An Integrative Medicine Approach to Primary Biliary Cholangitis

With primary biliary cholangitis, your bile ducts in the liver are slowly destroyed by an autoimmune process. This chronic inflammatory disease gradually injures the small bile ducts in your liver so that bile builds up and causes liver damage.

Although people of all sexes, ethnicities, and races are impacted, around the globe, this condition is most common in Scotland, Scandinavia,,and North East England. Primary biliary cholangitis usually begins before age 40 with a peak onset between 60 and 79 years old and is most common in females with a female-to-male ratio around 4–6:1.

Although the consequences of primary biliary cholangitis can be serious if left untreated, there are management options you can use to help address the disease and prevent liver problems. An integrative approach to primary biliary cholangitis looks at underlying factors contributing to inflammation and disease and works to bring greater balance to the body through diet, supplementation, and lifestyle changes. 

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What is Primary Biliary Cholangitis (PBC)?

Your liver sits in the upper right-hand corner of your abdomen and plays many important roles in keeping the body functioning. For example, the liver is responsible for detoxifying substances from the blood, making proteins that help to regular blood clotting, breaking down hemoglobin and storing iron from it, creating cholesterol and other proteins that transport fat throughout the body, storing and converting glucose into its storage form glycogen, helping the immune system function, and creating bile aids to help with the breakdown of dietary fat and removal of waste. 

The liver makes bile as it filters the blood and removes wastes like excess cholesterol and bilirubin from breaking down red blood cells, potassium, sodium, copper, and other metals, and water, and combines these waste products with bile salts. The liver then sends the bile to the gallbladder, which sits beneath the liver via a series of bile ducts. There, the bile is concentrated and stored until it is released into the small intestine to help with digestion.

With primary biliary cholangitis (formerly known as primary biliary cirrhosis), the body starts to attack the bile ducts running through the liver due to an autoimmune process. Over time, this creates excess inflammation that slowly degrades and scars the bile ducts within the liver (intrahepatic bile ducts). This makes it harder and harder for bile to flow through them so that bile fluid begins to back up into the liver and damage the liver tissue. Over time, scarring occurs in the liver and it gradually loses its ability to function normally causing cirrhosis of the liver. 

Early on in the process, you may not notice many symptoms of primary biliary cholangitis. But as the disease progresses, signs and symptoms of biliary disease begin to occur including fatigue, yellowing skin (jaundice), and itchy skin. These symptoms occur when the blocked bile begins to leak into your bloodstream and cannot reach your digestive system where it is needed to aid in fat digestion. Without enough bile to break down and absorb fats, you can experience fat malabsorption that causes diarrhea, elevated cholesterol, fat deposits under your skin (lipomas), weight loss, low levels of fat-soluble vitamins A, D, E, and K, and weakened bones with an elevated risk of osteopenia and osteoporosis from the failure to absorb fat-soluble vitamin D.

Once the spilled over bile damages and scars the liver too much, it can also impact the blood vessels that pass through the liver causing portal hypertension. High pressure in these veins can cause an enlarged liver and spleen, more frequent infections, easy bleeding and bruising, spider angiomas, swollen veins (varices), bleeding in the gastrointestinal tract, swelling in the legs and ankles (edema), and fluid building up in the abdomen (ascites). 

There are several contributing factors and causes of primary biliary cholangitis. Primary biliary cholangitis is an autoimmune condition where the immune system mounts a mistaken attack against the body’s own tissues instead of its usual targets of foreign substances and microbes. In this condition, the body produces anti-mitochondrial antibodies targeted against lipoic acids found in the dehydrogenase complex from the inner mitochondrial membrane of the bile ducts that result in white blood cells (T-cell lymphocytes) creating inflammation that contributes to the destruction of the bile ducts over time. 

Many factors contribute to the development of autoimmune diseases like primary biliary cholangitis including environmental exposures in people who have genetic susceptibility. Infections, such as those of the urinary tract, smoking, and toxic chemicals may all play a role. People with a family history of the disease are more likely to develop primary biliary cholangitis. 

Importance of Lab Testing in Integrative Medicine for PBC

Functional medicine laboratory testing can help uncover underlying factors contributing to the autoimmunity and chronic inflammation that causes primary biliary cholangitis. Testing can be used to monitor primary biliary cholangitis holistically and to help create an individualized management approach. 

Antibody Testing

The majority of patients with primary biliary cholangitis have antimitochondrial antibodies (AMA) in their blood. These antibodies are highly specific for primary biliary cholangitis, so a positive AMA in patients with cholestasis is sufficient for a diagnosis without a liver biopsy.

The Autoimmune Liver Disease Panel can be used to evaluate for the presence of AMA.

Liver Function Testing

A Hepatic Function Panel can be used to evaluate liver function markers. This can help monitor disease progression and response to treatment. 

Patients with primary biliary cholangitis typically have elevated levels of liver enzymes that indicate liver stress and damage, especially alkaline phosphatase.

Comprehensive Stool Test

A key factor in the autoimmunity underlying primary biliary cholangitis seems to be an imbalance in the microbes in the gut and a leaky gut barrier. Your gut microbiome is composed of trillions of microbes that interact with your immune system and regulate metabolic and other processes that have impacts all over your body. The gut communicates with and impacts the liver via the liver-gut axis with the liver receiving almost 75% of its blood supply from the intestine via the portal vein. 

This means that the liver is exposed to and has to process products that enter the gut, such as food, bacteria, chemicals, and their metabolites so diet, microbes, microbial metabolites, and bile acids all influence immunity and function of the gut and liver. If the gut barrier is disturbed and leaky gut develops, these substances can burden the liver and trigger the immune system to create excess inflammation and autoimmunity that occur in primary biliary cholangitis.  

Comprehensive stool testing can help provide an evaluation of some of the common underlying contributors of autoimmunity. The GI-MAP with Zonulin from Diagnostic Solutions provides insights into microbial imbalances, inflammation, digestion, immune function, and zonulin, a marker associated with a leaky gut.

Micronutrient Testing

Without enough bile entering the digestive tract, you cannot properly absorb fats and the fat-soluble vitamins, A, D, E, and K. These and other nutrients can be evaluated using a Micronutrients Panel.

Cholesterol Testing

Since high cholesterol is very common in primary biliary cholangitis, a Lipid Panel can help evaluate cholesterol balance. This test measures total cholesterol, HDL (“good” cholesterol), LDL (“bad” cholesterol), and triglycerides to assess fats in the blood. 

Additional Testing

In addition to blood testing to look at liver function and antimitochondrial antibodies, imaging of the liver and biliary system and/or a liver biopsy can help confirm the diagnosis of primary biliary cholangitis and assess the extent of liver damage. An abdominal ultrasound or magnetic resonance imaging (MRI) can be used to look at the structure of the biliary system and liver. 

If AMA testing is negative but symptoms are highly suggestive of primary biliary cholangitis, a liver biopsy can help confirm the diagnosis. This can usually be done at the bedside using a needle to extract a small tissue sample of the liver to examine under a microscope.

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Conventional Treatments for PBC

Conventionally, primary biliary cholangitis is treated with bile salts. For example,  ursodeoxycholic acid (UDCA), known as ursodiol (Actigall, Urso), is usually the first choice of a bile salt used to help clear bile from the liver and reduce liver damage. If no benefit is derived from UDCA treatment, a different bile salt called obeticholic acid (Ocaliva) is sometimes used.

In addition, symptoms of primary biliary cholangitis are targeted. For example, antihistamines such as diphenhydramine (Benadryl® or Aler-Dryl®), ultraviolet light therapy, or bile acid sequestrants like cholestyramine may be used to address itching. In some cases, fibrates (Tricor) are added to UDCA to reduce itching and liver inflammation. 

If primary biliary cholangitis does not respond to conventional medication and advanced scarring of the liver occurs, a liver transplant may be needed.

In addition to these traditional treatments for primary biliary cholangitis, managing potential complications is an important part of the treatment approach. Depending on the individual, supplementation for vitamin deficiencies, medications and/or lifestyle changes to address cholesterol, and weight-bearing exercise and vitamin D supplementation for osteopenia and osteoporosis may be valuable. 

Integrative Medicine Perspective on PBC

To help prevent progression and reduce inflammation, diet, supplementation, and integrative therapies can be used to adopt a whole-person approach. An integrative functional medicine approach looks at the individual and factors contributing to her health from many aspects. Not only does this help to support liver functioning by balancing liver-gut communication and reducing the inflammation and autoimmunity that occur in primary biliary cholangitis but it also helps the entire body come into better balance. 

Nutritional Recommendations

Since primary biliary cholangitis involves an autoimmune attack on the body, an anti-inflammatory diet can help reduce autoimmunity and balance inflammation. One anti-inflammatory way of eating that emphasizes nutrient-dense foods like whole fresh fruits and vegetables, fatty fish, and olive oil is the Mediterranean diet. This way of eating also avoids processed meats, sweets, sugary beverages, inflammatory fats, refined grains, and excess alcohol which has been shown to reduce inflammation and improve liver health. 

Since this type of liver disease can make you more susceptible to infection, avoid eating raw shellfish like oysters, undercooked fish and meat, and unpasteurized milk that can carry infection-causing bacteria.

To reduce the strain on your liver, avoid drinking alcohol or smoking. 

The Emotional Impact On Liver Disease

Many psychological and emotional factors impact the quality of life of people with liver disease. Studies show that an individual's perception of their physical, cognitive, emotional, and social functioning (Health-related quality of life (HRQOL)) can be strongly impacted by disease severity as well as accompanying stress, depression, and anxiety. 

Stress and the resulting physiologic impacts, such as increased cortisol, oxidative stress, and immune dysfunction, cause downstream effects that impact the mind, brain, and liver. For example, stress and psychological strain can impact inflammation and immune function via changes in the gut microbiome that also increase the risk of liver dysfunction. Therefore, addressing the whole person, including emotional and psychological health, not only improves liver outcomes but also recognizes the person beyond her disease. 

Natural and Alternative Treatments for PBC

An individualized supplementation regimen can help restore deficient nutrient levels, heal the gut, and complement the balancing of inflammation with an anti-inflammatory diet. Beneficial supplements for liver health include milk thistle, curcumin, saliva, probiotics, and vitamin D. In addition, traditional therapies can be used to improve liver function and bring greater balance to the body.

Beneficial Supplements For Liver Health

Here are some beneficial evidenced-based supplements for liver health:

Milk Thistle (Silybum marianum)

Milk thistle has a long history of use as a traditional remedy for liver conditions, which has immunomodulatory, antioxidant, and antifibrotic effects. Studies suggest that this herb, taken at a dose of 140 mg three times daily for one year, can help stop the progression of primary biliary cholangitis and improve liver function markers in the blood. 

Curcuma longa (Turmeric)

Curcumin is derived from turmeric and has well-studied anti-inflammatory properties. It has been shown to reduce bile duct injury and biliary fibrosis. 

Salvia miltiorrhiza

Salvia miltiorrhiza is a traditional Chinese herbal remedy that has been studied for its ability to reduce liver inflammation and fibrosis. The herb is known as red sage and has a long history of use in traditional medicines to reduce inflammation and address chronic inflammatory conditions.

Probiotics

Probiotic supplementation can help to restore a healthy balance of gut microbes and heal the intestinal barrier, providing an anti-inflammatory benefit in the gut and beyond. In particular, probiotics decrease bacterial toxins such as lipopolysaccharides (LPS) crossing from the gut to the liver which reduces the toxic burden on the liver and the immune system and lowers inflammation.

Probiotic supplementation may even benefit those with later-stage liver damage. Studies suggest that six weeks of oral probiotics increased blood flow through the liver and portal vein to improve symptoms of cirrhosis.

Vitamin D

Patients with primary biliary cholangitis are prone to develop deficiencies of fat-soluble vitamins like vitamin D which is associated with permeability of the intestinal barrier and autoimmunity. If testing shows that levels are insufficient, supplementation can be used to restore levels to an optimal range to improve immune function, decrease markers of intestinal permeability, and reduce liver fibrosis.

Complementary Therapies for Liver Health

Integrating complementary therapies and lifestyle measures into a treatment plan for primary biliary cholangitis can help improve liver, gut, and overall health and improve quality of life. 

Acupuncture

Traditional Chinese medicine has been traditionally used to address a variety of hepatic diseases including cirrhosis. Acupuncture involves inserting small needles at specific points to help balance the flow of qi and the body. Studies show that acupuncture at specific acupoints benefits patients with liver diseases like cirrhosis without toxicity or adverse reactions.

Adequate Rest and Managing Stress

Since leaky gut is a key factor that can trigger the autoimmunity underlying primary biliary cholangitis and chronic stress can worsen leaky gut, finding a meaningful stress management practice can be beneficial. Mind-body approaches such as yoga, meditation, prayer, time in nature, and breathwork can all help you manage stress and shift the body into a rest-and-digest mode. It is also crucial to get adequate daily sleep with at least a full 7-9 hours a night.

Exercise and Move Regularly

Regular moderate exercise can help maintain bone health and decrease excess inflammation. In addition, exercise that is not overly intense has also been shown to improve intestinal permeability.

Future Research in Integrative Medicine for PBC

While UDCA has been the first-line treatment for primary biliary cholangitis, up to 40% of patients do not have an adequate response after one year of therapy. As the science expands, new innovations in primary biliary cholangitis are emerging. Fibrates are commonly used to treat high blood lipids and work by targeting various peroxisome proliferator-activated receptors (PPAR). Since the PPARα receptor leads to activation of genes involved in bile acid and downregulation of genes involved in immune-related pathways that have anti-inflammatory and anti-fibrotic impacts, fibrates have been evaluated as a treatment for primary biliary cholangitis. Additional PPAR agonists are also in development that show promise in improving biliary and liver health with fewer side effects than fibrates. 

Another important pathophysiological pathway understudy involves nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase (NOX) 1 and NOX4. These enzymes are involved in the generation of oxidative stress that results in the death of liver cells and development of liver fibrosis that occurs in cirrhosis. For example, Setanaxib is a NOX1 and NOX4 inhibitor being evaluated for primary biliary cholangitis which shows promise for improving markers of cholestasis, inflammation, and liver fibrosis.

First-generation non-steroidal farnesoid X receptor (FXR) agonists like obeticholic acid have unpredictable metabolism and undesirable side effects such as pruritus, so second-generation FXR  agonists like tropifexor (LJN452), cilofexor (GS-9674), and EDP-305 are also under study as new treatments for primary biliary cholangitis. These are more selective and restrictive of FXR activation with more predictable pharmacokinetics. 

The science behind the pathogenesis of primary biliary cholangitis continues to expand, with studies identifying approximately 70 susceptibility gene loci that may contribute to disease. Areas of genetic focus that have been identified and are under study for developing new targeted therapies include antigen presentation by human leukocyte antigens, responses to tumor necrosis factor, effects of interleukin-12-related pathways, and B cell activation, maturation, and differentiation pathways.

Looking holistically at the whole person, mindfulness-based programs have been shown to benefit many chronic conditions, including helping to reduce stress, fatigue, and liver-related inflammation. A four- to eight-week mindfulness stress reduction program seems to improve mood and depression, increase sleep quality, and improve overall quality of life for both patients and caregivers with cirrhosis and has also been shown to improve inflammation, stress, and quality of life in autoimmune hepatitis. 

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Key Takeaways of The Integrative Medicine Approach to Primary Biliary Cholangitis

Chronic biliary cholangitis is a chronic inflammatory disease that causes scarring to the bile ducts that run through your liver to carry bile to the gallbladder. When your bile ducts are inflamed and become scarred, they get narrow and distorted, blocking the flow of bile. Bile then backs up into your liver where it damages the tissue and causes inflammation and eventually scarring or cirrhosis.

This autoimmune condition is marked by the presence of antimitochondrial antibodies that target bile ducts. Liver function testing can also help track the progress of disease and treatment impact. 

An integrative approach incorporates an anti-inflammatory diet, individualized supplementation, and integrative therapies to help reduce this autoimmunity and the resulting inflammation, rebalance the gut, and help the liver function more optimally. This patient-centered comprehensive approach tailors treatment to each person and addresses her whole self, looking at psychological, emotional, lifestyle, and physical aspects of well-being. When used in combination with conventional treatment approaches, this partnership of care provides a well-rounded approach to improving outcomes and quality of life.