Transcript Slide 1

Nonalcoholic fatty liver
disease in Patients of Primary
Hypothyroidism
Dr Madhukar Mittal MD, DM
Asst. Professor
Endocrine Unit, Department of Medicine
King George Medical University (earlier CSMMU)
Lucknow, India
Background
• Several endocrine disorders are known to have
increased risk for Nonalcoholic fatty liver diseae
(NAFLD)
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–
–
–
–
Diabetes mellitus
Hypothyroidism
Adrenal insufficiency
GH deficiency
PCOS
NAFLD spectrum
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Simple steatosis
Inflammatory steatohepatitis (NASH)
Fibro-fatty Liver (Increasing levels of fibrosis)
Cirrhosis
NAFLD Prevalence
• NAFLD
– 20% and 30% in Western adults1,2
– 90% in the morbidly obese3
• NASH (the more advanced form of NAFLD)
– 2–3% in the general population4
– 16 and 37% in the morbidly obese3
1Browning
JD et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity.
Hepatology 2004;40:1387
2Bedogni G et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver
study. Hepatology 2005;42:44
3Machado M et al. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006;45:600–6
4Neuschwander-Tetri BA et al. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology
2003;37:1202
Aims and Objectives
• Study to see for prevalence of NAFLD in
patients of primary hypothyroidism
• To evaluate metabolic parameters in this group
of patients with NAFLD
Material and Methods
• Consecutive primary hypothyroid patients
• Tested for antibodies against thyroid peroxidase
(TPO) and thyroglobulin (TG)
• Insulin resistance assessed
– Fasting insulin
– Homeostasis model assessment of insulin resistance
(HOMA-IR)
– Quantitative insulin-sensitivity check index (QUICKI)
USG grading
• USG abdomen done by two radiologists to grade
fatty liver
Feature at USG
Score
Liver echogenicity exceeds that of renal cortex and spleen
1
Attenuation of the ultrasound wave
1
Loss of definition of the diaphragm
1
Poor delineation of the intrahepatic architecture
1
Total Maximum Score
4
Jain KA et al. Spectrum of CT and sonographic appearance of fatty infiltration of the liver. Clin Imaging 1993;17:162
Saadeh S et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745
Tchelepi H et al. Sonography of diffuse liver disease. J Ultrasound Med 2002; 21: 1023
Zwiebel WJ. Sonographic diagnosis of diffuse liver disease. Semin Ultrasound CT MR 1995;16:8
NAFLD diagnosis
• NAFLD defined as
– USG score >2
– Fatty liver not resulting from
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Excessive alcohol consumption (>20 grams/day)
Drugs/Toxins (tamoxifen, methotrexate, amiodarone etc)
Infectious diseases (viral hepatitis etc)
Any other identifiable exogenous causes (Wilson disease,
Hemochromatosis, α-1 antitrypsin deficiency etc)
Statistical Analysis
• Data presented as mean + SD, median (interquartile
range) or N (%)
• Distribution of continuous data tested for normality
– Kolmogorov- Smirnov test
• Comparing between groups for continuous variable
– Student T test
– Mann Whitney test for non-uniformly distributed data
• Comparing categorical data
– Chi square test or Fisher exact test
• A two tailed p value <0.05 regarded as significant
• Statistical software SPSS15.0 (SPSS, Chicago, IL)
Results
Baseline Characteristics
Parameters
Values
N
71
Females, n (%)
64 (90.1)
Age (yr)
37.7 + 13.2
Age at diagnosis (yr)
35.4 + 13.1
BMI (Kg/m2)
26.6 + 6.1
TPO/TG positive, n (%)
60 (84.5)
TPO and TG, n (%)
39 (54.9)
Comaparison of thyroid antibody postive
vs. antibody negative patients
Parameters
TPO/TG +ve
(N=60)
TPO/TG –ve
(N=11)
P value
Age (yr)
36.2+13.0
46.0+14.1
0.024
Age at diagnosis (yr)
32.1+12.5
44.0+13.7
0.021
Fasting Insulin (μIU/ml)
12.47+7.11
6.27+2.92
0.014
HOMA-IR
2.90+1.72
1.30+0.77
0.010
QUICKI
0.345+0.045
0.393+0.077
0.033
BMI (Kg/m2)
26.1+5.4
25.4+6.4
0.738
FBS (mg/dl)
92.1+19.1
80.0+15.9
0.126
PPBS (mg/dl)
129.7+23.5
123.4+17.5
0.510
TG (mg/dl)
149.9+55.1
153.9+60.0
0.867
VLDL (mg/dl)
27.9+9.5
29.6+12.3
0.694
HDL (mg/dl)
40.9+12.2
48.3+12.3
0.154
NAFLD characteristics
Parameters
N
%
No of patients
32
45.1
Females
32
100
Grade 1
17
53.1
Grade 2
14
43.8
Grade 3
1
3.1
NAFLD positive vs. NAFLD negative patients
Parameters
NAFLD Present
(N=32)
NAFLD Absent
(N=39)
P value
BMI (Kg/m2)
27.6+4.4
24.6+5.6
0.046
SBP (mm of Hg)
131.3+14.5
124.7+10.4
0.038
DBP (mm of Hg)
77.3+10.5
78.1+12.8
0.778
SGOT/AST (U/L)
42.2+15.8
36.2+13.3
0.104
SGPT/ALT (U/L)
41.0+17.3
37.4+17.0
0.629
TG (mg/dl)
174.5+74.4
146.4+79.5
0.146
VLDL (mg/dl)
30.6+10.7
25.9+7.9
0.043
HDL (mg/dl)
38.8+10.5
46.0+11.8
0.012
FBS (mg/dl)
98.2+26.6
87.2+16.4
0.041
PPBS (mg/dl)
147.4+58.1
124.7+20.2
0.029
Fasting Insulin (μIU/ml)
12.4+6.2
10.1+7.5
0.272
HOMA-IR
2.99+1.65
2.18+1.67
0.103
QUICKI
0.339+0.036
0.369+0.067
0.102
TPO or TG +ve, n (%)
28
32
0.743
Discussion
NAFLD
• Non-alcoholic fatty liver disease affects all ethnic
groups
• Prevalence higher in Hispanic and European
Americans compared with African-Americans
NAFLD prevalence in India
Setting
N (M/F)
Age
Criteria
Prevalence
Risk Factors
Amarapurkar
D et al.
Annals of
Hepatology
2007
Population
730
(341/389)
>20yr
USG
18.9%
(M/F 24.6%/13.6%)
Age>40
Male
Central Obesity
BMI>25
Increased FBS
Uchil D et al.
JAPI 2009
Hospital
1003
(565/438)
18-60yr
USG
22.6%
(M/F 29%/13.9%)
waist
circumference
TG, Low HDLc, Blood
pressure, FBS
USG
24.5%
(M/F 26.9%/13.8%)
BMI
Singh SP et
Population
al. Trop
Gastroenterol
2004
159
NAFLD was seen in around half of hypothyroid patients
Chung GE et al.
• 2324 cases of hypothyroidism (overt and
subclinical)
• NAFLD based on USG
• 62% female
• NAFLD prevalence 30.2%
Non-alcoholic fatty liver disease across the spectrum of hypothyroidism.
J Hepatol. 2012 Jul;57(1):150-6
Thyroid antibody positivity
Parameters
TPO/TG +ve
(N=60)
TPO/TG –ve
(N=11)
P value
Age (yr)
36.2+13.0
46.0+14.1
0.024
Age at diagnosis (yr)
32.1+12.5
44.0+13.7
0.021
Fasting Insulin
12.47+7.11
6.27+2.92
0.014
HOMA-IR
2.90+1.72
1.30+0.77
0.010
QUICKI
0.345+0.045
0.393+0.077
0.033
Thyroid antibody positivity correlated with higher markers of insulin
resistance
• Low normal FT4 levels were significantly
associated with increased insulin resistance
Roos A et al. J Clin Endocrinol Metab 2007;92(2):491
NAFLD in hypothyroidism and metabolic
characteristics
Parameters
NAFLD Present
(N=32)
NAFLD Absent
(N=39)
P value
BMI (Kg/m2)
27.6+4.4
24.6+5.6
0.046
SBP (mm of Hg)
131.3+14.5
124.7+10.4
0.038
VLDL
30.6+10.7
25.9+7.9
0.043
HDL
38.8+10.5
46.0+11.8
0.012
FBS
98.2+26.6
87.2+16.4
0.041
PPBS
147.4+58.1
124.7+20.2
0.029
Fasting Insulin
12.4+6.2
10.1+7.5
0.272
HOMA-IR
2.99+1.65
2.18+1.67
0.103
QUICKI
0.339+0.036
0.369+0.067
0.102
Patients who had NAFLD had higher systolic blood pressure and
deranged metabolic parameters (higher BMI, FBS, PPBS, VLDL and low
HDL)
Health ABC study. Waring CA et al.
Clin Endocrinol 2012;76(6):911
• 2119 patients
• 684 initially identified with metabolic syndrome
• Higher TSH levels and subclinical
hypothyroidism with TSH>10 mIU/L significantly
associated with prevalent metabolic syndrome
• Each unit increase in TSH associated with 3%
increase in odds of prevalent metabolic
syndrome
Thyroid function and prevalent and incident metabolic syndrome in older adults: the health, ageing and body
composition (Health ABC) study. Warin CA et al. Clin Endocrinol 2012;76(6):911
Conclusion
• NAFLD seen in nearly half of primary
hypothyroid patients
• Insulin resistance higher in thyroid antibody
positive patients
• NAFLD associated with increased clustering of
parameters of metabolic syndrome
Limitations
• Histopathology (Liver Biopsy) not done
– USG cannot differentiate between Simple Steatosis
and NASH
• Larger sample size needed
Future Course
• Ongoing study
• Currently 142 patients included
• Noninvasive markers for liver cirrhosis
– AST to platelet ratio index (APRI)
– AST/ALT ratio (AAR)
– BARD score
Acknowledgement
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•
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Dr Neha Jain
Dr Anit Parihar
Dr Vivek Kumar
Dr Ravi Misra
Dr AK Vaish
Thank You
King George Medical University, Lucknow
S No
33.
Female (n=64)
Male (n=7)
P value
Age of patient
37.18+12.93
42.14+15.52
.352
Age at diagnosis
34.64+12.81
41.57+15.16
.191
BMI
27.23+6.04
21.75+4.28
.020
height
152.54+7.45
162+8.87
.001
weight
63.48+15.03
57.85+12.28
.346
Systolic BP
128.92+14.07
125.14+13.26
.502
Dystolic BP
78.21+10.88
81.71+24.21
.498
Initial TSH
33.66+48.06
22.03+20.98
.532
TPO
807.06+890.20
275.02+509.44
.163
TG
202.44+316.34
66.64+82.92
.060
S. bilirubin
1.06+2.00
1.01 +0.45
.945
SGOT
44.50+29.59
33.00+6.24
.313
SGPT
47.78+44.16
32.14+6.25
.357
SALP
194.17+101.14
190.85+58.94
.933
CHO
189.77+46.58
178.42+61.75
.563
TG
155.69+55.87
179.57+107.79
.353
LDL
108.69+42.30
103.50+22.48
.770
HDL
42.13+11.69
42.28+10.09
.970
VLDL
28.77+9.58
27.29+9.50
.702
Fasting insulin
12.78+7.93
8.37+3.13
.153
Fasting blood sugar
90.28+18.36
91.42+15.93
.876
Post prandial sugar
127.86+20.75
134.42+23.03
.441
Platelet count
1.66+0.68
1.58+0.75
.803
MCV
85.15+8.58
88.84+11.29
MCH
27.78+3.68
30.57+4.04
MCHC
31.79+2.21
33.71+2.14
MMSE
27.02+2.00
28.00+1.15
.211
HAMD
14.64+6.07
13.00+5.48
.499
SGOT/SGPT=AAR
1.11+0.39
1.05+0.24
.719
BARD
2.21+0.87
2.00+1.00
.555
AST/platelet=APRI
1.85+1.46
1.31+0.72
.335
HOMA
2.75+1.83
1.97+0.96
.278
QUICKI
1.52+0.32
1.40+0.16
.348
• NASH was first coined by Ludwig et al. in 1980
• the prevalence of NAFLD has risen rapidly in
parallel with the dramatic rise in population
levels of obesity and diabetes, resulting in
NAFLD now representing the most common
cause of liver disease in the Western world