Last Updated on February 20, 2020
Primary biliary cholangitis is a disease where there is chronic and progressive damage to intrahepatic bile ducts leading to cholestatic disease [reduction of bile flow]
It was earlier called primary biliary cirrhosis. The name was changed as the previous name reflected cirrhosis as part of the disease but cirrhosis occurs only in the late stage of the disease.
The cause of the disease is not known and thought to be autoimmune in nature. The major pathology of this disease is the destruction of the small-to-medium intrahepatic bile ducts, which leads to progressive cholestasis and often end-stage liver disease.
Destruction of the bile ducts decreases the flow of bile juices from the liver to the intestine. The bile helps in fat digestion and absorption of fat-soluble vitamins like A, D, E, and K.
Read more about Liver Anatomy, Structure and Function
Accumulated bile causes further destruction of liver cells and bile ducts, eventually leading to scarring and cirrhosis.
Primary biliary cirrhosis affects women more than men accounting for 75-90% cases.
The men who have the disease, however, are more likely to develop cancer of liver- hepatocellular carcinoma.
The disease affects the age group 40-65 years mainly though far younger and older patients have been described.
First-degree relatives have been found to have 500 times higher risk of developing primary biliary cholangitis than the normal population.
Pathophysiology of Primary Biliary Cholangitis
The exact mechanism is not known and is believed to be of autoimmune origin. The autoimmune reaction causes destruction of the small and medium intrahepatic bile ducts causing disruption of the normal bile flow. This causes the retention of the bile along with the retention and deposition of toxic substances which are normally excreted into the bile.
The retained toxic substances like copper and bile acids cause further destruction of the bile ducts and liver cells.
Exogenous estrogens are thought to contribute to the development of the disease and could be because the disease is found more in females.
It is also thought that cross-reactivity between antigens on the bacterial wall and the mitochondria could cause this disease.
Complications of Primary Biliary Cholangitis
Patients of primary biliary cirrhosis can develop following complications of the disease.
- Osteoporosis
- Fat-soluble vitamin deficiency
- Due to fat digestion impairment, the vitamins are not absorbed
- Increased levels of blood cholesterol and other lipids
- Esophageal Stricture
- Issues with esophageal motility
- Reflux disease
- Causes esophagitis
- May lead to stricture
- More common in patients with CREST syndrome
- Steatorrhea- Excess fat in stools
- Poor fat digestion and absorption
- Renal tubular acidosis
- Seen in about 50% cases
- May be due to copper deposition in kidneys or autoimmune phenomenon
- Hepatocellular carcinoma
- More common in men
- Asymptomatic bacteriuria [passage of bacteria in urine]
- Other autoimmune manifestations
- Decrease in platelet count
- Hypothyroidism
- Decrease in blood sugar levels or hypoglycemia [autoantibodies against insulin receptors]
- Transverse myelitis and necrotizing myelopathy caused by vasculitis may occur.
- Xanthomatous peripheral neuropathy [due to xanthomatous infiltrates in the nerve]
Staging of Primary Biliary Cholangitis
The staging was provided by
- Stage 1 or Portal Stage
- Portal inflammation
- Bile duct abnormalities
- Both
- Stage 2 or Periportal stage
- Periportal fibrosis
- Prominent enlargement of the portal tracts
- Stage 3 or Septal stage
- Septal fibrosis
- Marks the scarring stage
- Stage 4 or Cirrhosis
- Nodules with various degrees of inflammation
Clinical Presentation
Patients are asymptomatic for a long time. About one-fourth of patients of primary biliary cholangitis are incidentally diagnosed during a routine evaluation.
Fatigue is the first reported symptom and is seen in more than two-thirds of patients. Sleep abnormalities and day time sleepiness is also reported. The symptom is not related to any stage in particular.
The cause is not clear but is thought to be due to abnormalities of the hypothalamic-pituitary-adrenal axis, increased levels of proinflammatory cytokines like IL1, IL6, and decreased release of serotonin.
Itching or pruritus is noted by more than half of the patients with a small percentage having very severe itching.
The cause of itching is not clear and appears unrelated to the deposition of bile acids in the skin.
Pain in the abdomen is noted in the small subset of patients and usually occurs in the right upper quadrant.
In the early stages, the examination findings are normal. More and more findings are noted with advancing disease which are
- Liver enlargement
- Spleen enlargement
- Increased skin pigmentation
- Jaundice (seen in about 10%)
- Fat deposition on skin [xanthomas] and eyes [xanthelasmas]
- Dry mouth and dry eyes
- Findings of cirrhosis
- Spider nevi
- Palmar erythema
- Ascites [fluid in the abdomen]
- Muscle wasting
- Peripheral edema
- Signs of portal hypertension
Lab Studies
- Liver Function Tests
- Elevated aminotransferases [alanine transferase [ALT] and aspartate aminotransferase]
- Elevated alkaline phosphatase [ALP]
- γ -glutamyl transpeptidase
- Raised immunoglobulin levels esp. IgM
- Abnormal lipid profile
- Increased cholesterol levels
- Increased lipids in blood including HDL
- Increased erythrocyte sedimentation rate
- When liver function is severely affected [cirrhosis]
- Increased bilirubin level [bad prognostic sign]
- Increased prothrombin time
- Decreased albumin level
- Decreased platelet count is indicative of portal hypertension
- Antimicrobial antibodies
- Antibodies against mitochondrial enzymes
- Found in about 95% of the patients
- Highly specific
- Antinuclear antibodies
- Found in up to half of patients
Imaging
Imaging methods are abdominal ultrasonography, CT or MRI
Earlier images are normal or consist of nonspecific findings. Periportal intensity may be noted on MRI.
Enlargement of regional lymph nodes is found in a small percentage of patients.
After cirrhosis has developed, there is a nodular appearance of the liver and findings suggestive of portal hypertension [splenomegaly, varices, ascites).
Other Procedures
A liver biopsy is required for confirmation of the diagnosis. A percutaneous or laparoscopic biopsy can be done.
Read more about Liver Biopsy-Types, Indications, and Procedure
Read more about Types of Biopsies and Their Applications
Upper GI endoscopy is done in late cirrhosis when there are varices present.
Treatment
The medical treatment at best is an attempt to slow the rate of progression of the disease and to relieve symptoms.
After the late-stage has been reached, liver transplantation is the only life-saving procedure.
Drugs
Ursodeoxycholic acid is used to slow the progression of the disease.
It delays the need for transplantation. It is not very effective after cirrhosis has set in.
Obeticholic acid is the new drug that is used along with ursodeoxycholic acid in cases with less than the desired response. It can also be used as single-drug therapy in patients who do not tolerate ursodeoxycholic acid.
Immunosuppressive agents help to control immune reactions and can contribute in delaying the progression. The agents used are methotrexate, corticosteroids, and cyclosporine.
Antihistamines [cetrizine, fexofenadine, and others] are used for control of itching. But the itching or pruritis does not respond to therapy very well.
Cholestyramine and colestipol are used to sequestrate bile salts in the intestine [so that these are not absorbed]. They seem to be effective against itching.
Rifampin can be used in patients who do not respond to the above anti-itching drugs.
In severe refractory pruritis, plasmapheresis has been found to be effective.
In late stages, especially in patients with increased bilirubin, prolonged prothrombin time, and decreased albumin levels, liver transplantation should be considered and is the only life-saving procedure.
Selfcare by Patients of Primary Biliary Cholangitis
- For itchy skin
- Use moisturizer
- Avoid dry skin
- Avoid hot showers
- For dry eyes and mouth
- Artificial tears and saliva
- Sugarless lozenges
- Sugarless gum
- Dental hygiene
- Diet
- Maintain healthy food intake
- Limit sugar and fat
- Shun alcohol as it further damages the liver
- Fatigue
- Be physically more active
- Include exercise in lifestyle
- Plan activities according to your energy levels
- Osteoporosis
- Exercise
- Eat calcium-rich diet
- Calcium and vitamin D supplementation when needed
Prognosis or Outlook
Primary biliary cholangitis is a chronic liver disease that can be slowed but not cured. The prognosis of primary biliary cholangitis has improved over the last two decades. This is due to earlier diagnosis and improved treatment.
A patient with normal biochemistry has a slow progression of the disease. About half of these would develop symptoms in about 5 years from which point the survival range is further 5-10 years.
The treatment is known to slow the progression of the disease.
The serum bilirubin level is an important prognostic marker. Another one is the Mayo risk score.
Mayo risk score is calculated by a formula that takes into account bilirubin levels, albumin levels, prothrombin time, edema and age.
A value of serum bilirubin above 2 indicates a mean survival rate of around 4 years whereas when it is more than 10, the survival is about 1.4 years.
Fatigue levels have also been considered for the purpose fo prognosis. High levels of fatigue can predict mortality or the need for liver transplantation.
References
- Solis Herruzo JA, Solis Munoz P, Munoz Yague T. The pathogenesis of primary biliary cirrhosis. Rev Esp Enferm Dig. 2009 Jun. 101(6):413-23
- Scheuer P. Primary biliary cirrhosis. Proc R Soc Med. 1967 Dec. 60(12):1257-60.
- Bjornsson E, Kalaitzakis E, Neuhauser M, et al. Fatigue measurements in patients with primary biliary cirrhosis and the risk of mortality during follow-up. Liver Int. 2010 Feb. 30(2):251-8.
- Kim WR, Lindor KD, Locke GR 3rd, et al. Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology. 2000 Dec. 119(6):1631-6.
- Liermann Garcia RF, Evangelista Garcia C, et al. Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center. Hepatology. 2001 Jan. 33(1):22-7.
- Mang FW, Michieletti P, O’Rourke K, et al. Primary biliary cirrhosis, sicca complex, and dysphagia. Dysphagia. 1997 Summer. 12(3):167-70.
- Shapiro JM, Smith H, Schaffner F. Serum bilirubin: a prognostic factor in primary biliary cirrhosis. Gut. 1979 Feb. 20(2):137-40.
- American Liver Foundation. Primary biliary cholangitis (PBC, primary biliary cirrhosis). March 29, 2016. Available at http://www.liverfoundation.org/abouttheliver/info/pbc/. Accessed: Jan 3, 2020.
