Non-alcoholic fatty liver disease€¦ · Non-alcoholic liver disease (NAFLD) Steatohepatitis...

Non-alcoholic fatty liver disease

Volkan Demirhan Yumuk, MD

American Gastroenterology Association, Endocrine Society, Clinical Care Options

Clevaland Clinic Teaching Tools

In preparing my presentation most of the credit goes to:

Natural history & epidemiology

The magnitude of the problem

Clinical management of NASH-obesity

Clinical management of NASH-diabetes

Future treatment & management options

Learning objectives

Are you ready folks?

Non-alcoholic liver disease (NAFLD)

Steatohepatitis“NASH”

CirrhosisNormal Liver Steatosis“NAFL”

clinicaloptions.comChalasani N et al. AASLD Guidance. Hepatology 2018; 67:328-357.

Fatty liver with inflammation and

hepatocyte ballooning

Fatty liver without inflammation or

hepatocyte ballooning

Increasing fibrosisleading to cirrhosis,

hepatocellular carcinoma

HCC

http://www.clinicaloptions.com/

a. 25% and 3%

b. 5% and 0.5%

c. 60% and 15%

d. 50% and 0.5

e. 70% and 10%

1. What is the approximate prevalence of steatosis and NASH in the world’s population?

Estimated Global Prevalence of NAFLD: 25%

Younossi ZM, et al. Hepatology. 2016;64:73-84.

24%

31%

24%

13%

32%27%

Meta-analysis: NAFLD diagnosed by imaging (US, CT, MRI/SPECT; n=45 studies).

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Natural history of NAFLD over 8–13 years

de Alwis NMW, Day CP. J Hepatol 2008;48:S104–12Copyright © 2008 European Association for the Study of the Liver

Steatosis

NASH

F1−F2

fibrosis

HCC

Death/

LTx Cirrhosis

Advanced

F3

fibrosis

12−40%

5−10%

0−50%

8%

13%

25−50%

14%

25%

7%

Prevalence of NAFLD and NASH in people with T2DM and normal plasma AST or ALT

Patients with T2DM and normal AST or ALT evaluated for liver triglyceride content by H-MRS, insulin sensitivity, and adipose tissue insulin resistance (N = 103)

NA

FLD

Pre

vale

nce

(%

)

36%

P = .001

Obese by BMI (kg/m2)

Nonobese(n = 31)

30.0-34.9(n = 34)

35.0-39.9(n = 29)

≥ 40.0(n = 9)

36%

68%

90%

Portillo-Sanchez. J Clin Endocrinol Metab. 2015;100:2231. Stål. World J Gastroenterol. 2015; 21: 11077. clinicaloptions.com

100

80

60

40

20

0

‒ Prevalence of NAFLD in overall cohort: 50%

Among these people,prevalence of NASH: 56%


A 55-year-old male with past medical history of obesity (BMI of 41 kg/m2) and type 2 diabetespresents to you with abnormal liver enzymes discovered 3 months ago. Normal on physicalexamination. His laboratory tests revealed the following: aspartate aminotransferase (AST) 110, alanine aminotransferase (ALT) 135, with normal bilirubin, 𝛾-glutamyl transferase , alkaline phosphatase and prothrombin time. He had a liver ultrasonography that showeddiffuse increase in echogenicity and vascular blurring consistent with fatty infiltration. Yoususpect nonalcoholic fatty liver disease (NAFLD)

I have a case

The patient denies excessive alcohol intake or the use of any meds or herbalsupplements. Serologies for hepatitis B and C are negative and the iron studies arewithin normal limits. Based on the previous findings, you make a diagnosis of NAFLD.

a. NAFLD is considered the hepatic manifestation of insulin resistance

b. NAFLD has a histological spectrum ranging from staetosis to NASH to cirrhosis

c. Cardiovascular risk is increased in NAFLD

d. Obesity, type 2 DM and hyperlipidemia are risk factors for NAFLD

e. NASH is benign and does not progress to chronic liver disease

2. All of the following statements regarding NAFLD are trueexcept:

a. NAFLD is considered the hepatic manifestation of insulin resistance

b. NAFLD has a histological spectrum ranging from staetosis to NASH to cirrhosis

c. Cardiovascular risk is increased in NAFLD

d. Obesity, type 2 DM and hyperlipidemia are risk factors for NAFLD

e. NASH is benign and does not progress to chronic liver disease

2. All of the following statements regarding NAFLD are true except:

a. HCC is not a part of the NAFLD spectrum

b. Cirrhosis develops in about 5-10% of patients with NASH (F1-F2) within 10 yrs of diagnosis

c. Recurrence can ocur after liver Tx for NASH-related cirrhosis and steatosis

d. Liver disease is the leading cause of death in people with NAFLD

e. Cardiovascular disease is the leading cause of death in NASH

3. Your patient asks you about the natural history of NAFLD. Which of the following statements is correct?

a. HCC is not a part of the NAFLD spectrum

b. Cirrhosis develops in about 50% of patients with NASH (F1-F2) within 10 yrs of diagnosis

c. Recurrence can ocur after liver Tx for NASH-related cirrhosis and steatosis can be seenin up to 60% of transplant recipients

d. Liver disease is the leading cause of death in people with NAFLD

e. Cardiovascular disease is the leading cause of death in NASH

3. Your patient asks you about the natural history of NAFLD. Which of the following statements is correct?

Metabolic Consequences of NAFLD

↓ Insulinclearance

↑ Insulinresistance

↑ Glucoseproduction

↑ Cytokines (systemic

inflammation)

Heart disease: ATP generation Lipotoxicity Ischemia Diastolic dysfunction

↑ TG/ ↓ HDL

↑ Apo-B

Hyperinsulinemia Type 2 diabetes Atherogenesis Myocardialdysfunction

Cardiovascular disease

NAFLD

clinicaloptions.comCusi. Gastroenterology. 2012;142:711.


Bril. Endocrinol Metab Clin N Am. 2016;45:765. clinicaloptions.com

Mortality risk associated with isolated steatosis and NASH

Analysis of all-cause mortality in 6 separate studies among patients without NAFLD vs with

and without NASH• NAFLD determined by ultrasound; NASH determined by liver biopsy

40

30

20

10

0

Mo

rtal

ity

(%)

No NAFLD(14.5-yr follow-up)

Isolated Steatosis(13.3-yr follow-up)

NASH(13.0-yr follow-up)

Liver relatedCardiovascularOther


Chalasani. Hepatology. 2018;67:328. clinicaloptions.com

AASLD Guidance on CV Risk: Statins in Patients With NASH

“Patients with NAFLD are at high risk for cardiovascular morbidity and mortality. Thus, aggressive modification of CVD risk factors should be considered in all patients with NAFLD”

“Patients with NAFLD or NASH are not at higher risk for serious liver injury from statins. Thus, statins can be used to treat dyslipidemia in patients with NAFLD and NASH”

Statins recommended for reducing CV risk, not for resolving NASH “Clinical trials of statins as treatment for NASH are limitedand have shown inconsistent results”


a. Obtain serology for hepatitis B and C

b. Screen for alcohol abuse

c. Review current meds and herbals

d. Check fasting lipid panel

e. All of the above

4. Which of the following is indicated to further evaluatethe etiology of his mild transaminase elevation?

a. Obtain serology for hepatitis B and C

b. Screen for alcohol abuse

c. Review current meds and herbals

d. Check fasting lipid panel

e. All of the above

4. Which of the following is indicated to further evaluate theetiology of his mild transaminase elevation?

a. Start steroid therapy for autoimmune hepatitis

b. Obtain a liver biopsy for further evaluation

c. Refer to a hepatologist because his clinical picture is not consistent with NAFLD

d. No further evaluation for autoimmune hepatitis is necessary

e. Screen for other autoimmune diseases

5. As a part of your evaluation, you find that your patient has low titersof anti-SM Ab (<1: 40) and ANA (<1:160). What should you do next?

Considerations in Patients With Atypical NAFLD

Be sure to fully exclude Wilson’s disease (24-hr urine copper)

Low cholesterol (eg < 100 mg/dL): check ApoB, may be hypobetalipoproteinemia

Get a good diet history for unusual supplements

Corroborate minimal or no alcohol (especially if AST > ALT)

Lysosomal acid lipase deficiency?



a. Hyperlipidemia

b. Type 2 diabetes

c. Obesity

d. Younger age

e. AST/ALT ≧ 1

6. All the following are risk factors for NASH and may indicatethe need for a liver biopsy except?

Who Is at Risk for NASH and Advanced Fibrosis?

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Risk Factor for NAFLD[1]

Type 2 diabetes

Obesity

Dyslipidemia

Metabolic syndrome

Polycystic ovary syndrome

AASLD Recommendation[1]

In type 2 diabetes, suspect NAFLD and NASH and

determine patient’s risk of advanced fibrosis

Increasing number of metabolic diseases =

increasing risk of progressive liver disease

EASL-EASD-EASO Recommendation[2]

NAFLD screening recommended

in persons at high CVD risk, including type 2 diabetes or

metabolic syndrome

1. Chalasani. Hepatology. 2018;67:328. 2. EASL, EASD, EASO. J Hepatol. 2016;64:1388.


a. Ultrasonography

b. Computed tomography

c. Magnetic resonance

d. Fibroscan

e. All of the above

7. Non-invasive tests/ imaging studies for NAFLD

include which of the following?

NAFLD in people with vs without T2DM by diagnostic approach

Pooled results of patients with and without T2DM with NAFLD diagnosed by different means

Bril F. Diabetes Care. 2017;40:419. clinicaloptions.com

100

80

60

40

20

0

NA

FLD

Pre

vale

nce

(%

)

General populationT2DM

PlasmaALT

ComputedTomography

LiverUS

ControlledAttenuationParameter

1H-MRS


Bril F, Cusi K. Diabetes Care. 2017;40:419. clinicaloptions.com

Advanced fibrosis in people with vs without T2DM by diagnostic approach

Meta-analysis (N = 3229)

Pooled results of patients with and without T2DM

Ad

van

ced

Fib

rosi

sP

reva

len

ce (

%)

General populationT2DM

Fibro Test NAFLDFibrosis Score

Vibration-ControlledTransient

Elastography

80

60

40

20

100

0


Ultrasound or CT: Inadequate in Assessing NAFLD

US or CT may identify advanced cirrhosis

Portal hypertensive changes such as varices, ascites, splenomegaly

1. Dasarathy. J Hepatol. 2009;51:1061. 3. Rogier. Liver Transpl. 2015;21:690.

Method for Identifying Steatosis Sensitivity, % Specificity, % Comments

Ultrasound[1]

▪ Any degree▪ ≥ 20%

61100

10090

Inexpensive and accessible; cannot distinguish fibrosis/steatosis

CT without contrast[2]

▪ > 30% 79 97

Also useful in severely obese; affected by iron, fibrosis;

reduced accuracy with minimal steatosis

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US or CT cannot identify most NAFLD stages/severity

Cannot distinguish steatosis vs NASH or NASH fibrosis/early cirrhosis


Ultrasound & CT in assessing NAFLD

Leoni S et al.World J Gastroenterol 2018; 24(30): 3361-3373.

In normal US liver parenchyma is isoechoic to the renal paranchyma A1;Liver paranchyma becomes hyperechoic in steatosis A2.

In comparison to normal liver B1, a fatty liver liver appears hypodensecompared to spleen and hepatic veins B2 in computed tomography.

a. Transient elastography (TE)

b. NAFLD fibrosis score (NFS)

c. NAFLD fibrosis score (FIB-4)

d. All of the above

8. Non-invasive panels/imaging tests for significant fibrosis in patients with NAFLD includes which of the following?

NAFLD Fibrosis Score and FIB-4

Parameter

Age

AST

ALT

Platelet count

BMI

Albumin

Impaired fasting glucose/diabetes?

NAFLD Fibrosis Score[1]

Effect NPV or PPV, %

< -1.455Rules out fibrosis

88 to 93

> 0.676Predicts fibrosis

82 to 90

NAFLDFibrosisScore

FIB-4 Score[2,3] Effect NPV or PPV, %

< 1.3Rules out fibrosis

90

> 2.67 Predictsfibrosis

80

Indeterminate

High Cutoff (PPV)Low Cutoff (NPV)

Low Probability of F3/4 High Probability of F3/4

FIB-4Score

clinicaloptions.com1. Angulo. Hepatology. 2007;45:846. 2. Shah. Clin Gastroenterol Hepatol. 2009;7:1104. 3. McPherson. Gut. 2010;59:1265.


Noninvasive Staging of NASH: Imaging

Imaging Comments

Vibration-controlled transient elastography (VCTE) -- FibroScan

▪ Can be point of care▪ Can rule in/out advanced fibrosis

2D shear wave elastography▪ May require radiology referral but can be

point of care with minimal training

MR elastography/MR spectroscopy/ liver multiscan

▪ Requires radiology referral▪ Most accurate of the imaging modalities

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a. Hepatocyte balooning

b. Steatosis

c. Lymphoid follicles

d. Perisinusoidal inflammation

e. Mallory-Denk bodies

9. Which of the following is not a feature of NASH on liverbiopsy?

Liver Biopsy: The imperfect gold standard

• Benefits

– Establishes diagnosis of NASH

– Assesses early fibrosis

– Determines prognosis

– Rules out other processes: alpha-1 antitrypsin, iron overload, autoimmune component

• Limitations

– Risk of bleeding, pain

– Sampling variability (especially with IR biopsies if they are small)

– Long interval between serial biopsies to monitor disease progression

– Cost

clinicaloptions.comRockey. Hepatology. 2009;49:1017. Kleiner. Hepatology 2005;41:1313. Bedossa. Hepatology. 2012;56:1751.

Isolated Steatosis Steatohepatitis/NASH


Fibrosis Staging in NASH

F1: Perisinusoidal F2: Perisinusoidal + Portal

F3: Bridging Fibrosis F4: Cirrhosis

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Approach to initial assessment and consideration for a liver biopsy

Elevated liver enzymes or evidence of hepatic steatosis on imaging

Trial of 3-6 mos of diet and exercise for weight loss

Reassess every 6-12 mosLiver biopsy

Consider intraoperative biopsy if undergoing cholecystectomy or bariatric surgery

Presence of:▪ Diabetes▪ Metabolic syndrome▪ Older age

Baseline workup:▪ CBC, platelet count, ALT, AST, ALP, GGT, INR, total bilirubin, albumin▪ Rule out other causes of chronic liver disease (eg, viral hepatitis, autoimmune)▪ Fasting glucose and lipid levels, A1C

Unsuccessful

NoYes

▪ High AST:ALT▪ High AST:platelet▪ Decreased albumin or platelet count

Noureddin. Clin Liver Dis. 2012;1:104. clinicaloptions.com


a. Metformin

b. Ursodeoxycholic acid

c. Vitamin E

d. Pioglitazone

e. None of the above

10. New evidence suggests that which of the following is an effectivepharmacotherapy for NASH?

a. Metformin

b. Ursodeoxycholic acid

c. Vitamin E (400 IU bid)

d. Pioglitazone (30 mg qd)

e. None of the above

10. New evidence suggests that which of the following is an effectivepharmacotherapy for NASH?

Bril & Cusi, Diabetes Care 2017 40:419-430 clinicaloptions.com

Treatment of NASH

Treatment of NASH

Pioglitazone

Lifestyle Intervention

Weight reduction of 8-10%

Second-line therapies

Pharmacological treatment or

metabolic surgery

No response Not achieved

Control of other CV risk factors

Elevated A1C Elevated BP

Glucose controlMetformin

Blood pressure control

ARB or ACEI

Lipid-lowering therapyStatin

Add pioglitazone Add GLP-1RA or SGLT-2 inhibitors

Second-line therapies

Add fibrates to statins

Elevated TG and low HDL

Prediabetes or T2DM and/or obesity Definite NASH


EASO European guidelinesClinical care pathway for overweight and adults with obesity

Yumuk et al. Obes Facts. 2015;8:402-24.

Determine degree of overweight and obesity• Measure height (cm) and weight (kg) and calculate BMI (kg/m2)• Measure WC (cm)

If BMI ≥25 kg/m2* or WC ≥94 cm for men* or WC ≥80 cm for women*

AssessPresenting symptoms and underlying causes, comorbidities and health risks, weight loss history, lifestyle (nutrition and physical activity), eating behaviour, depression and mood disorders, chronic psychological stress, potential of weight loss to improve health, motivation to change, barriers to weight loss

Set goals and propose realistic, individualised and sustainable lifestyle changes at the long termWeight loss goal

5–15% of body weight or 0.5–1.0 kg/week

Management• Nutrition (reduce energy intake by 500-1000 kcal/day)• Physical activity (initially at least 150 min/week moderate aerobic exercise combined with 1–3 sessions/week

resistance exercise)• Cognitive behaviour therapy• Pharmacotherapy (BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with comorbidities, adjunct to lifestyle modification)• Bariatric/metabolic surgery (BMI ≥40 kg/m2 or BMI between 35.0–39.9 kg/m2 + comorbidities or BMI between

30.0–34.9 kg/m2 with T2D on individual basis. Consider if other weight loss attempts fail; requires lifelong medical prevention)

• Prevention and treatment of comorbidities

Weight loss goal is achieved

Assess effect on comorbidities, weight maintenance and weight regain• Regular monitoring of weight, BMI and WC• Reinforce lifestyle modification• Address other risk factors

Consider referring to obesity specialist services or Collaborating Centres for Obesity Management • If the person has complex disease states or needs that can

not be managed in primary or secondary care• If the underlying causes of obesity need to be assessed• If conventional treatment has failed• If specialist interventions are needed• If bariatric/metabolic surgery is needed

*BMI and WC cut-off points are different for some ethnic groups. T2D, type 2 diabetes; WC, waist circumference

Weight Loss: Weight Management Medications

Drug Daily Dose for Weight Loss MoAMean Weight Loss,

% Total Body WeightImproves NAFLD?

Orlistat[1,2] 360 mg POLipase inhibitor 8.78 (8.30 in NASH[2])

In small studiesbut not RCT[3]

Lorcaserin[1] 20 mg PO 5-HT2c serotonin receptor agonist

7.9 Not studied

Phentermine/topiramate[1]

7.5/46 mgor 15/92 mg PO

Multiple 9.6-12.4 Not studied

Naltrexone/bupropion[1]

32/360 mg POtitrated to max

Multiple 8.1 Not studied

Liraglutide[1] 3 mg SCtitrated to max

GLP-1 agonist 9.2 (5.5 in NASH*[4]) LEAN study*[4]

Mean efficacy criterion: significant difference in mean proportion achieving weight loss ≥ 5% drug vs placebo Categorical efficacy criterion: weight loss ≥ 5% in ≥ 35% of participants, with a significant and ≥ 2-fold difference in proportion achieving this in drug vs placebo groups

clinicaloptions.com1. Garvey. Endocr Pract. 2016;(suppl 3):1. 2. Harrison. Hepatology. 2009;49:80 3. Wang. Biomed Rep. 2018;9:90. 4. Armstrong. Lancet. 2015;387:679.

*Studied in NASH at 1.8-mg dose approved for diabetes, not 3-mg dose approved for weight loss.


Currently Available Pharmacologic Agents (Off Label)

Targeting Insulin Resistance

.

CompoundMechanism of

ActionTrial Primary Endpoint(s)

AASLD Recommendation as NASH Treatment

Metformin Multiple Multiple studies Various Not recommended

Pioglitazone PPARγ agonistPIVENS

Multiple studiesImprovement in NAS ≥ 2

without fibrosis worseningMay be used in patients with

biopsy-proven NASH

LiraglutideGLP-1 receptor

agonistLEAN*

Resolution of NASH without fibrosis worsening

Premature to consider GLP-1 receptor agonists


ActionTrial Name Primary Endpoint(s)


Vitamin E AntioxidantPIVENSTONIC

Improvement in NAS ≥ 2 without fibrosis worsening

May be used in nondiabeticadults with biopsy-proven

NASH

Targeting Oxidative Stress

*Phase IIb.



Targeting Pathophysiologic Processes

Steatohepatitis (NASH) CirrhosisNormal Liver Steatosis (NAFL)

Targets related to insulin resistance

and/or lipid metabolism

Targets related to lipotoxicity and oxidative stress

Targets related to inflammation and immune activation

Targets related to cell death

(apoptosis and necrosis)

Targets related to fibrogenesis and

collagen turnover

PPARγ: Pioglitazone PPARα/∂: ElafibranorGLP-1: Liraglutide,

SemaglutideFXR: OCA, GS-9674,

Tropifexor ACC: GS-0976 FGF19: NGM282SCD1: Aramchol Vitamin EFGF21: BMS-986036THR-β: MGL-3196, VK 2807

CCR2/5: CenicrivirocTLR4: JKB-121

ASK1: Selonsertib Galectin: GR-MD-02

NAFLD

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Antidiabetic Medications in NAFLD (Off Label)

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ActionTrial Primary Endpoint(s) Results


Metformin[1] Multiple Multiple studiesImprovement in liver

histologyNegative Not recommended

Sitagliptin[2] DPP-4 inhibitor Phase IIaChange in liver fat

by MRI-PDFFNegative Not addressed

Pioglitazone[1] PPARγ agonistPhase III PIVENS Multiple studies

Improvement in NAS ≥ 2 without fibrosis worsening

PositiveMay be used in patients

with biopsy-proven NASH

Liraglutide[1] GLP-1 receptor agonist

Phase IIb LEANResolution of NASH without

fibrosis worseningPositive

Premature to consider GLP-1 receptor agonists

Semaglutide[3] GLP-1 receptor agonist

Phase II Change in body weight, ALT PositivePremature to consider

GLP-1 receptor agonists

Exenatide[4] GLP-1 receptor agonist

Phase IIb Unpublished UnpublishedPremature to consider

GLP-1 receptor agonists

Empagliflozin[5] SGLT2 inhibitor E-LIFT Liver fat by MRI-PDFF Positive Not addressed

Canagliflozin[6] SGLT2 inhibitor Multiple Liver triglycerides by 1H-MRS Positive Not addressed

1.Chalasani. Hepatology. 2018;67:328. 2. Cui. J Hepatol. 2016;65:369. 3. O’Neil. Lancet. 2018;392:637. 4. Townsend. Aliment Pharmacol Ther. 2017;46:494. 5. Kuchay. Diabetes Care. 2018;41:1801. 6. Cusi. Diabetes Obes Metab. 2018;1-10.


Weight LossOutcome Among Patients

Achieving Weight LossPatients Sustaining

Weight Loss at 1 Yr[1]

≥ 10%[1] Fibrosis regression

(45% of patients)[1]

< 10%

≥ 7%[1] NASH resolution(64% to 90% of patients)*

18%

≥ 5%[1-3] Ballooning/inflammation improvement(41% to 100% of patients)* 30%

≥ 3%[1-4] Steatosis improvement(35% to 100% of patients*)

Not reported

Percentage of weight loss associated with histologic improvement in NAFLD

1. Vilar-Gomez. Gastroenterology. 2015;149:367. 2. Promrat. Hepatology. 2010;51:121. 3. Harrison. Hepatology. 2009;49:80. 4. Wong. J Hepatol. 2013;59:536. clinicaloptions.com

*Depending on degree of weight loss.


Bariatric surgery improves liver histology in people with obesity

• Prospective study in people with severe obesity patients with biopsy-validated NASH, ≥ 1 comorbidity factor for > 5 yrs, no chronic liver disease (N = 109)[1]

• Meta-analysis of 32 cohort studies of bariatric surgery in obese patients(n = 3093 biopsies)[2]

clinicaloptions.com1. Lassailly. Gastroenterology. 2015;149:379. 2. Lee. Clin Gastroenterol Hepatol. 2018;[Epub].

Characteristic Outcome

Mean reduction in NAS, points 2.39

Patients with resolution of NAFLD components, %▪ Steatosis▪ Inflammation▪ Ballooning▪ Fibrosis

66507640

Patients with new or worsening histologic NAFLD components, %

12

Outcome Baseline After 1 Yr

Mean BMI SD 49.3 8.2 37.4 7.0

Patients with NASH resolution, %

NA 85.0

Patients with fibrosis reduction, %

NA 33.8


Aminotransferases that remain elevated despite loss of ≧ 5% of body weight

Clinical features of advanced liver disease (eg. ascites, splenomegaly, jaundice)

Steatohepatitis on liver biopsy

Advanced fibrosis (stage≧ F3) on a non-invasive liver assessment

Pts who develop cirrhosis and have complications (eg. ascites, variceal bleeding) ora model for end-stage liver disease (1MELD) score ≧ 10 should be referred for a liver transplantation evaluation

When to refer to a hepatologist?

1MELD: Dx at least twice past week; serum creatinine, bilirubin, sodium and INR

An Integrated approach to obesity, diabetes, and NAFLD

• Multidisciplinary: hepatologist,

endocrinologist, cardiologist,

nutritionist, psychologist, exercise

specialist

• Cardiovascular risk reduction is

essential

– Manage dyslipidemia, hypertension,

smoking

• Screen and treat other comorbid

conditions

– Obstructive sleep apnea,

degenerative joint disease

• Choose diabetes medications that

reduce weight and liver fat

• Lifestyle interventions for all;

add obesity pharmacotherapy and

bariatric surgery when appropriate

• In patients with advanced liver

disease, choose or dose drugs for

diabetes or weight management

appropriately

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Transcript of Non-alcoholic fatty liver disease€¦ · Non-alcoholic liver disease (NAFLD) Steatohepatitis...