Nonalcoholic steatohepatitis: causes, symptoms, diagnosis, treatment

Nonalcoholic steatohepatitis - liver damage in persons 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 includes liver damage that does not histologically differ from alcoholic hepatitis. It develops most often in middle-aged women with increased body weight and increased blood glucose and lipid levels. Pathogenesis is not fully understood, but is most likely associated with insulin resistance (eg, in obese patients or in metabolic syndrome). In most cases, the disease is asymptomatic. Laboratory data indicate an increase in aminotransferase levels. The diagnosis should be confirmed by biopsy. Treatment of non-alcoholic steatohepatitis includes the elimination of risk factors and causes.

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

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

[1], [2], [3], [4], [5], [6],

What causes non-alcoholic steatohepatitis?

The cause of non-alcoholic steatohepatitis has not been fully established. Only factors are known with which nonalcoholic steatohepatitis is most often combined:

1. Metabolic factors: obesity, diabetes, hyperlipidemia, rapid weight loss, acute fasting, completely parenteral nutrition.
2. Surgical interventions: the imposition of sullowal anastomosis, gastroplasty for pathological obesity, the imposition of biliary pancreatic stoma, extensive resection of the jejunum.
3. Medicinal preparations: amiodarone, perhexylin maleate, glucocorticosteroids, synthetic estrogens, tamoxifen.
4. Other factors: jejunal diverticulosis with excessive bacterial multiplication, regional lipodystrophy, beta-lipoproteinemia, Weber-Christen disease.

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

Symptoms of non-alcoholic steatohepatitis

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

Biochemical blood test reveals an increase in the activity of ALAT and ASAT in 2-3 times.

Liver ultrasound reveals hyperechoinality ("brightness") of liver tissue due to diffuse fatty infiltration.

Histological picture

Characteristic signs of nonalcoholic steatohepatitis in liver biopsies 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 it is possible to spread inflammation to the portal and periportal areas; possibly the discovery of Mallory's hyaline bodies, but usually there are few, they are smaller and less noticeable than with alcoholic hepatitis. In case of severe disease, fibrosis or cirrhosis of the liver is possible in the future.

In general, in most patients, non-alcoholic steatohepatitis is benign and even asymptomatic. Decreased body weight may lead to the reverse development of non-alcoholic steatohepatitis.

Diagnosis of non-alcoholic steatohepatitis

The most frequent deviation in laboratory analyzes is an increase in the level of aminotransferases. In contrast to alcoholic liver disease, the ratio of AST / ALT in patients with non-alcoholic steatosis of the liver is usually less than 1. Sometimes the levels of alkaline phosphatase and gamma-glutamyltranspeptidase (GGT) increase. Hyperbilirubinemia, prolongation of prothrombin time and hypoalbuminemia are rare.

For the diagnosis is important evidence (history, friends and relatives), confirming the absence of alcohol abuse (for example, <20 g / day). Serological tests should confirm the absence of infectious hepatitis B and C (ie, tests for the surface antigen of the hepatitis B virus and antibodies to hepatitis C virus should be negative). With liver biopsy, there should be changes like alcoholic hepatitis, usually involving large fatty inclusions (macrospecific fat infiltration). Indications for liver biopsy are also unexplained symptoms of portal hypertension (splenomegaly or cytopenia) and an unexplained increase in the level of aminotransferases that persist for more than 6 months in patients with diabetes, obesity or hyperlipidemia. Instrumental studies including ultrasonography, CT and especially MRI, can identify hepatic steatosis. However, these studies can not detect the inflammation characteristic of non-alcoholic steatohepatitis, and help in differential diagnosis with other forms of steatosis of the liver.

[7], [8], [9], [10]

Diagnostic criteria

1. Moderate or severe fecal fatty degeneration and inflammation (lobular or portal) in the presence or absence of Mallory's hyaline bodies, signs of fibrosis or cirrhosis (according to a biopsy study of the liver).
2. Absence of alcohol abuse (consumption <40 g ethanol per week). Negative results of several randomized blood tests for the determination of alcohol in the blood and the presence in the blood serum of a marker of drinking alcohol - transferrin that does not contain sialic acids.
3. Absence of signs of infection with the hepatitis B and C virus.

[11], [12], [13], [14]

Treatment of non-alcoholic steatohepatitis

The only generally accepted treatment concept is to eliminate potential causes and risk factors. Such an approach may include stopping medications or toxic substances, reducing body weight and treating hyperlipidemia and hyperglycemia. The effectiveness of many other treatments (for example, ursodeoxycholic acid, vitamin E, metronidazole, metformin, betaine, glucagon, glutamine infusion) needs further research.

Forecast

Nonalcoholic steatohepatitis has a controversial prognosis. It is usually favorable, most patients do not develop liver failure or cirrhosis. However, some medications (eg, cytostatics) and metabolic disorders are associated with an acceleration in the development of non-alcoholic steatohepatitis.

[15], [16], [17]