Pregnancy with autoimmune liver disease ( hepatitis, cholangitis, cirrhosis) - Causes, Symptoms and Treatment .MF .
to autoimmune diseases of the liver are autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, unclassifiable (atypical) of the disease: autoimmune cholangitis, cryptogenic (idiopathic, seronegative) hepatitis and cirrhosis, cross syndromes in combination, including viral hepatitis.The prevalence and incidence of autoimmune diseases of the liver are growing steadily, includingdue to higher diagnostic quality, and they are recorded mainly in women of reproductive age.
Symptoms of autoimmune
liver disease symptoms are extremely diverse, non-specific and determined by the option of the disease, which can be latent (asymptomatic if the laboratory changes) oligosymptomatic (single symptoms, does not significantly affect the condition of patients), characterized by a symptom of acute hepatitis ormanifest complications in end-stage disease.
In all cases, a differential diagnosis of viral hepatitis, metabolic liver disease (alcoholic or non-alcoholic steatosis, steatohepatitis), li
Diagnostics liver autoimmune diseases
It includes a general analysis of blood, determination of serum total bilirubin and its fractions, cholesterol, total protein and protein fractions, AST, ALT, ALP, GGT, IgA, M, G, CEC,CRP, coagulation, rheumatoid factor, the LE-cell seromarkerov viral hepatitis B, C, D, G, TT, CMV, Epstein - Barr virus, herpes simplex 1 and 2 of types, uric acid, serum iron,TIBC, ferritin, transferrin, ceruloplasmin, copper in blood and daily urine, serum tumor markers (α-fetoprotein, CA 19-9, CEA) and serum markers of liver autoimmune diseases.The latter include autoantibodies to cellular and subcellular structures: Antinuclear antibodies (ANA), antimitochondrial antibody (AMA), antibodies to piruvatdekarboksilaznomu complex (AMA-M2), anti-smooth muscle cells (SMA), antibodies to microsomes liver or kidney 1sttype (LKM1), hepatic antibodies to soluble antigen (SLA), antibodies to pancreatic and hepatic antigen (LP), neutrophil cytoplasmic antibodies (ANCA), etc ..
probable autoimmune liver disease in the presence of liver disease symptoms regardless of previously establisheddiagnosis, includingchronic viral hepatitis, especially if they are combined with anemia and other cytopenias, a sharp increase in γ-globulin (IgG), autoimmune diseases, family history of autoimmune disease.;with unmotivated increase of ALT, AST, alkaline phosphatase, bilirubin, regardless of the severity of the changes;when combined hepatomegaly, splenomegaly lability with liver and spleen;in the presence of arthralgia, varicose veins of the esophagus (especially in the absence of ascites), the absence of encephalopathy in the late stages of cirrhosis of the liver, and the presence of xanthomas ksantellazm, pruritus, skin hyperpigmentation, and others associated with autoimmune liver disease states.
Initiate immunopathological processes in the liver are capable of many factors, most viruses are hepatitis A, B and C, measles, environmental factors, excessive ultraviolet radiation (including sun deck), drugs (hormonal contraceptives, diclofenac, ketoconazole,some gepatoprotektory, interferons, and others.).We discuss the likelihood of genetic susceptibility to autoimmune liver disease, associated in particular with C4AQO alleles and HLA haplotypes B8, B14, DR3, DR4, DW3.C4A gene associated with the development of autoimmune hepatitis in younger patients, HLA DR3-positive patients are more prone to early and aggressive course of the disease with less sensitivity to medication, HLA DR4-positive patients are more likely to extrahepatic manifestations of the disease.
In a number of cases of autoimmune liver disease first diagnosed in women in connection with pregnancy.At the same time, data on the development and course of pregnancy in patients with autoimmune liver disease, as well as their mutual influence is very poor.
The data that such diseases are accompanied by phenomena of hypogonadism, resulting in a lack of ovulation, amenorrhea and rare occurrence of pregnancy.However, in practice, reproductive disorders in patients with autoimmune liver disease is extremely rare, so in the early stages of the disease and pregnancy is possible, it occurs more frequently than in the later stages.The possibility of continuing the pregnancy and in women with autoimmune liver disease indicates the existence of the natural mechanisms that suppress the immune system and provide most of the successful completion of pregnancy.Development and maintenance of pregnancy is possible also due to adequacy of treatment with correct diagnosis and allows women to plan pregnancy for a period of remission.
Autoimmune hepatitis Autoimmune hepatitis
currently defined as unresolved, mainly periportal hepatitis, flowing with hypergammaglobulinemia, tissue autoantibodies and amenable to immunosuppressive therapy.There are 2 (sometimes 3) types of autoimmune hepatitis.Type 1 is associated with high titers of ANA and SMA.The term "AIH type 1" replaced the former definition of "lupoid hepatitis" and "autoimmune chronic active hepatitis."Autoimmune hepatitis type 2 is characterized by the presence of antibodies LKM-l, against the cytochrome P-450 11DG;often begins in childhood acute proceeds with a variety of extrahepatic manifestations;cirrhosis progresses faster than hepatitis type 1 (within 3 years, respectively, at 82 and 43% of patients).
Options autoimmune hepatitis:
1. malosimptomno asymptomatic or when accidentally found to have elevated ALT and AST.
2. Acute onset with severe until the development of fulminant hepatitis with the development of hepatic impairment (worse prognosis in patients with acute onset of illness by type of acute viral hepatitis, with the presence of signs of cholestasis, ascites, repeated episodes of acute hepatic encephalopathy).
3. Autoimmune hepatitis with dominant extrahepatic manifestations (arthralgia (joint pain), polymyositis (muscle pain), lymphadenopathy, pneumonia, pleurisy, pericarditis, myocarditis, fibrosing alveolitis, thyroiditis, glomerulonephritis, hemolytic anemia, thrombocytopenia, and nodular erythema. etc.)
options with dominant extrahepatic manifestations:
- Feverish manifested intermittent fever (low grade or febrile) combined with extrahepatic manifestations and increased ESR.- - Artralgichesky (arthralgia, myalgia, acute recurrent migratory polyarthritis involving large joints without their deformities, spinal joints) with late onset of jaundice.
- icteric, which should be differentiated from hepatitis A, B, E, and especially C, in which the antibodies in the serum can occur after a sufficiently long time after the onset of the disease.
- In the form of "masks" of systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, autoimmune thyroiditis, etc. ..
The most common autoimmune hepatitis debut nonspecific symptoms - weakness, fatigue, anorexia (weight loss, lack of appetite), decreased performance, myalgiaand arthralgia, fever up subfebrile, discomfort in the upper abdomen, mild jaundice of the skin and sclera, skin itch.Unlike hepatitis disease progresses, and within 1-6 months appear clear signs of autoimmune hepatitis.
symptoms of advanced stage of autoimmune hepatitis are characterized by varying degrees of severity of asthenic syndrome, fever, progressive jaundice, hepatosplenomegaly, arthralgia, myalgia, heaviness in the right upper quadrant, hemorrhagic rash does not disappear when pressed and leaving behind a brown-brown pigmentation, lupus and erythema nodosum., localized scleroderma, "spider veins", palmar erythema, etc.
diagnostic criteria for autoimmune hepatitis are increased ALT, AST, GGT in serum, hyper-γ-globulinemiya and elevated levels of IgG & gt; 1,5 times, increased erythrocyte sedimentation ratedata liver biopsy, a high titer of serum markers of autoimmune hepatitis (ANA, SMA and LKM-1 (in the credits of not less than 1:80 and 1:20 in adults in children, but the antibody titer may fluctuate and sometimes they even disappear, especiallyduring treatment with glucocorticosteroids (GCS)).
Pregnancy in patients with autoimmune hepatitis, especially in the process of low activity occurs often becausethe disease predominantly affects young women.Amenorrhea and infertility is usually accompanied by only a high activity of hepatic process.However, it does not exclude the development of a woman's pregnancy, as treatment of corticosteroids alone or in combination with azathioprine leads to remission of the disease, supported by low, rare - medium doses of drugs against which the reproductive function in women is reduced.Effective treatment leads to a significant increase in survival of patients with autoimmune hepatitis, even at the stage of liver cirrhosis, however patient can become pregnant and giving birth (often twice) for disease, includingafter undergoing a liver transplant.
course of pregnancy in patients with autoimmune hepatitis and the effects of pregnancy on the course of the disease is not well understood.Most researchers believe that pregnancy in patients with autoimmune hepatitis on a background of remission, supported by GCS, includingat the stage of compensated cirrhosis without signs of portal hypertension, is not a big risk to the woman and the fetus.Exacerbations of the disease during pregnancy are rare.Laboratory tests during pregnancy often improve, returning after giving birth to the level registered before pregnancy.However, the described cases of a significant impairment of a pregnant, requiring increasing doses of corticosteroids.However, controlled trials have not been conducted, and it is unclear what deterioration was due.
When high activity of autoimmune hepatitis, nekorrigiruemoy GCS condition worsens pregnant, violated the basic function of the liver may develop liver failure, preeclampsia, placental insufficiency, detachment normally situated placenta, bleeding in the sequence, and the postpartum period.Pathology of the fetus can be expressed in the signs of intrauterine hypoxia, malnutrition and prematurity due to placental insufficiency.The probability of fetal death in this case is quite high.Probability
acute autoimmune hepatitis usually exists in the first half of pregnancy or postpartum (usually within the first 1-2 months.).The aggravation of the disease in the postpartum period is noted in about half of patients.Exacerbation during pregnancy is typically associated with unrecognized until its active liver development process, but in this case the second half of pregnancy active autoimmune hepatitis are generally reduced, thereby reducing the dose to the minimum effective corticosteroids.
Normal termination of pregnancy occurs in the majority of women with autoimmune hepatitis.Adverse pregnancy outcomes are observed in a quarter of cases, including serious complications, which are probably associated with the presence of antibodies to SLA / LP.Frequency uncomplicated delivery progression of liver disease is reduced.Conversely, the frequency of spontaneous abortion and fetal death increases.In this context, patients to be liver cirrhosis stage suggested abortion in the early its terms (up to 12 weeks.), Although it can be stored at the persistent desire of women, if cirrhosis is not accompanied by signs of decompensation and severe portalnoy hypertension, accompanied by a high risk of life-threateningbleeding (often develops in the II and III trimester of pregnancy early).Maternal mortality in these cases reaches 50-90%.
high frequency of bleeding from esophageal varices in pregnant women suffering from cirrhosis of the liver, but it is absolutely contraindicated in pregnancy only to Grade III esophageal varices, includingwith erosive and ulcerative esophagitis.When I and II degree without esophagitis phenomena possible continuation of the pregnancy, but the patient in need of endoscopic control throughout pregnancy.Since such control is unrealistic in most maternity hospitals, the risk of prolongation of pregnancy in the presence of varicose veins of the esophagus is extremely large.Note that in the II trimester even in healthy women may develop transient varicose veins of the esophagus and stomach as a result of increased blood volume.
Primary biliary cirrhosis
Primary biliary cirrhosis - a chronic cholestatic granulomatous destructive inflammatory disease of the smallest bile ducts caused by autoimmune reactions, which leads to long-term cholestasis and able to progress to cirrhosis.Primary biliary cirrhosis is often associated with other autoimmune diseases - thyroiditis, CREST-syndrome, Sjogren's syndrome, rheumatoid arthritis, scleroderma, lupus, lymphadenopathy, myasthenia, endocrine disorders (polyglandular failure), as well as liver failure, portal hypertension, peptic ulcer bleeding, carcinomaliver, osteoporosis, etc. The disease mostly occurs in women over 40 years, but perhaps at an earlier age.In young women the disease manifests skin itch, as a rule, in II-III trimesters of pregnancy, but is regarded as the most frequently intrahepatic cholestasis of pregnancy (VHB).Diagnosis of primary biliary cirrhosis is made possible much later, with the progression of symptoms that often occur with repeated pregnancy or taking oral hormonal contraceptives.
in the development of primary biliary cirrhosis are 4 stages.Stage 1 - Initial (inflammatory stage), characterized limfoplazmokletochnoy infiltration of portal tracts, the destruction of the bile duct epithelial and basement membrane.In the 2nd stage (progressive inflammation) portal tracts expanded develops periportal fibrosis, periportal detected foci of inflammation, there is the proliferation of small bile ducts.In the third stage (septal fibrosis) detected signs of active inflammation, necrosis of the parenchyma, portal tracts zapustevayut and are replaced by scar tissue.The 4th stage is characterized by the formation of liver cirrhosis and its complications - appearing regeneration nodes are identified pockets of inflammation of different severity.
typical symptoms of primary biliary cirrhosis include fatigue, pruritus, cholestatic jaundice, hepatosplenomegaly, bone pain, muscle and skin hyperpigmentation, xanthelasma.In the later stages of joining ascites and esophageal varices.Primary biliary cirrhosis characterized by increased alkaline phosphatase activity in serum and 2-6 more times, GGT levels, cholesterol, bile acids, IgM (75% cases), titer (more than 1:40, 1: 160) AMA AMA-M2 (in 95% of cases), which are often correlated with the activity of PBC, can be detected in the pre-clinical stage and do not disappear during the entire period of illness.It noted a moderate increase in bilirubin, decrease in prothrombin index, hypocalcemia (due to malabsorption of vitamin D).Cases of AMA-negative PBC called autoimmune holangiopatiya.