I. Jean Davis, PhD, PA, AAHIVS Howard University College of Medicine.
Evaluation and Management of the HIV Patient with Non ......Evaluation and Management of the HIV...
Transcript of Evaluation and Management of the HIV Patient with Non ......Evaluation and Management of the HIV...
Evaluation and Management of the HIV Patient with Non Alcoholic Fatty Liver (NAFL)
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Steven C. Zell MD / AAHIVS Nevada AIDS ETC Key Educator
Program Director Primary Care Track
Rationale for Diagnosing NASH
Hepatic Steatosis
NAFL Basic definition: non alcoholic fatty deposition of the liver
Commonly referred to as Most patients will be in Equilibrium
Fat accumulation in the liver is associated with several features of insulin resistance even in
individuals whose weight is normal or who are moderately overweight
Non-inflammatory
No damage
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l i l ~
NASH basic definition: NAFL producing an adverse inflammatory response
The NAFLD Continuum
Steatohepatitis “NASH”
Cirrhosis Normal Liver Steatosis “NAFL”
NAFLD
Slide credit: clinicaloptions.com Chalasani. Hepatology. 2018;67:328.
Fatty liver with inflammation and
hepatocyte ballooning
Wor dw de preva ence: 25% 1.5% to 6.45%
Fatty liver without inflammation or
hepatocyte ballooning
Increasing fibrosis leading to cirrhosis,
hepatocellular carcinoma
steatosis, liver cell injury, and the unique zone 3 “chicken wire” fibrosis
Normal Histology of the LIver
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Histologic Biopsy Stages
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Y o u n o ssi Z M , et a l. H ep ato lo g y. 2016;64:73-84 .
Meta-analysis: NAFLD diagnosed by imaging (US, CT, MRI/SPECT; n=45 studies).
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Estimated Global Prevalence of NAFLD: 25%
24%
31%
24%
13%
32% 27%
Younossi. Hepatology. 2016;64:73. Slide credit: clinicaloptions.com
Prevalence and Natural History: Influence of HIV
40 % by 15% (NASH) by 20% = Cirrhosis
100 by 0.4 by 0.15 by 0.20 = 1.2 persons per 100
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Who Is at Risk for NASH and Advanced Fibrosis?
Risk Factor for NAFLD[1 AASLD Recommendation[1 EASL EASD EASO Recommendation[2
Type 2 diabetes In type 2 diabetes, suspect
Obesity
Dyslipidemia
Metabolic syndrome
Polycystic ovary syndrome
NAFLD and NASH and determine patient’s risk of
advanced fibrosis Increasing number of metabolic diseases =
increasing risk of progressive liver disease
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. Slide credit: clinicaloptions.com
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Liver Enzymes: Inadequate in Assessing NAFLD/NASH
• ALT (SGPT) can be normal in > 50% of individuals with NASH,
• ALT normal in 80% of individuals with NAFLD[1,2]
• ALT can be elevated in > 50% of individuals with NAFLD but without NASH
• In NAFLD, ALT is neither indicative nor predictive of NASH or fibrosis stage[3]: ‒ AST / ALT ratio of < 1.0 suggests non-ETOH liver damage
‒ ALT and AST not sensitive for NAFLD/NASH
1. Browning. Hepatology. 2004;40:1387. 2. Dyson. Frontline Gastroenterol. 2014;5:211. 3. Mofrad. Hepatology. 2003;37:1286.
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Identifying NASH: strategies to find fibrosis
Slide credit: clinicaloptions.com
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Liver Biopsy: The Imperfect Gold Standard
Isolated Steatosis Steatohepatitis/NASH
• Benefits • Limitations
‒ Establishes diagnosis of NASH ‒ Risk of bleeding, pain
‒ Assesses early fibrosis ‒ Sampling variability (especially
with IR biopsies if they are small) ‒ Determines prognosis
‒ Long interval between serial ‒ Rules out other processes: biopsies to monitor disease
alpha-1 antitrypsin, iron overload, progression autoimmune component
‒ Cost
Rockey. Hepatology. 2009;49:1017. Kleiner. Hepatology 2005;41:1313. Bedossa. Hepatology. 2012;56:1751. Slide credit: clinicaloptions.com
Identifying NASH and ≥ F2 Fibrosis: Newer Strategies
Because of limitations of liver enzymes, US, CT, and liver biopsy, better strategies and diagnostic tools are needed
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Noninvasive Staging Predictors of Advanced Fibrosis in NAFLD: Many Serum-Based Scores
Serum Based Score Components APRI (AST to platelet ratio index)[1] • AST, platelet count
FIB-4[1] • Age, ALT, AST, platelet count
• Age, ALT, AST, platelet count, BMI, albumin, NAFLD fibrosis score[2]
impaired fasting glucose/diabetes
BARD[3] • ALT, AST (AST/ALT ratio), BMI, diabetes
• Good negative predictive value for ruling out fibrosis
• Calculators freely available on the internet
• Various complex commercial tests also available
Slide credit: clinicaloptions.com 1. University of Washington. Clinical Calculators. 2. Dowman. Aliment Pharmacol. Ther. 2011;33:525. 3. Cichoż-Lach. 2012;18:CR735.
Noninvasive Staging of NASH: Imaging
Imaging Comments • Can be point of care • Can rule in/out advanced fibrosis
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Vibration-controlled transient elastography (VCTE) -- FibroScan
2D shear wave elastography • May require radiology referral but can be point of care with minimal training
MR elastography/MR spectroscopy/ • Requires radiology referral liver multiscan • Most accurate of the imaging modalities
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Summary
• Crucial to identify patients with NASH and patients with significant fibrosis
‒ These are the NAFLD patients at risk of progressing to advanced disease
• Lab studies • Imaging
‒ Liver enzymes such as ALT not ‒ Ultrasound showing cirrhosis sensitive for NAFLD/NASH
‒ Fatty infiltration= good sensitivity ‒ Noninvasive serum tests/scores have
good NPV; can identify those unlikely ‒ Inadequate for diagnosis of fibrosis to have NASH and significant fibrosis
‒ NASH Fibrosure ‒ CAT / MRI likely not cost effective
‒ Prevalence of NAFL
Slide credit: clinicaloptions.com
www.thelancet.com/gastrohep Vol2 March2017
Pathogenesis of NAFL to NASH and Cirrhosis
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Lifestyle Modifications for NAFL
• Weight loss to reduce BMI (>10%)
• Avoid alcohol / tyelnol / NSAIDs (in moderation)
• Screen for dyslipidemia
• Screen for co infection w Hep C and B
• R/o for HHE w Ferum saturation levels / consider ANA
• Screen for Insulin resistance: 2 hr. post-prandial BS f/u oral glucose load
• Metabolic syndrome: waist / IR / Htn / DLD
50 mg given= 75 IU units
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