Non-alcoholic steatohepatitis: causes, symptoms, diagnosis, treatment

Non-alcoholic steatohepatitis is a liver disorder in individuals who do not abuse alcohol, characterized by a combination of fatty degeneration and hepatitis (lobular or portal).

Nonalcoholic steatohepatitis is a syndrome that develops in patients who do not abuse alcohol and involves liver damage that is histologically indistinguishable from alcoholic hepatitis. It develops most often in middle-aged women with increased body weight and elevated blood glucose and lipid levels. The pathogenesis is not fully understood, but is most likely associated with insulin resistance (for example, in obese patients or with metabolic syndrome). In most cases, the disease is asymptomatic. Laboratory data indicate elevated aminotransferase levels. The diagnosis should be confirmed by biopsy. Treatment of nonalcoholic steatohepatitis includes eliminating risk factors and causes.

Nonalcoholic steatohepatitis (NASH) is diagnosed most often in women aged 40 to 60 years, many of whom are obese, have type 2 diabetes, or hyperlipidemia, but can occur in all age groups and in both sexes.

The prevalence of non-alcoholic steatohepatitis is not precisely known. According to Propst et al. (1995), among patients who underwent liver biopsy, it is 7-9%. Currently, non-alcoholic steatohepatitis is proposed to be considered as an independent disease (Sheth, Gordon, Chorpa, 1997).

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What causes nonalcoholic steatohepatitis?

The cause of non-alcoholic steatohepatitis has not been definitively established. Only the factors that are most often associated with non-alcoholic steatohepatitis are known:

1. Metabolic factors: obesity, diabetes mellitus, hyperlipidemia, rapid weight loss, acute starvation, total parenteral nutrition.
2. Surgical interventions: creation of junoilal anastomosis, gastroplasty for pathological obesity, creation of biliary pancreatic stoma, extensive resection of the jejunum.
3. Medicines: amiodarone, perhexiline maleate, glucocorticosteroids, synthetic estrogens, tamoxifen.
4. Other factors: jejunal diverticulosis with bacterial overgrowth, regional lipodystrophy, beta-lipoproteinemia, Weber-Christian disease.

The pathogenesis of non-alcoholic steatohepatitis is unclear. It is assumed that the main mechanisms of development of non-alcoholic steatohepatitis are accumulation of free fatty acids, triglycerides in the liver, activation of lipid peroxidation in the liver, which leads to accumulation of toxic intermediate products that stimulate development of inflammation in the liver, accumulation of fat in the liver also leads to stimulation of fibrosis formation in the liver (Lombardi, 1966).

Symptoms of Non-alcoholic Steatohepatitis

Non-alcoholic steatohepatitis is most often found in women, mainly aged 40-60 years. Obesity is observed in 70-100% of patients, diabetes mellitus in 35-75% of patients. Subjective symptoms of non-alcoholic steatohepatitis are caused mainly by the diseases with which it is combined. Along with this, there may be a feeling of discomfort in the abdominal cavity, pain in the right hypochondrium, weakness, malaise. Most patients have no specific complaints. The most characteristic objective sign of the disease is an enlarged liver.

A biochemical blood test reveals an increase in the activity of ALT and AST by 2-3 times.

Ultrasound of the liver reveals hyperechogenicity (“brightness”) of the liver tissue due to diffuse fatty infiltration.

Histological picture

Characteristic signs of non-alcoholic steatohepatitis in liver biopsy specimens are moderate or severe fatty degeneration (usually large-droplet), diffuse or localized mainly in the central zones of the lobules; cellular inflammatory infiltration (neutrophilic, lymphocytic, mixed), usually in the center of the lobules, but inflammation may spread to the portal and periportal zones; Mallory hyaline bodies may be detected, but usually there are few of them, they are smaller in size and less noticeable than in alcoholic hepatitis. In severe cases of the disease, fibrosis or cirrhosis of the liver may develop in the future.

In general, most patients with nonalcoholic steatohepatitis have a benign and even asymptomatic course. Weight loss can lead to the reversal of nonalcoholic steatohepatitis.

Diagnosis of non-alcoholic steatohepatitis

The most common laboratory abnormality is elevated aminotransferases. Unlike alcoholic liver disease, the AST/ALT ratio in patients with nonalcoholic fatty liver disease is usually less than 1. Alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) levels are sometimes elevated. Hyperbilirubinemia, prolongation of prothrombin time, and hypoalbuminemia are rare.

Evidence (history, friends and relatives) confirming the absence of alcohol abuse (eg, < 20 g/day) is important for diagnosis. Serologic studies should confirm the absence of infectious hepatitis B and C (ie, hepatitis B surface antigen and hepatitis C antibody tests should be negative). Liver biopsy should show changes consistent with alcoholic hepatitis, usually including large fatty deposits (macrovesicular fatty infiltration). Indications for liver biopsy also include unexplained signs of portal hypertension (splenomegaly or cytopenia) and unexplained elevations in aminotransferase levels that persist for more than 6 months in patients with diabetes mellitus, obesity or hyperlipidemia. Imaging studies including ultrasonography, CT and especially MRI may identify hepatic steatosis. However, these studies cannot detect the inflammation characteristic of nonalcoholic steatohepatitis and help in differential diagnosis with other forms of liver steatosis.

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Diagnostic criteria

1. Moderate or severe macroglobulin fatty degeneration and inflammation (lobular or portal) with or without Mallory hyaline bodies, signs of fibrosis or cirrhosis (according to liver biopsy data).
2. No alcohol abuse (<40 g ethanol/week). Negative results on several randomized blood tests for blood alcohol and the presence of the alcohol use marker, non-sialic acid-containing transferrin, in the serum.
3. No signs of infection with hepatitis B and C viruses.

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Treatment of non-alcoholic steatohepatitis

The only generally accepted treatment concept is to eliminate potential causes and risk factors. This approach may include discontinuing medications or toxic substances, weight loss, and treating hyperlipidemia and hyperglycemia. The effectiveness of many other treatments (eg, ursodeoxycholic acid, vitamin E, metronidazole, metformin, betaine, glucagon, glutamine infusions) requires further study.

Forecast

Nonalcoholic steatohepatitis has a controversial prognosis. It is generally favorable, with most patients not developing liver failure or cirrhosis. However, certain medications (eg, cytostatics) and metabolic disorders are associated with an accelerated progression of nonalcoholic steatohepatitis.

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