ueda2015 nafld, diabetes heart_dr.abdel-khalek

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التفضلالرجاء

المحمولقبأغالقصوىضرورةهناككاناذااو

وضعفياجعله

silentاوVibration

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Prof.& consultant Gastroenterology

&Diabetes

Military Medical Academy

NAFLD; Diabetes

&Heart

1- NAFLD

DV&C2- Its relation to DM

3- TT of NAFLD (diabetes

comorbidity)

A multi-faceted disease

for multi-disciplinary

preventive intervention

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A variably defined aggregate of disorders related to:

Insulin resistance

Diabetes type II

NAFLD

- Dixon JB, et al. Gastroenterology 2002;122-

- Expert panel on Detection Evaluation, and Treatment of High Blood

Cholesterol in Adults. JAMA 2001;285

NAFLD

The consequences

of NAFLD are

not confined to

the liver.

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Crosstalk of

visceral adipose

tissue and the

liver.

Buechler C, et al: WJG June , 2011 V. 17 (23)

Mitochondrial dysfunction (respiratory chain deficiency) , modulated by some genetic polymorphismT Asselah etal; Gut 2006;55

Systemic inflammation

hepatic IR

gut-liver

axis

TLR

Yasuhiro Miyake & Kazuhide Yamamoto

: Hepatology Research 2013; 43

In NAFLD,

Intestinal permeability

&the prevalence of

SIBO are increased.

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Vicious circle linking fatty liver to diabetes and diabetes to

progressive liver injury

in predisposed individuals

long-lasting/ decompensated

alone, or in the setting of MS

( May in non-cirrhotic)

NASH ,Pre-

diabetes,

+GGT &

triglycerides

and

insufficient

physical

activity.

Paola Loria, et al : Hepatology Research 2013; 43

T2 DM, 30-60% of NASH pat.

“Red flag”

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There is a very high prevalence of NAFLD (>55%) in individuals with T2DM.

Chalasani N, et al : HEPATOLOGY, June 2012

Also T2 DM is present in 30%-45% of patients with non alcoholic steato hepatitis (NASH) .

Harrison SA. : J Clin Gastroenterol 2006; 40

NAFLD is more frequent among obese (76%), and it is almost universal among diabetic people who are morbidly obese.

Del Gaudio A, et al : Obes Surg 2002;12

Epidemiology of diabetes & NAFLD

8 Ballestri S et al . World J Gastroenterol 2014 February 21; 20(7)g-GT= steatosis- IR&OS-

CAD &higher mortality

Atherogenic dyslipidemia and the hepatic secretion of

several pathogenic mediators into the bloodstream

Possible mechanisms leading to cardiac &arrhythmogenic complications in NAFLD

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: pentoxifyllineDiabetes

Incretins

Sylimarin

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NAFLD/NASH pathogenesis link treatmentComplex and multi-faceted disease often calling for multi-

disciplinary intervention.

- Statins, Ezitemibe

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Insulin sensitizers

Metformin improves insulin sensitivity and ALT-AST. It has no significant effect on liver histology.

According to current data, it can be given in patients with both NAFLD/NASH and type 2 DM.

TZDs improve insulin sensitivity, serum ALT-AST levels and histology in some cases, but there are some concerns about the safety of long-term therapy.These drugs are the best choice for the treatment of NAFLD in patients with T2 DM who are also candidates for ISA (Selection of appropriate patients for avoiding side effects)

Zeynel Abidin O. , Abdurrahman Kadayifci :World J Hepatol 2014April 27; 6(4)

TZDs decrease Risk of HCC development

Lai SW, et al : Am J Gastroenterol. 2012 Jan;107(1)

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Hypothesized that in NAFLD the DPP-4 enzymatic

activity is increased which might contribute to the development of type 2 diabetes and metabolic deterioration.

Incretins in non alcoholic fatty liver disease

Ga´bor Firneisz, et al : PLoS ONE ,August 2010 Vol 5 Issue 8

T Iwasaki, et al. www.hepato-gastroenterology.org 2011; 58(112): Ahead of print

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DPP-4 inhibitors might offer prevention of metabolic deterioration& control

of diabetes in NAFLD. Also may have impact on liver fibrosis (Effect on

hepatic stellate cells ).

A recent meta-analysis including 4442 patients indicated that liraglutide decreased aminotransferase levels and that this effect was dose-dependent.

A pilot study demonstrated that treatment with liraglutide had a good safety

profile and significantly improved liver function and histological features in

NASH patients with GI.

Armstrong MJ, Aliment Pharmacol Ther 2013;37

Eguchi Y, et al. : Hepatol Res. 2014 May 4

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Niemann-Pick C1-Like1(NPC1L1)Inhibitors. Ezetimibe

Hepatic NPC1L1 may facilitate hepatic cholesterol accumulation and ezetimibe may be a potential candidate for NAFLD.

In clinical trials, albeit on a small scale, ezetimibe improved biochemical parameters , hepatic enzymes and the histology.

M. Enjoji & M.Nakamuta, World Journal of Gastroenterology, vol. 16,no. 7, 2010.

M. Enjoji, et al., Lipids in Health and Disease, vol. 9, article 29, 2010.

*Statins can be used to treat dyslipidemia in patients with

NAFLD and NASH without increased risk for drug-induced liver

injury . Untill now , statins should not be used to specifically

treat NASH. (Strength – 1, Quality – B)

*Omega-3polyunsaturated fatty acid may be considered as the

first line agent to treat hypertriglyceridemia in NAFLD, but

not as specific treatment for NAFLD. (Strength – 1, Quality –

B)

NAGA CHALASANI, et al :GASTROENTEROLOGY 2012;142

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Treatment of

diabetes associating

Nash

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In addition to its anti-fibrotic effect

, it reduce BP, improve glucose

Tolerance & prevention of new-

onset T2 DM, thus contributing to

further reduce the risk of CVD

events.

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HOME MESSAGE

*Patients with T2DM should be always assessed for

NAFLD and vise versa to ensure early diagnosis

and medical care to prevent and minimize the

occurrence of NASH , DM & CVD.

*Awareness of NAFLD in general appears to be

disappointingly lacking in the medical community.

NAFLD should be viewed as a complex and

multi-faceted disease often calling for multi-

disciplinary intervention.

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Topics : including free papers

&case presentation: (speakers

of young doctors 25-35y. of age:

2000 LE as a gift for the best 2

doctor)

1- Diabetes association with

liver disease.

2- Liver in relation to

different specialties ,other

than diabetes

3- Liver VS diabetes & gut

dysmotility; intestinal dysbiosis

4-Obesity

5-Stem cell &

immunotherapy in diabetes

& liver disease

6-Improving

quality of life in chronic

diseases

7-Medical aspects of liver

transplantation

Mob. +2

012221337

50 Fax +2

23939382

E mail: akhalekhamed @gmail.com