Non-alcoholic fatty liver disease€¦ · Non-alcoholic liver disease (NAFLD) Steatohepatitis...
Transcript of 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
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?
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?
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?
Chalasani. Hepatology. 2018;67:328. clinicaloptions.com
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?
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?
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?
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?
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
CompoundMechanism of
ActionTrial Name Primary Endpoint(s)
AASLD Recommendation as NASH Treatment
Vitamin E AntioxidantPIVENSTONIC
Improvement in NAS ≥ 2 without fibrosis worsening
May be used in nondiabeticadults with biopsy-proven
NASH
Targeting Oxidative Stress
*Phase IIb.
Chalasani. Hepatology. 2018;67:328. clinicaloptions.com
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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CompoundMechanism of
ActionTrial Primary Endpoint(s) Results
AASLD Recommendation as NASH Treatment
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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