(Primary biliary cholangitis)
The primary biliary cirrhosis (PBC) is an autoimmune liver disease with progressive destruction of intrahepatic bile ducts, which may lead to the development of cholestasis, cirrhosis and ultimately liver failure. The patients are either asymptomatic or occur fatigue or symptoms of cholestasis (such. As itching, steatorrhea) or cirrhosis (such. As portals Hypertonsion, ascites) on. The laboratory tests show a cholestasis, increased IgM and characteristic for the primary biliary cirrhosis antimitochondrial antibodies in serum. For the diagnosis and staging of disease is a liver biopsy may be useful. Treatment consisting of ursodeoxycholic acid, cholestyramine (anti-itching), replacement of fat soluble vitamins and finally a liver transplantation in the final stage.
The primary biliary cirrhosis (PBC) is an autoimmune liver disease with progressive destruction of intrahepatic bile ducts, which may lead to the development of cholestasis, cirrhosis and ultimately liver failure. The patients are either asymptomatic or occur fatigue or symptoms of cholestasis (such. As itching, steatorrhea) or cirrhosis (such. As portals Hypertonsion, ascites) on. The laboratory tests show a cholestasis, increased IgM and characteristic for the primary biliary cirrhosis antimitochondrial antibodies in serum. For the diagnosis and staging of disease is a liver biopsy may be useful. Treatment consisting of ursodeoxycholic acid, cholestyramine (anti-itching), replacement of fat soluble vitamins and finally a liver transplantation in the final stage. Etiology The PBC is the most common liver disease with chronic cholestasis in adults. In most cases (95%) are concerned women aged 35-70 years. The PBC appears to run in families. A genetic predisposition, perhaps with the involvement of the X chromosome, is likely. There may be an inherited abnormality of immune regulation. Autoimmune mechanisms are adopted, since antibodies against an antigen of the inner mitochondrial membrane occur in> 95% of cases. However, these anti-mitochondrial antibodies (AMA), the serological hallmark of a PBC, non-cytotoxic and does not participate in the destruction of the Gallenepithelien are. The PBC is associated with other autoimmune diseases such. As rheumatoid arthritis, scleroderma, Sjogren’s syndrome, CREST syndrome, autoimmune thyroiditis and renal tubular acidosis. T cells attack the small bile ducts. The aim of the CD4 and CD8 T lymphocytes are the biliary epithelial cells. The trigger for the immunological attack on the bile ducts is unknown. The contact with a foreign antigen such. B. with an infectious (bacterial or viral), or toxic agent may represent the triggering event. These foreign antigens could structurally similar to endogenous proteins (molecular mimicry); the resulting immunological reaction would then autoimmune and self-sustaining. The destruction and the loss of the bile ducts lead to impaired bile formation and secretion (cholestasis). Retained toxic substances such as bile acids then cause further damage, particularly to the hepatocytes. thus the chronic cholestasis leads to liver inflammation and scarring in the Periportalfeldern. When the Progress Fiborse to cirrhosis, the inflammation decreases eventually. Autoimmune cholangitis is sometimes considered a separate disease. It is characterized by autoantibodies as antinuclear antibodies (ANA) and / or antibodies against smooth muscles and similar in the clinical course and response to treatment of PBC. However AMAs missing in autoimmune cholangitis. Symptoms and complaints than half of the patient’s symptoms. Symptoms can occur at any stage of the disease, they are made in a general fatigue or reflect the cholestasis (and the resulting fat malabsorption, vitamin deficiencies and osteoporosis caused), liver dysfunction or cirrhosis. The symptoms usually develop gradually. Itching, fatigue and mouth and eye dryness are initial symptoms in> 50% of patients and may precede other symptoms for months and years. Other initial manifestations are discomfort in the right upper quadrant (10%), an enlarged, hard, non-painful pressure liver (25%), splenomegaly (15%), hyperpigmentation (25%), xanthelasma (10%), and jaundice (10%) , Ultimately, all findings and complications of cirrhosis occur. In addition, peripheral neuropathy and other autoimmune diseases that are associated with the PBC can develop. Diagnostic determination of the liver (Function) parameter anti-mitochondrial antibody ultrasonography and, if necessary. MRCP liver biopsy In asymptomatic patients, a PBC is determined randomly when abnormal liver values, typically an increase of alkaline phosphatase and gamma-glutamyl transferase (GGT) show. The suspected PBC is middle-aged women with classic symptoms (eg unexplained pruritus, fatigue, pain in the right upper quadrant, jaundice.) Or found with elevated Cholestasewerten: increased alkaline phosphatase and ?-GT at only slightly elevated transaminases ( GPT and GOT). In early stages, the serum bilirubin is usually within the normal range; a bilirubin indicates disease progression and worsening of the prognosis. If the PBC is suspected, liver function tests should, serum IgM (elevated in PBC) are determined and AMA. ELISA (enzyme-linked immunosorbent assay) tests are sensitive to 95% and 98% specific for PBC; False-positive results can occur with autoimmune hepatitis (type 1). Other autoantibodies (z. B. ANA, smooth muscle antibodies, rheumatoid factor) can be detected. Extrahepatic biliary obstruction should be excluded. An ultrasound is often performed first, but ultimately a MRCP and occasionally ERCP is required. Usually, a liver biopsy is performed, unless the life expectancy is short or there is a contraindication. Liver biopsy confirmed the diagnosis. You can show in the early stages of the disease pathognomonic bile duct damage already. If the PBC progresses, it is morphologically indistinguishable from other forms of cirrhosis. Liver biopsy is also helpful in staging the PBC, which is divided into four histological stages: Stage 1: inflammation and / or abnormal connective tissue limited to the portal areas Stage 2: inflammation and / or fibrosis, limited to portal and periportal areas Stage 3 : bridging fibrosis stage 4: cirrhosis autoimmune cholangitis is diagnosed when AMA are absent in a patient who would be diagnosed otherwise a PBC. Prognosis The rate of progression of PBC is very different, mostly it proceeds in 15-20 years to terminal stages. The quality of life must be at PBC for many years do not deteriorate. Initially asymptomatic patients may develop symptoms at 2-7, but only about 10-15 years. If symptoms occur, the median life expectancy is 10 years. Predictors of rapid progression of the disease are: rapid worsening of symptoms advanced histological staging higher patient age presence of edema existence of associated autoimmune disorders of bilirubin, albumin, PT or INR The prognosis is worrying if the itch disappears, xanthomas shrink, jaundice developed and the serum cholesterol decreased. Therapy stabilization or regression of liver lesions treatment of complications (chronic cholestasis and hepatic failure), if necessary Liver transplantation Any alcohol intake and potentially hepatotoxic drugs should be avoided. Ursodeoxycholic acid (15 mg / kg p.o. once daily) reduces the hepatic damage, prolongs survival time and the time interval until the need for a liver transplant. About 20% of patients do not show biochemical improvement after ? 4 months of therapy; in these patients an advanced stage of the disease may be requiring a liver transplant within a few years. Other drugs for which a reduction of the liver damage was adopted, could not improve the clinical course or led to controversial results. Itching can cholestyramine (6-8 g po 2 times a day) appeal. This drug binds bile acids and can thus increase the fat malabsorption. If cholestyramine is taken long term, a supplement of fat soluble vitamins should be considered. Cholestyramine may reduce the absorption of ursodeoxycholic acid, which is why these drugs should not be administered concurrently. cholestyramine may also absorption of various drugs reduce; when patients a medicine that may be affected are taking, they should be advised to take the drug not within 3 hours before or after taking cholestyramine. Some patients with pruritus respond to ursodeoxycholic acid and ultraviolet light, others a therapeutic trial with rifampicin or an opiate such. As naltrexone, is required. Patients with fat malabsorption due to lack of bile salt should be treated with vitamin A, D, -E and -K supplements. For the prevention of osteoporosis, a physical activity and the use of bisphosphonates or raloxifene, in addition to taking calcium and vitamin D supplements, may be indicated. In later stages, the portal hypertension or complications of cirrhosis require treatment. Liver transplantation in PBC shows excellent results. The general indication is one of the decompensated liver disease (uncontrollable variceal bleeding, refractory ascites, intractable pruritus and hepatic encephalopathy). The survival rates after liver transplantation to be> 90% at 1 year,> 80% at 5 years and> 65% after 10 years. AMA may persist even after the transplant. In 15% of patients experience in the early years to a PBC recurrence and at> 30% within 10 years. The recurrent PBC after liver transplantation appears to have a benign course. Cirrhosis rarely occurs. Important points PBC is a chronic progressive cholestatic liver disease, which is caused by an autoimmune reaction in the small bile ducts and occurs almost exclusively in women aged 35-70 years. The PBC usually progresses to the terminal stage in 15-20 years. PBC is suspected in patients with unresolved increased alkaline phosphatase and ?-GT at only slightly elevated transaminases, in particular in constitutional symptoms or manifestations of cholestasis (z. B. pruritus, osteoporosis, vitamin D deficiency). IgM and anti-mitochondrial antibody are determined, and an imaging (to exclude extrahepatic bile duct obstruction) and performed a liver biopsy. The intake of hepatotoxins (including alcohol) must be stopped, and the treatment with ursodeoxycholic acid, which can delay a transplant. An indication for transplantation is (uncontrollable variceal bleeding, refractory ascites, intractable pruritus, hepatic encephalopathy) in decompensated liver disease.