1. Metabolic Syndrome and NAFLD
Dr. Mohamed A. Alsenbesy Assistant Professor & Head of Internal Medicine Department Qena Faculty of Medicine South Valley University (SVU), Egypt
Qena University Hospital

2. What is Metabolic Syndrome (MetS)??
A cluster of cardiovascular risk factors associated with obesity and insulin resistance.
is dramatically increasing in Western and developing countries.
Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of MetS.

4. Mtabolic Syndrome WHO (1998) AACE (2003) NCEP ATP III (2005)
WHO (1998)
AACE (2003)
NCEP ATP III (2005)
IDF (2005)
IDF (2009)
Criteria
IGT, IFG, T2D, or reduced insulin sensitivity plus any two of the following
IGT or IFG plus any of the following
Any three of the following
Increased WC plus any two of the following
Three out of five of the following
Obesity
Men:WHR> 0.90;Wome n:WHR>0.8 5 and/or BMI >30 kg/m 2
BMI ≥25 kg/m 2
WC ≥102 cm in men or ≥88 cm in women
Population- specific increased WC cutoffs
Population- and country-specific WC cutoffs
Glucose
IGT, IFG,or T2D
IGT or lFG
≥100 mg/dl(inclu ding T2D)
≥100 mg/dL
Triglycerides (TG)
TG ≥150 mg/dl
TG ≥150 mg/dl or on therapy lowering TG
TG ≥150 mg/dl
HDL- cholesterol( HDL-C)
HDL-C<40 mg/dl in men or HDL-C<50 mg/dl in women
HDL-C <40 mg/dl in men or HDL-C <50 mg/dl in women on therapy increasing HDL-C
HDL-C <40 mg/dl in men or HDL-C<50 mg/dl in women on therapy increasing HDL-C
HDL-C <40 mg/dl in men or HDL-C <50 mg/dl in women
Blood pressure
≥140/90 mmHg
≥130/85 mmHg
≥130/85 mmHg or on antihyperte nsive therapy
≥130/85 mmHg or on antihypertensive therapy

5. Diagnosis of Metabolic Syndrome
↑Waist circumference ≥89 ♀ - ≥102 cm♂
↑Triglycerides >150 mg/dL)
↓(HDL) cholesterol <40 ♂ - <50 mg/dL ♀
↑ Blood pressure ≥130/85 mm Hg
↑Fasting blood sugar ≥100 mg/dL
IDF 2015

7. Insulin effects on lipid Metabolism
↓ adipose tissue lipolysis.
↑ de novo lipogenesis (liver & adipose tissue).
↑ Hepatic VLDL Export
Insulin has a fat sparing effect

9. Insulin Resistance ↓ Utilisation of Glucose& ↑ Gluconeogenesis.
↑ Adipose tissue Lypolysis (failure to supress).
Preserved metabolic pathway for de novo hepatic Lipogenesis (selective Insulin resistance)

10. HOMA Model for IR

13. NAFLD
(NAFLD) is a clinico-pathological syndrome that ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) with varying amounts of fibrosis, and cirrhosis (Rinella,et.al JAMA 2015)

14. NAFLD To define (NAFLD) :
(A) Evidence of hepatic steatosis, either by imaging or by histology .
(B) No secondary causes of hepatic fat accumulation e.g significant alcohol consumption, use of steatogenic medications or hereditary disorders (AASLD Guidelines, 2012)

15. Steatosis ALD: > 21 drinks/week for ♂ - 14 for ♀ Amiodarone
Medications:
Amiodarone
Methotrexate
Tamoxifen
Corticosteroids
Diltiazem
Valproic acid

16. Common Causes of Secondary Hepatic Steatosis
Macrovesicular steatosis
- Excessive alcohol consumption
- Hepatitis C (genotype 3)
- Wilson’s disease
- Lipodystrophy
- Starvation
- Parenteral nutrition
- Abetalipoproteinemia
- Medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids)

17. Microvesicular steatosis
- Reye’s syndrome
- Medications (valproate, anti-retroviral medicines)
- Acute fatty liver of pregnancy
- HELLP syndrome
- Inborn errors of metabolism (e.g., LCAT deficiency, cholesterol ester storage disease, Wolman disease)

18. Fatty liver Normal liver
Liver is divided histologically into lobules. The center of the lobule is the central vein. At the periphery of the lobule are portal triads. Functionally, the liver can be divided into three zones, based upon oxygen supply. Zone 1 encircles the portal tracts where the oxygenated blood from hepatic arteries enters. Zone 3 is located around central veins, where oxygenation is poor. Zone 2 is located in between.

19. NAFLD: Emerging association
Polycystic ovary syndrome
Obstructive sleep apnea
Hypopituitarism
Hypogonadism
Pancreatic-duodenal resection

20. NAFLD
NAFLD is the most common liver disorder in Western countries,affecting 17–46% (AASLD Guidelines, 2012)
4th most common reason for liver transplant
Up to 20-40% adults
6 million children

21. Prevalence of NAFLD worldwide
20-30% in Europe according to 2 large multicenter population studies.
Asia: increased from 13% to 30% in Japan and reported in lower BMI
Africa: 90% in one study in Nigeria and maybe common in Egypt but this requires further studies. (clinical Dilemmas in NAFLD, 2016)

22. DM & CVD Mortality

23. NAFLD is a risk for CVS Eevents!!???
NAFLD is associated with an increased risk of fatal and non-fatal CVD events.
(Giovanni, J of Hepatol., 2016)

24. Insulin Resistance (IR) and NASH
Mechanism of inflammation is uncertain, but IR plays a role.
IR is proinflammatory with raised Cytokines & acute phase proteins.
IL6, TNF-α and IL-1β, CRP
↑ 3-hydroxbuterate and Acetoacetate in NASH more than simple steatosis.

25. NASH
NASH related HCC is the 2nd leading cause of HCC –related transplantation
(clinical Dilemmas in NAFLD, 2016)

26. Clinical Exceptions
Adults with conventionally treated hypopituitarism , who are deficient in growth hormones, are insulin resistant and have metabolic syndrome NAFLD?????
Genetic insulin receptor mutation

27. Diagnosis and Treatment
?????????????????????
US is less sensitve but mostly used.
Immaging and biopsy
Non invasive : Fibroscan (Transient Elastography) - NAFLD Fibrosis Score and cytokeratin-18

28. Fibroscan 502, Echosens – France Qena University Hospital

29. Future Treatments Modulating the gut microbiome. Adiponectin agonists.
GLP-1 analogues.
CC Chmokine receptor 2 & 5 antagonists.
Imm124-E

30. Inttragastric Balloon for Treatment of Obesity
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Inttragastric Balloon for Treatment of Obesity
Qena University Hospital

31. Thank You