Steatosis refers to the abnormal accumulation of triglycerides within hepatocytes and is considered pathological when more than 5% of hepatocytes contain fat.¹ Hepatic steatosis develops when lipid acquisition and synthesis exceed mechanisms responsible for lipid oxidation and export, resulting in progressive intracellular fat accumulation.²⁻⁴ Persistent lipid overload leads to hepatocellular injury, activation of inflammatory pathways, and stimulation of hepatic stellate cells, ultimately culminating in hepatic fibrosis and cirrhosis.⁵

For several decades, the term non-alcoholic fatty liver disease (NAFLD) was used to describe hepatic steatosis occurring in individuals without significant alcohol intake. However, increasing concerns emerged regarding the limitations of an exclusion-based definition that characterized disease by what it was not rather than what it was. The term “non-alcoholic” failed to adequately reflect underlying pathophysiology, contributed to diagnostic ambiguity, and inadequately recognized the frequent coexistence of metabolic dysfunction and alcohol consumption.⁶

To address these limitations, an international multisociety Delphi consensus proposed a revised nomenclature centered on the umbrella term Steatotic Liver Disease (SLD).⁶ This framework encompasses a spectrum of disorders characterized by hepatic steatosis and includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic alcohol-related liver disease (MetALD), alcohol-related liver disease (ALD), specific-etiology SLD, and cryptogenic SLD.⁶ The revised classification emphasizes causality and reflects the real-world overlap between metabolic and alcohol-related liver injury.

MASLD, the principal category within the new classification system, is defined by the presence of hepatic steatosis in association with at least one cardiometabolic risk factor.⁶ Common risk factors include obesity, type 2 diabetes mellitus, hypertension, dyslipidaemia, and insulin resistance.⁶ The disease is increasingly recognized as a multisystem disorder associated not only with liver-related morbidity but also with cardiovascular disease, chronic kidney disease, endocrine dysfunction, and several metabolic complications.⁷˒⁸

The global burden of fatty liver disease has risen dramatically over the past two decades. The worldwide prevalence of NAFLD, now largely represented by MASLD, has been estimated at approximately 25–30% of the adult population, making it one of the most common chronic liver diseases globally.⁹˒¹⁰ The prevalence continues to increase in parallel with the global epidemics of obesity, diabetes mellitus, and metabolic syndrome.¹¹

Progression of disease occurs across a broad clinical spectrum ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma.¹² The presence of MASH and fibrosis substantially increases liver-related mortality and overall mortality.¹³˒¹⁴ In addition, genetic factors such as polymorphisms in the PNPLA3 gene contribute significantly to susceptibility, disease progression, and development of complications.¹³˒¹⁴

Current guidelines recommend active evaluation of high-risk individuals, particularly those with obesity, type 2 diabetes mellitus, metabolic syndrome, dyslipidaemia, and persistently elevated liver enzymes.¹⁵ Non-invasive assessment tools including serum fibrosis scores and elastography-based imaging modalities have increasingly replaced liver biopsy for risk stratification in routine clinical practice.¹⁵

Alcohol-related liver disease remains another important contributor to hepatic steatosis and encompasses a spectrum ranging from simple steatosis to alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma.¹⁶˒¹⁷ The burden of alcohol-related liver disease correlates strongly with cumulative alcohol exposure, although metabolic risk factors frequently coexist and amplify liver injury.¹⁸˒¹⁹ Recognition of this overlap has led to the introduction of the MetALD category within the new SLD framework.⁶

Lifestyle modification remains the cornerstone of management across the entire spectrum of steatotic liver disease. Sustained weight reduction has been shown to improve steatosis, inflammation, and fibrosis, while optimization of cardiometabolic risk factors remains essential for preventing disease progression.²⁰

Despite the growing clinical importance of steatotic liver disease, data regarding the clinical profile and etiological distribution of newly defined SLD subtypes remain limited in the Indian population. Furthermore, evidence describing the burden of cardiometabolic risk factors among patients classified according to the contemporary SLD framework is scarce.

Therefore, the present study was undertaken to evaluate the clinical profile of patients with steatotic liver disease and to assess the distribution of cardiometabolic risk factors across various etiological categories in a tertiary care centre in North India.

Study Design This prospective observational study was conducted in the Department of Medicine, Pt. B.D. Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India over a period of one year on adult 200 patients recruited as per inclusion and exclusion criteria. The study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki and ethical approval was obtained from the Institutional Ethics Committee prior to initiation of the study. Written informed consent was obtained from all participants before enrolment. Patients diagnosed with steatotic liver disease (SLD) on ultrasonography attending outpatient, inpatient, or emergency services of the Department of Medicine were screened for inclusion. Inclusion Criteria • Patients diagnosed with steatotic liver disease on ultrasonography. • Patients willing to provide written informed consent. Exclusion Criteria • Patients unwilling to participate in the study. Diagnosis of steatotic liver disease was established by ultrasonographic demonstration of hepatic steatosis. A detailed clinical assessment was performed in all patients, including: • Demographic characteristics • Alcohol consumption history • Anthropometric measurements (BMI and waist circumference) • Blood pressure measurement • Assessment of comorbid illnesses • Medication history Biochemical evaluation was performed in all enrolled patients and included measurement of fasting blood sugar (FBS), glycated hemoglobin (HbA1c), liver function tests, lipid profile, and viral serology for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Based on clinical history, metabolic risk factors, alcohol consumption, laboratory findings, and the contemporary consensus nomenclature for steatotic liver disease (SLD), patients were classified into different etiological subtypes, namely metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic alcohol-related liver disease (MetALD), alcohol-related liver disease (ALD), specific-etiology steatotic liver disease, and cryptogenic steatotic liver disease. This classification facilitated assessment of the clinical profile and distribution of cardiometabolic risk factors across the various SLD categories. Statistical Analysis Data were entered into Microsoft Excel and analyzed using standard statistical methods. Continuous variables were expressed as mean ± standard deviation (SD), whereas categorical variables were expressed as frequencies and percentages. Chi-square test was used for categorical variables. A p-value <0.05 was considered statistically significant.

Baseline Characteristics of the Study Population

A total of 200 patients with ultrasonographically diagnosed steatotic liver disease were enrolled. The mean age of the study population was 49.84 ± 15.45 years (range 14–88 years). Males constituted 52.5% of the study population. Significant alcohol intake was present in 26.5% of patients, with a mean alcohol consumption of 59.16 ± 21.25 g/day.

Table 1. Baseline Characteristics of the Study Population (N = 200)

Body Mass Index Distribution

Anthropometric assessment revealed a high prevalence of excess body weight. Only 23.5% of patients had normal BMI values, whereas 76.0% had BMI ≥23 kg/m².

Table 2. Distribution of Body Mass Index

Overall, 27.0% of patients were overweight and 49.0% were obese. Morbid obesity (BMI ≥30 kg/m²) was present in 8.5% of participants. Increased waist circumference was observed in 49.0% of patients, indicating a substantial burden of central adiposity.

Distribution of Co-morbidities

Metabolic comorbidities were highly prevalent. Diabetes mellitus, hypertension, and dyslipidaemia were each present in 28.0% of patients.

Table 3. Distribution of Co-morbidities

While 31.5% of patients had no documented comorbidity, the remaining patients demonstrated a substantial burden of metabolic and systemic disorders.

Clinical Presentation

Gastrointestinal symptoms represented the most common mode of presentation and were reported by 56.0% of patients. However, 17.0% of patients were asymptomatic and diagnosed incidentally on imaging.

Cardiovascular symptoms were reported by 11.0% of patients, whereas neurological symptoms were observed in 9.5%.

Regarding medication use, 50.8% of patients were not receiving any long-term therapy. Antihypertensive medications (26.9%) and antidiabetic drugs (24.9%) were the most frequently prescribed medications.

Hepatotoxic drug exposure was uncommon. Approximately 96.0% of patients reported no exposure to known hepatotoxic medications.

Biochemical and Clinical Parameters

Table 4. Biochemical and Clinical Profile

The mean systolic and diastolic blood pressures were 121.72 ± 20.29 mmHg and 77.28 ± 11.97 mmHg respectively. Although 46.0% of patients were normotensive, 37.0% were in the pre-hypertensive range and 17.0% had overt hypertension.

Glycaemic abnormalities were common. Fasting blood glucose ≥100 mg/dL was observed in 35.0% of participants. Among those assessed for HbA1c, 33.8% fulfilled criteria for diabetes mellitus and 19.7% were pre-diabetic.

Among known diabetic patients, poor glycaemic control (HbA1c >8%) was present in 45.0%.

Liver enzyme analysis revealed elevated ALT values in 41.5% of patients, while 58.5% had normal ALT levels despite ultrasonographic evidence of steatosis.

Dyslipidaemia was highly prevalent. Hypertriglyceridaemia was observed in 59.5% of patients, whereas low HDL cholesterol was present in 67.0%.

Viral Serology

Viral markers were negative in the majority of patients (93.0%). Hepatitis C virus positivity was present in 3.5%, hepatitis B virus positivity in 2.5%, and HIV positivity in 1.5% of participants.

Etiological Classification of Steatotic Liver Disease

Table 5. Distribution of Various Etiologies of SLD

MASLD emerged as the predominant etiology, accounting for 70.0% of all cases. MetALD constituted 16.0% of the cohort, highlighting the clinically important overlap between metabolic dysfunction and alcohol consumption.

Among the 140 patients with MASLD, 30 (21.4%) fulfilled criteria for metabolic dysfunction-associated steatohepatitis (MASH).

Within the MetALD subgroup, disease was alcohol-predominant in 27 patients (84.4%) and MASLD-predominant in 5 patients (15.6%).

Overall, the study population was characterized by middle-aged predominance, substantial metabolic comorbidity, obesity, dysglycaemia, dyslipidaemia, and predominance of MASLD within the contemporary SLD framework.

The present study evaluated the clinical profile and etiological spectrum of steatotic liver disease (SLD) using the recently proposed nomenclature framework that replaces the traditional NAFLD classification.⁶ The study also examined the distribution of cardiometabolic risk factors among patients diagnosed with SLD and assessed the applicability of the MASLD–MetALD classification system in routine clinical practice.

A major finding of the present study was the predominance of MASLD, which accounted for 70.0% of all patients. This observation is consistent with contemporary evidence indicating that metabolic dysfunction represents the principal driver of hepatic steatosis globally.⁶˒⁹˒²⁹ The emergence of MASLD as the dominant subtype further validates the rationale behind the new nomenclature, which recognizes metabolic dysfunction as the cornerstone of disease pathogenesis rather than defining disease through exclusion of alcohol intake.⁶˒³⁵

The study population was predominantly middle-aged, with a mean age of approximately 50 years. Similar demographic patterns have been reported in previous epidemiological studies evaluating fatty liver disease across different populations.⁹˒²² The relatively balanced gender distribution observed in our study contrasts with earlier reports suggesting a male predominance, indicating that metabolic liver disease is increasingly affecting both sexes.

Obesity emerged as one of the most important characteristics of patients with SLD. More than three-fourths of participants had BMI values above Asian-specific thresholds and nearly half were obese. Central adiposity, reflected by increased waist circumference, was present in almost half of the study population. These findings support the pivotal role of adiposity and insulin resistance in the development of hepatic steatosis.²˒³˒²⁰˒²²

A substantial burden of cardiometabolic disease was evident. Diabetes mellitus, hypertension, and dyslipidaemia were each present in 28.0% of patients. Hypertriglyceridaemia and reduced HDL cholesterol were observed in 59.5% and 67.0% of participants respectively. These findings are consistent with previous studies demonstrating a strong association between MASLD and metabolic syndrome.⁷˒⁸˒²³ The clustering of multiple cardiometabolic risk factors in our cohort reinforces the concept that MASLD is a systemic metabolic disorder rather than a liver-limited disease.

Cardiovascular disease and chronic kidney disease were present in 8.5% and 6.5% of patients respectively. Previous meta-analyses have demonstrated that patients with MASLD have significantly increased risks of cardiovascular morbidity and mortality compared with the general population.⁷˒²³ Cardiovascular disease remains the leading cause of death among patients with MASLD, highlighting the need for multidisciplinary management strategies.⁷˒⁸

Glycaemic abnormalities were common in the present study. More than half of evaluated patients demonstrated either diabetes or prediabetes. Among known diabetics, poor glycaemic control was observed in 45% of cases. Type 2 diabetes mellitus is one of the strongest predictors of progression from steatosis to steatohepatitis and advanced fibrosis and significantly increases the risk of liver-related complications.¹⁵˒²³

Lean MASLD has emerged as an increasingly recognized clinical entity. Although most patients in our cohort were overweight or obese, a subset fulfilled criteria for lean MASLD. Previous studies have shown that lean MASLD may be associated with unique genetic susceptibility, particularly involving PNPLA3 polymorphisms, despite lower degrees of obesity.¹³˒²¹˒³⁰ Furthermore, lean MASLD has been associated with higher liver-related mortality despite lower rates of cirrhosis compared with non-lean disease.³³

Among patients classified as MASLD, approximately one-fifth fulfilled criteria for MASH. This finding is consistent with previous reports indicating that 20–30% of patients with MASLD develop steatohepatitis.¹² MASH is clinically important because fibrosis progression and adverse clinical outcomes correlate strongly with the presence of steatohepatitis and fibrosis stage.²⁴˒²⁶˒³⁶˒³⁷

An important observation in the present study was that 58.5% of patients had normal ALT levels despite ultrasonographic evidence of steatosis. Similar findings have been reported previously and emphasize that normal transaminases do not exclude clinically significant liver disease.¹⁵ Consequently, reliance on liver enzymes alone may result in under-recognition of patients with advanced fibrosis.

Recent advances in fibrosis assessment have substantially improved non-invasive evaluation of patients with MASLD. Several studies have demonstrated that fibrosis stage is the most important determinant of long-term prognosis.²⁶˒³⁶˒³⁷ Non-invasive tools such as FIB-4, NAFLD fibrosis score, transient elastography, shear wave elastography, and magnetic resonance elastography allow effective risk stratification without routine liver biopsy.²⁵˒²⁷

The introduction of MetALD represents a major advancement in disease classification. Traditionally, patients with metabolic dysfunction and moderate alcohol consumption were difficult to classify accurately. The new framework recognizes the continuum between metabolic and alcohol-related liver injury and acknowledges their synergistic effects on disease progression.⁶˒³⁵ In our study, MetALD accounted for 16.0% of patients, with alcohol-predominant disease observed in most cases. Similar observations have been reported previously, supporting the clinical relevance of this subgroup.³⁸

Hypothyroidism was identified in 6.0% of participants. Emerging evidence suggests that thyroid dysfunction contributes to the pathogenesis of MASLD through effects on lipid metabolism, insulin sensitivity, and hepatic fat accumulation.³⁴ The recent approval of thyroid hormone receptor-β agonists for MASH further supports the biological relationship between thyroid function and hepatic steatosis.³⁴

The low frequency of cryptogenic SLD observed in the present study further supports the effectiveness of the revised nomenclature in reducing the number of unclassified patients.⁶˒³⁵ By incorporating metabolic dysfunction and alcohol exposure into a unified framework, the SLD classification appears to provide greater diagnostic clarity and improved clinical applicability.

Overall, the findings of the present study support the growing body of evidence indicating that metabolic dysfunction is the principal determinant of steatotic liver disease and that the contemporary SLD nomenclature effectively captures the clinical heterogeneity encountered in real-world practice.