Jazwinski - NASH ACG June 2014 - American College of...
Transcript of Jazwinski - NASH ACG June 2014 - American College of...
Alison B. Jazwinski, MD, MHS
Management of Complications of NASH:
When to Biopsy? How to Treat?
Alison Jazwinski MD MHSAlison Jazwinski, MD, MHSAssistant Professor
University of Pittsburgh Medical Center
Clinical Case
• 31 yo female referred for evaluation of elevated liver enzymes x 1yearelevated liver enzymes x 1year.
• PMH: mild hyperlipidemia, BMI 28.2• Alcohol use described to be approximately 2
drinks per month. No viral hepatitis risk factors, autoimmune disease.
• Family history of diabetes, hypertension. Also notes that her father had elevated liver enzymes
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Alison B. Jazwinski, MD, MHS
Clinical Case
• ALT 346, AST 157, Alk Phos 115, Tbili 0.5• Viral hepatitis, autoimmune, and genetic
serologic markers are negative• RUQ US reveals hepatomegaly with fatty
infiltration
Would you do a liver biopsy?
Clinical Case
• Liver biopsy:– Severe macrovesicular steatosis involving >75% of
hepatocytes– NAFLD activity score 7 of 8– Fibrosis 2 of 4
How would you manage this patient?
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Alison B. Jazwinski, MD, MHS
Overview• Background
– Diagnosis and definitions– Natural historyNatural history
• Who to biopsy?– Indications for biopsy– Noninvasive markers
• How to treat– Lifestyle modification– Pharmacologic agents– Bariatric Surgery
Diagnosis of NAFLD
1. Evidence of hepatic steatosis (imaging/histology)
2. No significant alcohol consumption
3. No competing etiologies for steatosis
4. No co-existing causes for chronic liver disease
Chalasani N, et al. Hepatology. 2012: 2005
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Alison B. Jazwinski, MD, MHS
NAFLD and Alcohol Consumption
d k k d d k>21 drinks per week in men and >14 drinks per week in women is a reasonable definition for
significant alcohol consumption when evaluating patients with suspected NAFLD
Chalasani N, et al. Hepatology. 2012: 2005
GENETIC-Abetalipoproteinemia
Other conditions associated with steatosis
-Weber-Christian disease-Galactosemia
-Type 1 glycogen storage disease
-Wilson’s disease-Tyrosinemia
-Systemic carnitinedeficiency
NUTRITIONAL/INTESTINAL-Surgical: J-I bypass, B-P diversion
-TPN-Rapid weight loss
-Severe protein calorie malnutrition
-Jejunal diverticulosis with
DRUGS/TOXINS-Amiodarone
-Methotrexate-Tamoxifen/synthetic estrogens
Gl i idjbacterial overgrowth -Glucocorticoids
-Nucleoside analogs-Calcium channel blockers
Chalasani N, et al. Hepatology. 2012: 2005
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Alison B. Jazwinski, MD, MHS
DefinitionsNAFLD: Encompasses the entire spectrum of
fatty liver disease in individuals without significant alcohol consumption
Chalasani N, et al. Hepatology. 2012: 2005
DefinitionsNAFL: Presence of hepatic steatosis with no
evidence of hepatocellular injuryevidence of hepatocellular injury
Chalasani N, et al. Hepatology. 2012: 2005Brunt E. Clinical Liver Disease 2012:107
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Alison B. Jazwinski, MD, MHS
DefinitionsNASH: Presence of hepatic steatosis and
inflammation with hepatocyte injury p y j y(ballooning) with or without fibrosis
Chalasani N, et al. Hepatology. 2012: 2005Brunt E. Clinical Liver Disease 2012:107
Definitions
• NASH cirrhosis: present of cirrhosis with current or previous histologic evidence ofcurrent or previous histologic evidence of steatosis or steatohepatitis
• Cryptogenic cirrhosis: presence of cirrhosis with no obvious etiology. Patients with
t i i h i h il i h dcryptogenic cirrhosis are heavily enriched with metabolic risk factors such as obesity and metabolic syndrome
Chalasani N, et al. Hepatology. 2012: 2005
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Alison B. Jazwinski, MD, MHS
Natural History
• Patient with NAFLD have increased overall mortality compared to the general populationmortality compared to the general population
• The most common cause of death in patients with NAFL and NASH is cardiovascular disease
• Patients with NASH (but not NAFL) have an increased liver-related mortality rate
Chalasani N, et al. Hepatology. 2012: 2005
What is the role of liver biopsy?
1. Differentiate NAFL from NASH1. Differentiate NAFL from NASH
2. Stage disease
3. Rule out concurrent liver diseases (particularly iron overload and autoimmune)
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Alison B. Jazwinski, MD, MHS
Noninvasive markers of fibrosisTest name/Study(mild vs severe fibrosis)
Markers AUROCTraining
AUROCValidation
ELF Hyaluronic acic, TIMP1, P3NP NR 0.9
Modified ELF ELF + BMI, albumin, platelet count, albumin, AST/ALT ratio
NR 0.98
NAFLD fibrosis score Age, BMI, hyperglycemia, platelet count, albumin, AST/ALT ratio
0.77-0.93 NR
Fibrometer Glucose, AST, age, weight, ferritin, ALT, platelet count
0.929 0.888
Fibro test Α2-macroglobulin, haptoglobin,l b l
0.932 0.81apolipoprotein A1, GGT, tbili, ALT
BARD BMI, AST/ALT ratio, DM 0.81 0.78
BAAT BMT, ALT, TG 0.84 NR
FIB-4 Age, AST, ALT, platelet count 0.802 0.86
APRI AST/platelet x 100 0.86 NRAdapted from Noureddin and Loomba. Clinical Liver Disease 2012:104
Elevated ALT/AST and steatosis on imaging
Co-existing liver disease, possible
alternative dxYesNo
Algorithm for Liver biopsy
Work-up for alternative dx, biopsy
if needed
Diabetes or metabolic syndrome
BiopsyAST>ALT OR
Low serum albumin ORLow platelet count
No
No
Yes
Yes
Adapted from Noureddin and Loomba. Clinical Liver Disease 2012:104
BiopsyAge >65 OR
Family history of diabetes OR Family history of cirrhosis
ConsiderBiopsy
Re-assess q6mo
NoYes
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Alison B. Jazwinski, MD, MHS
Management of NASH
• Lifestyle interventions– Weight loss
• 3-5% of body weight improves steatosis• 10% of body weight improves inflammatory
activity
– Exercise 2-3 sessions per week for 30-60 minutes improves NAFLD even in absence of weight loss
Chalasani N, et al. Hepatology. 2012: 2005
Pharmacologic Agents
Ineffective Treatments:
Metformin
Ursodiol
Potential Treatments:
Statins
Pentoxifylline
Treatments for Specific groups
(guideline based):
Pioglitazone
Orlistat Obeticholic Acid
Probiotics
Vitamin E
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Alison B. Jazwinski, MD, MHS
Pioglitazone
Pros:Improvement in
Cons:-No improvement in fibrosis
“Pioglitazone can be used to treat steatohepatitis in patients with
-Improvement in steatosis and inflammation
p-Concerns regarding risk of
cardiovascular disease, congestive heart failure, bladder cancer and
bone loss-Weight gain
“Pioglitazone can be used to treat steatohepatitis in patients with biopsy proven-NASH. However it should be noted that the
majority of the patients that participated in clinical trials were non-diabetic and that long term safety and efficacy of pioglitazone in
patients with NASH is not established.” (Strength – 1, Evidence – B)
Chalasani N, et al. Hepatology. 2012: 2005
Vitamin EPros:
-Decrease in aminotransferases
Cons:-No effect on fibrosis
-Concerns about i d ll
“Vitamin E administered at daily dose of 800 IU/day improves liver histology in non-diabetic adults with biopsy-proven NASH and
therefore it should be considered first line pharmacotherapy for this
-Improvement in steatosis, inflammation, ballooning
increased all cause mortality and prostate
cancer in men
therefore it should be considered first line pharmacotherapy for this patient population. (Strength – 1, Quality – B).
“Until further data supporting its effectiveness become available, vitamin E is not recommended to treat NASH in diabetic patients,
NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.” (Strength – 1, Quality – B)
Chalasani N, et al. Hepatology. 2012: 2005
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Alison B. Jazwinski, MD, MHS
Bariatric Surgery
Lap Band
Roux-en-Y
Gastric sleeveWhattacheril and Chalasani. Clinical Liver Disease 2012:118
Bariatric Surgery
• Most studies show significant improvement in steatosis and inflammationsteatosis and inflammation
• May lead to increased fibrosis
• Not well studied in patients with cirrhosis
• Too early to recommend primarily for NASH but may have benefit
Whattacheril and Chalasani. Clinical Liver Disease 2012:118
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Alison B. Jazwinski, MD, MHS
Vitamin D deficiency
Hyper-ferritinemia
Pancreatic steatosis
Polycystic
Hypo-thyroidism
NAFLD
Colonic Adenomas
Coronary Artery
Disease
Hyper-uricemia
deficiencyOvary
Syndrome
AdenomasDiabetes
HypertensionObstructive
Sleep Apnea
Established and emerging associated diseases
Clinical Case Discussion
• Recommended – Weight loss of 10-15 lbs (starting weight 165lbs)– Regular exercise 2-3x per week for 30-60 minutes– Probiotics– Vitamin E 800IU daily
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Alison B. Jazwinski, MD, MHS
Take Home Points• NAFL is considered relatively benign, while NASH is a
progressive disease
• Biopsy should be performed in patients at high risk of having advanced disease – Patients with metabolic syndrome and elevated liver
enzymes
• Treatments are still limited for NASH– Vitamin E for patients without diabetes– Pioglitazone?– Lifestyle modification
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