Fatty liver disease (fatty hepatosis)

Main causes and classification

Classical etiological groups include alcoholic and metabolic steatosis (as a component of metabolic syndrome in type 2 diabetes mellitus, obesity, and dyslipidemia). Toxic and drug-induced steatosis, liver damage in protein malnutrition, and hypoxic states are also distinguished.

Fatty change serves as an accompanying sign of many severe pathologies:

• Viral hepatitis C: steatosis is a characteristic feature, and upon becoming chronic, it forms a specific histological pattern together with lymphoid infiltration of portal tracts, piecemeal necroses, and fibrosis.
• Massive progressive liver necrosis: fat vacuoles are identified in surviving hepatocytes against the background of total parenchymal breakdown.
• Blood system diseases: fatty (or protein) degeneration is combined with lymphocytic infiltration along the capsule and portal tracts.
• Liver cirrhosis: in alcoholic etiology of cirrhosis, it is precisely the accumulation of fat that gives the regenerative nodules a characteristic bright yellow color on cross-section.

Pathogenesis of diabetic steatosis

In diabetes mellitus, the leading triggering factor is insulin deficiency. Normally, insulin acts as a potent antilipolytic hormone that suppresses fat breakdown. In its absence, lipolytic hormones begin to dominate in the body, triggering the following pathological cascade:

1. Enhanced mobilization of fats from depots occurs, causing the level of fatty acids in the bloodstream to rise sharply.
2. The liver actively captures these acids and tries to enhance the synthesis of lipoproteins. However, it is unable to assimilate the entire incoming volume due to insufficient formation of apoprotein.
3. The formation of phospholipids is disrupted in hepatocytes, and the rate of fatty acid oxidation decreases.
4. All unprocessed excess is resynthesized into triglycerides, which accumulate in the cell cytoplasm.

A specific morphological feature of diabetic liver damage is the appearance of so-called "vacuolated" or "glycogen" nuclei. This phenomenon occurs due to the vacuolation of the nuclei of "fatty-changed" cells as a result of glycogen deposition in them. If the patient suffers from concomitant obesity, an alimentary factor (excessive intake of carbohydrates and fats with food) is added to the pathogenesis, but uncontrolled lipolysis still remains the leading mechanism leading to hyperlipidemia.

Alcoholic liver disease

The toxic effect of ethanol on hepatocytes triggers several mechanisms of fat accumulation at once. First, it stimulates the production of fatty acids directly inside liver cells and simultaneously enhances their mobilization from peripheral depots. Second, ethanol inhibits fat oxidation processes, forcing them to esterify more actively into triglycerides. Third, the transport function suffers significantly: lipoprotein synthesis decreases and their release outside the cell is impaired. Additionally, the synthesis and accumulation of cholesterol are enhanced in cell membranes, which increases their permeability.

Morphologically, fat deposits in alcoholism can be distributed both diffusely and in separate foci. Acute alcoholic hepatitis extremely rarely arises in healthy tissue—as a rule, it develops against the background of pre-existing long-standing fatty degeneration.

The prognosis of the disease directly depends on the duration of alcohol consumption. At the initial stages, the process is reversible: with complete abstinence, fat disappears from the cells within 2–4 weeks. However, with continued intoxication and repeated attacks of acute hepatitis, the disease relentlessly progresses, leading to the irreversible formation of liver cirrhosis.

Non-alcoholic fatty liver disease (NAFLD)

NAFLD is a common pathology in which steatosis is the starting point of the diagnostic algorithm. At the initial stage, fat is detected using imaging methods or histological examination. It is extremely important to notice the transition of simple steatosis to non-alcoholic steatohepatitis (NASH) in time.

To diagnose NASH, the simultaneous presence of a specific triad of features is required:

• Pronounced steatosis.
• Hepatocyte ballooning degeneration.
• Lobular inflammation.

Since reliable non-invasive diagnostic methods for steatohepatitis have not yet been developed, liver biopsy remains the unconditional "gold standard".

Class and exam questions

What else to study on this topic

• Features of lipid metabolism in the liver: the role of apoproteins and phospholipids.
• Histological picture of chronic viral hepatitis C.
• Differences between hydropic, ballooning, and fatty degeneration of hepatocytes.
• Morphological manifestations of nonspecific reactive hepatitis.
• Mechanisms of formation of regenerative nodules in postnecrotic cirrhosis.

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.