Hepatosplenomegaly: what is it, how to treat it?

The simultaneous pathological increase in the size of visceral organs such as the liver (in Latin - hepar) and the spleen (in Greek - splen) is defined in medicine as hepatosplenomegaly. In the section of symptoms and signs of ICD-10, its code is R16.2.

Epidemiology

Hepatosplenomegaly is not a nosological form and refers to symptoms, and usually there is no official statistics on the manifestation of symptoms, but can be recorded in separate clinical studies.

So, it is known that in about 30% of cases, an enlargement of the spleen is caused by hepatomegaly; with mononucleosis, hepatosplenomegaly is observed in 30-50% of cases, and with typhoid fever, an enlarged liver with severe jaundice and, to a lesser extent, swelling of the spleen is observed in a third of patients. In acute hepatitis A in more than 65% of patients, only the liver is enlarged, while the frequency of hepatolienal syndrome does not exceed 15-18%. [1]

According to WHO, chronic hepatosplenomegaly in children is widespread in rural sub-Saharan Africa, and the two most common infections leading to this condition are malaria and schistosomiasis.

Causes of the hepatosplenomegaly

A wide variety of diseases can cause hepatosplenomegaly syndrome, which is also called hepatolienal (from Latin lienem - spleen).

First of all, the reasons for the enlargement of the liver and spleen are associated with hepatotropic and systemic infections that affect them.

This is hepatosplenomegaly in  hepatitis  A, B, C, D and E, which is known to be of viral origin. The defeat of liver hepatocytes occurs by replication of the DNA of viruses and the body's immune response in response to their antigens.

Hepatosplenomegaly in mononucleosis is associated with damage to macrophages of the spleen and Kupffer's liver cells by the herpes virus type IV (Epstein-Barr virus). At the same time, there is an increase in lymph nodes (often generalized) - with a significant increase in the level of lymphocytes in the blood - and inflammatory edema of the spleen and liver, defined by doctors as prolonged lymphadenopathy, hepatosplenomegaly in combination with absolute lymphocytosis.

Inflammation of the liver with subsequent hepatosplenomegaly can also occur when infected with the herpes simplex virus type V - cytomegalovirus; in particular, hepatosplenomegaly is noted in pneumonia caused by  cytomegalovirus infection .

Possible hepatosplenomegaly with adenoviral infection, which causes acute inflammation of the respiratory system, and serotypes F40-41 - adenoviral gastroenteritis (especially in children). Pathogenesis is associated with the ability of DNA adenoviruses to penetrate into the lymph nodes and the systemic circulation, causing intoxication. Read -  Symptoms of adenovirus infection .

As one of the late symptoms, hepatosplenomegaly is observed with salmonellosis (when infected with intestinal bacteria Salmonella enterica); when infected with helminths of the Schistosomatidae family and the development of  schistosomiasis ; with  echinococcosis of the liver , visceral form of  leishmaniasis , in patients with  opisthorchiasis .

Hepatosplenomegaly almost always develops in malaria, the causative agent of which is Plasmodium malariae. The mechanism of development is explained by infectious disease specialists by the fact that plasmodium infects erythrocytes and enters the liver with blood flow, in the cells of which it multiplies. However, the painful enlargement of the liver and spleen begins in the erythrocyte phase. With this disease (often chronic, proceeding with relapses), there is a cyclic fever in combination with hepatosplenomegaly, nausea and vomiting; due to the death of red blood cells (hemolysis), yellowness of the skin may be observed. [2]

Hepatosplenomegaly in typhoid fever is also caused by hematogenous spread of enterobacteria Salmonella typhi affecting regional lymph nodes, liver and spleen cells, which cause focal infiltration of mononuclear cells circulating in the blood with the formation of typhoid granulomas in the tissues of organs and their inflammatory growth.

How hepatosplenomegaly occurs in tuberculosis (acute disseminated form), in detail in the publications:

• Tuberculosis and liver disease
• Tuberculous hepatitis
• Cirrhosis of the liver and hepatosplenomegaly, see -  Secondary biliary cirrhosis of the liver .

And with chronic alcoholism or severe poisoning, cirrhosis of the liver of toxic genesis and hepatosplenomegaly develop.

A number of hematological diseases lead to an increase in the liver and spleen. More than 70% of patients have lymphadenopathy and hepatosplenomegaly with leukemia, including acute leukemia (lymphoblastic leukemia), when leukemia cells - mutated immature white blood cells (blasts) - enter and accumulate in the lymph nodes, liver and spleen.

Chronic myeloid leukemia or chronic myeloid leukemia and hepatosplenomegaly are observed when the accumulated bone marrow myeloid cells (myeloblasts) accumulate in the spleen and liver with blood flow. But, according to experts, with this disease, the spleen is most often enlarged - splenomegaly. [3]

Hepatosplenomegaly develops with anemia, primarily sickle cell and pernicious, and in children - with congenital hemolytic anemia and thalassemia. Jaundice and hepatosplenomegaly (or the formation of many nodules in the liver and spleen parenchyma), which are characteristic of hemolytic anemia, are often similar to liver disease. [4]

It is not excluded by doctors and hepatosplenomegaly in heart failure caused by serious cardiac diseases with pathological changes in the structures of the heart, circulatory disorders and ischemia.

Transient enlargement of the spleen (transient splenomegaly) is possible in severe cases of acute pancreatitis - with splenic vein stenosis and / or simultaneous acute inflammation of the spleen. But pancreatitis and hepatosplenomegaly can be observed in patients with a reactive type of inflammation of the pancreas, as well as its rare form - autoimmune.

Risk factors

Chronic diseases of the hepatobiliary system and all of the above diseases and pathologies are risk factors for the development of hepatosplenomegaly syndrome. Experts include exposure to radiation, alcohol dependence, and decreased immunity to such factors - and not only in acquired immunodeficiency syndrome, but even during pregnancy.

Infection-related hepatosplenomegaly during pregnancy may be easier to develop because physiological immunosuppression puts pregnant women at increased risk of infection. In addition, in some cases, pregnancy provokes a partial blockage of blood flow in the portal vein of the liver with increased pressure in it - portal hypertension - in combination with hepatolienal syndrome.

Symptoms of the hepatosplenomegaly

In the clinical picture of diseases leading to an increase in the liver and spleen or accompanied by hepatolienal syndrome, its first signs - a constant feeling of heaviness on the right side in the hypochondrium, pain on palpation, weight loss, attacks of weakness - do not appear immediately.

In addition, in the first stage - with a mild degree of organ enlargement - blood tests may show a decrease in hemoglobin and white blood cells.

With further enlargement of the liver (by 20-40 mm) and spleen (by 10-20 mm), moderate hepatosplenomegaly is noted, and later - severe, significant hepatosplenomegaly, in which the increase in the size of the liver exceeds 40 mm, and the spleen - 20 mm.

And depending on this, symptoms such as abdominal pain in the upper right corner appear; nausea, vomiting, and bloating; dyspeptic disorders; dryness and pallor of the skin, and with liver disease and amyloidosis -  jaundice  with itchy skin; muscle and joint pain; enlarged lymph nodes. In some cases, pain in the left hypochondrium and hyperthermia may occur.

Etiologically associated hepatosplenomegaly and portal hypertension, which develop with hepatitis, cirrhosis, congenital fibrosis, tumors and parasitic infections of the liver, as well as subleukemic myelosis (myelofibrosis). [5] Early onset of signs of portal hypertension is usually associated with lesions of the portal and splenic veins. More information in the material -  Portal hypertension - Symptoms . 

Often with the same diseases against the background of portal hypertension and obliterating hepatic thrombosis (Budd-Chiari syndrome), hepatosplenomegaly and ascites are observed - the accumulation of fluid in the abdominal cavity.

Hepatosplenomegaly and thrombocytopenia (a low level of platelets in the blood) is a sign of increased functional activity of the spleen (hypersplenism) with the destruction of these blood cells. This occurs most often in patients with cirrhosis. For more information see -  Thrombocytopenia and Platelet Dysfunction

Black feces - melena in the presence of hepatosplenomegaly - are characteristic of congenital liver fibrosis and tyrosinemia in newborns.

The appearance in infants of symptoms such as generalized exfoliative dermatitis with erythroderma, swollen lymph nodes, alopecia and hepatosplenomegaly is observed in genetically determined Omenn's syndrome and  primary immunodeficiency .

If the enlargement of the liver and spleen (with their compaction) in a newborn is accompanied by alopecia areata, maculo-nodular rash (including mucous membranes), deformation of the long bones of the skeleton, then this is evidence of congenital syphilis.

In older children, hepatolienal syndrome and hair loss may be part of the clinical manifestation of autoimmune hepatitis. And in adults, this combination of symptoms occurs with an autoimmune disease such as sarcoidosis.

Hepatosplenomegaly in children

Hepatosplenomegaly is more common in children than in adults. In childhood, an enlarged liver and spleen may be associated with hepatitis and the above infections. So, hyperemia of the skin and mucous membranes, hepatosplenomegaly are characteristic of infectious rubella caused by Rubella virus, or Syphilis congenita - congenital syphilis.

The development of hepatolienal syndrome is noted in acute leukemia,  congenital liver fibrosis  and portal vein thrombosis, in  hereditary spherocytosis (Minkowski-Shoffard disease) , hereditary familial hemorrhagic angiomatosis.

One of the symptoms of hemolytic disease of newborns,  ductular hypoplasia (Alagille's syndrome) , hereditary cerebrosidosis (mutations of the glucocerebrosidase gene) -  Gaucher disease , as well as hepatosplenomegaly (Niemann-Pick disease) is hepatosplenomegaly in newborns and children of the first year of life. Read also -  Hepatomegaly in children  [6], [7]

Genetic syndrome of connective tissue dysplasia with hepatosplenomegaly in children can be caused by a  mixed disease of connective tissue of  autoimmune origin, in which the body produces antibodies to ribonucleoprotein U1 (U1-RNP). The disease manifests itself with symptoms characteristic of systemic lupus erythematosus, scleroderma and polymyositis.

The development of hepatosplenomegaly syndrome occurs in children with congenital (inherited mutations of genes encoding certain enzymes) disorders of carbohydrate metabolism - mucopolysaccharidoses, which are lysosomal storage diseases, in this case - the accumulation of glycosaminoglycans (mucopolysaccharides). These diseases include:

• cider Gurler (Gurler-Sheye) or  mucopolysaccharidosis, type I ;
• Sanfilippo syndrome -  type 3 mucopolysaccharidosis ;
• Maroto-Lamy syndrome - type VI mucopolysaccharidosis;
• Sly's syndrome -  mucopolysaccharidosis type VII .

In infants and young children, enlargement of the liver and spleen (with periodic fever) can result from tyrosinemia, a congenital metabolic disorder in which, due to inherited mutations in various genes, catabolism of the amino acid tyrosine is impossible.

Two such serious symptoms as hepatosplenomegaly and thrombocytopenia occur in adult patients with T-cell non-Hodgkin's lymphomas and certain other malignant neoplasms, vascular follicular hyperplasia of the lymph nodes (Castleman disease), and in children with hereditary Niemann-Pick disease, as well as with heart muscle disease - dilated cardiomyopathy.

Complications and consequences

Bleeding, blood in feces and vomit, functional liver failure and  hepatic encephalopathy  (in severe cases, with cytotoxic cerebral edema) are considered the most common complications and consequences associated with hepatosplenomegaly syndrome.

Diagnostics of the hepatosplenomegaly

In addition to palpation and percussion examination of the liver and spleen, a complete history (including family members) and patient complaints, the diagnosis of diseases leading to hepatosplenomegaly includes a wide range of laboratory and instrumental studies.

Required tests such as: general clinical and biochemical blood test, for the content of bilirubin in the blood; serum levels of total protein, albumin, C-reactive protein, aminotransferases, alkaline phosphatase, iron; for blood clotting; for the presence of IgM and IgG antibodies (to hepatitis viruses, LSP, LKM, etc.) - the so-called  blood test for liver function tests . The activity of some enzymes in the blood plasma is determined. A general urine test is taken, as well as a coprogram - to identify intestinal bacteria and helminths. An aspiration biopsy of the liver , lymph nodes, or bone marrow may be required .

Instrumental diagnostics are carried out, in particular, ultrasound of the spleen and liver, Doppler ultrasonography of the liver vessels. But more informative than ultrasound is the CT picture of hepatosplenomegaly, visualized by computed tomography of the abdominal cavity with contrast, CT and scintigraphy of the spleen and liver. [8]

In this case, hepatosplenomegaly, diffuse changes in the liver and reactive changes in the pancreas can be detected. In most cases, patients with liver cirrhosis, autoimmune hepatitis and fatty hypatosis have hepatosplenomegaly and  diffuse liver changes . Morphological changes in the liver and spleen are often observed, such as hyperplasia of cells of loose connective tissue (histiocytes), death of hepatocytes and fibrosis.

Differential diagnosis helps to establish the true cause of the enlargement of the liver and spleen. [9]

Treatment of the hepatosplenomegaly

In the presence of hepatosplenomegaly, the diseases that led to the development of this symptom are treated.

It is clear that the therapeutic methods used and the drugs prescribed depend on the underlying diagnosis.[10]

Read more:

• Hepatomegaly
• Enlarged liver
• Medicines for the treatment and restoration of the liver
• For how hepatitis is treated see publication -  Acute viral hepatitis

In rare cases, surgical treatment can also be used - removal of the spleen and part of the liver. Patients with severe and life-threatening conditions associated with hepatosplenomegaly may require liver transplantation.

In accordance with the diagnosis, a diet is prescribed, for example:

• Diet for hepatitis B
• Diet for chronic hepatitis
• Diet for liver cirrhosis

With mucopolysaccharidosis, diet therapy is of an elimination nature (with the exception of lactose and galactose).

Prevention

The causes of hepatosplenomegaly are varied, so it may not always be possible to prevent it. And the prevention of hepatolienal syndrome, first of all, involves the fight against the causes of diseases of the liver and spleen.

Forecast

The specific outcome and prognosis of hepatosplenomegaly depends on many factors, including its etiology, severity, and treatment.