Primary biliary cirrhosis

Description:

Primary biliary cirrhosis - the autoimmune disease of a liver which is shown in the form of an oligosymptomatic chronic destructive not purulent cholangitis, passing a cholestasia stage which comes to the end with formation of cirrhosis.

Primary biliary cirrhosis - a cholestatic disease of a liver of an unknown etiology which is suffered more often by women at the age of 40-60 years.

Symptoms of Primary biliary cirrhosis:

Primary biliary cirrhosis women (the ratio of women and men makes 10:1) are ill preferential, is more often at the age of 35 years and are more senior. Primary biliary cirrhosis makes 6-12% among all cirrhoses of a liver.

At primary biliary cirrhosis small intra hepatic bilious channels are involved in granulematozny reactions with their gradual obliteration and an outcome in cirrhosis. At primary biliary cirrhosis inflammatory autoimmune destruction of the smallest intra hepatic bilious courses is followed by blockade of biliation and receipt of its components in blood, is combined with periportal hepatitis, a step necrosis of hepatocytes and development fibrous септ, extending from portal paths to the center of a segment. These processes define progressing of an initial stage of a disease - chronic cholestatic hepatitis in cirrhosis at first septal, and then makronodulyarny type.

4 consecutive morphological stages of evolution of primary biliary cirrhosis were originally described:

Stage of not purulent destructive cholangitis.

Stage of duktulyarny proliferation with a new growth of bilious tubules and the subsequent their destruction that is followed by destruction of a boundary plate of portal paths inflammatory infiltrates, step necroses of periportal hepatocytes and a cholestasia (bilious blood clots in periportal tubules).

Scarring stage with considerable reduction of inflammatory reaction and number of the intra lobular and interlobular bilious tubules and development coming from portal highways in a segment fibrous септ in combination with the expressed cholestasia.

End-stage - development of the nodal or mixed cirrhosis type with a cholestasia against the background of sharp depletion of a parenchyma of a liver bilious tubules. Symptoms of a disease accrue gradually, being shown by a skin itch with jaundice and without it.

The most typical initial symptom of primary biliary cirrhosis observed at 50-64% of patients is the skin itch, intermittent in the beginning, and then constant, amplifying after a bathtub and at night. Quite often the itch proceeding of half a year up to 5-10 years (before emergence of cholestatic jaundice), happens the only symptom of a disease and can not be followed by a hepatomegalia, jaundice or an astenovegetativny syndrome. In this regard patients are often treated concerning a prurigo, neurodermatitis, allergic diseases of skin, itch.

Meanwhile the persistent itch of skin has to suggest first of all an idea of a possibility of a disease of internals, but not skin. The itch is observed not only at a cholestasia, but also at 50% of patients at a lymphogranulomatosis, a polycythemia and other myeloproliferative diseases. Damage of a liver already at this stage is confirmed at most of patients with the activity of an alkaline phosphatase and leucineaminopeptidase of blood serum increased more than by 2-3 times, the hypercholesterolemia and a hyper aminotransferasemia often takes place. The skin itch at primary biliary cirrhosis is caused by irritation of skin receptors the bile acids which are not excreted by a liver which come to blood from the struck intra hepatic bilious ways. Disturbance of biliary secretion leads to decrease in absorption in intestines of absorption of vitamin D and to development of osteoporosis, osteomalacy and steatorrhea.

Increase in SOE, pain in the field of the right hypochondrium, sometimes with fever, emergence skin ксантелазм in the field of a century, palms, elbows and buttocks, a joint pain and muscles can be initial symptoms. The dark brown xanthopathy (melanoderma), at first in shovels, and then diffusion, takes place at 53% of patients already at initial stages of a disease. Moderately expressed hepatomegalia at an initial stage of a disease is noted at 50% of patients, the splenomegaly usually develops at late stages. Slowly accruing cholestatic jaundice with the conjugated hyperbilirubinemia moderated at an initial stage can be one of the first symptoms at 50-60% of patients. Duration of a disease reaches 20-25 years and more.

Are characteristic of the developed stages of primary biliary cirrhosis a bystry aggravation of symptoms of the patient, intensive jaundice with a painful skin itch and traces having combed on skin, skin xanthomas and ksantelazma (at 50% of patients), a hepatomegalia, it is frequent with a splenomegaly, a hypersplenism and other symptoms of portal hypertensia; the akholichny chair containing traces of stercobilin and dark brown urine (with positive reaction to bilirubin). Various damages of skin are often observed: the depigmentation centers, similar to vitiligo, on a grayish-brown background, papular and vesicular rash. "Skin" symptoms of cirrhosis - teleangiectasias and a palmar erythema at primary biliary cirrhosis, as a rule, are absent. At late stages of primary biliary cirrhosis osteomalacy, osteoporosis and a periosteal new growth of a bone often develop (increase in trailer phalanxes of fingers - drum sticks). Osteoporosis is expressed in a backbone, edges and pelvic bones and quite often is followed by compression fractures of nizhnegrudny and lumbar vertebras, edges and tubular bones. The megalgia in a backbone is a symptom of late stages of primary biliary cirrhosis.

The skin itch in an end-stage often weakens or disappears at the progressing hepatocellular insufficiency. The xanthopathy amplifies, the dense cutaneous dropsy as is defined at a scleroderma. Histologically the hyperkeratosis comes to light. Disturbance of biliary secretion conducts to an atrophy of fibers of a small bowel and development of a sprue of fat-soluble A, D, E, K vitamins. In process of increase of a cholestasia the creatorrhea, osteoporosis with the subsequent osteomalacy and pathological changes, a xerophthalmia and a hemorrhagic syndrome progresses. Destruction of a firm plate of teeth leads to their shaking and loss. The liver becomes huge and often occupies the right and left hypochondrium, the spleen increases, there is a varicosity of a gullet and stomach (portal hypertensia), but ascites is observed seldom and only in an end-stage. Patients die at the phenomena of hepatocellular insufficiency which complications of primary biliary cirrhosis can initiate: portal hypertensia, ulcer bleedings, fractures of bones. Refer rare development of a carcinoma of a liver to late complications of primary biliary cirrhosis, quite often pervichnoy biliary cirrhosis accompanies cholelithiasis.

For biliary cirrhosis the systemacity of defeat which is shown preferential change of excretory glands is natural: the lacrimal, salivary, a pancreas, kidneys (a glomerulonephritis - tubulointerstitsialny nephrite) and vessels (vasculites) of various bodies.

Shyegren's syndrome comes to light at 70-100% of patients with primary biliary cirrhosis in the presence of the expressed cholestasia. The dry keratoconjunctivitis is characterized by dryness and feeling of sand in eyes, absence of dacryagogue, then the xerostomia develops (dryness in a mouth). The polyglandular syndrome is shown by atrophic gastritis, a duodenitis, vneshnesekretorny insufficiency of a pancreas, a maldigestiya, malabsorption and the subsequent steatorrhea. In emergence of this syndrome the circulating cell-bound immune complexes supporting IgM, and cross immune responses caused by a community of antigens of bilious channels, sialadens, kidneys play a role. The papillitis, hypotonia of a small bowel are characteristic also of a polyglandular syndrome дуоденостаз.

Changes of bones are shown by a resorption of a bone tissue and system osteoporosis and osteomalacy. The pulmonary syndrome at primary biliary cirrhosis is shown by a picture of a pneumosclerosis and a fibroziruyushy alveolitis. Exocrine disturbances can be shown hyper - and a hypothyroidism, an amenorrhea, a dysmenorrhea, insufficiency of a hypothalamus, hypofunction of bark of adrenal glands.

Associated diseases at primary biliary cirrhosis of preferential autoimmune nature: a pseudorheumatism, Hashimoto's thyroiditis, a myasthenia, a Gee's disease at adults. The immunodeficiency at patients with primary biliary cirrhosis against the background of long immunodepressive therapy is connected with high frequency by emergence of new growths of extrahepatic localization (a breast cancer, necks of uterus, a bladder, a bronkhokartsinom, alveolar cancer, a colon cancer, Hodzhkin's lymphoma).

At laboratory researches often find the expressed hypochromia or normokhromny anemia raised by SOE, the considerable conjugated bilirubinemia (> 170 µmol/l), a giperfosfatazemiya (it is frequent> 1000 µmol/l), a hypercholesterolemia to 12-17 mmol/l and more (in a final stage of a disease the level of cholesterol of blood decreases to norm or below it), a hyperproteinemia, the expressed disproteinemia with increase in concentration of ß-and at - blood globulins, a moderate hyper aminotransferasemia.

Reasons of Primary biliary cirrhosis:

Primary biliary cirrhosis draws great attention in connection with growth of incidence and lack of essential shifts in clarification of an etiology, pathogeny and opportunities of therapy of a disease. Now the noninfectious nature of primary biliary cirrhosis and the leading value in its pathogeny of autoimmune cellular reactions on the "transplant against the owner" type is authentically established. A role of a transplant is played by own liver of the patient. Damage of a liver at primary biliary cirrhosis can be result of the abnormal immune response directed against histocompatibility antigens (HLA) of cells of a duktulyarny epithelium. At the reaction of rejection of a hepatic transplant caused by incompatibility of HLA antigens of the replaced liver and the owner at the donor the chronic not purulent destructive cholangitis indistinguishable from observed at primary biliary cirrhosis develops. At patients with primary biliary cirrhosis dominance of genotypes of HLA-DR3, DR4 or DR2 is noted. Proteins of the DR series define type of an immune response.

At primary biliary cirrhosis insufficiency of immune suppressor system which can serve as a marker of genetic predisposition comes to light.

The antigens absorbed from bile or an epithelium of bilious tubules, meeting the circulating antibodies, cause formation of periduktulyarny granulomas at primary biliary cirrhosis. Thus, autoimmune processes are responsible for the cholestasia phenomena at cholestatic hepatitis and primary biliary cirrhosis.

Despite immune genesis, treatment by immunodepressants (Prednisolonum, Azathioprinum) contrary to autoimmune HAG causes the moderate symptomatic, generally "bleaching" effect, i.e. intensity of jaundice and an itch of integuments decreases. Immunodepressants do not stop progressing of primary biliary cirrhosis and promote development of one of serious complications - osteoporosis.

Treatment of Primary biliary cirrhosis:

Effective methods of treatment of primary biliary cirrhosis do not exist today. The diet at primary biliary cirrhosis is reduced on fat (40-50 g/days), preferential contains vegetable oil.

Prolonged use of glucocorticosteroids is dangerous because of a potentsiirovaniye by them osteoporosis and osteomalacy, and is ineffective as they as well as Azathioprinum, do not extend, and shorten life of patients, despite reduction of clinical symptoms of a disease rather. Prednisolonum is appointed as symptomatic cure for the resistant itch which is not facilitated from reception of a holestiramin and ursodezoksikholevy acid. In such cases small daily doses of hormone (10-15 mg) every other day, or on 5-7,5 mg daily are applied.

Results of treatment of primary biliary cirrhosis D-Penicillaminum are contradictory. Drug promotes removal of excess of the copper collecting in a liver at primary biliary cirrhosis owing to a cholestasia and disturbance of excretion of copper in bile. D-Penicillaminum slows down also synthesis of collagen and has immunodepressive properties: normalizes the IgM level and the circulating cell-bound immune complexes of blood serum. At primary biliary cirrhosis it is applied, raising doses from 150 to 300-600 mg/days, in combination with B6 vitamin. Serious complications at treatment of primary biliary cirrhosis are possible D-Penicillaminum: oppression of a marrowy hemopoiesis with a cytopenia and development of sepsis, a nephrotic syndrome with a proteinuria more than 3 g/days, Gudpascher's syndrome, tuastenia gravis, ulcerations of skin and mucous membranes, fever, arthralgias, mialgiya.

Symptomatic therapy at primary biliary cirrhosis is directed to reduction of a skin itch. Ion-exchange resin холестирамин reduces an itch by means of removal with excrements of excess of bile acids with which drug forms not absorbed complexes. Drug appoint 12-16 g/days in a dose (on 1 h l. on a glass of water or juice 3 times a day) in 40 min. prior to a breakfast, in 40 min. after a breakfast and in 40 min. prior to a lunch, i.e. in hours when the greatest number of bile acids comes to intestines. Against the background of treatment holestiraminy moderate decrease in a cholesterinemia and bilirubinemia is often observed. Prolonged use of a holestiramin can promote development of osteoporosis as this drug increases removal of calcium with urine. Similar, sometimes even more expressed antipruritic action drug from absorbent carbon Biligninum, and also урсофальк, урсосан (ursodezoksikholevy acid), pectins possesses. Ursodezoksikholevy acid belongs to means of pathogenetic therapy as reduces a cholestasia, increases holesekretorny function of a liver. At reception of an ursofalk positive dynamics of the immunological and biochemical disturbances specific to primary biliary cirrhosis is observed. Ursofalk appoint at the rate of 7 mg/kg of body weight within two and more months. All dose of drug is accepted once for the night. Usually the dose of ursodezoksikholevy acid makes 500 mg/days, appoint drug 1-2 years.

As a result of the multicenter researches conducted in Canada, France, North America it is shown that long therapy (2-4 years) by means of ursodezoksikholevy acid improves survival level without transplantation of a liver at patients primary biliary cirrhosis with moderately severe and a severe disease. The effect with poorly expressed process was not found in patients, it is possible because the disease does not progress to a final stage for 4 years.

As a result of use of a medical combination of ursodezoksikholevy acid (500 mg a day) and a methotrexate (10 mg/day) during 1 year at patients primary biliary advantage in comparison with use only of ursodezoksikholevy acid therefore ursodezoksikholevy acid in combination with a methotrexate should not be used as the proved, reliable and standard therapy is shown to the tsirrozoyena.

For the purpose of reduction of a resorption of a bone tissue (osteomalacy and osteoporosis) appoint D2 vitamin (ergocalciferol, a synthetic analog of D3 vitamin) orally in a dose of 3 thousand ME/days (6 drops of Solutio oleosa at contents in 1 ml 25 thousand of ME). At osteomalacy ergocalciferol is entered in oil on 100-120nsc. ME/month. At primary biliary cirrhosis disintoxication infusional therapy of 5% by glucose solution with vitamins or GIKS is applied. At primary biliary cirrhosis it is inexpedient to use drugs of phospholipids (Essentiale of N) and silimarinsoderzhashchy drugs (karsit, legalonum) as they can strengthen a cholestasia.

Use of antifibrous drugs - a hlorbutsil and colchicine leads to improvement of biochemical indicators. Hemosorption at primary biliary cirrhosis is ineffective.

Thus, primary biliary cirrhosis, also as well as primary sclerosing cholangitis (the fibrous inflammation of a biliary path which is often combined with nonspecific ulcer colitis), the classical cholestatic disturbances which are characterized by the progressing inflammatory destruction of bilious channels represent. In both cases characteristic symptoms are disturbances of bilious secretion and a delay of biliation. Both in that and in other case increase in activity of an alkaline phosphatase and at-glyutamiltranspeptidazy often are the first symptoms of a disease. Level of serumal bilirubin increases only in far come disease stages, however it is the most exact laboratory indicator. Typical symptoms are jaundice, an itch and fatigue. In end-stages at patients cirrhosis with all corresponding complications develops.

Characteristic symptoms of primary biliary cirrhosis: at 95% of patients positive anti-mitochondrial antibodies are defined, at the majority - the IgM level is increased. At 5% of patients antinuclear antibodies take place. The disease affects generally women of middle age. The retrograde holangiografiya reveals normal bilious channels.

Characteristic signs of primary sclerosing cholangitis: existence of multiple stenoses and prestenotichesky expansions (by results of a retrograde holangiografiya) therefore patients periodically have a bacterial cholangitis. This disease develops generally at the men having nonspecific ulcer colitis. Anti-mitochondrial antibodies negative and IgM level often normal.

At the last stages of both diseases of the only effective method of treatment transplantation of a liver is. An effective method of medicamentous correction is treatment by ursodezoksikholevy acid. Monotherapy of primary biliary cirrhosis corticosteroids, Azathioprinum or a methotrexate is insufficiently effective, however, perhaps, these drugs increase effect of ursodezoksikholevy acid at their combined use. In case of primary sclerosing cholangitis value of immunosuppressive treatment is discussed while endoscopic expansion of stenoses of the main channels leads to reduction of a cholestasia.