Primary biliary kolbitis ( PBC ), formerly known as primary biliary cirrhosis , is an autoimmune disease of the liver. This results from the slow, progressive damage of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Slower damage to liver tissue can cause scarring, fibrosis, and ultimately cirrhosis.
Common symptoms are fatigue, itching and, in more severe cases, jaundice. In the early cases, there may be only changes in the blood test.
PBC is a relatively rare disease, affecting up to 1 in 3-4,000 people. This is more common in women, with sex ratios of at least 9: 1 women for men.
This condition has been recognized since at least 1851 and was named "primary biliary cirrhosis" in 1949. Since cirrhosis is a feature of only advanced disease, the name change to "primary biliary cholangitis" was proposed by patient advocacy groups in 2014.
Video Primary biliary cholangitis
Signs and symptoms
People with PBC experience tiredness (80 percent) that causes daytime sleepiness; more than half of them have severe fatigue. Itching (pruritus) occurs in 20-70 percent. People with heavier PBC may develop jaundice (the eyes and skin become yellow). PBC damages bone density and there is an increased risk of fracture. Xanthelasma (skin lesions around the eyes) or other xanthoma may be present as a result of elevated cholesterol levels.
PBC can eventually develop into cirrhosis of the liver. This in turn can lead to a number of symptoms or complications:
- Fluid retention in the stomach (ascites) in more advanced disease
- An enlarged spleen in a further disease
- Esophageal varices in more advanced disease
- hepatic encephalopathy, including coma in extreme cases of further disease.
People with PBC sometimes also have findings of associated extrahepatic autoimmune disorders such as rheumatoid arthritis or SjÃÆ'¶gren syndrome (in up to 80 percent of cases).
Maps Primary biliary cholangitis
Cause
PBC has an immunological basis, and is classified as an autoimmune disorder. This results from the slow, progressive damage of the small bile ducts of the liver, with intralobular ducts and the Canals of Hering (intrahepatic ducts) affected in early disease. This leads to the development of fibrosis, cholestasis and, in some people, cirrhosis.
Most people with PBC (90 percent) have anti-mitochondrial (AMAs) antibodies against complex pyruvate dehydrogenase (PDC-E2), an enzyme complex found in mitochondria. People who are negative to AMA are usually found to be positive when more sensitive detection methods are used.
People with PBC may also have been diagnosed with other autoimmune diseases, such as rheumatological, endocrinological, gastrointestinal, pulmonary, or dermatological conditions, suggesting a shared genetic and immune disorder. Common associations include SjÃÆ'¶gren syndrome, systemic sclerosis, rheumatoid arthritis, lupus, hypothyroidism and gluten-sensitive enteropathy.
A genetic predisposition to disease has been considered important for some time. The evidence for this includes PBC cases in family members, identical twins both have conditions (concordance), and PBC grouping with other autoimmune diseases. In 2009, a group of Canadian-led researchers reported in the New England Journal of Medicine the results of the first PBC genome association study. This study revealed that part of the IL12 signaling cascade, especially the polymorphisms of IL12A and IL12RB2, is important in the aetiology of disease in addition to the HLA region. In 2012, two independent PBC association studies increased the total number of genomic areas associated with 26, involving many genes involved in cytokine regulation such as TYK2 , SH2B3 and TNFSF11.
An environmentally negative Gram ababacterium - Novosphingobium aromaticivorans has been associated with this disease with several reports indicating the etiological role for this organism. This mechanism appears to be a cross-reaction between bacterial proteins and mitochondrial proteins from liver cells. The CD101 gene encoding may also play a role in the host's vulnerability to the disease.
There is a failure of immune tolerance to complex pyrolysed mitochondria dehydrogenase (PDC-E2), and this may also occur with other proteins, including gp210 pore proteins and nuclear p62. Gp210 has increased expression in the bile ducts of patients positive for anti-gp210, and this protein may be associated with prognosis.
Diagnosis
To diagnose PBC, it needs to be distinguished from other conditions with similar symptoms, such as autoimmune hepatitis or primary sclerosing cholangitis (PSC).
- Abnormalities in liver enzyme tests are common and increased gamma-glutamyl transferase and alkaline phosphatase (ALP) are found in early disease. Increased bilirubin occurs in advanced disease.
- Antimitocondria antibodies are characteristic serologic markers for PBC, which are present in 90-95 percent of patients and only 1 percent of controls. PBC patients have an AMA against complex pyruvate dehydrogenase (PDC-E2), an enzyme complex found in mitochondria. People who are AMA negative but with diseases similar to PBC have been found to have an AMA when more sensitive detection methods are used.
- Other auto-autobodies may exist:
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- Measurement of antinuclear antibodies is not diagnostic for PBCs because they are not specific, but may have a role in prognosis.
- Anti-glycoprotein-210 antibodies, and lower anti-p62 degree antibodies, correlate with disease progression to late-stage liver failure. Anti-gp210 antibodies were found in 47 percent of PBC patients.
- Anti-centromere antibodies are often correlated with developing portal hypertension.
- Anti-np62 and anti-sp100 are also found in connection with PBC.
- Inflammation of the bile duct, characterized by intraepithelial lymphocytes, and
- Periductal epithelial granulomata.
- Stage 1 - Stage Portal : Triad is of normal size; inflammation of the portal, damage to the bile ducts smooth. Granulomas are often detected at this stage.
- Stage 2 - Stage Periportal : An enlarged Triad; periportal fibrosis and/or inflammation. Usually characterized by bile duct proliferation findings.
- Stage 3 - Septal Stage : Septa fibrous is active and/or passive.
- Stage 4 - Biliary Cirrhosis : There are nodules; garland or jigsaw puzzle patterns.
- Ursodeoxycholic acid (UDCA), marketed as Ursodiol and others, is the most commonly used treatment. It helps reduce cholestasis and improve liver function tests. It has minimal effect on symptoms and whether it improves controversial results. A Cochrane review from 2012 showed no significant benefits on important outcomes including death, liver transplantation or PBC symptoms, even if some biochemical and histologic parameters were increased.
- To relieve the itching caused by circulating bile acids, which are usually removed by the liver, cholestyramine (bile sequestrant acid) can be prescribed to absorb bile acids in the intestine and is removed, rather than reentering the bloodstream.. Other drugs that do this include stanozolol, naltrexone, and rifampicin.
- Specific treatments for fatigue, which may be debilitating in some patients, are limited and undergo trials. Several studies have shown that Provigil (modafinil) may be effective without damaging the liver. Although modafinil is no longer protected by patents, the limiting factor in its use in the US is cost. The manufacturer, Cephalon, has entered into agreements with generic modafinil producers to provide payments in exchange for delaying their modafinil sales. The FTC has filed a lawsuit against Cephalon for alleging anti-competitive behavior.
- People with PBC may have fat absorption that depends on Vitamins A, D, E, K. Proper supplementation is recommended when bilirubin increases.
- People with PBC have a higher risk of osteoporosis and esophageal varices compared with the general population and others with liver disease. Screening and treatment of these complications is an important part of PBC management.
- As with all liver diseases, alcohol consumption is contraindicated.
- In advanced cases, a liver transplant, if successful, results in a favorable prognosis.
- Farnesoid X-receptor agonists, obeticholic acid (marketed as Ocaliva), have been licensed by various regulatory authorities, including the US Food and Drug Administration, as orphans in an accelerated approval program. Obeticholic acid, which is a modified bile acid, results in a decrease in the alkaline phosphatase level of biomarkers, a substitute endpoint for clinical benefit in PBC. This is indicated for the treatment of PBC in combination with ursodeoxycholic acid in adults with an inadequate response to UDCA, or as monotherapy in adults who can not tolerate UDCA. Additional studies are underway to verify and illustrate the clinical benefits.
- Other drugs undergoing clinical studies on non-UDCA responders include fibrates, such as fenofibrate and bezafibrate, which are porphyry proliferator-promoting pan-peroxisome receptor (PPAR) agonists with anti-inflammatory and choleretic effects (increased bile secretion). Bezafibrate has been shown to increase biomarkers including alkaline phosphatase, but has not been licensed in PBC.
- Halaman Sirosis Biliary Utama dari National Digestive Diseases Information Clearinghouse
- Ultrasound ultrasound, MR (MRCP) scans or CT scans are usually performed to remove blockages into the bile ducts. This may be necessary if a condition that causes secondary biliary cirrhosis, such as bile duct disease or other gallstones, needs to be excluded. Liver biopsy may be helpful, and if uncertainty persists as in some patients, retrograde endoscopic cholangiopancreatography (ERCP), bile duct investigation endoscopy, may be performed.
Most patients can be diagnosed without invasive investigation, because the combination of anti-mitochondrial antibodies and cholestatic liver enzyme tests is considered diagnostic. However, a liver biopsy is needed to determine the stage of the disease.
Liver biopsy
On microscopic examination of liver biopsy specimens, PBC is characterized by destruction of the interlobular bile ducts. These histopathological findings in primary biliary cholangitis include the following:
Histopathological Stages
Treatment
No drug is known, but the drug can slow down development so that normal life and quality of life can be achieved for many patients.
Prognosis
Serum bilirubin levels are an indicator of PBC prognosis, with levels of 2-6 mg/dL having an average survival time of 4.1 years, 6-10 mg/dL 2.1 years and above 10 mg/dL having an average time survival 1.4 years.
After a liver transplant, the recurrence rate may be as high as 18 percent at five years, and up to 30 percent at 10 years. There is no consensus on risk factors for the recurrence of the disease.
Complications of PBC can be associated with chronic cholestasis or cirrhosis of the liver. Chronic cholestasis leads to osteopenic bone disease and osteoporosis, along with hyperlipidemia and vitamin deficiency.
Patients with PBC have an increased risk of hepatocellular carcinoma compared with the general population, as found in other cirrhotic patients. In patients with advanced disease, one series found 20 percent in men and 4 percent in women.
Epidemiology
PBC is a chronic autoimmune liver disease with female sex dominance with females: a male ratio of at least 9: 1 and peak incidence in the fifth decade of life. In some areas of the US and the UK, the prevalence is estimated to be as high as 1 in 4000. This is much more common than in South America or Africa, which is probably due to better recognition in the US and UK. Level 1 relatives may have as many as 500 times increased prevalence, but there is a debate if these risks are greater in relatives of the same or subsequent generations.
History
In 1851, Addison and Gull described the clinical features of progressive obstructive jaundice in the absence of mechanical obstruction of the large bile ducts. Although most of Ahrens' credit sources were coining in 1950, Dauphinee and Sinclair have used the name primary biliary cirrhosis for this disease in 1949. The association with anti-mitochondrial antibodies was first reported in 1965 and the presence they are recognized as early markers, pre-cirrhosis diseases.
Society and culture
Support group
PBC Foundation
The PBC Foundation is an international charity that offers support and information to people with PBCs, their families and friends. It's a campaign to increase recognition of disorders, improve diagnosis and treatment, and estimate more than 8000 people undiagnosed in the UK. The Foundation has supported research on PBC including the development of the quality of life of the size of PBC-40 published in 2004 and helped establish the PBC Genetic Study. It was founded by Collette Thain in 1996, after she was diagnosed with the condition. Thain was awarded an Order of MBE from the United Kingdom in 2004 for his work with the Foundation. The PBC Foundation helps start a name change campaign in 2014.
Organization PBCers
The PBC organization is a US-based nonprofit support group established in 1996 and supports greater awareness of new diseases and treatments. It has supported the initiative to change the name.
Name
In 2014 the PBC Foundation, with the support of the PBC Organization, the PBC Society (Canada) and other patient groups, advocated the name change from "primary biliary cirrhosis" to "primary biliary cholangitis," noting that most PBC patients do not have cirrhosis and that "cirrhosis" often have a negative connotation of alcoholism. Patient and professional groups are investigated. Support for name change comes from professional bodies including the American Association for the Study of Liver Diseases and the European Association for the Study of the Heart. Advocate for published nickname changes to adopt a new name in the double hepatology journal in autumn 2015.
References
External links
Source of the article : Wikipedia
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