- Prevalence statistics
- What is the difference between primary and secondary cirrhosis?
- What changes occur in the immune composition of the patient's blood?
- Changes in liver structure
- Symptoms of biliary cirrhosis
- Syndromes of liver damage
- Combination with other autoimmune diseases
- How is diagnostics performed?
- Complications and Forecast
- Related Videos
Cirrhosis means the loss of functioning cells, their replacement by scar tissue. Biliary cirrhosis causes prolonged congestion of bile( cholestasis).It is established that it is more often detected in women of mature age. The result of the destruction of the body is hepatic insufficiency. In the ICD it is counted in the general group of "fibrosis and cirrhosis of the liver" with code K74.The disease is divided into primary and secondary.
Prevalence statistics for
Primary biliary cirrhosis( PBC) in 90% of cases are women 35-70 years old. Among the adult population, the prevalence is 23-25 per 1,000,000. Different data for the territories and countries are due to the low availability of diagnostic tests.
The disease is detected among members of the same family from sisters, twins, mothers and daughters. The conducted studies showed that the share of family cases of biliary cirrhosis in large cities is from 1 to 7% of all cases of primary disease.
Most often inheritance is done by the maternal line to the daughters. It is important that the descendants from the second generation of signs of the disease appear at a younger age.
What is the difference between primary and secondary cirrhosis?
The division of biliary cirrhosis into 2 groups is associated with the study of the cause of the pathological changes. In the primary process, it has not yet been possible to identify the exact etiology of the disease. It has been established that in the bile ducts the inflammatory process( cholangitis) is continuously asymptomatic.
There is proliferation( proliferation) of the inner layer of the epithelium. The accumulation of bile acids causes and supports inflammation in the hepatic parenchyma. Around the central zones of the lobes develops fibrosis.
The changes concern only intrahepatic ducts
One of the established facts is the detection of specific antibodies in 95% of cases precisely at PBC.Antigens are substances of the inner membrane of the mitochondria of the cells of the epithelium. As it turned out, they do not destroy cells, do not destroy the ducts, cause accumulation of certain types of T-lymphocytes. A similar mechanism of lesion refers to autoimmune diseases.
Primary form of the disease is often combined with vasculitis, scleroderma, celiac disease, rheumatoid arthritis, autoimmune thyroiditis, which also affects the immune system of the body and there is a violation of its regulation.
Predisposing factors include:
- hereditary predisposition;
- decreased immunity;
- has a history of infection, especially viral infections( most likely the effects of herpes and Epstein-Barr viruses).
Secondary is called biliary cirrhosis with a clear cause. In these cases, obstruction of the ducts is caused:
- by stones;
- structure anomalies;
- with postoperative scars;
- edematous pancreas with pancreatitis;
- enlarged lymph nodes with lymphadenitis.
What changes occur in the immune composition of the patient's blood?
Antimitochondrial antibodies are formed by type M( IgM) immunoglobulins. Scientists studied 9 kinds of antigens to the mitochondrial membrane, of which:
- M2 - are present in all cases with primary biliary cirrhosis, are considered pathognomonic( defining the disease);
- M4 - detect when biliary duct disease is combined with autoimmune hepatitis;
- M8 - is detected with a severe progressive form of the disease;
- M9 - indicates the early stage of biliary cirrhosis.
In addition to antimitochondrial antibodies, antibodies are detected at PBC liver:
- antinuclear to cell nuclei( 20-40% of cases);
- to smooth muscle proteins( in half of patients);
- on other components of the bile duct( 60%);
- to the acetylcholine receptor;
- is antilymphocytic;
- is antiplatelet;
- is a rheumatoid factor.
They are little specific for diagnosis.
The arrow shows the overgrown duct in the lobule of the liver
Changes in the structure of the liver
The study of histological features allowed to identify four stages in the formation of biliary cirrhosis. They are more typical for the primary process. The initial( first) - in the ducts of the hepatic lobules reveal chronic inflammation with infiltrates, the destruction of epithelial cells begins. Outside the ducts, inflammation does not go away.
The second - around the proliferation of scar tissue, the number of epithelial cells increases. Foci of germination are formed in the hepatic parenchyma. The number of passages is reduced.
Third( fibrosis) - connective tissue from the foci extends to all lobules of the liver. At the same time, multiple areas of inflammation develop. There is a stagnation of bile.
Fourth( actually cirrhosis) - most ducts absent, expressed stagnation of bile, lobules of the liver are replaced with a connective tissue.
Symptoms of biliary cirrhosis
Clinical manifestations of the primary and secondary forms are the same. The initial manifestation of the disease( in the first stage) patients consider skin darkening( although in fact the pathological process began long before this).
Brown spots appear first on the back in the area of the scapula, on the joints on the extensor surface, then on other areas( in 25% of cases).Caused by impaired pigmentation and melanin deposition. There are changes, called skin lichenization( coarsening, thickening, more pronounced emphasis of the pattern).
Skin itching torments a person in half the cases several months and years. Patients most often turn to a dermatologist.
Symptom is caused by accumulated bile acids in the blood, they irritate the nerve endings on the skin. In addition, in the diseased liver special substances( pruritigens) are formed that promote skin itching.
Xantelasms are formed on the eyelids( in every tenth patient) - small yellow protruding formations in the form of plaques from cholesterol. They can be located on the skin of the chest, palms, back, in the area of the extensor surface of the elbows and knee joints, on the buttocks.
Possible dull pain in the hypochondrium on the right, a feeling of heaviness, bitterness in the mouth. Deterioration of patients is associated with overeating fatty foods, drinking alcohol. The liver is enlarged and moderately painful in 25% of patients, and the spleen is in 15%.
Skin yellowness and sclera( in 10% of patients) is caused by the discharge of bilirubin into the blood. Jaundice in most patients develops within six months or two years after the first occurrence of pruritus. In ¼ of patients, they appear together.
The presence of one jaundice without itching of the skin is not typical for biliary cirrhosis.
The rapidly increasing intensity of jaundice is considered an unfavorable sign of high activity of the process. In pregnant women in the third trimester, itching and icterus are regarded as a manifestation of temporary cholestasis.
Often join: muscle pain, fatigue, weakness. Symptoms such as "hepatic palms" and "vascular asterisks" on the face in the initial stage are rare. Patients do not turn to the doctor at this stage, they try to treat themselves with herbs, rubbing. Many manifestations are associated with age or menopausal disorders.
Progression of the process is accompanied by a sharp increase in symptoms. Intense itching of the skin does not allow to fall asleep, it torments a person during the day, intensifies after a warm bath. The combs swell, the body is covered with a rash. On the skin are formed healing scabs, white spots, similar to vitiligo.
The liver and spleen increase to large sizes, dense on palpation. The pain in the hypochondrium on the right becomes intense. Due to severe weakness, disability is lost. The lack of energy is determined by a decrease in biochemical reactions in the hepatic tissue. Appetite worsens, body weight falls. There may be an increase in temperature.
Expanded esophageal veins visible in fibroadastroscopy
Increased pressure in the portal vein system due to compression by scar tissue leads to widening of the esophagus and parts of the stomach. Therefore, signs of gastric bleeding with vomiting of blood, black stools are possible. Bleeding is supported by delayed synthesis in the liver of prothrombin and coagulation system substances.
The change in the digestive process is manifested in nausea, vomiting, pain along the entire abdomen, unstable stool( inclinations to diarrhea).It is caused by insufficient intake of bile into the intestine.
Violated bilirubin exchange causes darkening of the urine and a change in the color of the feces to a light gray hue.
Avitaminosis - arises from the loss of liver function to synthesize vitamins, proteins, impaired digestion and processing of food in the intestines. The syndrome of malabsorption( impaired absorption) of fat-soluble vitamins is caused by the atrophy of the villi of the small intestine.
Vitamin D deficiency is manifested by pain in the joints( "biliary rheumatism"), bones, ribs, spine. Rarely, osteoporosis develops, which is judged by frequent fractures, the appearance of cracks in the bones against the background of minor physical exertion. Patients are destroyed and teeth fall out.
Reduced absorption of vitamin A causes visual impairment, aggravates skin manifestations of
To reduce the intake of vitamin K, the development of hemorrhagic syndrome is typical. Simultaneously, the patient can detect the manifestation of glomerulonephritis, lesions of the salivary glands, and other hepatic syndromes.
In the 3-4 stages of the disease, the patient manifests:
- ascites - fluid transfer to the abdominal cavity, abdominal enlargement, widening of the subcutaneous veins around the navel;
- signs of encephalopathy - drowsiness during the day and insomnia at night, mental changes, a sharp decline in memory, headaches.
Syndromes of liver damage
In clinical manifestations of biliary cirrhosis of the liver, doctors distinguish a number of syndromes:
- Sjogren's syndrome - is revealed most often. It is formed in connection with the simultaneous damage of the lacrimal and salivary glands, the cessation of their functioning. It is manifested by dry eyes, oral cavity, inflammation of the salivary glands( parotitis).
- Polyglangular syndrome - immune complexes affect the endocrine organs. The pancreas is especially sensitive. Violation of insulin production. In women, production of sex hormones ceases, which is manifested in the absence of menstruation, in men - secondary sexual characteristics change, testicles become atrophied, impotence occurs. There is a hypofunction of the adrenal cortex and hypothalamus.
- Pulmonary syndrome - the lung tissue loses its airiness, the septa between the acini are thickened, fibrosis is formed.
Combination with other autoimmune diseases
Primary biliary cirrhosis has the same pathogenesis with other autoimmune diseases, so in diagnosis, attention is drawn to a combination of symptoms of systemic damage. Most often manifested in conjunction with connective tissue diseases( rheumatoid arthritis, lichen planus, dermatomyositis, systemic lupus erythematosus).4% of patients have scleroderma with skin lesions, face, shins, dry eyes, lack of saliva.
Every fifth patient has an autoimmune thyroiditis, cases of diffuse toxic goiter are known. Atrophy of the jejunal mucosa resembles celiac disease, in sigmoid and direct - causes ulcerative colitis. The relationship of simultaneous development in cholestasis of autoimmune thrombocytopenia, myelitis of nerve endings is proved.
From the kidneys, membranous glomerulonephritis is observed. Due to the increased deposition of copper in the tubules, tubular acidosis forms. Usually, an infection with further signs of pyelonephritis joins.
In the bile ducts, besides the autoimmune process, pigment type stones are formed. They rarely cause a clinic for cholelithiasis, they do not move into the common bile duct. Insufficiency of the pancreas is important.
In 80% of patients on MRI in the gates of the liver, there are enlarged lymph nodes, hypertrophy of the pericardium and lymph nodes of the mesentery
. Male patients have been associated with colon cancer, lymphogranulomatosis, prostate and bronchial tumors.
How is the diagnosis performed?
In diagnostics, always exclude other similar in clinical manifestations of liver disease. To identify biliary cirrhosis of the liver, it is necessary to study the patient's complaints, to clarify the features of heredity, to analyze the functioning of the liver by possible laboratory tests, to connect immunological studies, and instrumental methods.
Evaluation of laboratory data
In the general blood test, anemia, an increase in ESR, leukocytosis, pancytopenia in the case of the development of the hypersplenism syndrome are detected. Urinalysis shows an increased protein content, bilirubinuria in the absence of urobilin. Stool analysis gives a negative or slightly positive test for stercobilin.
In biochemical studies of blood on the characteristic syndrome of cholestasis indicate:
- hyperbilirubinemia( due to the growth of the conjugated fraction);
- growth of gamma globulins, decrease of albumin fraction;
- increased content of enzymes( alkaline phosphatase, glutamyltranspeptidase, aminotransferases);
- increased concentration of bile acids( especially lithocholic);
- impaired fat metabolism with altered ratio of cholesterol, phospholipids, beta-lipoproteins;
- growth of non-esterified fatty acids;
- iron content is reduced, and copper is increased.
Changes can be detected with asymptomatic flow. Immunological blood tests in PBC show a drop in the total number of T-lymphocytes, an increase in the content of immunoglobulins of type M, less often IgA and IgG, the presence of antimitochondrial antibodies in the early stages. Sometimes it is found in the serum antibodies to thyroglobulin, rheumatoid factor.
Role of instrumental examination of
Among the instrumental techniques, signs of biliary cirrhosis help to detect the following diagnostic methods. Ultrasound of the liver and bile ducts - the growth of liver size, no changes in the large bile ducts are recorded. In 1/3 of patients, concrements are found in the biliary tract.
Spleen ultrasound is a typically significant increase in organ size. Computer and magnetic resonance tomography is performed for the purpose of differential diagnosis. Fibroesophagogastroduodenoscopy - at the stage of cirrhotic changes in the liver, an enlarged venous network of the stomach and esophagus is seen. The study is necessary to establish the cause of secondary biliary cirrhosis.
A radioisotope study with a drug labeled with iodine isotopes reveals the extent of damage to liver tissue
Cholangiography is performed by intravenous injection of a contrast agent( only if the bilirubin content is 4 times higher than normal).In this case, extrahepatic bile ducts are visible, most often without changes.
What does a liver biopsy give?
In the study of the histological picture, the main importance is attached to identifying signs of destruction of intrahepatic interlobular and septal passages. The establishment of the stage of the disease is not the main one. Because the changes differ in the foci, they develop at different rates on each site.
There are no clear morphological differences between the stages. The greatest difficulties arise when comparing the II and III stages. With asymptomatic flow, you can identify the third stage of the process. A study of biopsy samples in dynamics showed that one stage can stably hold for many years.
Differential diagnostics of
To resolve the issue of prescribing treatment for biliary cirrhosis, it is first of all necessary to distinguish between primary and secondary disease. The primary process is differentiated:
- with sclerosing cholangitis;
- with active hepatitis with cholestasis;
- by medicinal hepatitis( to the expressed cholestasis the reception of anabolic hormones, Aminazine, oral contraceptives, Methyltestosterone, Chlorpropamide, sulfonamides);
- by liver and bile duct cancer.
The patient is prescribed a mandatory diet that excludes alcoholic beverages, any substances that irritate the liver, which have the most powerful allergic effect: fatty meat, fried and smoked dishes, spicy sauces, chocolate, coffee and cocoa, seasonings, citrus fruits, strawberries and strawberries, currants.
Recommended food cooked by steaming, steaming or stewing, meatballs, meatballs, fish, vegetable casseroles, low-fat soups, dairy products, low-fat curd, mild cheese. Apples, plums, pears can be added if the attending physician permits. To normalize the outflow of bile, the drugs from ursodeoxycholic acid are most often shown.
The drug has to take long courses, it has an antifibrotic effect.
Hepatoprotectors( Essentiale, Karsil, LIV-52, Phosphogliv, Esliver, Hofitol, Silymarin, Hepabene) help protect liver cells from destruction, delay the formation of cirrhosis. For the removal of skin itch recommend: antihistamines( little effective), cholestyramine, ultraviolet irradiation. With the goal of replenishing the balance of vitamins prescribed: vitamin D with calcium, Retinol or Aevit, Calcitonin.
The use of corticosteroids in combination with immunosuppressants( Azathioprine, Penicillamine, Chlorambucil) gives an improvement, but is undesirable because of the activation of osteoporosis. Cyclosporine A, Methotrexate is prescribed by prolonged courses under the control of a negative effect on the kidneys, combined with Colchicine. In the secondary process, antibiotics may be required.
Surgical methods are used in primary biliary cirrhosis to provide bile outflow( transjugular intrahepatic portosystemic shunting) or portocaval shunting with the installation of stents. The method briefly delays the terminal stage of the disease.
It is proven that removing gallstones, if they do not cause acute symptoms, should not be, the operation is not tolerated by the patients. The most important intervention in this pathology is liver transplantation. The secondary form shows the removal of the gallbladder to prevent stagnation of bile.
Complications and prognosis
Biliary cirrhosis is complicated by the following conditions:
- bleeding from the esophagus;
- by hepatic encephalopathy( rare);
- cholangiocarcinoma - the degeneration of inflammation into a cancerous tumor.
Patients have a 4.4-fold increase in the likelihood of developing breast cancer. With primary cirrhosis, the survival prognosis is unfavorable. The treatment allows prolonging life for a maximum of 15 years. Lethal outcome comes from bleeding or hepatic coma.
Survival after liver transplantation for five years is 60-70%.The condition improves noticeably, although antibodies remain in the blood of patients, so in ¼ cases the process recurses and a second operation is necessary.
The primary form of biliary cirrhosis so far relates to incurable diseases. Applied treatment options do not confirm in practice the expected effectiveness. Patients should be identified at an early stage, especially at risk, and begin treatment in the preclinical stage of the disease.