European Journal of Cardiovascular Medicine

Non-alcoholic fatty liver disease (NAFLD) is a progressive hepatic condition characterized by the accumulation of fat, primarily in the form of triglycerides, in more than 5–10% of the liver’s weight. Unlike liver diseases caused by alcohol consumption, hepatotoxic drugs, hepatitis C, or malnutrition, NAFLD is strongly associated with metabolic syndrome, obesity, type 2 diabetes mellitus, sedentary lifestyle, and inappropriate pharmacotherapy. It includes a spectrum of liver abnormalities, ranging from simple steatosis (fat accumulation without inflammation) to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Alarmingly, NAFLD is rapidly becoming the most prevalent chronic liver disease worldwide, including in India, where prevalence estimates range from 9% to as high as 53%, depending on population subsets and diagnostic methods. Urban Asian Indians with obesity or diabetes are particularly at risk.A major challenge in managing NAFLD is its silent nature; most patients remain asymptomatic, and the condition is often discovered incidentally through mildly elevated liver enzymes. However, normal transaminase levels do not necessarily rule out NAFLD or NASH, complicating early detection. While imaging studies like ultrasound and MRI can detect liver fat, they are not cost-effective for population-wide screening, especially in resource-limited settings. This underscores the urgent need for affordable, simple, and reliable biomarkers that can help identify at-risk individuals before the disease progresses.Recent studies have explored possible links between NAFLD and other systemic conditions, particularly hypothyroidism and elevated serum ferritin levels. Hypothyroidism, characterized by low thyroid hormone production, contributes to weight gain, fatigue, and metabolic slowdown—factors that can exacerbate NAFLD. Similarly, serum ferritin, a marker of iron stores and an acute-phase reactant, may be elevated due to systemic inflammation or iron overload—both of which are implicated in NAFLD pathogenesis. Elevated ferritin levels have been associated with hepatic inflammation, oxidative stress, and fibrosis, while low ferritin levels generally indicate iron deficiency. Understanding the correlation between serum ferritin, thyroid dysfunction, and NAFLD could provide an economical, non-invasive approach to early screening and risk stratification.In India, where healthcare resources are often stretched and access to specialized diagnostics is limited, the socioeconomic burden of NAFLD is substantial. The disease is now a leading cause of cirrhosis, HCC, and liver transplantation, further straining the healthcare system. As NAFLD shares risk factors with other non-communicable diseases (NCDs) like diabetes, hypertension, and dyslipidemia, it is essential to integrate its screening and management into broader NCD control programs. Enhancing public and clinical awareness, improving early detection methods, and promoting lifestyle interventions are critical steps. Investigating novel, low-cost screening biomarkers—such as serum ferritin levels in conjunction with thyroid profiles—offers promising avenues for reducing the disease burden and guiding timely interventions for at-risk populations.

AIM

This study sought to elucidate the correlation between non-alcoholic fatty liver disease and hypothyroid individuals.

Non-alcoholic fatty liver disease (NAFLD) is a progressive hepatic condition characterized by the accumulation of fat, primarily in the form of triglycerides, in more than 5–10% of the liver’s weight. Unlike liver diseases caused by alcohol consumption, hepatotoxic drugs, hepatitis C, or malnutrition, NAFLD is strongly associated with metabolic syndrome, obesity, type 2 diabetes mellitus, sedentary lifestyle, and inappropriate pharmacotherapy. It includes a spectrum of liver abnormalities, ranging from simple steatosis (fat accumulation without inflammation) to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Alarmingly, NAFLD is rapidly becoming the most prevalent chronic liver disease worldwide, including in India, where prevalence estimates range from 9% to as high as 53%, depending on population subsets and diagnostic methods. Urban Asian Indians with obesity or diabetes are particularly at risk.A major challenge in managing NAFLD is its silent nature; most patients remain asymptomatic, and the condition is often discovered incidentally through mildly elevated liver enzymes. However, normal transaminase levels do not necessarily rule out NAFLD or NASH, complicating early detection. While imaging studies like ultrasound and MRI can detect liver fat, they are not cost-effective for population-wide screening, especially in resource-limited settings. This underscores the urgent need for affordable, simple, and reliable biomarkers that can help identify at-risk individuals before the disease progresses.Recent studies have explored possible links between NAFLD and other systemic conditions, particularly hypothyroidism and elevated serum ferritin levels. Hypothyroidism, characterized by low thyroid hormone production, contributes to weight gain, fatigue, and metabolic slowdown—factors that can exacerbate NAFLD. Similarly, serum ferritin, a marker of iron stores and an acute-phase reactant, may be elevated due to systemic inflammation or iron overload—both of which are implicated in NAFLD pathogenesis. Elevated ferritin levels have been associated with hepatic inflammation, oxidative stress, and fibrosis, while low ferritin levels generally indicate iron deficiency. Understanding the correlation between serum ferritin, thyroid dysfunction, and NAFLD could provide an economical, non-invasive approach to early screening and risk stratification.In India, where healthcare resources are often stretched and access to specialized diagnostics is limited, the socioeconomic burden of NAFLD is substantial. The disease is now a leading cause of cirrhosis, HCC, and liver transplantation, further straining the healthcare system. As NAFLD shares risk factors with other non-communicable diseases (NCDs) like diabetes, hypertension, and dyslipidemia, it is essential to integrate its screening and management into broader NCD control programs. Enhancing public and clinical awareness, improving early detection methods, and promoting lifestyle interventions are critical steps. Investigating novel, low-cost screening biomarkers—such as serum ferritin levels in conjunction with thyroid profiles—offers promising avenues for reducing the disease burden and guiding timely interventions for at-risk populations.

AIM

This study sought to elucidate the correlation between non-alcoholic fatty liver disease and hypothyroid individuals.

Table 1: Baseline Characteristics of Patients

The mean BMI of the participants was 29.4 ± 3.5 kg/m^2, indicating a tendency towards overweight or obesity.Thyroid function tests showed elevated mean TSH (14.8 ± 4.5 µIU/mL), suggesting significant hypothyroidism.Mean serum ferritin level was considerably high at 271 ± 55.4 µg/L

Table 2: Prevalence of NAFLD in Hypothyroidism Patients

NAFLD was present in 71% (76/107) of hypothyroid patients, highlighting a strong association between hypothyroidism and fatty liver disease.

Table 3: Comparison of Thyroid Function between NAFLD Grades

Patients with severe NAFLD (Grade 3) had significantly higher TSH levels (37.1 ± 9.6 µIU/mL) and lower free T3 and free T4 compared to those with mild or no NAFLD.

Table 4: Correlation between TSH and Serum Ferritin Levels and between between Serum Ferritin and Liver Enzymes

Significant positive correlations were observed between ferritin and ALT (r = 0.58, p < 0.001) as well as ferritin and AST (r = 0.51, p < 0.001), supporting the role of ferritin in liver injury.

Table 5: Relationship of NAFLD Severity with Insulin Resistance

Patients with severe NAFLD had higher HOMA-IR values (5.2 ± 1.5), indicating greater insulin resistance. This is a significant difference as p value is 0.001

Table 6: Prevalence of Metabolic Syndrome in Study Participants

67.3% of study participants had metabolic syndrome, reinforcing its strong association with NAFLD.

Table 7: Logistic Regression Analysis for Predictors of NAFLD

TSH (OR 1.5, p < 0.001), serum ferritin (OR 1.8, p < 0.001), and BMI (OR 1.3, p = 0.002) were significant independent predictors of NAFLD.

Figure: Association of Gender with NAFLD

NAFLD was significantly more common in females (48/58) compared to males (28/49) (p = 0.007), suggesting a gender-based predisposition.

NAFLD is significantly associated with age as X2=7.27, p=0.007 which is significant.

Table 8 Association of Family History with NAFLD Cases

Patients with a family history of NAFLD showed a significant correlation with disease presence (p = 0.003), especially when both parents were affected.

This study highlights a strong association between hypothyroidism and NAFLD, with serum ferritin levels playing a significant role in the severity of the disease. These findings align with previous studies that have examined the link between thyroid dysfunction and liver disease.

Our study reported a higher prevalence of NAFLD in hypothyroid patients, reinforcing the role of thyroid dysfunction in hepatic steatosis. Furthermore, our study revealed a significant correlation between TSH and serum ferritin (r = 0.62, p < 0.001), supporting the hypothesis that increased ferritin levels may contribute to liver injury and fibrosis in NAFLD.

Participants with NAFLD were significantly older, as evidenced by the mean age differences (p = 0.01). This finding aligns with previous research indicating that NAFLD prevalence increases with age. The study population had a mean age of 45.3 years with a standard deviation of 10.4, highlighting that the majority of the population is relatively young. Despite this, age remains a critical factor in the development of NAFLD.

Numerous studies have reported that the risk of diabetes increases with age. For example, Mohan et al. (2005) and Ramachandran et al. (2010) found a similar trend in Indian populations. This consistency emphasizes that age is a critical factor in NAFLD risk prediction.

 Our findings regarding lipid abnormalities in hypothyroid NAFLD patients (elevated LDL and triglycerides with decreased HDL) are consistent with studies by Bano et al. (2019), which reported dyslipidemia as a contributing factor to NAFLD in hypothyroid individuals. The increased prevalence of metabolic syndrome (67.3%) in our cohort further aligns with the work of Targher et al. (2010), who emphasized the interplay between metabolic dysfunction, insulin resistance, and NAFLD.

In addition, we observed a higher mean ferritin level in obese individuals (250.9 ± 45.1 µg/L), which is comparable to findings by Kowdley et al. (2012), who noted that elevated ferritin in obese NAFLD patients was linked to increased oxidative stress and hepatic inflammation. Our study further supports this as we found significant correlations between ferritin and ALT (r = 0.58, p < 0.001) and AST (r = 0.51, p < 0.001).

Finally, logistic regression analysis identified TSH, serum ferritin, and BMI as independent predictors of NAFLD.

So this study reinforces the complex relationship between hypothyroidism, NAFLD, and serum ferritin levels. The strong correlation between these parameters suggests that thyroid function should be routinely assessed in NAFLD patients. Future research with larger cohorts and longitudinal studies is needed to further elucidate these associations and potential therapeutic implications. This Study suggests that gender does play a pivotal role in the prevalence of NAFLD within this study population, which is consistent with some epidemiological studies showing similar NAFLD prevalence in both genders.

A significant association was found between BMI and NAFLD (p = 0.001), indicating that higher BMI is a strong risk factor for NAFLD. Similarly, the abdominal girth score was significantly higher in participants with NAFLD (p < 0.05), underscoring the importance of central obesity as a risk factor. This supports the hypothesis that obesity, particularly central obesity, is closely linked to NAFLD.The relationship between obesity and diabetes risk is well-documented. Studies by WHO (2016) and Hu et al. (2001) have established that higher BMI is a significant risk factor for developing NAFLD and diabetes.

Physical activity levels showed a strong association with NAFLD status (p = 0.001). Participants with lower physical activity scores had higher rates of NAFLD, reinforcing the role of a sedentary lifestyle in the development of this condition. Regular exercise appears to be a protective factor against NAFLD.Studies by Helmrich et al. (1991) and Hu et al. (2003), have identified physical inactivity as a major risk factor for diabetes.

Regarding gender differences, our study found a higher prevalence of NAFLD in females (p = 0.007).

Significant association was found between family history and NAFLD status (p = 0.59). This might suggest that genetic predisposition, at least as captured by family history, is less influential in this population compared to lifestyle and metabolic factors. This finding is similar to Meigs et al 2000 in this study Family history is a well-established risk factor for diabetes

This study highlights a strong association between hypothyroidism and NAFLD, with serum ferritin levels playing a significant role in the severity of the disease. These findings align with previous studies that have examined the link between thyroid dysfunction and liver disease.

Our study reported a higher prevalence of NAFLD in hypothyroid patients, reinforcing the role of thyroid dysfunction in hepatic steatosis. Furthermore, our study revealed a significant correlation between TSH and serum ferritin (r = 0.62, p < 0.001), supporting the hypothesis that increased ferritin levels may contribute to liver injury and fibrosis in NAFLD.

Participants with NAFLD were significantly older, as evidenced by the mean age differences (p = 0.01). This finding aligns with previous research indicating that NAFLD prevalence increases with age. The study population had a mean age of 45.3 years with a standard deviation of 10.4, highlighting that the majority of the population is relatively young. Despite this, age remains a critical factor in the development of NAFLD.

Numerous studies have reported that the risk of diabetes increases with age. For example, Mohan et al. (2005) and Ramachandran et al. (2010) found a similar trend in Indian populations. This consistency emphasizes that age is a critical factor in NAFLD risk prediction.

 Our findings regarding lipid abnormalities in hypothyroid NAFLD patients (elevated LDL and triglycerides with decreased HDL) are consistent with studies by Bano et al. (2019), which reported dyslipidemia as a contributing factor to NAFLD in hypothyroid individuals. The increased prevalence of metabolic syndrome (67.3%) in our cohort further aligns with the work of Targher et al. (2010), who emphasized the interplay between metabolic dysfunction, insulin resistance, and NAFLD.

In addition, we observed a higher mean ferritin level in obese individuals (250.9 ± 45.1 µg/L), which is comparable to findings by Kowdley et al. (2012), who noted that elevated ferritin in obese NAFLD patients was linked to increased oxidative stress and hepatic inflammation. Our study further supports this as we found significant correlations between ferritin and ALT (r = 0.58, p < 0.001) and AST (r = 0.51, p < 0.001).

Finally, logistic regression analysis identified TSH, serum ferritin, and BMI as independent predictors of NAFLD.

So this study reinforces the complex relationship between hypothyroidism, NAFLD, and serum ferritin levels. The strong correlation between these parameters suggests that thyroid function should be routinely assessed in NAFLD patients. Future research with larger cohorts and longitudinal studies is needed to further elucidate these associations and potential therapeutic implications. This Study suggests that gender does play a pivotal role in the prevalence of NAFLD within this study population, which is consistent with some epidemiological studies showing similar NAFLD prevalence in both genders.

A significant association was found between BMI and NAFLD (p = 0.001), indicating that higher BMI is a strong risk factor for NAFLD. Similarly, the abdominal girth score was significantly higher in participants with NAFLD (p < 0.05), underscoring the importance of central obesity as a risk factor. This supports the hypothesis that obesity, particularly central obesity, is closely linked to NAFLD.The relationship between obesity and diabetes risk is well-documented. Studies by WHO (2016) and Hu et al. (2001) have established that higher BMI is a significant risk factor for developing NAFLD and diabetes.

Physical activity levels showed a strong association with NAFLD status (p = 0.001). Participants with lower physical activity scores had higher rates of NAFLD, reinforcing the role of a sedentary lifestyle in the development of this condition. Regular exercise appears to be a protective factor against NAFLD.Studies by Helmrich et al. (1991) and Hu et al. (2003), have identified physical inactivity as a major risk factor for diabetes.

Regarding gender differences, our study found a higher prevalence of NAFLD in females (p = 0.007).

Significant association was found between family history and NAFLD status (p = 0.59). This might suggest that genetic predisposition, at least as captured by family history, is less influential in this population compared to lifestyle and metabolic factors. This finding is similar to Meigs et al 2000 in this study Family history is a well-established risk factor for diabetes

1. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med. 1999;107(5):450–5.
2. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55:434. 2. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med 1997; 126:137.
3. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346(16):1221–31.
4. Sanyal AJ; American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002;123(5):1705–25.
5. Younossi ZM. Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2008;28(1):2–12.
6. Harrison SA, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2004;8(4):861–79.
7. Patel V, Chatterji S, Chisholm D, Ebrahim S, Gopalakrishna G, Mathers C, Mohan V, Prabhakaran D, Ravindran RD, Reddy KS. Chronic diseases and injuries in India. Lancet. 2011;377(9763):413–28
8. Mohan V, Farooq S, Deepa M, Ravikumar R, Pitchumoni CS. Prevalence of non-alcoholic fatty liver disease in urban south Indians in relation todifferent grades of glucose intolerance and metabolic syndrome. Diabetes Res Clin Pract. 2009;84(1):84–91.
9. Mohan, V., Deepa, R., Deepa, M., Somannavar, S., & Datta, M. (2005). A simplified Indian Diabetes Risk Score for screening for undiagnosed diabetic subjects. *Journal of the Association of Physicians of India*, 53, 759-763.
10. Ramachandran, A., Snehalatha, C., Vijay, V., & King, H. (2002). Impact of poverty on the prevalence of diabetes and its complications in urban southern India. *Diabetic Medicine*, 19(2), 130-135.
11. World Health Organization. (2016). Global report on diabetes.
12. Hu, F. B., Manson, J. E., Stampfer, M. J., Colditz, G., Liu, S., Solomon, C. G., & Willett, W. C. (2001). Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. *New England Journal of Medicine*, 345(11), 790-797.
13. Helmrich, S. P., Ragland, D. R., Leung, R. W., & Paffenbarger Jr, R. S. (1991). Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. *New England Journal of Medicine*, 325(3), 147-152.
14. Meigs, J. B., Cupples, L. A., & Wilson, P. W. (2000). Parental transmission of type 2 diabetes: the Framingham Offspring Study. *Diabetes*, 49(12), 2201-2207.