Microvesicular steatosis (MVS) is a serious form of acute fatty liver disease characterized by the accumulation of fat within liver cells (hepatocytes). This fat appears as numerous, small lipid droplets that fill the cytoplasm without displacing the cell’s nucleus, unlike the more common macrovesicular steatosis. MVS pathology indicates a profound disruption of the cell’s internal machinery, often leading to rapid progression to severe liver dysfunction. Because MVS is consistently linked to acute liver failure, it requires immediate medical recognition and intervention.
Underlying Causes and Risk Factors
The root cause of microvesicular steatosis is a fundamental failure of the hepatocyte’s energy production system, specifically the mitochondria. Mitochondria break down fatty acids through beta-oxidation to generate energy. When this process is inhibited, fatty acids cannot be metabolized and accumulate as triglycerides, forming the characteristic small droplets. This severe metabolic disruption differentiates MVS from the moderate impairment associated with the more benign macrovesicular form.
Drug toxicities that directly poison the mitochondria are a significant cause of MVS. Valproic acid, an anticonvulsant, is a well-documented example, causing mitochondrial structural changes and inhibiting beta-oxidation enzymes. Older antibiotics, such as high-dose tetracycline, and certain nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV treatment (e.g., zidovudine and didanosine) also interfere with mitochondrial function. This interference leads to a lack of energy production and a buildup of toxic lipid intermediates, rapidly overwhelming the liver.
Acute, acquired conditions that disrupt mitochondrial function also cause MVS, most notably Reye’s Syndrome. This syndrome typically affects children recovering from a viral illness (like influenza or chickenpox) who were given aspirin. The combination of the viral infection and the drug impairs oxidative phosphorylation and fatty acid breakdown. This metabolic failure results in the accumulation of fatty acids and ammonia, causing both liver damage and brain swelling.
Acute Fatty Liver of Pregnancy (AFLP) is a unique cause that occurs late in the third trimester. AFLP results from a gene-environment interaction, often involving a mother who is heterozygous for a fatty acid oxidation defect, such as long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. If the fetus is homozygous for this defect, it produces fatty acid intermediates that the mother’s partially deficient liver cannot clear. The accumulation of these toxic metabolites in the maternal liver precipitates acute microvesicular steatosis and liver failure.
MVS can also be the initial presentation of inherited disorders of fatty acid oxidation (FAO), which are genetic defects impairing specific enzyme function. These autosomal recessive conditions include Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD), LCHAD deficiency, and Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD). In affected infants or children, a metabolic stressor like fasting or illness can trigger a crisis because their bodies cannot efficiently use fat stores for energy. This inability leads to the rapid accumulation of fatty acids in the liver, causing the microvesicular change and often severe hypoglycemia.
Recognizing the Clinical Signs
The onset of microvesicular steatosis is acute, often presenting with non-specific symptoms that delay diagnosis. Patients typically report general malaise, profound fatigue, and persistent gastrointestinal distress, including nausea and loss of appetite. Abdominal pain, frequently localized to the upper right quadrant, may also be an early finding. These initial complaints quickly give way to the alarming signs of acute liver failure.
The systemic collapse of liver function leads to a cascade of observable physical findings. Jaundice (yellowing of the skin and eyes) is common, reflecting the liver’s inability to process bilirubin. The synthetic function of the liver fails, resulting in coagulopathy, which is a severe impairment of the blood clotting process. This manifests as easy bruising or uncontrolled bleeding, measured by a prolonged prothrombin time.
Severe hypoglycemia (dangerously low blood sugar) is a particularly dangerous clinical sign. It occurs because the liver cannot perform gluconeogenesis or break down fatty acids for fuel. Since the brain relies heavily on glucose, this hypoglycemia contributes to neurological symptoms. Furthermore, the failure to detoxify neurotoxins, particularly ammonia, leads to hepatic encephalopathy, a spectrum of neuropsychiatric changes.
Early signs of encephalopathy are subtle, presenting as confusion, difficulty concentrating, or changes in the sleep-wake cycle. As the condition worsens, the patient may develop slurred speech, lethargy, and asterixis (a characteristic flapping tremor of the hands). Without prompt intervention, this neurological decline progresses rapidly to stupor and eventually coma. Systemic involvement often extends beyond the liver, with acute kidney failure and pancreatitis being common complications.
Diagnostic Procedures and Confirmation
Diagnosing microvesicular steatosis relies on laboratory findings, imaging studies, and a tissue biopsy. Initial blood tests reveal the acute liver injury and associated metabolic derangements. Liver enzyme levels, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are typically elevated but often less dramatically than in other forms of acute hepatitis. A marked prolongation of the Prothrombin Time (PT) and International Normalized Ratio (INR) is more indicative of synthetic failure, suggesting the liver is failing to produce clotting factors.
The metabolic profile provides powerful diagnostic clues, often showing severe hypoglycemia because impaired mitochondrial function prevents the liver from releasing glucose. Elevated blood ammonia levels are also frequently observed, correlating directly with the severity of hepatic encephalopathy and the liver’s inability to clear this neurotoxin. This combination of acute liver failure with profound hypoglycemia strongly suggests a microvesicular process.
Imaging techniques like abdominal ultrasound and computed tomography (CT) scans are useful for initial assessment but have limitations. These modalities can detect fatty infiltration by showing a bright or dense liver, but they cannot reliably distinguish between microvesicular and macrovesicular fat droplets. Advanced magnetic resonance imaging (MRI) can quantify total liver fat content accurately but still lacks the definitive microscopic detail required for a specific diagnosis.
The gold standard for confirming microvesicular steatosis remains the liver biopsy. This procedure is often performed using a transjugular approach due to the high risk of bleeding associated with the patient’s coagulopathy. Microscopic examination is essential to visualize the characteristic pathology. The diagnosis is confirmed by finding hepatocytes distended with fine, foamy lipid vacuoles that leave the nucleus in its central position. This clearly differentiates it from macrovesicular steatosis, where a large, single fat droplet pushes the nucleus to the side. The presence of diffuse microvesicular fat, combined with the clinical picture of acute liver failure, provides final confirmation.