Prevalence of Non Alcoholic Fatty Liver Disease (NAFLD) in - PowerPoint Presentation

Slide1

Prevalence of Non Alcoholic Fatty Liver Disease (NAFLD) in obese and non-obese Hypothyroid subjects

Prof. Sandeep Garg

Department of Medicine

Maulana Azad Medical College

New Delhi

INDIASlide2

INTRODUCTION

Non-alcoholic fatty liver disease (NAFLD) - most common cause of chronic liver disease in developed countries (prevalence of 20–30% in the adult population).

NAFLD in children related to the increasing rates of childhood obesity worldwide

1

Non alcoholic

steatohepatitis

(NASH) is currently the third leading indication for liver transplantation (LT) in the United States

2

Advanced age, diabetes type 2, impaired glucose tolerance, and obesity, are risk factors for NAFLD.

It is anticipated that cirrhosis due to these conditions may surpass other causes of cirrhosis in a near future.

1.

Dunn W,

Schwimmer

JB. The obesity epidemic and

nonalcoholic

fatty liver disease in children.

Curr

Gastroenterol

Rep. 2008; 10:67–72.

2

.

Wong R, Cheung R, Ahmed A.

Nonalcoholic

Steatohepatitis

Is the Most Rapidly Growing Indication for Liver Transplantation in Patients With

Hepatocellular

Carcinoma in the U.S. Hepatology.2014.;59(6):2188-95.Slide3

Pathogenesis of NAFLD :

Excess of lipid accumulation within the liver and equilibrium between synthesis and utilisation gets deranged.

A

three-hit hypothesis

has been proposed.

- The first hit involves the accumulation of lipid in liver.

- The second hit-initiation of an inflammatory response and

the cell death .- hallmark

- The third hit is a defective repair and regenerative response.

Diagnosis of NAFLD -

evidence of hepatic

steatosis

on imaging or histology, and other causes of liver disease or

steatosis

have been excluded.Slide4

Ultrasonography

detects fatty liver if more than 33%

steatosis

is there which appears as a diffuse increase in hepatic

echogenicity

, or “bright liver”.,

USG offers a fairly accurate diagnosis of moderate-to-severe hepatic

steatosis

, with reported

sensitivity

ranging from

81.8% to 100.0%

and

specificity

as high as

98%.

*

Liver biopsy still remains the ‘golden standard’ for confirming or excluding the diagnosis of NASH

*

Lee SS, Park SH, Kim HJ, Kim SY, Kim MY, Kim DY,

Suh

DJ, Kim KM,

Bae

MH, Lee JY, Lee SG, Yu ES. Non-invasive assessment of hepatic

steatosis

: prospective comparison of the accuracy of imaging examinations. J

Hepatol

. 2010; 52: 579-585.Slide5

NAFLD - >5% of

hepatocytes

are

steatotic

in patients who do not consume excessive alcohol consumption

(<20 g/day for women and <30 g/day for men)

-

simple

steatosis

(fat without hepatic inflammation or

hepatocellular

injury- seen in

70-90%

)

-

steatohepatitis

(fat with

hepatocellular

injury and inflammation

10-30%- NASH

)

- NASH-------

 (25-40%)

Hepatic fibrosis ----------

 Cirrhosis of Liver (20-30%)*

*

Wong VW, Wong GL,

Choi

PC, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010;59:969–74.Slide6

The thyroid gland is significantly involved in energy homeostasis, lipid and carbohydrate metabolism, regulation of body weight and

adipogenesis

.

In a clinical setting, subclinical hypothyroidism has been associated with metabolic syndrome, cardiovascular mortality and disturbance of lipid metabolism

*

Hypothyroidism is a treatable condition and if it is a risk factor

factor

for NAFLD this can be useful in preventing the progression to NASH and subsequently to CLD.

*

Rodondi

N, den

Elzen

WP, Bauer DC,

Cappola

AR,

Razvi

S, Walsh JP,

Asvold

BO,

Iervasi

G,

Imaizumi

M,

Collet

TH,

Bremner

A,

Maisonneuve

P,

Sgarbi

JA,

Khaw

KT,

Vanderpump

MP, Newman AB,

Cornuz

J, Franklyn JA,

Westendorp

RG,

Vittinghoff

E,

Gussekloo

J. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA.2010; 304: 1365-1374.

.Slide7

The present presentation is the part of the study where prevalence of NAFLD was seen in non obese , non diabetic hypothyroid patient.

We want to see that whether some other mechanism, other than insulin resistance are the cause of the NASH and finally NAFLD in the hypothyroid patientsSlide8

Aim:

To find out the prevalence of NAFLD in Obese and

Non obese hypothyroid patients.

Type of study:

Prospective

analytical study

Study Area:

D

epartment

of Medicine in Maulana Azad Medical College associated with

LokNayak

Hospital .

Study population:

Patients were selected from Endocrinology clinic from Dec 2014 to May 2014. A total of 41 patients were selected.

Slide9

Inclusion criteria:

All diagnosed hypothyroid patient for more than 2 years with a serum TSH>5.5mIU/L with or without treatment.

Exclusion Criteria:

Diabetic patients( as per ADA criteria)

Patients with hypertension BP >130/80mm Hg

Alcohol consumption of > 20 gm/ day for men and > 10gm / day for women.

Past history of jaundice

On going pregnancy and post-partum female

Patients on drugs causing

dyslipidemia

Patients on

steatohepatic

drug intake (

tamoxifen

,

glucorticoids

,

isoniazid

,

amiodarone

,

methotrexate

)Slide10

MATERIALS AND METHODS

41 subjects were chosen who were diagnosed as a case of

hypothyroidism TSH > 5.5

mIU

/L.

A written and informed consent was taken from each patients.

They were divided into two groups based on their BMI.

The non obese group included subjects with BMI < 28.5kg/m

2

and the obese were the

pateints

with BMI of > 28.5 kg/m

2

.

Both the groups were subjected to the blood tests including

complete

hemogram

, KFT’s, LFT’s, complete lipid profile total serum

protein and albumin, serum electrolytes and

ultrasonography

for

the diagnosis of NAFLD. Slide11

Patients were asked to come early morning fasting for blood investigations and abdominal

ultrasonography

. The

ultrasonographer

was unaware of the patient’s medical

history and the study group in which they were enrolled.

A positive case was diagnosed with diffusely increased

echogenicity

(“bright”) in liver greater than kidney, with vascular blurring, and deep attenuation of ultrasound signal.

Data collected was tabulated and a detailed descriptive analysis was done.

- Statistical analysis was performed using SPSS 22.0 version.

- A p values of <0.05 was considered significant.

- Person correlation co-efficient was used to correlate the

variablesSlide12

RESULTS

Out of 41 patients these there were 20 obese and 21 non obese subjects.

The results are shown in table no.1

The prevalence of NAFLD in these 41 subjects was 56.09%.

The prevalence of NAFLD in non-obese hypothyroid subjects was 47.6% as compared to 65% in the obese subjects. Slide13

Table no. 1 Baseline characteristics and prevalence of NAFLD

Non Obese (21)

Obese(20)

Age yr

36.14±2.74

37.75±2.21

Gender , female n(%)

17(80.9)

16(80)

BMI(kg/m

2

)

24.90±0.51

33.25±0.47

ALT (IU/L)

36.19±4.58

47±3.08

AST(IU/L)

38.04±5.35

48.6±3.08

Total Cholesterol(mg/dl)

171±11.16

182.55±9.45

HDL(mg/dl)

40.9±.899

40.5±0.73

LDL(mg/dl)

129±6.286

146±7.883

Triglyceride (mg/dl)

152±15.35

175±9.89

S TSH (mIU/L)

15.68±4.5

15.225±3.15

NAFLD, n(%)

10 (47.6)

13(65)Slide14

Hypothyroidism and NAFLD

The prevalence of NAFLD in these 41 subjects was 56.09%. The prevalence in non-obese and obese was 47.6% and 65% respectively.

The USG grading for NALFD were positively correlated with increasing S TSH values in both obese as well as non obese subjects r(18)=0.64 and r (19)= 0.733, p<0.05 respectively.

The USG grading for NAFLD correlated positively with increasing BMI in the obese hypothyroid subjects r(18)= 0.642 with p<0.05.

However no correlation to BMI and USG grading was found in non-obese groupSlide15

LFT’s and Hypothroidism

The prevalence of abnormal ALT> 40 IU/L was 14.28% in non-obese and 55% in obese. Increasing ALT levels were significantly correlated with increasing S TSH ( r= 0.604, p=0.04) and BMI (r=0.719, p=0.01) in obese subjects.

Among the subjects with

ultrasonographically

diagnosed NAFLD the prevalence of abnormal ALT was 30% in the non obese and 76.9% in the obese subjects.Slide16

Lipid profile and Hypothyroidism

The mean Total cholesterol, LDL and triglycerides levels were higher in obese as compared to non-obese subjects (table no. 1).

The triglyceride and the total cholesterol showed a significant positive correlation with increasing BMI amongst the obese subjects

Table no. 2 : Correlation r(

18

) values OF lipid profile in

hypothyroid obese subjects with BMI.

( r /p values) BMI

kg/m

2

LDL

0.64(p<0.05)

T cholesterol

0.52(p<0.05)

Triglyceride

0.44

(p<0.05)Slide17

The deranged LDL showed a positive significant correlation with increasing S. TSH in hypothyroid obese subjects.

There was positive correlation TG as well as total cholesterol levels with increasing TSH. However it was

not significant

.

Table no. 3 : Correlation r(

18

) values OF lipid profile in

hypothyroid obese subjects with Serum TSH.

TSH

LDL

r(18)=

0.7 (p=.001)

T cholesterol

r(18)= 0.39 (p=.08)

Triglyceride

( r(18) =0.50 (p=.07)Slide18

Conclusion and Summary

Our study showed that there is a high prevalence of NAFLD in hypothyroid subjects more so in obese hypothyroid subjects.

Hypothyroidism leads to obesity which further increases the risk of NAFLD.

The findings of fatty liver on USG were positively correlating with the increasing serum TSH levels.

Our study results were in consensus with the study done by A.

Eshraghian

et al

34

where it was shown that elevated serum ALT levels was an independent predictors of NAFLD in hypothyroid patients.

Slide19

THANK YOUSlide20

Possible mechanisms of liver dysfunction in Hypothyroidism

Hypothyroidism leads to an increased risk of

hyperlipidemia

38

which leads to increased fatty acid oxidation and hepatic output of triglycerides leading to altered lipid

peroxidation

39

which further leads to liver cell damage .

Decreased thyroid function is also associated with insulin resistance, which is a hallmark of hepatic

steatosis

, as well a as feature of the metabolic syndromeSlide21

limitations

The sample size was small to find more correlation between USG findings and

dyslipidemia

.

Our diagnosis of NAFLD was based on USG findings however liver biopsy is need for confirmation therefore the prevalence might even be higher as USG cannot detect

steatosis

below 30%.Slide22

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Schwimmer

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nonalcoholic

fatty liver disease in children.

Curr

Gastroenterol

Rep. 2008; 10:67–72.

Wong R, Cheung R, Ahmed A.

Nonalcoholic

Steatohepatitis

Is the Most Rapidly Growing Indication for Liver Transplantation in Patients With

Hepatocellular

Carcinoma in the U.S. Hepatology.2014.;59(6):2188-95.

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. 2014 Jul 7; 20(25): 8102–8109.

Published online 2014 Jul 7.

doi

: