria!
Adult Criteria Pediatric Criteria
At least 1 out of 5 At least 1 out of 5
BMI 225 kg/m? (23 Asia) OR WC >94 cm (men) and O BMI 285th percentile for age/sex (BMI z-score = +1) OR
80 cm (women) OR ethnicity-adjusted equivalent WC >95th percentile OR ethnicity-adjusted equivalent
Q Fasting serum glucose 25.6mmol/L (100 mg/dL) OR Q Fasting serum glucose 25.6 mmol/L (2100 mg/dL) OR
2-hour postoad glucose level 27.8 mmol/L (2140 mg/dL) | serum glucose 211.1 mmol/L (2200 mg/dL) OR 2-hour
OR HbAtc 25.7% (39 mmol/L) OR type 2 diabetes OR post-load glucose levels > 7.8 mmol (140 mg/dL) OR
treatment for type 2 diabetes HbAïc 25.7% (39 mmol/L) OR already diagnoseditreated
Blood pressure 2130/85 mmHg OR specific en 2 recs
antihypertensive drug treatment A Blood pressure age <13 years, BP 295th percentile OR
: 2130/80 mmHg (whichever is lower); age 213 years,
Q Plasma triglycerides 1.7mmolL (150 mg/dL) OR asl 2
pida né at (150 mold), 130/85 mmHg OR specific antihypertensive
drug treatment
enr ae mg/dL; men) | O Plasma triglycerides ages <10 years, 21.15 mmol/L
ipa lowering rentrent (2100mg/dL); age 210 years, 21.70 mmol/L (2150 mg/dL)
OR lipid-lowering treatment
Plasma HDL-cholesterol 51.0 mmol/L (40 mg/dL) OR
lipid-lowering treatment
1. Rineia ME eta. Ann Hepat 2024:29:101133 PeerView.com
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Adult Criteria Pediatric Criteria
At least 1 out of 5 At least 1 out of 5
BMI 225 kg/m? (23 Asia) OR WC >94 cm (men) and O BMI 285th percentile for age/sex (BMI z-score = +1) OR
80 cm (women) OR ethnicity-adjusted equivalent WC >95th percentile OR ethnicity-adjusted equivalent
Q Fasting serum glucose 25.6mmol/L (100 mg/dL) OR Q Fasting serum glucose 25.6 mmol/L (2100 mg/dL) OR
2-hour postoad glucose level 27.8 mmol/L (2140 mg/dL) | serum glucose 211.1 mmol/L (2200 mg/dL) OR 2-hour
OR HbAtc 25.7% (39 mmol/L) OR type 2 diabetes OR post-load glucose levels > 7.8 mmol (140 mg/dL) OR
treatment for type 2 diabetes HbAïc 25.7% (39 mmol/L) OR already diagnoseditreated
Blood pressure 2130/85 mmHg OR specific en 2 recs
antihypertensive drug treatment A Blood pressure age <13 years, BP 295th percentile OR
: 2130/80 mmHg (whichever is lower); age 213 years,
Q Plasma triglycerides 1.7mmolL (150 mg/dL) OR asl 2
pida né at (150 mold), 130/85 mmHg OR specific antihypertensive
drug treatment
enr ae mg/dL; men) | O Plasma triglycerides ages <10 years, 21.15 mmol/L
ipa lowering rentrent (2100mg/dL); age 210 years, 21.70 mmol/L (2150 mg/dL)
OR lipid-lowering treatment
Plasma HDL-cholesterol 51.0 mmol/L (40 mg/dL) OR
lipid-lowering treatment
1. Rineia ME eta. Ann Hepat 2024:29:101133 PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
Diagnosis of MASLD!
Steatotic Liver Disease
sis identified by imagin
(Hepat bioy
atient meet any of
cardiometabolic criteria?
of steatos
sf alcohol intake) or
other combination
1.Rinela ME eta. Ann Hepat 2024:29:101133 PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Steatotic Liver Disease
sis identified by imagin
(Hepat bioy
atient meet any of
cardiometabolic criteria?
of steatos
sf alcohol intake) or
other combination
1.Rinela ME eta. Ann Hepat 2024:29:101133 PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
MASLD Epidemiology and Rising Prevalence
Globally, the overall prevalence of MASLD is 32%,
while the prevalence of MASH is between 12% and 14%!
Geographical Differences in the Prevalence of MASLD Worldwide?*
+ Prevalence is
significantly higher y nn 5; In one study, ~70% of
among those with T2D E DE À = x patients with T2D have
and visceral obesity*7 = Z MASLD (steatosis) and
+ Among those with ay : 15% have clinically
obesity, the prevalence b 3 significant liver fibrosis
of MASH is 25% to 4 (stages 2F2), consistent
30%, while ~30% to Er) ep = with other recent population
40% of people with ver disease based studies in the
diabetes have MASH*7 ER we United States°.19
Eto
DEEE
mem
1. Harrison SA et al. Hopatal 2021:75:284-201. 2. Teng ML et al. Cin Mol Hepatal.2023:29(suppl) 532-542. 3. Riaz K et al. Lancet Gastroenterol Hepatol.
2022.7:851-861. 4. Younossi ZM et al. Hepatology. 2016:64:73-84. 5. Younossi ZM et al. J Hepatol. 2019:71.783-801. 6. Kim D etal. Hepat In 2019,13:205-213.
7, Kanwal F et al. Cin Gastroenterol Hepote.2016:14:301-8.e1-2 8. Lomonaco R et al Diabetes Caro. 2021,44:300-406. 9. Ciarduo Set a. Diabetes Car. PeerViéw.
2021:44:519-525. 10, Barb D etal. Obesity (Siver Spring). 2021.29-1960-1980. 'eerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
Globally, the overall prevalence of MASLD is 32%,
while the prevalence of MASH is between 12% and 14%!
Geographical Differences in the Prevalence of MASLD Worldwide?*
+ Prevalence is
significantly higher y nn 5; In one study, ~70% of
among those with T2D E DE À = x patients with T2D have
and visceral obesity*7 = Z MASLD (steatosis) and
+ Among those with ay : 15% have clinically
obesity, the prevalence b 3 significant liver fibrosis
of MASH is 25% to 4 (stages 2F2), consistent
30%, while ~30% to Er) ep = with other recent population
40% of people with ver disease based studies in the
diabetes have MASH*7 ER we United States°.19
Eto
DEEE
mem
1. Harrison SA et al. Hopatal 2021:75:284-201. 2. Teng ML et al. Cin Mol Hepatal.2023:29(suppl) 532-542. 3. Riaz K et al. Lancet Gastroenterol Hepatol.
2022.7:851-861. 4. Younossi ZM et al. Hepatology. 2016:64:73-84. 5. Younossi ZM et al. J Hepatol. 2019:71.783-801. 6. Kim D etal. Hepat In 2019,13:205-213.
7, Kanwal F et al. Cin Gastroenterol Hepote.2016:14:301-8.e1-2 8. Lomonaco R et al Diabetes Caro. 2021,44:300-406. 9. Ciarduo Set a. Diabetes Car. PeerViéw.
2021:44:519-525. 10, Barb D etal. Obesity (Siver Spring). 2021.29-1960-1980. 'eerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
Natural History of MASLD'
30% to 40% of patients.
20% to 30% 20% stage 3 win olthons de
over 3 years over 2 years from liver disease
Fibrosis Cirrhosis
MASLD ASH
13-16 million
60-80 milion 15.20 miion
Americans Stage 1-3
1-2 million
1.5% to 2%
per year
Liver failure Liver death
Risk of death in MASH
1: Cardiovascular disease
2: Cancer
3: Liver
Liver transplant
Multiple sources: 40+ studies
PeerView.com
1. Loomba Ret al. Col 2021:184:2537:2564,
Copyright © 2000-2024, PeerView
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30% to 40% of patients.
20% to 30% 20% stage 3 win olthons de
over 3 years over 2 years from liver disease
Fibrosis Cirrhosis
MASLD ASH
13-16 million
60-80 milion 15.20 miion
Americans Stage 1-3
1-2 million
1.5% to 2%
per year
Liver failure Liver death
Risk of death in MASH
1: Cardiovascular disease
2: Cancer
3: Liver
Liver transplant
Multiple sources: 40+ studies
PeerView.com
1. Loomba Ret al. Col 2021:184:2537:2564,
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MASLD Is Part of a Systemic Disease With Strong
Associations With Components of Metabolic Syndrome‘?
+ Hypertension
2 Penpneral vascular dseme q
2 Coronary artery o €
+ Moore dysfunction
© Hear fare wth preserved =
ection fraction
Circulating factors
Insuin resistance, teasing + Cytokines
toimpared tasting gueose _4===}"»| + Proinfammatory
MASLO extracelular vesicles
Hee + Hepatokines
+ Adipokines
B-cell dysfunction
120
+ Intammaton
+ Insuin resistance, leasing +
to dysregulated lipolysis H
+ Vascular injury H
+ Chronic Kidney disease #7
1. Chakravarthy MV, Neuschwander-Te BA. Endocrine Diabetes Metab. 2020600112. nay
2 ntpsverfoundatonergiver-iseasesatty ver-dseaseInonalcohole seatohepatts- MASMMASH-causes-rsk factors PeerView.com
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Associations With Components of Metabolic Syndrome‘?
+ Hypertension
2 Penpneral vascular dseme q
2 Coronary artery o €
+ Moore dysfunction
© Hear fare wth preserved =
ection fraction
Circulating factors
Insuin resistance, teasing + Cytokines
toimpared tasting gueose _4===}"»| + Proinfammatory
MASLO extracelular vesicles
Hee + Hepatokines
+ Adipokines
B-cell dysfunction
120
+ Intammaton
+ Insuin resistance, leasing +
to dysregulated lipolysis H
+ Vascular injury H
+ Chronic Kidney disease #7
1. Chakravarthy MV, Neuschwander-Te BA. Endocrine Diabetes Metab. 2020600112. nay
2 ntpsverfoundatonergiver-iseasesatty ver-dseaseInonalcohole seatohepatts- MASMMASH-causes-rsk factors PeerView.com
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Epidemiology and Prevalence of the Relationship Between
Metabolic Conditions and MASLD'
Among adults aged 250 years with type 2 diabetes (N = 540)
80 100
80 mObese
60
= & = Nonobese
g 4
E Es
3 4
5 40 s
E 3
a ge 40
é
20
20
0
MASLD At-Risk MASH Cirrhosis. MASLD At-Risk MASH Cirrhosis
1. Mita Net al Alimant Pharmacol Ther. 2024 [Epub ahead of pit PeerView.com
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Metabolic Conditions and MASLD'
Among adults aged 250 years with type 2 diabetes (N = 540)
80 100
80 mObese
60
= & = Nonobese
g 4
E Es
3 4
5 40 s
E 3
a ge 40
é
20
20
0
MASLD At-Risk MASH Cirrhosis. MASLD At-Risk MASH Cirrhosis
1. Mita Net al Alimant Pharmacol Ther. 2024 [Epub ahead of pit PeerView.com
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Interconnections Between MASLD, T2D, and the Metabolic Syndrome
and Risk of CVD and Cardiac/Arrhythmic Complications*
+
MASLD
T2D and the CVD and other
(hepatic steatosis
and fibro:
metabolic syndrome cardiac diseases
+
Established and Potent isk Factors for CVD/Cardiac Diseases in MASLD
+ Atherogenic dyslipidemia + Steatotic hepatocyte-derived extracellular vesicles
+ T2D + Plasminogen activator inhibitor-1
+ Other metabolic syndrome features, such as + Gut-derived factors (such as modified bile acids,
hypertension and abdominal obesity trimethylamine oxide, lipopolysaccharide, aromatic acid
+ Proinflammatory cytokines, such as C-reactive metabolites, p-Cresyl sulphate, indoxyl sulphate, short-chain
protein, IL-6, and fetuin-A fatty acids, and incretins)
+ Reactive oxygen species + MASLD-related genotypes, such as GCKR variants
1.Loomba Rt al Cl 2021:184:2537-2664. PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
and Risk of CVD and Cardiac/Arrhythmic Complications*
+
MASLD
T2D and the CVD and other
(hepatic steatosis
and fibro:
metabolic syndrome cardiac diseases
+
Established and Potent isk Factors for CVD/Cardiac Diseases in MASLD
+ Atherogenic dyslipidemia + Steatotic hepatocyte-derived extracellular vesicles
+ T2D + Plasminogen activator inhibitor-1
+ Other metabolic syndrome features, such as + Gut-derived factors (such as modified bile acids,
hypertension and abdominal obesity trimethylamine oxide, lipopolysaccharide, aromatic acid
+ Proinflammatory cytokines, such as C-reactive metabolites, p-Cresyl sulphate, indoxyl sulphate, short-chain
protein, IL-6, and fetuin-A fatty acids, and incretins)
+ Reactive oxygen species + MASLD-related genotypes, such as GCKR variants
1.Loomba Rt al Cl 2021:184:2537-2664. PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Pathogenesis and Progression of MASLD!
Genetic Metabolic Gut microbiome immune-mediated
susceptibility dysfunction ‘composition ‘mechanisms
DOU UD
Driving factors
n
for progres:
Healthy liver MASLD Cirrhosis
20%-30% 10%-30% 10%-20% 4%-27%
> > ad zy
r=; 7
First Hit ‘Second Hit Cirrhotic A ‘Neoplastic ra
Hepatic triglyceride Lipotoxicity + Hepatocyte apoptosis + Oncogenic
accumulation ROS generation + Hepatic inflammation transformation
Obesity ER stress + ECM deposition + Cancer survival
T2DM (insulin resistance) ‘Mitochondrial (fibrosis) and proliferation
Inactive lifestyle dysfunction
Disease pathogenesis
1. Wang Y et al. Front Pharmacol. 2024; 14:1336216, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Genetic Metabolic Gut microbiome immune-mediated
susceptibility dysfunction ‘composition ‘mechanisms
DOU UD
Driving factors
n
for progres:
Healthy liver MASLD Cirrhosis
20%-30% 10%-30% 10%-20% 4%-27%
> > ad zy
r=; 7
First Hit ‘Second Hit Cirrhotic A ‘Neoplastic ra
Hepatic triglyceride Lipotoxicity + Hepatocyte apoptosis + Oncogenic
accumulation ROS generation + Hepatic inflammation transformation
Obesity ER stress + ECM deposition + Cancer survival
T2DM (insulin resistance) ‘Mitochondrial (fibrosis) and proliferation
Inactive lifestyle dysfunction
Disease pathogenesis
1. Wang Y et al. Front Pharmacol. 2024; 14:1336216, PeerView.com
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Potential Therapeutic Targets for MASH’
1. Dufour eta. Gut 2022:71:2129-2104 PeerView.com
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1. Dufour eta. Gut 2022:71:2129-2104 PeerView.com
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GLP-1 Action in Pancreas, Liver, and Gut!2
4 Pancreas protein and enzyme biosynthesis
4 Pancreatic enzyme secretion
pou QE"
insulin secretion
4 Insulin biosynthesis:
y Apoptosis
EEC
1. Drucker DJ. Col Metab. 2018:27:740-756. 2. Wang X-C et al. World J Gastroentorol.201420-14821-14830.
PeerView.com/RNX827
Liver
+ Reduces hepatic steatosis
by modulating the insulin
signaling pathway
Reduces hepatocyte steatosis
by enhancing the unfolder
protein response and promoting
macroautophagy
Protect hepatocytes from
fatty acid-related death by
inhibiting dysfunctional ER
stress response
PeerView.com
Copyright © 2000-2024, PeerView
4 Pancreas protein and enzyme biosynthesis
4 Pancreatic enzyme secretion
pou QE"
insulin secretion
4 Insulin biosynthesis:
y Apoptosis
EEC
1. Drucker DJ. Col Metab. 2018:27:740-756. 2. Wang X-C et al. World J Gastroentorol.201420-14821-14830.
PeerView.com/RNX827
Liver
+ Reduces hepatic steatosis
by modulating the insulin
signaling pathway
Reduces hepatocyte steatosis
by enhancing the unfolder
protein response and promoting
macroautophagy
Protect hepatocytes from
fatty acid-related death by
inhibiting dysfunctional ER
stress response
PeerView.com
Copyright © 2000-2024, PeerView
Making Informed Management Decisions
in MASLD/MASH
Noninvasive Monitoring of Disease Progression
Alina M. Allen, MD, MS
Associate Professor of Medicine
Director, MASLD Clinic
Division of Gastroenterology and Hepatology
Mayo Clinic
Rochester, Minnesota
Copyright © 2000-2024, PeerView
in MASLD/MASH
Noninvasive Monitoring of Disease Progression
Alina M. Allen, MD, MS
Associate Professor of Medicine
Director, MASLD Clinic
Division of Gastroenterology and Hepatology
Mayo Clinic
Rochester, Minnesota
Copyright © 2000-2024, PeerView
Risk Factors for MASLD/MASH Progression‘?
Overweight/T2D/metabolic syndrome
Hypertension
Elevated triglycerides/lipids
Intestinal microbiota
22 metabolic risk factors
Incidental finding of hepatic steatosis or elevated
aminotransferases
Advanced MASLD Fibrosis Score or fibrosis on biopsy
(METAVIR stage 3/4)
Steatosis on imaging
1. Kanwal F et a. Gastroenterology. 2021;161:1657-1660. 2. Schuppan D et al. J Hepatol. 2018;68:238-250. 3, Jarvis H et al. PLoS Med. 2020.17:e1003100, PeerView.com
PeerView.com/RNX827 Copyright 24, Pi
Overweight/T2D/metabolic syndrome
Hypertension
Elevated triglycerides/lipids
Intestinal microbiota
22 metabolic risk factors
Incidental finding of hepatic steatosis or elevated
aminotransferases
Advanced MASLD Fibrosis Score or fibrosis on biopsy
(METAVIR stage 3/4)
Steatosis on imaging
1. Kanwal F et a. Gastroenterology. 2021;161:1657-1660. 2. Schuppan D et al. J Hepatol. 2018;68:238-250. 3, Jarvis H et al. PLoS Med. 2020.17:e1003100, PeerView.com
PeerView.com/RNX827 Copyright 24, Pi
Newer Noninvasive Tests vs Invasive Methods
for Advanced Fibrosis‘?
Method Benefits Limitation:
Highly accurate vs other noninvasive markers = R
8 AnArLo Convenient dvd aies age <8 y and 28 y
Fibrosis Score Uses routine clinical data DE
Erosion negative peace vals Large proportion of indeterminate scores.
Reliability/accuracy reduced by BMI
Point-of-
Noninvasive Liver siliness N ei an sit >30 kg/m?, high ALT, cholestasis, congestion,
roma tees crac nonfasting state, and operator experience
FibroScan/VCTE High negative predictive value Cannot predict MASH accurately
a Highly accurate vs other noninvasive methods Not widely available
2
en, Can be used in BMI up to 35 kg/m ‘Cannot predict MASH accurately
Time consuming
Painful
‘Sampling error
Invasive Liver biopsy Gold standard Cost
Complication risk
Not appropriate or possible
for all patients with MASLD
4. Kanwal F et al Gast 2021:161:16571660. 2. Balakrishnan M, Loomba R. J Cin Gastroenterol, 202054:107-113. E
3. Sam Va a Word Casta! DIE ZBATEATE PeerView.com
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for Advanced Fibrosis‘?
Method Benefits Limitation:
Highly accurate vs other noninvasive markers = R
8 AnArLo Convenient dvd aies age <8 y and 28 y
Fibrosis Score Uses routine clinical data DE
Erosion negative peace vals Large proportion of indeterminate scores.
Reliability/accuracy reduced by BMI
Point-of-
Noninvasive Liver siliness N ei an sit >30 kg/m?, high ALT, cholestasis, congestion,
roma tees crac nonfasting state, and operator experience
FibroScan/VCTE High negative predictive value Cannot predict MASH accurately
a Highly accurate vs other noninvasive methods Not widely available
2
en, Can be used in BMI up to 35 kg/m ‘Cannot predict MASH accurately
Time consuming
Painful
‘Sampling error
Invasive Liver biopsy Gold standard Cost
Complication risk
Not appropriate or possible
for all patients with MASLD
4. Kanwal F et al Gast 2021:161:16571660. 2. Balakrishnan M, Loomba R. J Cin Gastroenterol, 202054:107-113. E
3. Sam Va a Word Casta! DIE ZBATEATE PeerView.com
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Exploring Noninvasive Tests:
Fibrosis-4 (FIB-4) Index!
Fibrosis-4 (FIB-4) Index
Predicts advanced fibrosis in the liver
+ Age (years)
+ ALT (U/L)
+ AST (U/L)
+ Platelet count (x 10%L)
Understanding the score
Score <1.3 Score >2.67
Rules out Predicts
advanced
fibi
advanced
fibrosis
(Sn: 74%
Indeterminate
index is superior to seven other
noninvasive markers of fibrosis
1. Shah AG et al. Gin Gastroenterol Hepatol 2008:7:1104-1112.
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Fibrosis-4 (FIB-4) Index!
Fibrosis-4 (FIB-4) Index
Predicts advanced fibrosis in the liver
+ Age (years)
+ ALT (U/L)
+ AST (U/L)
+ Platelet count (x 10%L)
Understanding the score
Score <1.3 Score >2.67
Rules out Predicts
advanced
fibi
advanced
fibrosis
(Sn: 74%
Indeterminate
index is superior to seven other
noninvasive markers of fibrosis
1. Shah AG et al. Gin Gastroenterol Hepatol 2008:7:1104-1112.
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Exploring Noninvasive Tests:
Enhanced Liver Fibrosis (ELF) Score‘?
Proprietary Blood Test That Delivers
Information on Liver Fibrosis Severity
Algorithm incorporating three common
serum biomarkers
+ HA (hyaluronic acid)
+ PIIINP (amino-terminal propeptide
of type Ill procollagen)
+ TIMP-1 (tissue inhibitor of metalloproteinase-1)
Understanding the score
Score 7.7 Score 9.8
Predicts fibrosis
Score 11.3
Predicts cirrhosis
Sp: 98%) (Sn: 83%; Sp: 97%)
1. Lienghagen Ret al. J Hopatot 2013:50:236-242. 2. Fagan KJ etal Liver In 2015;35:1672-1681,
PeerView.com/RNX827
14
ELF Score
o 1 2 3 4
Modified METAVIR Fibrosis Stage
+ ELF 29.8 is associated with advanced fibrosis
PeerView.com
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Enhanced Liver Fibrosis (ELF) Score‘?
Proprietary Blood Test That Delivers
Information on Liver Fibrosis Severity
Algorithm incorporating three common
serum biomarkers
+ HA (hyaluronic acid)
+ PIIINP (amino-terminal propeptide
of type Ill procollagen)
+ TIMP-1 (tissue inhibitor of metalloproteinase-1)
Understanding the score
Score 7.7 Score 9.8
Predicts fibrosis
Score 11.3
Predicts cirrhosis
Sp: 98%) (Sn: 83%; Sp: 97%)
1. Lienghagen Ret al. J Hopatot 2013:50:236-242. 2. Fagan KJ etal Liver In 2015;35:1672-1681,
PeerView.com/RNX827
14
ELF Score
o 1 2 3 4
Modified METAVIR Fibrosis Stage
+ ELF 29.8 is associated with advanced fibrosis
PeerView.com
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Head-to-Head Comparison Between MEFIB, MAST, and
FAST for Detecting Significant Fibrosis in MASLD'
Study population
563 biopsy-proven MASLD patients from two
cohorts in the United States and Japan
OS cohort ‘YorSnama cohort
n=249 nat
Endpoints
Diagnostic models for detecting significant
fibrosis and “at risk” MASH defined
NAS 24 and fibrosis stage 22
Procedures performed
2D MRE, MRI-PDFF, VCTE, CAP, FIB-4, liver histology
Models assessed
MEFIB (includes MRE and FIB-4)
Rule-in: 23.3 kPa and FIB-4 21.6
Rule-out: MRE <3.3 kPa and FIB-4 <1.6
vs
MAST (includes MRI-PDFF, MRE, and AST)
Rule-in: >0.242
Rule-out: <0.165
vs
FAST (includes CAP, LSM by VCTE, and AST)
Rule-in: 20.67
Rule-out: <0.35
1. Kim 8K eta. J Hepatol. 2022:77:1482-1490.
PeerView.com/RNX827
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Copyright
FAST for Detecting Significant Fibrosis in MASLD'
Study population
563 biopsy-proven MASLD patients from two
cohorts in the United States and Japan
OS cohort ‘YorSnama cohort
n=249 nat
Endpoints
Diagnostic models for detecting significant
fibrosis and “at risk” MASH defined
NAS 24 and fibrosis stage 22
Procedures performed
2D MRE, MRI-PDFF, VCTE, CAP, FIB-4, liver histology
Models assessed
MEFIB (includes MRE and FIB-4)
Rule-in: 23.3 kPa and FIB-4 21.6
Rule-out: MRE <3.3 kPa and FIB-4 <1.6
vs
MAST (includes MRI-PDFF, MRE, and AST)
Rule-in: >0.242
Rule-out: <0.165
vs
FAST (includes CAP, LSM by VCTE, and AST)
Rule-in: 20.67
Rule-out: <0.35
1. Kim 8K eta. J Hepatol. 2022:77:1482-1490.
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Copyright
Head-to-Head Comparison Between MEFIB, MAST, and
FAST for Detecting Significant Fibrosis in MASLD'
MEFIB is superior to MAST or FAST
for the detection of significant fibrosis
Mere
os
Eu
3
Bos u
02 ere
10 08 08 04
Specificity
MEFIB has a high PPV (95%) and a high NPV (90%) to detect
1. Kim BK etal. J Hepatol. 2022:77:1482-1490,
PeerView.com/RNX827
10
os
os
Sensitivity
o
10 08 08 08
Specificity
and may be used as a two-step strategy
MEFIB is superior to MAST or FAST
for the detection of “at risk” MASH
mere
4
r L auroc pe en r
Fos mene TETE
02 wre orwosnor ON
Paste —o1a7(0010075) «mi
2 0
PeerView.com
Copyright © 2000-2024, PeerView
FAST for Detecting Significant Fibrosis in MASLD'
MEFIB is superior to MAST or FAST
for the detection of significant fibrosis
Mere
os
Eu
3
Bos u
02 ere
10 08 08 04
Specificity
MEFIB has a high PPV (95%) and a high NPV (90%) to detect
1. Kim BK etal. J Hepatol. 2022:77:1482-1490,
PeerView.com/RNX827
10
os
os
Sensitivity
o
10 08 08 08
Specificity
and may be used as a two-step strategy
MEFIB is superior to MAST or FAST
for the detection of “at risk” MASH
mere
4
r L auroc pe en r
Fos mene TETE
02 wre orwosnor ON
Paste —o1a7(0010075) «mi
2 0
PeerView.com
Copyright © 2000-2024, PeerView
2023 AASLD MASLD Practice Guidance Recommends
the Use of Noninvasive Tests!
Clinical Suspicion for Fatty Liver Disease
CES
+ Reviewiperform primary/secondary risk assessment
+ Consider additional stratification with MRE, eT!
Gtmepatology
FIB-4>2.67
Consider referral
Intermediate!
high risk
PCP follow-up
Reassess periodically Secondary risk assessment
+ Flor
Consider
liver biopsy
Suspect
cirrhosis
anced liv
Refer for further
Cirrosis-based
management
1. ine ME et al. Hopatlogy. 2023:77:1707-1836. PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
the Use of Noninvasive Tests!
Clinical Suspicion for Fatty Liver Disease
CES
+ Reviewiperform primary/secondary risk assessment
+ Consider additional stratification with MRE, eT!
Gtmepatology
FIB-4>2.67
Consider referral
Intermediate!
high risk
PCP follow-up
Reassess periodically Secondary risk assessment
+ Flor
Consider
liver biopsy
Suspect
cirrhosis
anced liv
Refer for further
Cirrosis-based
management
1. ine ME et al. Hopatlogy. 2023:77:1707-1836. PeerView.com
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Making Informed Management Decisions
in MASLD/MASH
Novel and Emerging Pharmacologic Agents for MASLD/MASH
Rohit Loomba, MD, MHSc
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Director, MASLD Research Center
Adjunct Professor, Division of Epidemiology
University of California at San Diego
La Jolla, California
t © 2000-2024, PeerView
in MASLD/MASH
Novel and Emerging Pharmacologic Agents for MASLD/MASH
Rohit Loomba, MD, MHSc
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Director, MASLD Research Center
Adjunct Professor, Division of Epidemiology
University of California at San Diego
La Jolla, California
t © 2000-2024, PeerView
AGA Risk-Based Guidelines
for the Management of MASLD/MASH!
Low Risk Intermediate Risk High Risk
FIB-4 <1.3 or
t available
Management by hepatologist with multidisciplinary team
dietitian, endocrinologist, cardiologist, others
Lifestyle intervention Yes Yes Yes
Yes; greater need for structured
Weight loss Yes; may benefi from structured = Yes; strong need for structured
recommended weight loss programs, anti-obesity Abell celeb ainsi, ‘weight loss programs, anti-obesity
if overweight or obese medications, bariatric surgery phe medications, bariatric surgery
Pharmacotherapy
press Not recommended Yes Yes
CVD risk reduction Yes Yes Yes
Prefer medications = ;
Diabetes care Siren vi eye MASH eft mediators vit fac in
(pioglitazone, GLP-1 RA) (Grae een SEEPS)
PeerView.
1. Kamal Fetal. Gastoentoroogy 2021:1611057-1660. ew.com
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for the Management of MASLD/MASH!
Low Risk Intermediate Risk High Risk
FIB-4 <1.3 or
t available
Management by hepatologist with multidisciplinary team
dietitian, endocrinologist, cardiologist, others
Lifestyle intervention Yes Yes Yes
Yes; greater need for structured
Weight loss Yes; may benefi from structured = Yes; strong need for structured
recommended weight loss programs, anti-obesity Abell celeb ainsi, ‘weight loss programs, anti-obesity
if overweight or obese medications, bariatric surgery phe medications, bariatric surgery
Pharmacotherapy
press Not recommended Yes Yes
CVD risk reduction Yes Yes Yes
Prefer medications = ;
Diabetes care Siren vi eye MASH eft mediators vit fac in
(pioglitazone, GLP-1 RA) (Grae een SEEPS)
PeerView.
1. Kamal Fetal. Gastoentoroogy 2021:1611057-1660. ew.com
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Establishing Treatment Goals’?
Short-Term Goals
Long-Term Goals
Reduce liver fibrosis
Prevent progression + Improve clinical
to cirrhosis outcomes by reducing
cardiovascular and
hepatic complications
1. Sanyal Ad et al. Hopatology. 2015:81:1382-1405. 2. Flozo © et al. Drugs. 2015.75:1373-1392, 3. Fiozof C etal. Hepatol Commun, 2017,1:577:56. PeerView.com
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Short-Term Goals
Long-Term Goals
Reduce liver fibrosis
Prevent progression + Improve clinical
to cirrhosis outcomes by reducing
cardiovascular and
hepatic complications
1. Sanyal Ad et al. Hopatology. 2015:81:1382-1405. 2. Flozo © et al. Drugs. 2015.75:1373-1392, 3. Fiozof C etal. Hepatol Commun, 2017,1:577:56. PeerView.com
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Comparative Guidelines!
AASLD 2023
+ Semaglutide for T2D/obesity in patients with MASH
+ Pioglitazone to improve MASH
+ Vitamin E for MASH without T2D
+ Do NOT use for MASH: metformin, ursodeoxycholic acid,
dipeptidyl peptidase-4, statins, and silymarin
+ Low risk: pharmacotherapy not recommended
+ Indeterminate risk: individualize therapy
+ High risk: recommend pharmacotherapy
EASL-EASD-EASO 2016
For MASH with fibrosis/early MASH with high risk of progression
+ Metformin: insufficient evidence
+ Pioglitazone: for MASH with T2D (off-label outside T2D)
itial data favorable; insufficient evidence
+ Vitamin E: for adults who are noncirrhotic nondiabetic with
MASH; more data needed
+ UDCA: no effect observed
+ Omega-3 fatty acids: insufficient data to support use
+ Statins: no benefit or harm to liver disease
NICE 2016
For MASH with fibrosis
Metformin: not mentioned
Pioglitazone: consider use regardless of
GLP-1 RAs: not mentioned
UDCA: not mentioned
Omega-3 fatty acids: not recommended
Statins: continue use if already taking; stop if liver enzymes
elevate (x2 within 3 months)
Vitamin E: consider use regardless of diabetes status
1. Rinela ME tal. Hepatology. 2023:77:1797-1895.. 2. Kanwal Fetal. Gastroenterology. 2021:181:1857-1860. 3. European Association fr he Study ofthe Liver et a.
J'Hopatol 2016:54:1388-1402. 4, Basu R et al. Mayo Cin Proc. 2022,97:1700-1716. 5. aps New nee or uk/gudance/ng40iresources/nonalcoholc-taiy.hver-
‘isease-nafis-assesament.and management pof-1837461227401
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AASLD 2023
+ Semaglutide for T2D/obesity in patients with MASH
+ Pioglitazone to improve MASH
+ Vitamin E for MASH without T2D
+ Do NOT use for MASH: metformin, ursodeoxycholic acid,
dipeptidyl peptidase-4, statins, and silymarin
+ Low risk: pharmacotherapy not recommended
+ Indeterminate risk: individualize therapy
+ High risk: recommend pharmacotherapy
EASL-EASD-EASO 2016
For MASH with fibrosis/early MASH with high risk of progression
+ Metformin: insufficient evidence
+ Pioglitazone: for MASH with T2D (off-label outside T2D)
itial data favorable; insufficient evidence
+ Vitamin E: for adults who are noncirrhotic nondiabetic with
MASH; more data needed
+ UDCA: no effect observed
+ Omega-3 fatty acids: insufficient data to support use
+ Statins: no benefit or harm to liver disease
NICE 2016
For MASH with fibrosis
Metformin: not mentioned
Pioglitazone: consider use regardless of
GLP-1 RAs: not mentioned
UDCA: not mentioned
Omega-3 fatty acids: not recommended
Statins: continue use if already taking; stop if liver enzymes
elevate (x2 within 3 months)
Vitamin E: consider use regardless of diabetes status
1. Rinela ME tal. Hepatology. 2023:77:1797-1895.. 2. Kanwal Fetal. Gastroenterology. 2021:181:1857-1860. 3. European Association fr he Study ofthe Liver et a.
J'Hopatol 2016:54:1388-1402. 4, Basu R et al. Mayo Cin Proc. 2022,97:1700-1716. 5. aps New nee or uk/gudance/ng40iresources/nonalcoholc-taiy.hver-
‘isease-nafis-assesament.and management pof-1837461227401
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Data on Pharmacologic Agents for MASLD/MASH!
proved pharmacologic agent for MAS!
isk patients + Lifestyle modification + control of CVD and T2D
ee © + Lifestyle modification + workup (to confirm fibrosis stage) + referral
Vitamin E (800 1U/d)
+ Without T2D, large RCT: improved steatohepatitis
+ With T2D, small RCT: no benefit
+ With or without T2D, retrospective study: transplant-free survival and lower rates of
High-risk hepatic decompensation
patients Pioglitazone
+ 5 RCTs: improves liver histology, steatohepatitis with MASH with or without T2D
Thiazolidinedione
+ Meta-analysis with or without T2D: resolution of MASH and reversal of advanced fibrosis
+ Weight gain
1.Kanwal F et al. Gastroenterology. 2021:161:1657-1869 PeerView.com
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proved pharmacologic agent for MAS!
isk patients + Lifestyle modification + control of CVD and T2D
ee © + Lifestyle modification + workup (to confirm fibrosis stage) + referral
Vitamin E (800 1U/d)
+ Without T2D, large RCT: improved steatohepatitis
+ With T2D, small RCT: no benefit
+ With or without T2D, retrospective study: transplant-free survival and lower rates of
High-risk hepatic decompensation
patients Pioglitazone
+ 5 RCTs: improves liver histology, steatohepatitis with MASH with or without T2D
Thiazolidinedione
+ Meta-analysis with or without T2D: resolution of MASH and reversal of advanced fibrosis
+ Weight gain
1.Kanwal F et al. Gastroenterology. 2021:161:1657-1869 PeerView.com
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MASH Agents in Phase 3 Clinical Development!
Agent Target (Mechanism) Trial, Patients, and Primary Endpoint(s)
Resmetirom
Lanifibranor oxidative stress
Efruxifermin regulation
Lipotoxicity MAESTRO-NASH (n = 2,000, fibrosis stage 2-3)
(TRB agonist) + MASH resolution with 22-point improvement in NAS without worsening of fibrosis
D ESSENCE
”
Lae + Resolution of steatohepatitis and no worsening of lve fibrosis
a + Improvement in lve fibrosis and no worsening of steaiohepatitis
CI + Time-to-frst iver-related clinical event
Lipotoxicity/ NATIVS (n = ~1,000, fibrosis stage 2-3)
(PPARalBIy agonist) * Resolution of MASH and improvement of fibrosis
Metabolic pathway svNCHRONY Histology (n = ~1,000, fibrosis stage 2-3)
(GF21 mimic) + Resolution of MASH and a 21 stage improvement in fibrosis
Metabolic pathway ENLIGHTEN-Fibrosis (n = ~1,050, fibrosis stage 2-3)
regulation + Improvement of fibrosis 21 stage without worsening of MASH
(FGF21 mimic) + MASH resolution without worsening of fibrosis.
1. htps:linieatalsgovstudyNCT03000420. 2 Mtps Inia govistud y NCTOSB22181. 3 ps Iciar gowstudyNCTO4E49728, iS
ps win inca gov sud NCTOS2IS710. . hp cial» vta NCTOGS 18169, je PeerView.com
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Agent Target (Mechanism) Trial, Patients, and Primary Endpoint(s)
Resmetirom
Lanifibranor oxidative stress
Efruxifermin regulation
Lipotoxicity MAESTRO-NASH (n = 2,000, fibrosis stage 2-3)
(TRB agonist) + MASH resolution with 22-point improvement in NAS without worsening of fibrosis
D ESSENCE
”
Lae + Resolution of steatohepatitis and no worsening of lve fibrosis
a + Improvement in lve fibrosis and no worsening of steaiohepatitis
CI + Time-to-frst iver-related clinical event
Lipotoxicity/ NATIVS (n = ~1,000, fibrosis stage 2-3)
(PPARalBIy agonist) * Resolution of MASH and improvement of fibrosis
Metabolic pathway svNCHRONY Histology (n = ~1,000, fibrosis stage 2-3)
(GF21 mimic) + Resolution of MASH and a 21 stage improvement in fibrosis
Metabolic pathway ENLIGHTEN-Fibrosis (n = ~1,050, fibrosis stage 2-3)
regulation + Improvement of fibrosis 21 stage without worsening of MASH
(FGF21 mimic) + MASH resolution without worsening of fibrosis.
1. htps:linieatalsgovstudyNCT03000420. 2 Mtps Inia govistud y NCTOSB22181. 3 ps Iciar gowstudyNCTO4E49728, iS
ps win inca gov sud NCTOS2IS710. . hp cial» vta NCTOGS 18169, je PeerView.com
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Resmetirom: MAESTRO-NASH Phase 3 Trial in Patients
With NASH With F1B, F2, or F3 Liver Fibrosis!
Resmetirom is the only treatment approved by the FDA for treatment of NASH wi
F2 or F3
rosis
NASH Resolution Wi Fibrosis Improvement by 21 Stage Change in LDL Cholesterol
No Worsening of Fibrosis With No Worsening Level at Week 24, %
of NAFLD Activity Score
” Pe Peon 197 pe p<
7 72
¿> 259 a” 3
¡25 #25 a
H B E
El E
3” =” 2
& ES [3
15 15 ES
> 10 2
6 -
€
ot of 20
Placebo Resmetiom Resmetirom rer Placebo Resmelirom Resmetirom
(n=318) 80mg 100 mg (n=318) 100 mg (n=321) 60mg 100mg
(n=316) — (n=321) ao cad (n=322) — (n=323)
1. Harrison SA et aN Engl J Med, 2024:300 07-500, PeerView.com
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With NASH With F1B, F2, or F3 Liver Fibrosis!
Resmetirom is the only treatment approved by the FDA for treatment of NASH wi
F2 or F3
rosis
NASH Resolution Wi Fibrosis Improvement by 21 Stage Change in LDL Cholesterol
No Worsening of Fibrosis With No Worsening Level at Week 24, %
of NAFLD Activity Score
” Pe Peon 197 pe p<
7 72
¿> 259 a” 3
¡25 #25 a
H B E
El E
3” =” 2
& ES [3
15 15 ES
> 10 2
6 -
€
ot of 20
Placebo Resmetiom Resmetirom rer Placebo Resmelirom Resmetirom
(n=318) 80mg 100 mg (n=318) 100 mg (n=321) 60mg 100mg
(n=316) — (n=321) ao cad (n=322) — (n=323)
1. Harrison SA et aN Engl J Med, 2024:300 07-500, PeerView.com
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Resmetirom: MAESTRO-NASH Phase 3 Trial in Patients
With NASH With F1B, F2, or F3 Liver Fibrosis!
Most Frequent Adverse Resmetirom, 80 mg Resmetirom, 100 mg Placebo
Events” (n = 322) (n = 323) ( 21)
Adverse events affecting >10% of patients in any group
Diarrhea 87 (27.0) 108 (33.4) 50 (15.6)
COVID-19 69 (21.4) 54 (16.7) 66 (20.6)
Nausea 71 (22.0) 61 (18.9) 40 (12.5)
Arthralgia 48 (14.9) 35 (10.8) 40 (12.5)
Back pain 35 (10.9) 27 (8.4) 38 (11.8)
Urinary tract infection 33 (10.2) 27 (8.4) 27 (8.4)
Fatigue 33 (10.2) 26 (8.0) 28 (8.7)
Pruritus 26 (8.1) 37 (11.5) 22 (6.9)
Vomiting 28 (8.7) 35 (10.8) 17 (6.3)
Adverse events are sted for those that occurred in more than 5% of patents in ether lnirano grup vr,
1 Harson SA et al N Engl Med. 2024390 497-508, PeerView.com
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With NASH With F1B, F2, or F3 Liver Fibrosis!
Most Frequent Adverse Resmetirom, 80 mg Resmetirom, 100 mg Placebo
Events” (n = 322) (n = 323) ( 21)
Adverse events affecting >10% of patients in any group
Diarrhea 87 (27.0) 108 (33.4) 50 (15.6)
COVID-19 69 (21.4) 54 (16.7) 66 (20.6)
Nausea 71 (22.0) 61 (18.9) 40 (12.5)
Arthralgia 48 (14.9) 35 (10.8) 40 (12.5)
Back pain 35 (10.9) 27 (8.4) 38 (11.8)
Urinary tract infection 33 (10.2) 27 (8.4) 27 (8.4)
Fatigue 33 (10.2) 26 (8.0) 28 (8.7)
Pruritus 26 (8.1) 37 (11.5) 22 (6.9)
Vomiting 28 (8.7) 35 (10.8) 17 (6.3)
Adverse events are sted for those that occurred in more than 5% of patents in ether lnirano grup vr,
1 Harson SA et al N Engl Med. 2024390 497-508, PeerView.com
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Semaglutide: NN9931-4296 Phase 2 Trial
in Patients With NASH and F2 or F3 Fibrosis!
Resolution of NASH With No Worsening Improvement in Liver Fibrosis Stage
of Liver Fibrosis (Primary Endpoint) With No Worsening of NASH
(Confirmatory Secondary Endpoint)
OR = 3:36 (96% Cl, 120-386)
400. ‘OR = 2.71 (95% Cl, 1.06-7.56) 100 22156 (08% CI, 0.864810)
13% of patients treated so OR = 6.87 (95% Cl, 260-1759) 50 al Na cti ui
ith 0.4-4 i 80 P<.00i
WE Od semagkitae. ae 70 OR = 1.42 (95% i, 062-228)
experienced improved x ss “6 mars
weight loss vs 1% 2 = go} “ g à
it 5 E
with placebo 1,1 Y & io se 3
22 3
20 47 2
10 i 10
o o
Semagiside Semaglside Semagitide Placebo Semaghide Semaglsice Semagiuide.— Placebo
img Om emo mes) img 02mg Dame mes)
CCR (nt) CCE)
Semaglutide treatment was associated with higher rates of nausea, constipation, and vomiting than placebo;
malignant neoplasm occurred in 1% of patients in the semaglutide treatment group vs 0% in the placebo group
1. Newsome PN etal. NV Engl Med, 2021;384:12:1119-1126 PeerView.com
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in Patients With NASH and F2 or F3 Fibrosis!
Resolution of NASH With No Worsening Improvement in Liver Fibrosis Stage
of Liver Fibrosis (Primary Endpoint) With No Worsening of NASH
(Confirmatory Secondary Endpoint)
OR = 3:36 (96% Cl, 120-386)
400. ‘OR = 2.71 (95% Cl, 1.06-7.56) 100 22156 (08% CI, 0.864810)
13% of patients treated so OR = 6.87 (95% Cl, 260-1759) 50 al Na cti ui
ith 0.4-4 i 80 P<.00i
WE Od semagkitae. ae 70 OR = 1.42 (95% i, 062-228)
experienced improved x ss “6 mars
weight loss vs 1% 2 = go} “ g à
it 5 E
with placebo 1,1 Y & io se 3
22 3
20 47 2
10 i 10
o o
Semagiside Semaglside Semagitide Placebo Semaghide Semaglsice Semagiuide.— Placebo
img Om emo mes) img 02mg Dame mes)
CCR (nt) CCE)
Semaglutide treatment was associated with higher rates of nausea, constipation, and vomiting than placebo;
malignant neoplasm occurred in 1% of patients in the semaglutide treatment group vs 0% in the placebo group
1. Newsome PN etal. NV Engl Med, 2021;384:12:1119-1126 PeerView.com
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Semaglutide: NN9931-4296 Phase 2 Trial
in Patients With NASH and F2 or F3 Fibrosis!
Semaglutide Semaglutide Placebo
0.4-mg Group, n ( Group, n (%)
(n= 81) (n= 80)
‘Adverse events from any system organ
class, according to preferred terme
Nausea 24 (30) 29 (37) 34 (42) 9(11)
Constipation 13 (16) 17 (22) 18 (22) 10 (12)
Decreased appetite 16 (20) 18 (23) 18 (22) 4(5)
Diarrhea 23 (29) 22 (28) 16 (20) 1114)
Vomiting 14 (18) 17 (22) 12 (15) 2(2)
Back pain 70 5(6) 10 (12) 7(9)
Headache 7) 10 (13) 10 (12) 8(10)
Nasopharyngitis 11 (14) 15 (19) 10(12) 12(15)
Arthralgia o 46) 9(11) 7(9)
Fatigue 7e) 8(10) 7(9) 7(9)
Abdominal pain 9(11) 8(10) 6(7) 3(4)
‘Abdominal distension 4(1) 8 (10) 4(5) 46)
Dyspepsia 46) 9(12) 46) 5(6)
* Adverse events with an incidence ofa
‘Newsome PN et a. N Engl J Med.
10% ny sien group ae shown. PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
in Patients With NASH and F2 or F3 Fibrosis!
Semaglutide Semaglutide Placebo
0.4-mg Group, n ( Group, n (%)
(n= 81) (n= 80)
‘Adverse events from any system organ
class, according to preferred terme
Nausea 24 (30) 29 (37) 34 (42) 9(11)
Constipation 13 (16) 17 (22) 18 (22) 10 (12)
Decreased appetite 16 (20) 18 (23) 18 (22) 4(5)
Diarrhea 23 (29) 22 (28) 16 (20) 1114)
Vomiting 14 (18) 17 (22) 12 (15) 2(2)
Back pain 70 5(6) 10 (12) 7(9)
Headache 7) 10 (13) 10 (12) 8(10)
Nasopharyngitis 11 (14) 15 (19) 10(12) 12(15)
Arthralgia o 46) 9(11) 7(9)
Fatigue 7e) 8(10) 7(9) 7(9)
Abdominal pain 9(11) 8(10) 6(7) 3(4)
‘Abdominal distension 4(1) 8 (10) 4(5) 46)
Dyspepsia 46) 9(12) 46) 5(6)
* Adverse events with an incidence ofa
‘Newsome PN et a. N Engl J Med.
10% ny sien group ae shown. PeerView.com
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Lanifibranor: NATIVE Phase 2b Trial
in Patients With Noncirrhotic NASH?2
Primary Endpoi Secondary Endpoint: Secondary Endpoint:
Reduction of 22 Points improvement of 21 Stage in Fibrosis Resolution of NASH and
in SAF Activity Score and and No Worsening of NASH No Worsening of Fibrosis
No Worsening of Fibrosis
P= .008 Peon p<
on Y 1 y | 1 of 1
= P= 01 de En Pe a Pros
4 42
40 40
® x 3
FE) 2 go} , 2
= 20 = 20 5
E H
10 10
0 + 0 + 0 +
Placebo — Lanifbranor * Lanifibranor Placebo — Lanifbranor Lanifbranor Pte antros” Lens
(n=81) 800mg 1200mg (n=81) 00mg 1,200 mg (n=81) 1,200 mg
(n= 83) (n= 83) (n=83) (n=83) De 8 (n= 83)
1. Franeque SM et al. N Engl J Med, 2021;385:1647-1558, 2. Francque SM et al, EASL 2021. Virtual Abstract OS-1044, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
in Patients With Noncirrhotic NASH?2
Primary Endpoi Secondary Endpoint: Secondary Endpoint:
Reduction of 22 Points improvement of 21 Stage in Fibrosis Resolution of NASH and
in SAF Activity Score and and No Worsening of NASH No Worsening of Fibrosis
No Worsening of Fibrosis
P= .008 Peon p<
on Y 1 y | 1 of 1
= P= 01 de En Pe a Pros
4 42
40 40
® x 3
FE) 2 go} , 2
= 20 = 20 5
E H
10 10
0 + 0 + 0 +
Placebo — Lanifbranor * Lanifibranor Placebo — Lanifbranor Lanifbranor Pte antros” Lens
(n=81) 800mg 1200mg (n=81) 00mg 1,200 mg (n=81) 1,200 mg
(n= 83) (n= 83) (n=83) (n=83) De 8 (n= 83)
1. Franeque SM et al. N Engl J Med, 2021;385:1647-1558, 2. Francque SM et al, EASL 2021. Virtual Abstract OS-1044, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
Lanifibranor: NATIVE Phase 2b Trial
in Patients With Noncirrhotic NASH‘
Mon Feet A ee nn
Diarthea 10 (12) 8 (10) 1)
Fatigue 11(13) 3) 8(10)
Nausea 76) 8(10) 3 (4)
Weight gain 7(8) 8 (10) 00)
Peripheral edema 7(8) 5 (6) 2(2)
Headache 78) 46) 46)
‘Abdominal pain 5 (6) 46) 46)
Dizziness Qu] 20) 3)
Anemia sm 10) 00)
Constipation 5 (6) 3(4) 6(7)
Increase in aminotransferase levels 3(4) 5(6) 11)
1 Francque SM et al. N En J Med, 20212851547-1558.2. Franeque SM et al EASL 2021. Vital Abstract OS-1044 PeerView.com
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in Patients With Noncirrhotic NASH‘
Mon Feet A ee nn
Diarthea 10 (12) 8 (10) 1)
Fatigue 11(13) 3) 8(10)
Nausea 76) 8(10) 3 (4)
Weight gain 7(8) 8 (10) 00)
Peripheral edema 7(8) 5 (6) 2(2)
Headache 78) 46) 46)
‘Abdominal pain 5 (6) 46) 46)
Dizziness Qu] 20) 3)
Anemia sm 10) 00)
Constipation 5 (6) 3(4) 6(7)
Increase in aminotransferase levels 3(4) 5(6) 11)
1 Francque SM et al. N En J Med, 20212851547-1558.2. Franeque SM et al EASL 2021. Vital Abstract OS-1044 PeerView.com
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Efruxifermin: HARMONY Phase 2b Trial in Patients
With NASH and F2 or F3 Fibrosis!
Fibrosis Improvement 21
Stage and No Worsening
of NASH at Week 24
100
80
x
“5 60
8
é 40
» 41
20
Ñ a
ot
NASH Resolution Fibrosis Improvement 21
and No Worsening Stage and NASH Resolution
of Fibrosis at Week 24 at Week 24
100 100
80 76° 80
i a
yy 50 y 50
3 EJ El
Es Edo
20
410
29
15 20
u 2
ot o
Placebo EFX 28 mg EFX 50 mg
(n=41) (n=38) (n=34)
*P< 05 vs placebo. ? P= 01 vs placebo. <P = 001 vs placebo.
1. Harrison SA et a. AASLD 2022 Presentation 5006
PeerView.com/RNX827
Placebo EFX28mg EFX 50 mg Placebo EFX28 mg EFX 50 mg
(n=41) (n=38) (n=34) (n=41) —(n=38) (n=34)
PeerView.com
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With NASH and F2 or F3 Fibrosis!
Fibrosis Improvement 21
Stage and No Worsening
of NASH at Week 24
100
80
x
“5 60
8
é 40
» 41
20
Ñ a
ot
NASH Resolution Fibrosis Improvement 21
and No Worsening Stage and NASH Resolution
of Fibrosis at Week 24 at Week 24
100 100
80 76° 80
i a
yy 50 y 50
3 EJ El
Es Edo
20
410
29
15 20
u 2
ot o
Placebo EFX 28 mg EFX 50 mg
(n=41) (n=38) (n=34)
*P< 05 vs placebo. ? P= 01 vs placebo. <P = 001 vs placebo.
1. Harrison SA et a. AASLD 2022 Presentation 5006
PeerView.com/RNX827
Placebo EFX28mg EFX 50 mg Placebo EFX28 mg EFX 50 mg
(n=41) (n=38) (n=34) (n=41) —(n=38) (n=34)
PeerView.com
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Efruxifermin: HARMONY Phase 2b Trial in Patients
With NASH and F2 or F3 Fibrosis!
Placebo Efruxifermin 28mg Efruxifermin 50 mg Total
(%) 0), n (%) (n=43),n (%) (N = 126),
Any TEAEs with an incidence
en oman 21 (49) 29 (73) 34 (79) 84 (67)
Diarrhea 8 (19) 16 (40) 17 (40) 41 (33)
Nausea 10 (23) 11 (28) 18 (42) 39 (31)
Injection-site erythema 8(19) 8 (20) 8 (20) 24 (19)
Increased appetite 2(5) 8 (20) 10 (23) 20 (16)
COVID-19 3(7) 4(10) 9(21) 16 (13)
Headache 5(12) 6(15) 5(12) 16 (13)
Vomiting 4(9) 6(15) 6(14) 16 (13)
Injection-site bruising 2(5) 7 (18) 4(9) 13 (10)
Frequent bowel movements 10) 9 (23) o 10 (8)
Injection-site pruritus 1(2) 3(8) 6(14) 10 (8)
Injection-site rash 1(2) 3(8) 6(14) 10 (8)
1. Harrison SA et al. Lancet Gastroenterol Hepatol 2023::1080-1093, PeerView.com
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With NASH and F2 or F3 Fibrosis!
Placebo Efruxifermin 28mg Efruxifermin 50 mg Total
(%) 0), n (%) (n=43),n (%) (N = 126),
Any TEAEs with an incidence
en oman 21 (49) 29 (73) 34 (79) 84 (67)
Diarrhea 8 (19) 16 (40) 17 (40) 41 (33)
Nausea 10 (23) 11 (28) 18 (42) 39 (31)
Injection-site erythema 8(19) 8 (20) 8 (20) 24 (19)
Increased appetite 2(5) 8 (20) 10 (23) 20 (16)
COVID-19 3(7) 4(10) 9(21) 16 (13)
Headache 5(12) 6(15) 5(12) 16 (13)
Vomiting 4(9) 6(15) 6(14) 16 (13)
Injection-site bruising 2(5) 7 (18) 4(9) 13 (10)
Frequent bowel movements 10) 9 (23) o 10 (8)
Injection-site pruritus 1(2) 3(8) 6(14) 10 (8)
Injection-site rash 1(2) 3(8) 6(14) 10 (8)
1. Harrison SA et al. Lancet Gastroenterol Hepatol 2023::1080-1093, PeerView.com
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Pegozafermin: ENLIVEN Phase 2b Trial in Patients
With NASH and F2 or F3 Fibrosis!
Fibrosis Improvement 21 Stage Without
Worsening of NASH
Diferenee, 20 percentage points
(95% Cl, 501o 35.0) P= 008
NASH Resolution
Without Worsening of Fibrosis
Ditlerence, 24 percentage points
(5% Cl, 10.0t0370)
a, Ts 1 70, tere, 2 pescerage ponte 1
(85% CI, 5.00 320) P= 008 (65% CI, 80 330)
| pon
60
40 | Dierence, 14 percentage points Dierence, 35 percentage points
(95% Ci, 9.010380) % (65% Cl, 10010390)
x
= 40
$ 37
¿a 26
= 23
20
10
2
A ~~ ~~~ A os,
Placebo Pegozafermin Pegozafermin Pegozafermin Placebo Pegozafermin Pegozafermin Pegozafermin
(n=61) 15mgevery 30mgevery 44mg every (n=61) 15mgevey 30mgevery 44 mg every
week week 2weeks week week 2weeks
(n= 14) (n= 66) (n= 51) (n= 14) (n= 66) (n=51)
1. Loomba Ret al. N Engl J Med. 2023:389:-998-1008
PeerView.com/RNX827
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Copyright © 2000-2024, PeerView
With NASH and F2 or F3 Fibrosis!
Fibrosis Improvement 21 Stage Without
Worsening of NASH
Diferenee, 20 percentage points
(95% Cl, 501o 35.0) P= 008
NASH Resolution
Without Worsening of Fibrosis
Ditlerence, 24 percentage points
(5% Cl, 10.0t0370)
a, Ts 1 70, tere, 2 pescerage ponte 1
(85% CI, 5.00 320) P= 008 (65% CI, 80 330)
| pon
60
40 | Dierence, 14 percentage points Dierence, 35 percentage points
(95% Ci, 9.010380) % (65% Cl, 10010390)
x
= 40
$ 37
¿a 26
= 23
20
10
2
A ~~ ~~~ A os,
Placebo Pegozafermin Pegozafermin Pegozafermin Placebo Pegozafermin Pegozafermin Pegozafermin
(n=61) 15mgevery 30mgevery 44mg every (n=61) 15mgevey 30mgevery 44 mg every
week week 2weeks week week 2weeks
(n= 14) (n= 66) (n= 51) (n= 14) (n= 66) (n=51)
1. Loomba Ret al. N Engl J Med. 2023:389:-998-1008
PeerView.com/RNX827
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Pegozafermin: ENLIVEN Phase 2b Trial in Patients
With NASH and F2 or F3 Fibrosis!
Pegozafermin,
‘Adverse event from any system organ
class, according to preferred term
Nausea 6(9) 4(19) 23 (32) 119)
Diarrhea 46) 5 (24) 14 (19) 8(14)
Injection-site erythema 3(4) 3(14) 11 (15) 36)
Increased appetite 11 2(10) 10 (14) 40)
‘Vomiting 2(3) 16) 10 (14) 2(4)
coviD-19 6 (9) 16) 9(12) 5(9)
Urinary tract infection sm 0 8(11) 2(4)
Injection-site rash 11 o 7(10) 2(4)
Muscle spasms: 10 16) 7 (10) o
Headache sm 2(10) 6 (8) sm
Sinusitis 3) 0 23) 7(12)
Lower abdominal pain o 3(14) 11 o
Procedural pain 10 3(14) o 1(2)
1.Loomba R et al. NE J Med. 2023:380:998-1008, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
With NASH and F2 or F3 Fibrosis!
Pegozafermin,
‘Adverse event from any system organ
class, according to preferred term
Nausea 6(9) 4(19) 23 (32) 119)
Diarrhea 46) 5 (24) 14 (19) 8(14)
Injection-site erythema 3(4) 3(14) 11 (15) 36)
Increased appetite 11 2(10) 10 (14) 40)
‘Vomiting 2(3) 16) 10 (14) 2(4)
coviD-19 6 (9) 16) 9(12) 5(9)
Urinary tract infection sm 0 8(11) 2(4)
Injection-site rash 11 o 7(10) 2(4)
Muscle spasms: 10 16) 7 (10) o
Headache sm 2(10) 6 (8) sm
Sinusitis 3) 0 23) 7(12)
Lower abdominal pain o 3(14) 11 o
Procedural pain 10 3(14) o 1(2)
1.Loomba R et al. NE J Med. 2023:380:998-1008, PeerView.com
PeerView.com/RNX827 Copyright © 2000-2024, Peerview
Tactics for Integrating Existing and New Agents
Into Management Plans
+ Clinical efficacy: both MASH resolution and one-stage improvement in fibrosis
+ Safety: safe use in the intended population
Algorithm to Identify Who Needs to Be Treated
Exclude patients who should not be treated with the drug
+ Two clinical trials showing consistent results and in definitive
outcomes-based trial
Record CVD risks; liver disease adjudication committee separate
from DSMB
Avoid patients with elevated phosphatidylethanol or who should not
be treated
Liver biopsy evaluation process
+ Three readers: mode read or consensus read
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Into Management Plans
+ Clinical efficacy: both MASH resolution and one-stage improvement in fibrosis
+ Safety: safe use in the intended population
Algorithm to Identify Who Needs to Be Treated
Exclude patients who should not be treated with the drug
+ Two clinical trials showing consistent results and in definitive
outcomes-based trial
Record CVD risks; liver disease adjudication committee separate
from DSMB
Avoid patients with elevated phosphatidylethanol or who should not
be treated
Liver biopsy evaluation process
+ Three readers: mode read or consensus read
PeerView.com
PeerView.com/RNX827 Copyrigh
Experts vs Al:
Optimal Management of MASLD/MASH
The Monitoring and Treatment Challenge
Rohit Loomba, MD, MHSc Alina M. Allen, MD, MS
Professor of Medicine Associate Professor of Medicine
Chief, Division of Gastroenterology Director, MASLD Clinic
M and Hepatology Division of Gastroenterology
Director, MASLD Research Center and Hepatology
Adjunct Professor, Mayo Clinic
Division of Epidemiology Rochester, Minnesota
University of California at San Diego
La Jolla, California
Copyright © 2000-2024, Peerview
Optimal Management of MASLD/MASH
The Monitoring and Treatment Challenge
Rohit Loomba, MD, MHSc Alina M. Allen, MD, MS
Professor of Medicine Associate Professor of Medicine
Chief, Division of Gastroenterology Director, MASLD Clinic
M and Hepatology Division of Gastroenterology
Director, MASLD Research Center and Hepatology
Adjunct Professor, Mayo Clinic
Division of Epidemiology Rochester, Minnesota
University of California at San Diego
La Jolla, California
Copyright © 2000-2024, Peerview
Answer This Question
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
PeerView.com/RNX827
How can | help you today?
A 51-year-old man has obstructive sleep apnea and type 2 diabetes mellitus. His HbA1c
is 9 mmol/mL, BMI is 32, AST is 41 units/mL, ALT is 50 units/mL, and platelet count is
200. He has no history of liver disease or habitual alcohol consumption. Based on
sensitivity/specificity, invasiveness, and diagnostic needs, what test would be best to
assess this patient for MASLD or MASH?
How can | help you today?
A 51-year-old man has obstructive sleep apnea and type 2 diabetes mellitus. His HbA1c
is 9 mmol/mL, BMI is 32, AST is 41 units/mL, ALT is 50 units/mL, and platelet count is
200. He has no history of liver disease or habitual alcohol consumption. Based on
sensitivity/specificity, invasiveness, and diagnostic needs, what test would be best to
assess this patient for MASLD or MASH?
| Optimal Testing © You
Methods A51-year-old man has obstructive sleep apnea and type 2 diabetes mellitus. His HbA1c is 9
mmoi/mL, BMI is 32, AST is 41 units/mL, ALT is 50 units/mL, and platelet count is 200. He has
no history of liver disease or habitual alcohol consumption. Based on sensitivity/specificity,
invasiveness, and diagnostic needs, what test would be best to assess this patient for MASLD
or MASH?
ChatBot
Given the patient's risk factors and elevated liver enzymes, a noninvasive approach is
Warranted. Transient elastography (FibroScan) is ideal. It offers high sensitivity and specificity for
liver fibrosis detection, crucial in diabetes patients. FibroScan provides liver stiffness
measurement (LSM) and controlled attenuation parameter (CAP), aiding in diagnosis without
invasiveness. This approach balances diagnostic accuracy with patient comfort. Given the
patient's profile and absence of liver disease history or alcohol consumption, FibroScan serves
as the preferred initial test to evaluate for metabolic dysfunction-associated steatotic liver
disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH).
Copyright © 2000-2024, PeerView
Methods A51-year-old man has obstructive sleep apnea and type 2 diabetes mellitus. His HbA1c is 9
mmoi/mL, BMI is 32, AST is 41 units/mL, ALT is 50 units/mL, and platelet count is 200. He has
no history of liver disease or habitual alcohol consumption. Based on sensitivity/specificity,
invasiveness, and diagnostic needs, what test would be best to assess this patient for MASLD
or MASH?
ChatBot
Given the patient's risk factors and elevated liver enzymes, a noninvasive approach is
Warranted. Transient elastography (FibroScan) is ideal. It offers high sensitivity and specificity for
liver fibrosis detection, crucial in diabetes patients. FibroScan provides liver stiffness
measurement (LSM) and controlled attenuation parameter (CAP), aiding in diagnosis without
invasiveness. This approach balances diagnostic accuracy with patient comfort. Given the
patient's profile and absence of liver disease history or alcohol consumption, FibroScan serves
as the preferred initial test to evaluate for metabolic dysfunction-associated steatotic liver
disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH).
Copyright © 2000-2024, PeerView
| Optimal Testing © You
Methods A51-year-old man has obstructive sleep apnea and type 2 diabetes mellitus. His HbA1c is 9
mmol/mL, BMI is 32, AST is 41 units/mL, ALT is 50 units/mL, and platelet count is 200. He has
no history of liver disease or habitual alcohol consumption. Based on sensitivity/specificity,
invasiveness, and diagnostic needs, what test would be best to assess this patient for MASLD
or MASH?
ChatBot
Given the patient's risk factors and elevated liver enzymes, a noninvasive approach is
warranted. Transient elastography (FibroScan) is ideal. It offers high sensitivity and specificity for
liver fibrosis detection, crucial in diabetes patients. FibroScan provides liver stiffness
measurement (LSM) and controlled attenuation parameter (CAP), aiding in diagnosis without
invasiveness. This approach balances diagnostic accuracy with patient comfort. Given the
patient's profile and absence of liver disease history or alcohol consumption, FibroScan serves
as the preferred initial test to evaluate for metabolic dysfunction-associated steatotic liver
disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH).
Shouldn't FIB-4 be assessed first?
w.com/RNX827 Copyright © 20 , PeerView
Methods A51-year-old man has obstructive sleep apnea and type 2 diabetes mellitus. His HbA1c is 9
mmol/mL, BMI is 32, AST is 41 units/mL, ALT is 50 units/mL, and platelet count is 200. He has
no history of liver disease or habitual alcohol consumption. Based on sensitivity/specificity,
invasiveness, and diagnostic needs, what test would be best to assess this patient for MASLD
or MASH?
ChatBot
Given the patient's risk factors and elevated liver enzymes, a noninvasive approach is
warranted. Transient elastography (FibroScan) is ideal. It offers high sensitivity and specificity for
liver fibrosis detection, crucial in diabetes patients. FibroScan provides liver stiffness
measurement (LSM) and controlled attenuation parameter (CAP), aiding in diagnosis without
invasiveness. This approach balances diagnostic accuracy with patient comfort. Given the
patient's profile and absence of liver disease history or alcohol consumption, FibroScan serves
as the preferred initial test to evaluate for metabolic dysfunction-associated steatotic liver
disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH).
Shouldn't FIB-4 be assessed first?
w.com/RNX827 Copyright © 20 , PeerView
[Optimal Testing You
Methods, Shouldn't FIB-4 be assessed first?
ChatBot
You're correct; my apologies for the oversight. Considering the patient's profile and the need for a
noninvasive initial assessment, calculating the FIB-4 score should indeed be the first step. FIB-4
score is derived from readily available clinical parameters like age, AST, ALT, and platelet count,
offering a simple yet valuable tool for assessing liver fibrosis risk. It's noninvasive and provides
insight into the likelihood of significant fibrosis, aiding in the decision for further diagnostic steps
if necessary. Therefore, assessing the FIB-4 score first aligns with the patient's profile and
diagnostic needs
w.com/RNX827 Copyright © 2000-2024, PeerView
Methods, Shouldn't FIB-4 be assessed first?
ChatBot
You're correct; my apologies for the oversight. Considering the patient's profile and the need for a
noninvasive initial assessment, calculating the FIB-4 score should indeed be the first step. FIB-4
score is derived from readily available clinical parameters like age, AST, ALT, and platelet count,
offering a simple yet valuable tool for assessing liver fibrosis risk. It's noninvasive and provides
insight into the likelihood of significant fibrosis, aiding in the decision for further diagnostic steps
if necessary. Therefore, assessing the FIB-4 score first aligns with the patient's profile and
diagnostic needs
w.com/RNX827 Copyright © 2000-2024, PeerView
[ Optimal Testing © You
Methods Shouldn't FIB-4 be assessed first?
ChatBot
You're correct; my apologies for the oversight. Considering the patient's profile and the need for a
noninvasive initial assessment, calculating the FIB-4 score should indeed be the first step. FIB-4
score is derived from readily available clinical parameters like age, AST, ALT, and platelet count,
offering a simple yet valuable tool for assessing liver fibrosis risk. It's noninvasive and provides
insight into the likelihood of significant fibrosis, aiding in the decision for further diagnostic steps
if necessary. Therefore, assessing the FIB-4 score first aligns with the patient's profile and
diagnostic needs
What is his FIB-4 score?
w.com/RNX827 Copyright © 2000-2024, PeerView
Methods Shouldn't FIB-4 be assessed first?
ChatBot
You're correct; my apologies for the oversight. Considering the patient's profile and the need for a
noninvasive initial assessment, calculating the FIB-4 score should indeed be the first step. FIB-4
score is derived from readily available clinical parameters like age, AST, ALT, and platelet count,
offering a simple yet valuable tool for assessing liver fibrosis risk. It's noninvasive and provides
insight into the likelihood of significant fibrosis, aiding in the decision for further diagnostic steps
if necessary. Therefore, assessing the FIB-4 score first aligns with the patient's profile and
diagnostic needs
What is his FIB-4 score?
w.com/RNX827 Copyright © 2000-2024, PeerView
Optimal Testing You
Meucee) What is his FIB-4 score?
sie ChatBot
The FIB-4 score can be calculated using the following formula
FIB-4 = (age x AST)/(platelet count x VALT)
Plugging in the values
Age = 51 years
AST = 41 units/L
ALT = 50 units/L
Platelet count = 200 (10°9/L)
FIB-4 = 1.48
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Meucee) What is his FIB-4 score?
sie ChatBot
The FIB-4 score can be calculated using the following formula
FIB-4 = (age x AST)/(platelet count x VALT)
Plugging in the values
Age = 51 years
AST = 41 units/L
ALT = 50 units/L
Platelet count = 200 (10°9/L)
FIB-4 = 1.48
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Answer This Question
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Optimal Testing You
ker What is his FIB-4 score?
ses ChatBot
The FIB-4 score can be calculated using the following formula
FIB-4 = (age x AST)/(platelet count x VALT)
Plugging in the values:
Age = 51 years
AST 1 units/L
ALT = 50 units/L
Platelet count = 200 (10°9/L)
FIB-4 = 1.48
Does this patient have MASLD/MASH?
PeerView.com/RNX827
ker What is his FIB-4 score?
ses ChatBot
The FIB-4 score can be calculated using the following formula
FIB-4 = (age x AST)/(platelet count x VALT)
Plugging in the values:
Age = 51 years
AST 1 units/L
ALT = 50 units/L
Platelet count = 200 (10°9/L)
FIB-4 = 1.48
Does this patient have MASLD/MASH?
PeerView.com/RNX827
| Optimal Testing You
Methods Does this patient have MASLD/MASH?
ChatBot
Based on the FIB-4 score of approximately 1.48, this suggests a low risk of advanced fibrosis.
However, FIB-4 alone is not sufficient to diagnose or rule out metabolic dysfunction-associated
steatotic liver disease (MASLD). Additional assessments, such as imaging studies (eg, transient
elastography) and/or liver biopsy, may be needed for a comprehensive evaluation. Given the
patient's clinical profile with obesity, type 2 diabetes mellitus, and obstructive sleep apnea,
further investigation is warranted to assess the extent of liver involvement and determine if
MASLD/MASH is present.
w.com/RNX827 Copyright © 2000-2024, PeerView
Methods Does this patient have MASLD/MASH?
ChatBot
Based on the FIB-4 score of approximately 1.48, this suggests a low risk of advanced fibrosis.
However, FIB-4 alone is not sufficient to diagnose or rule out metabolic dysfunction-associated
steatotic liver disease (MASLD). Additional assessments, such as imaging studies (eg, transient
elastography) and/or liver biopsy, may be needed for a comprehensive evaluation. Given the
patient's clinical profile with obesity, type 2 diabetes mellitus, and obstructive sleep apnea,
further investigation is warranted to assess the extent of liver involvement and determine if
MASLD/MASH is present.
w.com/RNX827 Copyright © 2000-2024, PeerView
Answer This Question
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
[ Optimal Testing | © You
Methods Does this patient have MASLD/MASH?
ChatBot
Based on the FIB-4 score of approximately 1.48, this suggests a low risk of advanced fibrosis.
However, FIB-4 alone is not sufficient to diagnose or rule out metabolic dysfunction-associated
steatotic liver disease (MASLD). Additional assessments, such as imaging studies (eg, transient
elastography) and/or liver biopsy, may be needed for a comprehensive evaluation. Given the
patient's clinical profile with obesity, type 2 diabetes mellitus, and obstructive sleep apnea,
further investigation is warranted to assess the extent of liver involvement and determine if
MASLD/MASH is present.
What test should be done next?
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Methods Does this patient have MASLD/MASH?
ChatBot
Based on the FIB-4 score of approximately 1.48, this suggests a low risk of advanced fibrosis.
However, FIB-4 alone is not sufficient to diagnose or rule out metabolic dysfunction-associated
steatotic liver disease (MASLD). Additional assessments, such as imaging studies (eg, transient
elastography) and/or liver biopsy, may be needed for a comprehensive evaluation. Given the
patient's clinical profile with obesity, type 2 diabetes mellitus, and obstructive sleep apnea,
further investigation is warranted to assess the extent of liver involvement and determine if
MASLD/MASH is present.
What test should be done next?
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
{Optimal Testing You
pios What test should be done next?
sie ChatBot
Considering the patient's risk factors and the need for further evaluation, transient elastography
(TE) or FibroScan would be the next appropriate test. TE is a noninvasive imaging technique
that assesses liver stiffness, providing valuable information about the presence and severity of
liver fibrosis in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD).
It offers a quick and reliable assessment without the invasiveness of a liver biopsy, making it
suitable for patients with comorbidities like obesity and type 2 diabetes mellitus. TE results can
help guide management decisions and monitor disease progression in these patients.
Copyright © 2000-2024, PeerView
pios What test should be done next?
sie ChatBot
Considering the patient's risk factors and the need for further evaluation, transient elastography
(TE) or FibroScan would be the next appropriate test. TE is a noninvasive imaging technique
that assesses liver stiffness, providing valuable information about the presence and severity of
liver fibrosis in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD).
It offers a quick and reliable assessment without the invasiveness of a liver biopsy, making it
suitable for patients with comorbidities like obesity and type 2 diabetes mellitus. TE results can
help guide management decisions and monitor disease progression in these patients.
Copyright © 2000-2024, PeerView
Answer This Question
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
Before we move on, please take
a moment to answer this question
on MASLD/MASH assessment.
PeerView.com/RNX827 Copyright © 2000-2024, PeerView
[ Optimal Testing © You
pios What test should be done next?
sie ChatBot
Considering the patient's risk factors and the need for further evaluation, transient elastography
(TE) or FibroScan would be the next appropriate test. TE is a noninvasive imaging technique
that assesses liver stiffness, providing valuable information about the presence and severity of
liver fibrosis in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD).
It offers a quick and reliable assessment without the invasiveness of a liver biopsy, making it
suitable for patients with comorbidities like obesity and type 2 diabetes mellitus. TE results can
help guide management decisions and monitor disease progression in these patients.
The patient's CAP is 289 dB/m and liver stiffness is 8 kPa. Is pharmacotherapy
warranted at this time for MASH associated fibrosis?
PeerView.com/RNX827 Copyright © 20 , PeerView
pios What test should be done next?
sie ChatBot
Considering the patient's risk factors and the need for further evaluation, transient elastography
(TE) or FibroScan would be the next appropriate test. TE is a noninvasive imaging technique
that assesses liver stiffness, providing valuable information about the presence and severity of
liver fibrosis in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD).
It offers a quick and reliable assessment without the invasiveness of a liver biopsy, making it
suitable for patients with comorbidities like obesity and type 2 diabetes mellitus. TE results can
help guide management decisions and monitor disease progression in these patients.
The patient's CAP is 289 dB/m and liver stiffness is 8 kPa. Is pharmacotherapy
warranted at this time for MASH associated fibrosis?
PeerView.com/RNX827 Copyright © 20 , PeerView
Optimal Testing
Methods
You
The patient's CAP is 289 dB/m and liver stiffness is 8 kPa. Is pharmacotherapy warranted
at this time for MASH associated fibrosis?
ChatBot
With a CAP of 289 dB/m indicating hepatic steatosis and liver stiffness of 8 kPa suggesting
minimal fibrosis, pharmacotherapy for liver fibrosis may not be warranted now. Lifestyle
modifications, including weight loss and glycemic control, remain the comerstone of
management. Regular monitoring is essential to assess disease progression and determine the
need for pharmacotherapy in the future, ensuring optimized care for the patient's metabolic
dysfunction-associated steatotic liver disease (MASLD).
Copyright © 2000-2024, PeerView
Methods
You
The patient's CAP is 289 dB/m and liver stiffness is 8 kPa. Is pharmacotherapy warranted
at this time for MASH associated fibrosis?
ChatBot
With a CAP of 289 dB/m indicating hepatic steatosis and liver stiffness of 8 kPa suggesting
minimal fibrosis, pharmacotherapy for liver fibrosis may not be warranted now. Lifestyle
modifications, including weight loss and glycemic control, remain the comerstone of
management. Regular monitoring is essential to assess disease progression and determine the
need for pharmacotherapy in the future, ensuring optimized care for the patient's metabolic
dysfunction-associated steatotic liver disease (MASLD).
Copyright © 2000-2024, PeerView
Conclusions!
Resmetirom was recently approved for the treatment of MASH in adults
with moderate to advanced liver fibrosis (stages F2 to F3)
MASH neeas to be treated, as well as the key metabolic abnormalities,
such as obesity, type 2 diabetes, and cardiovascular risk
There are new metabolic targets associated with liver disease improvement
in patients with MASH; several new promising therapies are on the horizon
Patients who are at risk for MASH can be identified
in routine clinical practice by sequential noninvasive tests
1. KanwalF et al. Gastroontrelogy. 2021:181:1857-1669. PeerView.com
PeerView.com/RNX827 Copyright © 200
2024, PeerView
Resmetirom was recently approved for the treatment of MASH in adults
with moderate to advanced liver fibrosis (stages F2 to F3)
MASH neeas to be treated, as well as the key metabolic abnormalities,
such as obesity, type 2 diabetes, and cardiovascular risk
There are new metabolic targets associated with liver disease improvement
in patients with MASH; several new promising therapies are on the horizon
Patients who are at risk for MASH can be identified
in routine clinical practice by sequential noninvasive tests
1. KanwalF et al. Gastroontrelogy. 2021:181:1857-1669. PeerView.com
PeerView.com/RNX827 Copyright © 200
2024, PeerView
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