Background: Non–alcoholic fatty liver disease is defined as accumulation of fat in the hepatocytes in the absence of significant alcohol consumption. It is chronic health problem with a clinical spectrum ranging from asymptomatic increase in the liver enzymes, which is a precursor of cirrhosis and hepatocellular carcinoma. Material and Methods: This study was conducted among 150 patients of hypothyroidism and 150 controls selected on basis of inclusion and exclusion criteria. Laboratory investigations including fasting lipid profile, fasting blood sugar, liver function tests and thyroid profile were performed in all participants of both study groups. Results: Fatty liver was found in 57.33% of cases of hypothyroidism compared to only 22.67% of controls. Statistical analysis showed that the overall difference in incidence of fatty liver between both groups was highly significant (P<0.01). In subsets of patients with BMI<23 kg/m2 and with BMI in the range of 23–24.9 kg/m2, the presence of fatty liver on ultrasound was significantly more frequent in hypothyroidism cases compared to controls (P<0.01). Conclusion: Recognition of the risk factors for NAFLD and their early and effective management is an important aspect of good management strategy.
Non-alcoholic fatty liver disease is defined as accumulation of fat in the hepatocytes in the absence of significant alcohol consumption. It is chronic health problem with a clinical spectrum ranging from asymptomatic increase in the liver enzymes, which is a precursor of cirrhosis and hepatocellular carcinoma.1,2 Pathophysiological mechanisms causing Non-alcoholic fatty liver disease is linked to the metabolic syndrome and insulin resistance, it is considered the hepatic component of metabolic syndrome.3,4
Association with metabolic syndrome and diabetes mellitus, Non-alcoholic fatty liver disease has been thought to be linked with other endocrine and metabolic disorders.5 Thyroid gland has significant role in lipid and carbohydrate metabolism.6 This has also led to the hypothesis of a possible association between hypothyroidism and the development of Non-alcoholic fatty liver disease. Recent studies have indicated that hypothyroidism may be a significant risk factor for development and progression of Non-alcoholic fatty liver disease and adequate treatment of the former may improve the latter.7,8 Primary and secondary prevention by managing the risk factors are the most important tools to control the epidemic of chronic metabolic disorders including Non-alcoholic fatty liver disease.
A prospective cross-sectional study was conducted at tertiary care center Sardar Patel Medical College and Associated Group of Hospitals, Bikaner in patients with hypothyroidism. A total of 150 patients with hypothyroidism and 150 age, gender, and race matched control subjects without hypothyroidism seen in the general medicine clinic were included. The study was conducted over a total duration of 24 months (December 2021 to November 2023). All patients diagnosed with hypothyroidism aged >20 years and with alcohol consumption <15 g/day were considered for inclusion. Patients with a history of any liver disease, diabetes mellitus were excluded. Relevant laboratory investigations including fasting lipid profile, fasting blood sugar, liver function tests and thyroid profile were performed in all participants of both study groups. Anthropometric parameters including weight, height and body mass index (BMI) were recorded for both groups. BMI was calculated using standard formulae and individuals in both groups were further classified according to BMI according to Asian standards (normal range18.5–22.9, overweight 23.0–24.9, obese>25 kg/m2).9
The diagnosis of Non-alcoholic fatty liver disease was made on the basis of radiological findings and liver enzyme derangement. Abdominal ultrasound scanning was done in all participants to look for evidence and grade of hepatic steatosis, calculated according to echogenicity and attenuation. Any rise of serum transaminase levels (SGOT/SGPT) above the normal range was noted in both study groups. The data collected from the two groups were tabulated and statistically analyzed using SPSS statistical software
In our study, there was no statistically significant difference between the groups with regard to age and gender. The majority of patients in the two groups were aged 41–60 years (54% of cases and 58% of controls). Comparison of anthropometric parameters in the two groups showed that hypothyroid patients were significantly in weight (P<0.05) than the control group. Patients in the hypothyroidism group were found significantly BMI level than the control group (P<0.01). The comparison of the lipid parameters of the two groups showed significantly higher levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) cholesterol in patients with hypothyroidism compared to the control group (P<0.05). The ultrasonographic evidence of fatty liver in the case and control groups showed in table 2. Fatty liver was found in 57.33% of cases of hypothyroidism compared to only 22.67% of controls. Statistical analysis showed that the overall difference in incidence of fatty liver between both groups was highly significant (P<0.01). In subsets of patients with BMI<23 kg/m2 and with BMI in the range of 23–24.9 kg/m2, the presence of fatty liver on ultrasound was significantly more frequent in hypothyroidism cases compared to controls (P<0.01). However, results were statistically similar in the obese subset in the two groups with respect to presence of fatty liver on ultrasound (P>0.05). On stepwise logistic regression analysis of the patients’ data (Table 3), the risk of development of NAFLD was significantly associated with presence of hypothyroidism (odds ratio [OR]2.15, 95% confidence interval [CI] [1.15–5.15, P<0.03). Other important parameters which showed statistically significant association with NAFLD were BMI (OR 1.25, 95% CI 1.18–1.35, P<0.001) and serum cholesterol levels (OR 1.03, 95% CI 1.02–1.12, P<0.02). Other variables included in the regression analysis (age, gender, LDL, high-density lipoprotein, TG and very-low-density lipoprotein) did not show any significant association with development of non-alcoholic fatty liver disease.
Table 1 – Results of Patients according to different parameters
|
Parameter |
Cases (n=150) |
Control (n=150) |
p value |
|
Age |
44.89 ± 14.62 |
48.28 ± 18.16 |
0.07 |
|
Weight |
65.79 ± 13.15 |
59.46 ± 11.59 |
0.0001 |
|
Height |
1.52 ± 0.03 |
1.58 ± 0.02 |
0.0001 |
|
BMI |
32.52 ± 6.07 |
26.12 ± 5.72 |
0.0001 |
|
FBS |
99.85 ± 12.13 |
112.82 ± 25.53 |
0.0001 |
|
SGOT |
70.28 ± 18.08 |
65.45 ± 11.26 |
0.05 |
|
SGPT |
76.89 ± 28.59 |
71.15 ± 34.86 |
0.12 |
|
S. Alk Phos |
102.49 ± 44.99 |
128.15 ± 28.92 |
0.0001 |
|
TC |
188.13 ± 44.98 |
142.85 ± 42.56 |
0.0002 |
|
TG |
211.47 ± 77.56 |
183.86 ± 67.85 |
0.001 |
|
HDL |
36.89 ± 11.05 |
32.15 ± 8.17 |
0.0001 |
|
LDL |
60.55 ± 22.18 |
44.12 ± 11.15 |
0.0001 |
|
VLDL |
28.46 ± 11.07 |
28.65 ± 12.84 |
0.89 |
Table 2 – Distribution of cases and control according to fatty liver and BMI
|
|
Fatty Liver Grade 1 |
Fatty Liver Grade 2 |
Fatty Liver Grade 3 |
|||
|
BMI |
Case |
Control |
Case |
Control |
Case |
Control |
|
<23 |
2 |
1 |
4 |
0 |
2 |
0 |
|
23–24.9 |
3 |
1 |
5 |
0 |
1 |
0 |
|
>25 |
35 |
21 |
28 |
11 |
6 |
0 |
Table 3 – Odds ratio and p value of parameters
|
Variable |
Coefficient |
SE |
OR |
95% CI |
p value |
|
BMI |
0.21 |
0.44 |
1.25 |
1.18 – 1.35 |
0.001 |
|
Hypothyroidism |
0.84 |
0.46 |
2.15 |
1.15–5.15 |
0.03 |
|
TC |
0.03 |
0.01 |
1.03 |
1.02 – 1.12 |
0.02 |
Hypothyroidism has been associated with insulin resistance, metabolic syndrome and dyslipidaemia. Non-alcoholic fatty liver disease is one of the hepatic components of metabolic syndrome.3 Ultrasonographic evidence of fatty liver was significantly higher in hypothyroidism patients. Our findings are consistent with other studies, even in children and adolescents.10,11 In our study, we did not notice any change in severity of Non-alcoholic fatty liver disease with thyroid hormone replacement therapy, but there are some recent data which suggest that appropriate thyroxine therapy is helpful in control of Non-alcoholic fatty liver disease in hypothyroidism patients.12 Recognition of the risk factors for Non-alcoholic fatty liver disease and their early and effective management is an important aspect of good management strategy. The present study confirms the association between hypothyroidism and Non-alcoholic fatty liver disease in population in India, with the former being a significant independent risk factor for the latter.
Recognition of the risk factors for NAFLD and their early and effective management is an important aspect of good management strategy. The present study confirms the association between hypothyroidism and NAFLD, with the former being a significant independent risk factor for the latter.