Fatty Liver — Symptoms, Causes & Treatment | MyMedicPlus

Fatty liver disease (hepatic steatosis) is a condition characterised by pathological accumulation of lipid (primarily triglycerides) within hepatocytes, defined histologically as steatosis in more than 5% of liver cells. It encompasses two major clinical entities: Non-alcoholic fatty liver disease (NAFLD) — arising in the absence of significant alcohol use (below 21 units/week for men, below 14 units/week for women) and representing the hepatic manifestation of the metabolic syndrome; and Alcoholic fatty liver disease (AFLD) — directly caused by excessive alcohol consumption. NAFLD is the most common liver condition worldwide, affecting approximately 25% of the global adult population (38% in the Middle East, 30% in South America, 24% in Europe) — an estimated 1.7 billion people. In high-income countries with high obesity prevalence, NAFLD affects 40–46% of adults. The NAFLD spectrum ranges from simple steatosis (benign prognosis in most) through non-alcoholic steatohepatitis (NASH — steatosis + inflammation + ballooning hepatocyte injury with or without fibrosis, present in 25% of NAFLD patients) to cirrhosis and hepatocellular carcinoma. NASH is now the fastest-growing indication for liver transplantation in the USA and Europe, overtaking hepatitis C. The condition is often asymptomatic until advanced fibrosis or cirrhosis is established — making screening of high-risk populations (obesity, type 2 diabetes, metabolic syndrome) essential for early detection. The 2023 Delphi consensus renamed NAFLD as 'metabolic dysfunction-associated steatotic liver disease' (MASLD) to better reflect its metabolic aetiology.

NAFLD is caused by the metabolic syndrome and insulin resistance — which increase hepatic fatty acid delivery (from increased lipolysis of peripheral adipose tissue and de novo lipogenesis), impair fatty acid oxidation (mitochondrial dysfunction), and reduce hepatic lipid export (reduced VLDL synthesis). Key risk factors and their effect sizes: obesity (BMI above 30 — present in 70–80% of NAFLD patients; visceral adiposity — measured by waist circumference — is more important than total BMI); type 2 diabetes (3-fold increased NAFLD risk; NASH and fibrosis are more common in diabetics); insulin resistance and metabolic syndrome (the primary pathophysiological driver); dyslipidaemia (hypertriglyceridaemia above 1.7 mmol/L and low HDL below 1.0 mmol/L in men or below 1.3 mmol/L in women). Genetic polymorphisms: PNPLA3 (patatin-like phospholipase domain-containing protein 3) rs738409 G allele — the strongest common genetic risk variant — present in 45% of Hispanics (highest NAFLD risk) and 20% of Europeans; TM6SF2 E167K variant; MBOAT7 polymorphisms; HSD17B13 splice variant (protective). Hypothyroidism (impairs lipid metabolism), polycystic ovary syndrome (PCOS), and obstructive sleep apnoea (intermittent hypoxia causes oxidative stress and mitochondrial dysfunction) are important secondary causes of NAFLD. Drug-induced steatosis: amiodarone, tamoxifen, methotrexate, corticosteroids, valproate, total parenteral nutrition, and nucleoside analogues cause secondary NAFLD. AFLD results from ethanol metabolism to acetaldehyde — which damages mitochondria, stimulates hepatic de novo lipogenesis, and promotes gut barrier dysfunction with increased hepatic exposure to lipopolysaccharides.

Most people with simple steatosis and early NAFLD are entirely asymptomatic — the condition is discovered incidentally during abdominal imaging (ultrasound, CT, or MRI for other indications) or as unexplained liver enzyme elevation on blood tests. When present, symptoms are non-specific and insensitive: right upper quadrant heaviness or dull discomfort (from hepatomegaly and distension of the liver capsule — Glisson's capsule — present in more severe disease); fatigue and reduced exercise tolerance (common, multifactorial); and nausea. Clinical examination may reveal hepatomegaly (in 50–75% of NAFLD patients — a palpable, smooth, non-tender liver edge below the right costal margin) — though the liver may be impalpable in obese patients. As NAFLD progresses to NASH with advanced fibrosis or cirrhosis, features of portal hypertension develop: splenomegaly, peripheral oedema, ascites, and — in decompensated cirrhosis — hepatic encephalopathy (confusion, asterixis), jaundice, and spontaneous bacterial peritonitis. Features of the metabolic syndrome: central obesity, hypertension, acanthosis nigricans (darkened skin folds indicating severe insulin resistance), and signs of type 2 diabetes. Complications of cirrhosis: haematemesis from oesophageal varices, hepatocellular carcinoma (HCC — 2–3% annual risk in NASH cirrhosis), and progressive liver failure requiring transplantation.

Liver biochemistry: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the primary screening tests — elevated in NAFLD but may be within normal limits even in advanced fibrosis (normal AST/ALT does not exclude significant NAFLD). The AST:ALT ratio below 1 is characteristic of NAFLD; above 2:1 in AFLD ('alcoholic hepatitis pattern'). GGT (gamma-glutamyl transferase) elevation is sensitive for alcohol use and NAFLD but non-specific. Alkaline phosphatase may be elevated in cholestatic disease. Abdominal ultrasound: the first-line imaging investigation — the echogenic ('bright') liver pattern indicates steatosis with sensitivity 60–94% when steatosis exceeds 30%. Ultrasound cannot reliably detect steatosis below 30% and cannot stage fibrosis. Liver stiffness measurement: transient elastography (FibroScan — ultrasound-based shear wave measurement, reported in kilopascals): the standard non-invasive tool for assessing liver fibrosis (F0–F4 METAVIR scale); liver stiffness above 7 kPa indicates significant fibrosis (F2+), above 9.6 kPa suggests advanced fibrosis (F3+), above 12–15 kPa indicates cirrhosis. Serum fibrosis panels: FIB-4 index (age × AST / (platelet count × √ALT)) — below 1.30 rules out advanced fibrosis (AUROC 0.80); above 2.67 warrants further evaluation. NAFLD Fibrosis Score (NFS). MRI-PDFF (proton density fat fraction): the most accurate quantitative method for measuring liver fat percentage, used in clinical trials and specialist centres. Liver biopsy (percutaneous): remains the gold standard for confirming NASH, staging fibrosis (METAVIR F0–F4), and grading activity (NAS — NAFLD Activity Score) — reserved for cases where non-invasive tests are indeterminate, clinical trial eligibility assessment, or to guide treatment decisions when fibrosis stage significantly impacts management.

Weight loss is the cornerstone of NAFLD management and the only intervention proven to improve all histological parameters including fibrosis: 5–7% weight loss reduces hepatic steatosis; 7–10% weight loss reduces NASH activity; above 10% weight loss causes fibrosis regression in a significant proportion of patients (40–50% of patients with at least 10% weight loss achieve at least one stage fibrosis regression). Target: 7–10% of total body weight through caloric restriction and aerobic exercise. Mediterranean diet (high in olive oil, legumes, fish, and fresh vegetables; low in red meat and refined carbohydrates) is the most evidence-based dietary pattern for NAFLD. Structured aerobic exercise (150–200 minutes per week of moderate intensity) independently reduces liver fat and NASH activity. Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy): highly effective for morbidly obese patients with NAFLD — achieves NASH resolution in 80–85% and fibrosis regression in 50% at 1 year. Pharmacotherapy: Resmetirom (Rezdiffra): the first FDA-approved drug specifically for NASH with moderate-to-advanced fibrosis (F2–F3) — a liver-directed thyroid hormone receptor-beta agonist that reduces hepatic lipogenesis and improves mitochondrial function; approved March 2024 (FDA) after the MAESTRO-NASH trial showed significant NASH resolution and fibrosis improvement vs placebo. Semaglutide (GLP-1 receptor agonist — currently approved for type 2 diabetes and obesity): reduces liver fat by 30–40% and significantly reduces NASH activity (NASH resolution in 59% vs 17% placebo in the STELLAR trial); liver fibrosis reduction requires ongoing phase 3 confirmation. Pioglitazone (thiazolidinedione): improves NASH histology in diabetic and non-diabetic NAFLD — reduces steatosis, inflammation, and ballooning (NAS improvement) but does not reliably improve fibrosis; causes weight gain and fluid retention; appropriate for NAFLD patients with established diabetes. Vitamin E (800 IU/day natural alpha-tocopherol): improves NASH histology in non-diabetic adults (PIVENS trial) but increases cardiovascular risk with long-term use at this dose — reserved for specific non-diabetic patients. AFLD: complete alcohol abstinence is mandatory; severe alcoholic hepatitis (Maddrey's Discriminant Function above 32) — prednisolone 40 mg/day for 28 days reduces short-term mortality.

NASH-related cirrhosis is the third most common indication for liver transplantation in the USA and the fastest growing — a trajectory driven by the obesity and diabetes epidemics. From simple steatosis, progression to NASH occurs in 25% of patients; 15–25% of NASH patients develop cirrhosis within 10–20 years; decompensated cirrhosis from NAFLD carries a 3–5 year mortality above 50% without transplantation. Hepatocellular carcinoma (HCC) develops in NAFLD patients — the majority of NAFLD-associated HCC cases (approximately 50%) arise in the absence of cirrhosis, unlike viral hepatitis-associated HCC; annual surveillance with 6-monthly abdominal ultrasound ± AFP is recommended in NASH cirrhosis. Portal hypertension from fibrosis and cirrhosis causes oesophageal and gastric varices (risk of life-threatening haematemesis), hepatic encephalopathy (cerebral dysfunction from failure to clear nitrogenous gut-derived toxins — ammonia, mercaptans — requiring lactulose and rifaximin), spontaneous bacterial peritonitis (in-hospital mortality 10–20%), and hepatorenal syndrome (functional renal failure precipitated by sepsis or excessive diuresis). Cardiovascular disease is the leading cause of death in NAFLD overall — NAFLD independently increases cardiovascular mortality 2-fold beyond traditional risk factors from shared metabolic pathway abnormalities. Type 2 diabetes progression is accelerated in NAFLD — insulin resistance worsens reciprocally with hepatic fat accumulation.

Maintain a healthy body weight through Mediterranean or low-carbohydrate diet and regular aerobic exercise (150+ minutes per week). Limit or eliminate alcohol consumption. Control blood pressure, blood sugar, and cholesterol through lifestyle and medication. Avoid hepatotoxic medications and over-the-counter supplements without medical guidance. Annual monitoring of liver function, fasting glucose, and lipid panel is recommended for those at risk. GLP-1 receptor agonists and bariatric surgery offer significant metabolic benefit in obese patients with NAFLD and concurrent type 2 diabetes. Regular surveillance with FibroScan or FIB-4 index scoring every 1–2 years allows early detection of fibrosis progression and timely intensification of lifestyle or pharmacological intervention before cirrhosis develops.

Seek emergency care immediately for: yellowing of the skin or eyes (jaundice) appearing rapidly; confusion or drowsiness (hepatic encephalopathy — a sign of acute-on-chronic liver failure); vomiting blood or passing black tarry stools (variceal bleeding from portal hypertension — a medical emergency requiring urgent endoscopy). See your GP within 2 weeks if a routine blood test shows elevated ALT or AST levels (above 40 IU/L) — even mildly raised liver enzymes warrant investigation to exclude fatty liver disease and other liver conditions. If you have obesity, type 2 diabetes, or metabolic syndrome with confirmed fatty liver on ultrasound, ask for referral to a hepatologist or gastroenterologist for FibroScan assessment — this non-invasive test measures liver stiffness to detect fibrosis (scarring) early. Liver function tests should be monitored annually in all patients with confirmed NAFLD/MASLD. If resmetirom (Rezdiffra) or GLP-1 receptor agonist therapy is being considered, specialist referral is required. Never start herbal or dietary supplements claiming to 'detox' the liver without medical advice — some (e.g., kava, green tea extract, high-dose niacin) are hepatotoxic.