Assessing Liver Function in Detoxification: When to Order Comprehensive Liver Panels

More than 100 million people in the United States have some form of liver disease, but only 1.8% have been diagnosed. At least 80 million adults have fatty liver disease without knowing it. (29) The liver plays many crucial roles in the body, and any degree of impairment can significantly impact overall health. In this article, we will focus on the liver's critical role in detoxifying and eliminating harmful substances from the body. Interpreting comprehensive liver panels through a functional medicine lens aids in evaluating optimal liver functioning to support the body's inherent capacity to detox – without the need for expensive and (potentially) unnecessary liver cleanses. 

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The Liver's Role in Detoxification

The liver is a reddish-brown organ that weighs about three pounds and sits in the upper right abdominal quadrant, under the ribcage. The liver is responsible for over 500 vital functions, including the production of bile, proteins, and cholesterol; the conversions between glucose and glycogen to balance blood sugar; making immune factors to help the immune system protect the body against infections; and the metabolism and clearance of waste products and harmful substances from the body. 

Substances absorbed through the digestive tract are initially transported to the liver via the portal vein before entering the systemic circulation – a phenomenon called first-pass metabolism. This allows the liver to metabolize and neutralize substances before they reach other organs. It serves as a protective mechanism, preventing potentially harmful compounds from exerting their effects on the body.

The neutralization and removal of harmful substances from the body encompass a series of biochemical reactions in the liver known as detoxification or biotransformation. This process involves two main phases that transform toxins into water-soluble compounds that can be easily excreted from the body through the gastrointestinal tract and kidneys.

In Phase I biotransformation, the liver modifies the chemical structure of toxins and drugs through reduction, oxidation, or hydrolysis reactions catalyzed by cytochrome P450 (CYP450) enzymes. These reactions produce polar substances more amenable to subsequent processing. (18)

Phase II metabolism involves the addition of water-soluble molecules to the Phase I end-products through reactions like sulfation, glucuronidation, methylation, and acetylation. Phase II conjugation forms water-soluble products that can be eliminated through urine or bile. (18) 

Indicators of Liver Health

Sluggish liver metabolism and impaired detoxification processes can manifest through a spectrum of signs and symptoms. One prominent manifestation of compromised liver function is persistent fatigue. When the liver cannot efficiently process toxins, this leads to an accumulation of harmful substances that can contribute to feelings of exhaustion and lethargy. Additionally, individuals with suboptimal liver function may experience digestive issues such as bloating, constipation, diarrhea, nausea, and loss of appetite.

The skin is an often forgotten organ that supports elimination through sweating. In cases where the liver is not functioning optimally, the body will compensate by eliminating more toxins through sweat. This can cause increased body odor and skin conditions like acne, eczema, or other rashes.

Hormonal imbalances can be associated with liver dysfunction because the liver plays an important role in metabolizing excess hormones to be eliminated from the body. Irregular menstrual cycles, premenstrual syndrome (PMS), and other signs and symptoms of hormonal imbalance may signal an impaired liver's ability to metabolize hormones effectively.

The liver influences emotional and cognitive health through the multidirectional communication network between the gut, liver, and brain – collectively known as the gut-liver-brain axis. Cognitive impairments, such as dementia and hepatic encephalopathy, can be observed in overt liver disease. However, milder forms of brain fog, difficulty concentrating, and mood swings may occur with toxic overload related to slow liver detoxification. (52)

Individuals with sluggish liver metabolism may also exhibit sensitivity to environmental factors, such as strong odors, chemical exposures, and alcohol, as the liver's detoxification capacity may be insufficient to handle external toxins adequately.

Understanding Comprehensive Liver Panels

Comprehensive liver panels, like the Hepatic Function Panel by Access Med Labs, analyze blood samples for enzymes and proteins that reflect liver health and functioning. Below are some of the biomarkers most commonly used to assess liver function.

Aspartate Amiontransferase (AST)

AST is an enzyme in the liver, heart, pancreas, muscles, and other tissues that assists in the breakdown of amino acids. When cells are damaged, AST can leak into the bloodstream, and levels will increase.

Alanine Aminotransferase (ALT)

ALT is an enzyme in the liver that helps convert proteins into energy for liver cells. When the liver is damaged, ALT is released into the bloodstream, and blood levels increase. Because ALT mainly exists in the liver, it is a more specific indicator of liver conditions that elevated AST levels. 

Alkaline Phosphatase (ALP)

ALP is an enzyme primarily in the liver but also in the bile duct, bones, kidneys, intestines, and placenta. Elevated ALP can indicate hepatobiliary dysfunction, bone disorders, and other metabolic conditions. When ALP is high, your doctor will likely order an ALP isoenzyme test to determine where excess ALP originates. 

Proteins

Total protein measures the total amount of two classes of proteins found in blood. Albumin is one protein class critical in maintaining fluid balance and transporting vitamins, enzymes, and hormones through the blood. Globulins comprise 40% of proteins in the blood and play an important role in immunity. Low levels of total protein, albumin, and globulin can indicate a problem in liver, kidney, and gastrointestinal function. 

Total Bilirubin

Bilirubin is the waste product formed during the breakdown of red blood cells. Unconjugated (indirect) bilirubin is carried to the liver for processing. The liver converts unconjugated bilirubin to conjugated (direct) bilirubin, which can be mixed in bile to be eliminated from the body through stool. High levels of bilirubin can indicate liver dysfunction. 

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When to Order Comprehensive Liver Panels

Ordering comprehensive liver panels is a clinical decision informed by various criteria and conditions, serving as a diagnostic and monitoring tool in diverse medical contexts. The rationale for requesting these panels is rooted in the need to assess liver health, detect potential disorders, and guide appropriate interventions.

The primary indication for ordering a liver panel is the suspicion of liver disease through clinical manifestations such as unexplained fatigue, abdominal pain and swelling, jaundice, edema, itchy skin, pale stools, easy bruising, and nausea or vomiting. Abnormal liver function tests on a screening test, such as a comprehensive metabolic panel (CMP), may also prompt healthcare providers to investigate liver health more thoroughly.

Individuals with pre-existing liver conditions, such as hepatitis, non-alcoholic fatty liver disease (NAFLD), cirrhosis, or autoimmune liver disorders, require regular monitoring of liver function. Depending on the severity and stability of the disease, repeat testing is generally recommended at intervals of every three months to one year. Comprehensive liver panels thoroughly assess biomarkers, enabling healthcare providers to gauge disease progression, treatment efficacy, and overall liver health. Certain medications, including those for chronic conditions or specific therapies, may have hepatotoxic effects. Monitoring liver function in patients taking these medications is essential to identify early signs of drug-induced liver injury and adjust treatment plans accordingly.

In functional medicine, liver panels are often ordered, even in the absence of overt liver disease, to assess liver capacity as it pertains to whole-body health. This is particularly relevant for individuals with symptoms related to environmental toxin exposure, hormonal imbalances, digestive dysfunction, and skin conditions.

Interpreting Liver Panel Results

Interpreting liver panel results is a nuanced process that requires a comprehensive understanding of normal ranges, recognizing patterns, and discerning the implications of abnormal findings. Healthcare professionals, alternative medicine practitioners, and those in functional medicine are trained to detect trends in liver panel results indicative of the liver needing additional support.

Familiarity with normal reference ranges for each biomarker in the liver panel is essential to understand what constitutes normal and abnormal levels. While normal reference ranges may vary slightly between different laboratories, the table below outlines the general normal ranges for the key liver markers discussed above.

Deviations from these ranges can signify potential issues. Elevations in ALT, AST, and ALP may point to hepatocellular and biliary injury and inflammation. Elevated total bilirubin can result from liver dysfunction or hemolysis (red blood cell destruction). Doctors will order direct and indirect bilirubin as follow-up tests to pinpoint the source of the problem. Decreased total protein, albumin, and globulin levels may suggest impaired liver synthetic function or malnutrition. 

In addition to interpreting these biomarkers independently from one another, it's important to look for patterns between them. For example, the AST/ALT ratio is often used as a clue to the etiology of underlying liver dysfunction. An AST/ALT ratio greater than 2 is indicative of alcoholic liver disease, whereas a ratio less than 1 is suggestive of hepatitis and cholestatic syndromes. (1)

Functional providers will utilize a narrower reference scale to differentiate between "normal" and "healthy." Standard reference ranges are based on current percentiles based on the average population. As the population becomes less healthy, averages may diverge from optimal levels. For example, concerning ALT, a 2002 study concluded that the upper limits of normal for ALT should be 30 U/L for men and 19 U/L for women. Keeping these optimal reference ranges in mind, functional medicine providers can more easily detect functional deviations from normal liver function and intervene at earlier stages to prevent the development of frank liver pathology and disease.

Results that fall outside of the standard reference range warrant additional testing to confirm and diagnose the cause of liver injury. Further testing may be performed to rule out viral hepatitis (Hep A, B, C Ab Panel w/ Reflex by Access Med Labs), iron overload, Wilson's disease (Ceruloplasmin by DHA Lab), autoimmune disorders (Autoimmune Liver Disease Panel by Immunosciences Lab, Inc.), alpha-1 antitrypsin deficiency, or hepatocellular carcinoma (AFP by Access Med Labs). A referral to a hepatologist or gastroenterologist may be prudent for specialized evaluation and management. (53)

In regards to assessing liver detoxification pathways, specialty labs can measure specific markers that can provide information about exposure to chemicals, liver disease, and the ability of the liver to eliminate toxins. The Hepatic Detox Profile by Doctor's Data measures mercapturic acid and D-glucaric acid, which reflect the body's exposure to xenobiotics and the liver's capacity to convert and eliminate them.

Advanced Liver Testing and Technologies

Advanced liver imaging technologies offer a more nuanced and detailed assessment of liver health than serum biomarkers. These advanced approaches are crucial in diagnosing specific liver conditions, evaluating disease severity, and guiding personalized treatment strategies. Healthcare professionals, including those in alternative and functional medicine, leverage these technologies to enhance their understanding of liver pathology.

Liver ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are the primary imaging modalities to visualize the liver. Ultrasound is a non-invasive imaging technique that helps assess liver size, detect gross abnormalities, and identify conditions such as fatty liver disease, tumors, or cysts. CT offers detailed cross-sectional images, aiding in the evaluation of liver structure and blood vessels and the identification of lesions. MRI provides high-resolution images, which are particularly beneficial for assessing liver tissue and blood flow. (12)

The gold-standard method for evaluating the presence of inflammatory and fibrotic changes within the liver is a liver biopsy. However, less invasive technologies have been developed to test for liver fibrosis. The first is ultrasound elastography, which measures movement caused by ultrasound waves as an indicator of fibrosis. MR elastography (MRE) utilizes MRI technology to create a visual map that shows the stiffness across the liver and provides information on the degree of fibrosis present. (12) 

Integrating Liver Health in Detoxification Strategies

Liver health is profoundly influenced by various lifestyle factors and conditions, encompassing dietary choices, alcohol consumption, and exposure to toxins. A balanced and health-conscious approach is crucial for maintaining optimal liver function. Dietary habits significantly impact liver health, with excessive consumption of processed foods, high-fat diets, and added sugars contributing to conditions like NAFLD. Moderate alcohol intake is generally manageable for the liver, but excessive or chronic alcohol consumption can lead to alcohol-related liver disease (ALRD), causing inflammation and liver damage. Exposure to other toxins, such as pollutants, pesticides, and industrial chemicals, also risks liver health. 

A holistic lifestyle approach that emphasizes eating a nutrient-rich diet, maintaining a healthy weight, practicing moderate alcohol consumption, and minimizing exposure to environmental toxins can go a long way in supporting optimal liver health and preventing liver dysfunction. Studies show that the following foods and supplements can promote the function of the liver's detoxification enzymes:

• Cruciferous vegetables (e.g., broccoli, Brussels sprouts, kale)
• Allium vegetables (e.g., onions, garlic, leeks)
• Apiaceous vegetables (e.g., carrots, celery, parsley)
• Grapefruit
• Resveratrol
• Fish oil
• Quercetin
• Lycopene

Certain herbs, such as milk thistle, turmeric, dandelion root, and artichoke, are also heavily backed by research as being hepatoprotective, anti-inflammatory, and supportive of detoxification pathways.

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Comprehensive Liver Panels for Detoxification: Key Takeaways

Using comprehensive liver panels to thoroughly evaluate biomarkers indicative of the liver's capacity for effective detoxification is an important aspect of functional medicine. These panels, encompassing various enzymes and proteins, offer valuable insights into liver health, aiding in the early detection of abnormalities and potential disorders. Emphasizing a proactive approach to liver health, regular monitoring through comprehensive panels becomes pivotal for maintaining optimal detoxification capacity. By understanding and addressing liver function early on, healthcare professionals and individuals can implement targeted interventions, lifestyle modifications, and personalized strategies to optimize the liver's role in detoxification, contributing to holistic well-being and the prevention of long-term health implications. Regular assessments thus form a cornerstone in the proactive management of liver health and the preservation of effective detoxification mechanisms.