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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