Primary biliary cirrhosis (PBC) is an inflammation with chronic and slowly progressive scarring of bile ducts in the liver. If left untreated, or if a patient does not adequately respond to treatment, chronic inflammation and fibrosis can advance to cirrhosis.
The bile ducts carry a fluid called bile from the liver to the gallbladder, where it is stored. When food enters the stomach after a meal, the gallbladder contracts, and the bile ducts carry bile to the duodenum, the first part of the small intestine, for use in digestion. The liver makes bile, which is made up of bile acids, cholesterol, fats, and fluids. Bile helps the body absorb fats, cholesterol, and fat-soluble vitamins. Bile also carries cholesterol, toxins, and waste products to the intestines, where the body removes them. When chronic inflammation, or swelling, damages the bile ducts, bile and toxic wastes build up in the liver, damaging liver tissue. This damage to the liver tissue can lead to cirrhosis, a condition in which the liver slowly deteriorates and is unable to function normally. In cirrhosis, scar tissue replaces healthy liver tissue, partially blocking the flow of blood through the liver.
The buildup of scar tissue that causes cirrhosis is usually a slow and gradual process. In the early stages of cirrhosis, the liver continues to function. However, as cirrhosis gets worse and scar tissue replaces more healthy tissue, the liver will begin to fail. Chronic liver failure, which is also called end-stage liver disease, progresses over months, years, or even decades. With end-stage liver disease, the liver can no longer perform important functions or effectively replace damaged cells.
Causes
Autoimmune System – Most research suggests the disease is an autoimmune condition. The immune system usually protects the body from harmful substances such as bacteria and viruses by attacking and destroying them. In autoimmune diseases, the immune system instead attacks the body’s own tissues. In primary biliary cirrhosis, the immune system attacks the bile ducts.
Genetic Factor – Genetic factors may make a person prone to develop primary biliary cirrhosis. Primary biliary cirrhosis is more common in people who have a parent or sibling-particularly an identical twin-with the disease. Genetic factors may also make some people prone to develop other autoimmune diseases. People with primary biliary cirrhosis may have other autoimmune conditions such as rheumatoid arthritis or autoimmune thyroiditis. A person who has genetic factors for primary biliary cirrhosis may be more likely to develop the disease after exposure to chemicals or infections, such as urinary tract infections.
Environmental Factors – Environmental factors may have a potential causative role – infection, chemicals, smoking. It may trigger or worsen the disease.
Risk Factors
PBC is most commonly diagnosed after the age of 40 years. Of patients with PBC, 90% are women. The prevalence is higher in northern European population groups and lower in Japan. Disease prevalence estimates have ranged from 40 to 400 cases per 1,000,000 population, with an incidence between 4 and 30 cases per 1,000,000 per year. In particular the following women are most at risk –
- Women who are middle aged or older
- Women who have a family history of PBC.
Symptoms
Some people with PBC will never get any symptoms of the disease. Clear symptoms of PBC are constant tiredness (for some people this can be severe) and intense itching in any part of the body. Itching, also known as pruritus, may be a result of your liver’s inability to process bile. It is thought that bile acids are not the cause of the itching but rather other chemicals that are retained in the body. As with tiredness, the severity of the itching will vary from person to person. Severity is not an indication of the amount of liver damage.
Other symptoms that may develop usually include the following –
- Dry eyes and/or dry mouth
- Constant or variable ache or discomfort in the upper right hand side, below your ribs
- Indigestion, nausea or poor appetite
- Arthritis (inflammation of the joints)
- Pain in the bones
- Mottled palms with red or pink blotches
- Diarrhoea
- Dark urine and/or stools
- Jaundice – yellowing of the skin and whites of the eyes.
Tiredness and itching are generally the first symptoms to appear while jaundice is usually associated with the later stages of the disease.
Complications
Most complications of primary biliary cirrhosis are related to cirrhosis and start after primary biliary cirrhosis progresses to cirrhosis. In some cases, portal hypertension and esophageal varices may develop before cirrhosis.
- Edema and Ascites
- Portal Hypertension
- Varices
- Splenomegaly
- Hepatic encephalopathy
- Gallstones and bile duct stones
- Metabolic bone diseases
- Liver cancer
- Steatorrhea
Treatment
Medications – Stuies suggest ursodiol (Actigall, Urso) to treat primary biliary cirrhosis. Ursodiol is a nontoxic bile acid that people can take orally. Ursodiol replaces the bile acids that are normally produced by the liver, which are more toxic and can harm the liver. Treatment with ursodiol can reduce levels of bilirubin and liver enzymes in the blood. Early treatment with this medication reduces the likelihood of needing a liver transplant and improves survival. Researchers continue to explore other drugs for treating primary biliary cirrhosis. Immunosuppressant drugs, in particular methotrexate (Trexall, Rheumatrex) and colchicine (Colcrys), have been widely used, but their effectiveness remains unproved.
Surgery – A health care provider may consider a liver transplant when cirrhosis leads to liver failure or treatment for complications is ineffective. Liver transplantation is surgery to remove a diseased or an injured liver and replace it with a healthy liver or part of a liver from another person, called a donor.
Lifestyle Changes – People with cirrhosis should not drink any alcohol or take any illegal substances, as both will cause more liver damage. People with cirrhosis should avoid complementary and alternative medications, such as herbs. People with cirrhosis should be careful about starting new medications and should consult a health care provider before taking prescription medications, over-the-counter medications, or vitamins. Many vitamins and prescription and over-the-counter medications can affect liver function.
Alternative Treatment
Vitamin B complex is a group of vitamins (B1, thiamine; B2, riboflavin; B3, niacin; B5, pantothenic acid; B6, pyridoxine; folic acid; betaine; inositol; and B12, cyanocobalamin) that differ from each other in structure and the effect they have on the human body. The B vitamins (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine) play a vital role in numerous metabolic functions including enzyme activities.
Folic acid (vitamin B4) is an important member of the B complex family, known for reducing harmful levels of homocysteine (a sulfur-containing amino acid) known to be a major culprit in heart disease. At normal levels, homocysteine plays a vital role in the biosynthesis of cysteine, which assists glutathione in the liver to detoxify carcinogens and other toxins, but without adequate methylation, which is provided by folic acid and other B vitamins, biochemical reactions generated from beneficial byproducts of homocysteine cannot occur.
Choline is another of the B complex vitamins, essential for the use of fats in the body.
Selenium is a trace element that acts by several mechanisms, including detoxifying liver enzymes, exerting anti-inflammatory effects, and providing antioxidant defense.
Zinc is used in numerous drugs and preparations that are protective: zinc oxide in skin ointments; zinc stearate in acne and eczema preparations; and zinc permanganate to treat bladder inflammation. Zinc deficiency features weakness, decreased taste and appetite, lengthy wound healing, and risk of infection. Zinc levels that are low have also been related to the progression of cirrhosis to hepatic encephalopathy.
Coenzyme Q10 (CoQ10) is an excellent antioxidant that is protective for a liver that has been damaged by ischemia (reduced blood flow). CoQ10 is also an important component of healthy metabolism.
N-acetyl-cysteine (NAC) is a substance that acts as an antioxidant or free-radical scavenger. Most scientific articles related to liver protection with NAC emphasize this effect.
S-Adenosyl Methionine (SAMe) is a methylation agent (a methyl group donor) and is necessary for the synthesis of glutathione, necessary for liver health.
Polyenylphosphatidylcholine (PC) is one of the most important substances for liver protection and health and is a primary constituent of the cell membrane. As such, PC is necessary for integrity of liver cells.
Alpha-lipoic acid is an antioxidant that has been shown to decrease the amount of hepatic fibrosis associated with liver injury. Both of these mechanisms suggest it has promise for cirrhosis.
Acetyl-L-carnitine is the biologically active form of the amino acid L-carnitine that has been shown to protect cells throughout the body from age-related degeneration. By facilitating the youthful transport of fatty acids into the cell mitochondria, acetyl-L-carnitine facilitates conversion of dietary fats to energy and muscle.
Taurine is a conditionally essential amino acid produced from cysteine by the body. It is abundantly found in the body, particularly the central nervous system where it is thought to have a regulating influence. Taurine is a crystallized acid that comes from bile, which is produced by the liver.
L-glutamine is a nonessential amino acid that has benefits for the liver and intestines, particularly for those who use NSAIDs (nonsteroidal anti-inflammatory drugs). L-glutamine may also be useful in neutralizing the effects of alcohol and strengthening the immune system.
L-arginine is an essential amino acid. L-arginine is also a key building block for repair of damaged tissue.
Branched-Chain Amino Acids are considered to be essential amino acids because humans cannot survive unless these amino acids are present in the diet. BCAAs are needed for the maintenance of muscle tissue and appear to preserve muscle stores of glycogen (stored form of carbohydrates that can be converted into energy).
Silymarin (also known as milk thistle or Silybum marinum) is a member of the aster family (Asteraceae) that has been used as a medicinal plant since ancient times and is widely used in traditional European medicine.
Reference –
http://patient.info/doctor/primary-biliary-cirrhosis-pro
https://www.aasld.org/sites/default/files/guideline_documents/PrimaryBillaryCirrhosis2009.pdf
https://www.interceptpharma.com/research-development/therapeutic-areas/primary-biliary-cirrhosis/
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=186
http://www.liver.ca/liver-disease/types/primary-biliary-cirrhosis.aspx
http://www.nhs.uk/conditions/Primary-biliary-cirrhosis/Pages/Introduction.aspx
http://emedicine.medscape.com/article/171117-overview
http://www.pbcfoundation.org.uk/about-us/services
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00154-3/fulltext?rss%3Dyes
http://www.surgery.ucsf.edu/conditions–procedures/primary-biliary-cirrhosis.aspx