Autoantibodies in Liver Disease: An Clinical Evaluation

What Are Liver Diseases?

Liver diseases are defined as dysfunction of the liver as a result of certain viral infections, exposure of the liver to various toxins, and metabolic or autoimmune disorders. The liver is titled as the largest organ of the human body. The role it plays to keep the bodily functions in check is invaluable. To sum up the major functions of the liver:

1. Filtration of the toxins and other harmful chemicals present in the blood.

2. Digestion of substrates (fats) is aided by bilirubin secreted by the liver. The bile helps in removing waste products as well.

3. Metabolism of substances (drugs) to avail easier utilization by the body.

4. Synthesizes proteins and regulates blood clotting.

5. Stores energy in the form of glycogen that is later converted into glucose as energy stores are depleted.

Liver diseases are characterized by damage to the liver function that progresses gradually over time. For ease of one’s understanding, liver diseases are divided into various stages based on their progression.

• Stage 1: Hepatitis is marked by an increase in the inflammation of the liver tissues. The inflammatory response is the body’s way of fighting an infection associated with liver damage.

• Stage 2: Fibrosis of the liver involves stiffening of the liver tissues, leading to fibrous scar tissue formation. The blood flow of the liver is severely impacted.

• Stage 3: Cirrhosis of the liver refers to the advanced fibrosis of the liver tissue that is beyond any repair. The scarring is irreversible at this stage of the liver disease.

• Stage 4: Liver failure is the end-stage liver disease, which indicates complete loss of liver function. The liver is no longer able to regenerate itself or improve its efficacy. The only way to survive is to find a new liver that can be transplanted before serious damage has been incurred to other organ systems of the body.

What Are the Symptoms of Liver Disease?

Liver diseases are asymptomatic in their early stages. The first remarkable symptom is acute hepatitis, which is an inflammatory response produced by the body. During this short phase, the body tries to fight the infection hard. This phase typically presents with abdominal pain, stomach ache, fever, and nausea. However, if the infection persists, the acute phase transits to the chronic phase of hepatitis. As the liver disease progresses, the symptoms begin to worsen. The first sign of the later-stage liver disease is disrupted bile flow. The bile produced is leaked into the bloodstream, resulting in serious complications, including jaundice, dark-colored urine, light-yellow stools, digestion issues, weight loss, fatigue, and loss of muscle mass. Other advancing liver disease symptoms include yellowish fat deposits on skin and eyes, clubbing of nails, fluid accumulation in the abdomen (ascites), edema of the hands and feet, irregular menses in females, and gynaecomastia in males.

What Causes Liver Diseases?

Several causes are reported to induce acute or chronic liver disease. Liver diseases may be incurred due to

1. Viral infections as observed in hepatitis A, B, and C virus infections.

2. Alcohol-induced liver disease as a result of chronic heavy alcohol consumption.

3. Toxic hepatitis is incurred when one is subjected to certain drugs or chemicals that may prove to be toxic to the liver tissues.

4. Metabolic-induced liver disease is precipitated by chronic conditions like obesity, high cholesterol levels in the blood, and hypertension.

5. Cardiovascular diseases that impair the flow of blood available to the liver may also result in chronic liver damage.

6. Autoimmune liver diseases that involve healthy liver tissue scarring and biliary stasis. The body's defense system is responsible for the incidence of this type of liver damage that involves the production of autoantibodies.

This article reviews the role of autoantibodies in liver diseases. It spreads some insight into major autoimmunity-mediated liver diseases like autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).

What Are Autoantibodies?

High levels of autoantibodies are present in the blood sera of a patient affected with autoimmune liver disease. Autoantibodies findings are one of the hallmarks of diagnosing immunity-mediated liver diseases. However, they may also be present in liver diseases that are not autoimmune in origin like hepatitis, alcohol-induced liver disease, and drug-induced liver disease. The autoantibodies are classified into two distinct categories:

1. Non-organ-specific autoantibodies include antinuclear antibodies (ANA), smooth muscle antibodies, antimitochondrial antibodies (AMA), and antibodies to liver-kidney microsome type-1 (LKM-1).

2. Organ-specific autoantibodies include antibodies to soluble liver antigen (SLA) and antibodies to asialoglycoprotein receptor (ASGPR).

The findings of the above-mentioned antibodies are helpful in the diagnosis of autoimmune liver disease. The three diseases discussed here are:

• Primary Biliary Cholangitis (PBC)

This disease occurs predominantly in women aged between 40 and 60. About 5 people in every 100,000 people are affected with this chronic and progressive autoimmune liver disease. PBC is characterized by inflammatory chemicals, granulomas, and damaged biliary ducts. The majority of the time, the disease advances to stage 3 and stage 4 of liver disease, namely cirrhosis and end-stage liver failure. Portal hypertension may also be observed in some cases. The presence of fatigue is a common symptom among PBC patients, accompanied by abdominal complaints and sicca syndrome (dry eyes and mouth). The autoantibodies that show sera-positive include antimitochondrial autoantibodies (AMA) and, to a certain extent, antinuclear autoantibodies (ANA). In cases with sera-negative autoantibodies, a liver biopsy can be performed to obtain a confirmed diagnosis of PBC disease.

• Autoimmune Hepatitis (AIH)

This autoimmune disease is 3 times more common in women compared to men. The clinical manifestations of the disease highly differ from one person to another, thereby making it challenging to make a timely diagnosis. General symptoms include fatigue, malaise, loss of appetite, and joint aches and pains. The AIH can be categorized into two subtypes namely AIH type 1 and type 2. Type 1 AIH is more commonly observed and is characterized by the presence of elevated levels of antinuclear autoantibodies (ANA), and smooth muscle autoantibodies (SMA). Type 2 AIH is rare and is characterized by the presence of anti-liver-kidney microsome antibodies (LKM-1).

• Primary Sclerosing Cholangitis (PSC)

This autoimmune disease is reported to affect extrahepatic and intrahepatic biliary ducts. Its incidence is recorded to be 1.5 times more in men compared to women. The people affected with PSC are found to be sera-positive for perinuclear anti-neutrophil cytoplasmic antibodies (ANCA). However, liver biopsy is considered to be the most reliable diagnostic tool for PSC disease.

Conclusion

The indication of autoantibodies may provide some insight into the type and severity of liver disease present but is not the preferred choice of diagnostic approach by many clinicians. On the other hand, a liver biopsy can provide certain confirmations on the presence of disease; however, getting a liver biopsy can prove to be a major event for some patients. Therefore, the laboratory tests carried out to confirm sera autoantibodies must be performed by an expert practitioner. The clinician and the concerned laboratory must establish a good communication platform with the patient’s well-being as the primary goal to keep in mind.