MASLD & Fatty Liver

A clinical overview by Dr. Chetan Kalal, DM (Hepatology), Associate Director — Hepatology & Liver Transplant, Gleneagles Hospital, Mumbai Picture this: you are in your early thirties, your weight is normal, you exercise three times a week, and your last blood test came back unremarkable. Then an abdominal ultrasound — done incidentally during a routine health check — shows something unexpected. Fat in the liver. Fatty liver disease, in a person who does not fit a single conventional risk factor for it. This scenario is no longer rare. Hepatology clinics across India are seeing a steady increase in exactly this kind of patient. The condition has a name — lean MASLD, part of the broader spectrum now called Metabolic Dysfunction-Associated Steatotic Liver Disease — and understanding why it happens is not an academic question. Without the right explanation, there is no right treatment plan. The Old Risk Profile No Longer Tells the Whole Story Fatty liver was historically associated with obesity, type 2 diabetes, and heavy alcohol intake. Those associations are real, but they are not the complete picture. A substantial proportion of patients with confirmed hepatic steatosis carry a normal BMI, have no diabetes, and drink little or no alcohol. In Indian clinical practice, this pattern is common enough that lean MASLD is now considered a distinct and important entity — one that is underdiagnosed precisely because patients and clinicians alike assume that a normal weight rules out the diagnosis. Why It Happens: The Real Causes 1. Genetics — PNPLA3, TM6SF2, and the South Asian disadvantage The most significant driver of lean MASLD is genetic. Variants in the PNPLA3 gene impair the liver’s ability to export triglycerides, causing fat to accumulate within liver cells even when dietary intake and body weight are entirely normal. The TM6SF2 variant works through a related mechanism, reducing hepatic lipid secretion. Both are associated with a higher risk of not just fatty liver but also more advanced liver disease — fibrosis and cirrhosis — independent of weight or metabolic status. These risk variants are substantially more prevalent in South Asian populations than in Europeans. This genetic reality helps explain a pattern that has puzzled many Indian patients: fatty liver diagnosed in a lean, fit individual with no obvious lifestyle risk factor. The liver did not malfunction because of what the patient ate or weighed — the predisposition was written into their genetics from the start. 2. Visceral fat and sarcopenic obesity — the hidden adiposity BMI measures total body weight relative to height. It does not tell you where the fat is stored. A person with a perfectly normal BMI can carry significant amounts of visceral fat — fat that accumulates around the abdominal organs, rather than under the skin — and visceral fat is metabolically far more harmful than subcutaneous fat. It drives insulin resistance, systemic inflammation, and hepatic fat deposition at levels that body weight alone would not predict. A related but distinct phenomenon is sarcopenic obesity: low skeletal muscle mass combined with excess body fat, occurring in a person who appears thin or normal. With less muscle available to absorb and metabolise glucose, the liver compensates by converting the excess into fat. The result is fatty liver in someone who looks lean — and who may never be flagged for further investigation because their outward appearance suggests good metabolic health. 3. Insulin resistance before the diabetes label Many patients with lean MASLD have measurable insulin resistance — meaning their tissues respond poorly to insulin — even when their fasting blood glucose and HbA1c fall within normal limits. This is a pre-diabetic metabolic state that does not yet meet the diagnostic threshold for type 2 diabetes, so it is rarely tested for in the context of a routine health check. The liver is exquisitely sensitive to insulin signalling. When that signalling is impaired, the liver receives conflicting instructions: it upregulates fat synthesis and simultaneously reduces fat export. The combination produces steatosis in the absence of overt hyperglycaemia — a condition that a standard blood glucose test will entirely miss. 4. Diet quality, not just calorie count Two people can consume similar total calories and have very different liver outcomes depending on what those calories consist of. Fructose — found in soft drinks, packaged fruit juices, and added sugars in processed food — is metabolised almost exclusively in the liver, and in excess, it is shunted directly into fat synthesis. Refined carbohydrates and ultra-processed foods drive similar hepatic lipogenic pathways. A person eating what they would describe as a “normal” diet — not overeating, not obviously unhealthy — can still be delivering a daily fructose and refined carbohydrate load that a genetically susceptible liver cannot handle. No visible weight gain is required for this process to cause measurable liver damage over years. 5. Hormonal triggers — hypothyroidism and PCOS Hypothyroidism reduces the rate at which the liver clears fat; even subclinical hypothyroidism (where thyroid hormone levels are low-normal but TSH is elevated) can be sufficient to cause steatosis. This is reversible with appropriate thyroid treatment, making it one of the most important and under-recognised causes of fatty liver in lean patients — particularly in women. Polycystic ovarian syndrome (PCOS) is independently associated with insulin resistance and elevated androgens, both of which promote hepatic fat accumulation. Young women with PCOS carry a meaningful risk of developing fatty liver even at normal body weight, and liver assessment is warranted as part of their long-term metabolic monitoring. 6. Medications that cause hepatic steatosis Several commonly used drugs can cause or worsen fatty liver as a direct effect, regardless of the patient’s baseline metabolic risk. The list includes corticosteroids used for inflammatory conditions, tamoxifen prescribed for breast cancer, valproate for epilepsy, and methotrexate used in rheumatological disease. Patients on any of these agents who develop raised liver enzymes deserve formal hepatological evaluation — not simply a repeat blood test in three months. 7. The gut-liver connection The gut microbiome communicates directly with the liver via the