Biliary cirrhosis is an autoimmune condition characterized by degeneration of the small and medium bile ducts and subsequent scarring of the liver parenchyma. It occurs due to an obstruction of the intrahepatic or extrahepatic bile flow and can be primary or secondary, depending on the etiology. Primary biliary cirrhosis is mainly viewed as an autoimmune disease, whereas secondary biliary cirrhosis is a result of underlying pathologies.
Primary biliary cirrhosis (PBC)
Primary biliary cirrhosis is an autoimmune disease . Approximately 1/4th of the patients affected by it tend to be asymptomatic when the diagnosis is made; the latter is established after abnormal laboratory values are detected during a routine examination or one conducted for different reasons . The most common symptom experienced by patients is fatigue. The vast majority of the patients initially present with fatigue as the sole symptom and its existence increases the already elevated mortality rate of primary biliary cirrhosis    .
Pruritus is the second most common symptom experienced by up to half of the patients with an undiagnosed PBC and is believed to be caused by bile pigments which accumulate on the skin or by central opioid neurotransmission. Pain is reported, located in the right upper abdominal quadrant, in cases of advanced disease, jaundice also occurs.
With a reference to the signs of PBC, the most prominent include hepatomegaly, hyperpigmentation, splenomegaly, xanthelasma and signs related to cirrhosis and end-stage liver diseases, such as ascites and spider naevus.
Secondary biliary cirrhosis (SBC)
Similarly to PBC, secondary biliary cirrhosis tends to produce no symptoms in the initial stages and it is diagnosed when examinations are carried out for other medical reasons. When it does produce symptoms, those mainly include fatigue, jaundice, and pruritus. Pain in the right upper abdominal quadrant, hyperpigmentation, and osteoporotic symptoms can also complete the clinical picture and the patient may sometimes present in a febrile status.
Sjogren's syndrome is often associated with SBC and tends to present with a dry mouth and dry eyes. Night blindness and xanthelasma are common manifestations observed in a patient with secondary biliary cirrhosis.
Entire Body System
When it does produce symptoms, those mainly include fatigue, jaundice, and pruritus. [symptoma.com]
PBC is a cholestatic autoimmune liver disease in which fatigue is experienced by at least half of patients. [bmj.com]
Managing fatigue At the moment, no medicines are specifically recommended for treating the fatigue caused by PBC. [hse.ie]
Multiple Congenital Anomalies
Affected patients present a variable phenotype with pre- and post-natal macrosomia, distinctive facial dysmorphism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. [ncbi.nlm.nih.gov]
Although activation of A2bAR induced cAMP and intracellular Ca2 signals, only the Ca2 signals were linked to IL-6 upregulation. [ncbi.nlm.nih.gov]
Patients may have a low platelet count because of an enlarged spleen causing easy bruising. Hepatic encephalopathy : The liver also helps remove waste products from the bloodstream. [medicinenet.com]
Cirrhosis can lead to easy bruising, nosebleeds, gallstones, intense itching, kidney failure and liver cancer. It is most commonly caused by alcoholism and hepatitis. Too much iron in the body causes hemochromatosis. [bshr.com]
bruising and abnormal bleeding, most often from swollen veins in the digestive tract Confusion or problems thinking Pale or clay-colored stools The health care provider will do a physical exam. [medlineplus.gov]
bruising and abnormal bleeding, most often from swollen veins in the digestive tract Confusion or problems thinking Pale or clay-colored stools Exams and Tests The health care provider will do a physical exam. [mountsinai.org]
The symptoms are often very vague; they may include abdominal pain or fatigue. As the condition progresses, symptoms like jaundice (yellowing of skin or eyes), fatty stools, itching and fatty deposits under the skin or eyelids occur. [nyp.org]
Some patients experience no symptoms, while others may experience symptoms such as: Fatigue Itchy skin Abdominal pain Dry eyes Dry mouth Yellowing of the skin and eyes (jaundice) Darkening of the skin Swollen feet and ankles Accumulation of abdominal [columbiasurgery.org]
If you have been diagnosed with Biliary Cirrhosis and do not experience any symptoms such as yellowish skin, itchiness or abdominal pain then it must be in the early stage. You still qualify for the graded death benefit policy. [highrisklifeinsuranceagency.com]
It has a lengthy latent period, usually followed by the sudden appearance of abdominal pain and swelling, hematemesis, dependent edema, or jaundice. [medical-dictionary.thefreedictionary.com]
pain Over time, PBC may result in numerous serious complications. [everydayhealth.com]
Other side effects include: loose stools thinning hair nausea (feeling sick) vomiting Corticosteroids PBC sometimes occurs alongside autoimmune hepatitis. [hse.ie]
Early symptoms may include: Nausea and belly pain Fatigue and loss of energy Fatty deposits under the skin Fatty stools Itching Poor appetite and weight loss As liver function worsens, symptoms may include: Fluid buildup in the legs (edema) and in the [medlineplus.gov]
Liver, Gall & Pancreas
When it does produce symptoms, those mainly include fatigue, jaundice, and pruritus. [symptoma.com]
Life expectancy is about 5 years for symptomatic patients after the onset of jaundice. [medical-dictionary.thefreedictionary.com]
Patients may suffer from jaundice, which may be delayed. Jaundice is a rare occurrence in PBC without the simultaneous condition of cirrhosis, likely because the level of intrahepatic bile duct loss is not significant enough. [consultant360.com]
Affecting chiefly middle-aged women, it is characterized by chronic cholestasis (accumulation of bile in the liver) with pruritis, jaundice, and hypercholesterolemia with xanthomas, and malabsorption. [healthcentral.com]
With a reference to the signs of PBC, the most prominent include hepatomegaly, hyperpigmentation, splenomegaly, xanthelasma and signs related to cirrhosis and end-stage liver diseases, such as ascites and spider naevus. [symptoma.com]
[…] placebo and D-penicil. age at registration in years. sex a factor with levels male and female. year number of years between enrollment and this visit date, remaining values on the line of data refer to this visit. ascites a factor with levels No and Yes. hepatomegaly [rdrr.io]
Itching of the skin Jaundice Dry Eye Dry mouth Portal hypertension Ascites Splenomegaly (enlarge spleen) Esophageal varices ( engorge vein in lower end of esophagus) Cholesterol deposits in skin- Xanthoma over arms and upper body Xanthoma around eyes Hepatomegaly [epainassist.com]
/insidious/asymptomatic 20/22/6 41.7/45.8/12.5 Cirrhosis at presentation 17 35.4 Fatigue 29 60.4 Jaundice 27 56.3 Anorexia 24 50.0 Abdominal fullness 21 43.8 Splenomegaly 16 33.3 Abdominal pain 16 33.3 Ascites 12 25.0 Arthralgia 10 20.8 Edema 8 16.7 Hepatomegaly [slideshare.net]
An interesting aspect of this case is the patient's osteoporosis confirmed by densitometry. Osteoporosis is a frequent extra hepatic manifestation of PBC. [scielo.br]
Medications Medications are used to reduce cholestasis, improve liver function, relieve itching and fatigue, and to treat complications such as varices and osteoporosis. [columbiasurgery.org]
This could lead to your bones becoming weak and brittle, a condition known as osteoporosis. Osteoporosis affects around one-third of people with primary biliary cirrhosis (PBC). [your.md]
Supplements of calcium and vitamin D are needed to help prevent osteoporosis or slow its progression. Weight-bearing exercises, bisphosphonates, or raloxifene may also help prevent or slow osteoporosis. [merckmanuals.com]
Other symptoms may eventually develop, including: jaundice, which leads to a yellowing of the eyes and skin fatty deposits under the skin fluid retention dry eyes and mouth In the later stages of the disease, some people develop osteoporosis, arthritis [oregonclinic.com]
Clinical characteristics Prevalence : 50-200 case/1 million in Western Europe & North American Presentation – heterogeneous Variable – no symptoms/signs to fulminant hepatic failure Malaise, anorexia, nausea, vomiting, abdominal pain, itching Arthralgia [slideshare.net]
A trial of corticosteroids in patients with idiopathic granulomatous hepatitis who are symptomatic, with fever, myalgias, and arthralgias, may be helpful. Empirical antituberculous therapy should be considered before instituting corticosteroids. [clevelandclinicmeded.com]
This sense of lack of belief in those around them can contribute to the social isolation exemplified by Tilly’s description, and which patients are always prone to because of their lack of physical capability. [bmj.com]
Hynes A, Duggan C, Jones S, Crossey M, Stansfield G, MacNicol C, Wilkins J, Wilhelmsen E, Raymode P, Lee HJ, Durant E, Bishop R, Ncube N, Tripoli S, Casey R, Cowley C, Miller R, Houghton K, Ducker S, Wright F, Bird B, Baxter G, Keggans J, Hughes M, Grieve [ncbi.nlm.nih.gov]
In the initial stages of the disease, liver functions tests are expected to reveal pathologically elevated levels of γ-glutamyl transpeptidase (γ-GT) and alkaline phosphatase (ALP) . These two abnormal findings are usually the ones to be discovered during a routine examination and alongside a corresponding clinical picture with jaundice, fatigue and right upper abdominal quadrant pain, they raise suspicion towards PBC.
Aminotransferase levels are usually slightly elevated and bilirubin measured in the blood is also primarily normal. If the end-stage liver disease is present, serum bilirubin will be increased. The great majority of SBC patients are also found to have antimitochondrial autoantibodies (AMA) and those who test negative with the standard laboratory methods, tend to re-test positive when more sensitive methods are employed . Serum immunoglobulin M (IgM) is also elevated in such patients. In order for a definitive diagnosis to be established, a liver ultrasonography and a magnetic resonance cholangiopancreatography (MRCP) or an endoscopic retrograde cholangiopancreatography (ERCP) are required. A liver biopsy will reveal findings compatible with PBC, such as inflammation of the bile ducts with depositions of intraepithelial lymphocytes and periductal epithelioid granuloma . Through a liver biopsy, PBC can be classified into four distinct stages, depending on the particular histopathologic characteristics.
The diagnostic approach is similar to that of primary biliary cirrhosis. A thorough medical history is required, including a potential history of gallstones, surgical procedures, alcohol ingestion, and medications. Laboratory tests with include liver function tests in order to detect pathologic concentrations of ALP and γ-GT, serum bilirubin and aminotransferases. Plain radiographs and a liver biopsy will help to reach a definitive diagnosis of secondary biliary cirrhosis.
This review provides a current perspective on potential new approaches to treatment in PBC, and highlights some of the challenges we face in evaluating and effectively implementing those treatments. Copyright 2016 Elsevier Inc. All rights reserved. [ncbi.nlm.nih.gov]
Liver transplantation is the only treatment that will cure primary biliary cirrhosis. A liver transplant is considered when complications cannot be controlled by treatment. [british-liver-trust.org.uk]
Treatment of Esophageal Varices- Surgical treatment Treatment Of Liver Failure- Liver Transplant- The next and the only definitive treatment as of now is liver transplant. [epainassist.com]
Treatment for PBC There is no cure for PBC, but treatment can help slow the progression of disease and associated symptoms. [betterhealth.vic.gov.au]
Others (13) have observed that patients with a decline of serum alkaline phosphatase of more 50% achieved an excellent long-term prognosis. [albi-france.org]
The serum bilirubin level is a marker of prognosis Common Primary Biliary Cirrhosis (PBC) exam questions for medical students, finals, OSCEs and MRCP PACES Perfect revision for medical students, finals, OSCEs and MRCP PACES [oxfordmedicaleducation.com]
Early PBC prognosis advocated Biochemical response to ursodeoxycholic acid at 6 months is a better predictor for primary biliary cirrhosis prognosis than the current standard of 1 year, study results suggest. [news-medical.net]
What is the Long Term Prognosis? Because doctors are able to diagnose primary biliary cholangitis very early, prognosis is much better than it was in the past since treatment can begin before severe damage occurs to the liver. [liversupport.com]
It occurs in patients who underwent liver transplantation for a different etiology. We present the case of a 56-year-old woman who was diagnosed with primary biliary cirrhosis and had liver transplantation for refractory pruritis. [ncbi.nlm.nih.gov]
It occurs due to an obstruction of the intrahepatic or extrahepatic bile flow and can be primary or secondary, depending on the etiology. [symptoma.com]
The etiology of PBC is poorly understood; however, several lines of evidence suggest an environmental factor that triggers a series of immune-mediated inflammatory reactions in the bile ducts in a genetically susceptible individual. [dovepress.com]
Its etiology is still not entirely understood, but clinical, laboratory and histopathologic findings strongly suggest an autoimmune process. [scielo.br]
This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options. [ncbi.nlm.nih.gov]
Prince MI, James OF ; The epidemiology of primary biliary cirrhosis. Clin Liver Dis. 2003 Nov7(4):795-819. [patient.info]
Epidemiology of primary biliary cirrhosis Prevalence 4 in 100,000 Males:Females 1:9 Peak incidence around 50 years Commonest in northern Europeans, least common in Africans. [oxfordmedicaleducation.com]
General Epidemiology: Female male ( 9:1).  Usually middle age. Associated with other autoimmune conditions ( Sjögren syndrome, progressive systemic sclerosis, celiac disease ). Etiology: Autoimmune. [librepathology.org]
Pathophysiology: Septal bile duct attacked. Treatment: Ursodeoxycholic acid. May be indication for transplant. Microscopic Features: "Florid duct lesion":  Intraepithelial lymphocytes - in bile duct - key feature. [librepathology.org]
Pathophysiology and recent findings of primary biliary cirrhosis complicated by systemic sclerosis. Ohira H1, Watanabe H. Hepatol Res. 2013 Dec 6. 2. Questionnaire based assessment of risk factors for primary biliary cirrhosis. [epainassist.com]
Approximately 80% of patients with PSC have inflammatory bowel disease, more commonly ulcerative colitis than Crohn’s disease. 21 Pathophysiology and Natural History The pathophysiology of PSC is unclear, but there is evidence suggesting an autoimmune [clevelandclinicmeded.com]
[…] higher risk for first-generation relatives of patients with PBC, compared to the general population Past or present smoking (EASL, 2017) Frequent use of nail polish or hair dyes Female sex Previous pregnancies Recurrent mucosal infection (EASL, 2017) Pathophysiology [arupconsult.com]
Reksten TR, Jonsson MV: Sjögren's syndrome: an update on epidemiology and current insights on pathophysiology. Oral Maxillofac Surg Clin North Am 2014;26:1-12. [karger.com]
A genetic disease that prevents the body from removing extra copper. Having high copper levels can cause life-threatening damage to the body’s organs. [bshr.com]
Can primary biliary cirrhosis be prevented? Since the cause of the disease is not known, it is not possible to prevent PBC. However, medications may be able to slow the progression of the disease and control the symptoms. [medicinenet.com]
UDCA is thought to help prevent liver damage by changing the composition of the bile and reducing inflammation (swelling) of the liver. [hse.ie]
- Jones DE. Pathogenesis of primary biliary cirrhosis. Gut. 2007;56:1615-1624.
- Prince MI, Chetwynd A, Craig WL, et al. Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut. 2004 Jun; 53(6):865-70.
- Prince M, Chetwynd A, Newman W, et al. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology. 2002; 123:1044-1051.
- Jones EA. Fatigue complicating chronic liver disease. Metab Brain Dis. 2004 Dec; 19(3-4):421-9.
- Forton DM, Patel N, Oatridge A, et al. Fatigue in primary biliary cirrhosis. Gut. 2005 Mar; 54(3):438.
- Jones DE, Bhala N, Burt J, et al. Four year follow up of fatigue in a geographically defined primary biliary cirrhosis patient cohort. Gut. 2006 Apr; 55(4):536-41.
- Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. July 2009. Hepatology. 50 (1): 291–308.
- Vierling, JM. Primary biliary cirrhosis and autoimmune cholangiopathy. Clinics in liver disease. Feb 2004. 8 (1): 177–94.
- Nakanuma Y, Tsuneyama K, Sasaki M, Harada K. Destruction of bile ducts in primary biliary cirrhosis. Aug 2000. Baillière's Best Practice & Research. Clinical Gastroenterology. 14 (4): 549–70.