Drugs and Liver Disease
The Function of the Liver
The liver plays an extremely important role in the body. It ensures the removal of toxins and has numerous other functions, including:
- Fat metabolism: The liver cells — or hepatocytes — are able to process dietary and stored fats into energy. In addition, the liver acts as a key player in our exocrine systems by producing bile acids, which are secreted into our digestive tracts. There, they function to break down and facilitate the intestinal absorption of fats that we consume in our diet. Supplementing this activity, the liver also synthesizes cholesterol to aid in fat transport.
- Carbohydrate metabolism: The liver helps to regulate blood sugar by utilizing stored glycogen when glucose levels are low and removing it from the blood when levels are high.
- Protein metabolism: The liver breaks down proteins and converts amino acids into useable energy, or further processes them into needed macronutrients. Ammonia is a toxic byproduct of this process. As ammonia builds, the liver further modifies it into a chemical known as urea, which travels through the circulation to the kidneys, where it is safely released in urine.
Further functions of the liver include 1,2:
- Producing circulating proteins that help blood clot normally.
- Breaking down old blood cells.
- Processing the hemoglobin protein found in red blood cells in order to salvage/recycle the iron that it contains.
- Storing minerals (such as iron) and vitamins to release when necessary.
- Removing bacteria and other foreign bodies from the bloodstream.
- Eliminating excess bilirubin, a component released from red blood cells that are damaged or otherwise at the end of their lifecycle which can be harmful to the body and brain.
How the Liver Metabolizes Drugs
When blood enters the liver via the portal vein, it carries nutrients as well as drugs and other toxic substances the individual may have consumed 1. The liver’s job is to detoxify these drugs and remove the byproducts resulting from the process of metabolism 1.
The majority of drugs are fat-soluble, meaning that they are difficult to pass in urine. The enzymes in the liver work to break down these substances and convert them into water-soluble forms, which can then pass in bile and/or urine.
A hepatocyte, or liver cell, contains several sub-cellular organelles that serve as the primary sites of drug metabolism. Additionally, there are dozens of hepatic enzymes that contribute to a complicated chain of events that eventually result in the breakdown of drugs (and other liver toxins).
Not everyone metabolizes drugs at the same rate. Different genetic and physiological characteristics can influence the speed at which an individual metabolizes a drug. A few influential factors are as follows:
- Inherited enzyme structure.
- The flow of substances from the liver to the bile.
- Microorganisms present in the gut.
- Overall nutrition.
Certain medical conditions can slow drug metabolism. These include:
- Kidney disease.
- Shock (reduction in systemic blood flow).
- Heart failure.
- Liver disease.
Even different drugs themselves can alter the rate of metabolism; some drugs fall into the class of enzyme inducers, which boost metabolism, while others are classified as enzyme inhibitors, which reduce the speed in which a drug is broken down.
In many cases, the liver is able to metabolize drugs (and other toxins) without significant damage to the organ itself. However, when persistent detoxifying demands are made of the hepatic system – for example, when drugs are taken in excess, when the frequency of drug use is on the order of daily or hourly, or when multiple substances are consumed simultaneously – drugs can cause significant, cumulative damage to the liver.
Drug-Induced Liver Injury (DILI)
While some drugs, such as acetaminophen (also known as Tylenol), elicit predictable and dose-dependent effects on the liver, others may have unforeseeable results, oftentimes unrelated to dose 3. DILI typically occurs within three months of beginning the drug, but it can vary from a couple hours to a year after drug initiation 4.
One example of DILI is drug-induced hepatitis, which is characterized by inflammation of the liver 5. This condition can be caused by a number of different drugs. Below are just a few of the many medications that can cause drug-induced hepatitis 5:
- Acetaminophen (often contained in fever reducers and painkillers like Percocet and Vicodin).
- Nonsteroidal anti-inflammatory drugs:
- Birth control pills.
- Anabolic steroids.
These drugs, among others, can cause drug-induced hepatitis even in moderate doses. It’s important that you take your medication exactly as prescribed and avoid drinking alcohol while taking it 5.
If you have drug-induced hepatitis or any other drug-induced liver damage, your physician will likely tell you to stop taking the medication immediately 5. The symptoms usually dissipate once the individual stops taking the drug, although medical treatment may be necessary in cases of excessive acetaminophen consumption 5.
Factors that Raise Your Risk of DILI
A few risk factors that increase a person’s chance of experiencing drug-induced liver injury include 3, 6:
- Drinking alcohol.
- Being 18 years of age or older.
- Genes that affect a user’s response to drugs.
- Other diseases, such as HIV or liver disease.
- Illicit drug abuse.
- Taking medication or drugs in excess.
- Combining drugs and/or alcohol.
When your doctor prescribes you a medication that is known to cause liver damage, you will want to make sure to tell him or her what other medications you’re on in the case of possible drug interactions.
Alcohol and the Liver
When alcohol reaches the liver, it is broken down and excreted through the urine. This process produces many harmful by-products, such as free radicals and acetaldehyde, that may play a part in liver toxicity 8. If consumed in moderation, the liver typically has no problem with alcohol metabolism, but chronic and long-term alcohol abuse can lead to significant liver damage 8.
Two major conditions caused by excessive alcohol consumption are cirrhosis and alcoholic hepatitis.
Cirrhosis is characterized by scarring of the liver, which blocks the flow of bile and blood and inhibits proper functioning. The harm caused by cirrhosis of the liver is irreversible, but early detection can prevent further damage 9.
Some signs and symptoms of cirrhosis include 9:
- Redness of palms.
- Mental confusion.
- Hand tremor (asterixis).
- Jaundice (yellowing of skin and eyes).
- Weight loss.
- Abdomen swelling (peritoneal ascites).
- Swelling of limbs (peripheral edema).
- Generalized edema (anasarca).
Alcoholic hepatitis, which is often seen in heavy drinkers, often co-occurs with cirrhosis 10 and is most often seen in people between the ages of 40 and 60-years-old 11. Alcoholic hepatitis is fatal in approximately 30-50% of those affected by the disease 11.
Some signs and symptoms of alcoholic hepatitis are 10:
- Enlarged liver.
- Rapid heart rate.
- Pain in right upper quadrant (abdominal region below right ribcage).
Individuals with alcoholic hepatitis may have a variant of the disease called alcoholic steatohepatitis, which presents as pathological fat accumulation in the liver. It is caused by an increased production of fatty acids due to poor nutrition 12.
Severe forms of alcoholic hepatitis may lead to the following complications 10:
- Portal hypertension (high blood pressure in the liver’s major vein).
- Deficient clotting mechanisms leading to bleeding issues.
- Kidney failure.
- Hepatic encephalopathy (brain dysfunction due to liver damage and accumulation of toxins in the blood).
Individuals afflicted with alcoholic hepatitis are more vulnerable to infections, such as 10:
- Bacterial peritonitis.
- Bacterial pneumonia.
- Urinary tract infections
Although not actually caused by alcohol use, hepatitis C, which is an infection leading to liver inflammation 20, is very common among those who abuse alcohol 19. Chronic hepatitis C that goes untreated can lead to liver damage and liver cancer 20.
When combined with heavy alcohol intake, the amount of harm done to the liver is compounded 19. Those with hepatitis C that consume alcohol have an increased risk of developing liver disease and cirrhosis 19. For this reason, patients who are diagnosed with hepatitis C should abstain from drinking any alcohol.
Drugs that Can Damage the Liver
There are certain drugs and drug classes that have a higher likelihood of damaging the liver. These substances include 3, 5, 7:
- Tetracyclines (doxycycline, minocycline, tetracycline).
- Statins (treats high cholesterol).
- Halothane (anesthetic).
- Birth control pills.
Supplements and herbs (Can lack thorough testing and are not tightly regulated)
- Comfrey tea.
- Excess vitamin A and iron.
- Pyrrolizidine alkaloids.
- Camellia sinensis (in black and green tea).
- Pennyroyal oil (used in production of teas).
Over the counter pain-relievers:
- Nonsteroidal anti-inflammatory drugs:
- Anabolic steroids.
Symptoms of Liver Damage
If you or someone you love may be at risk of substance induced hepatic injury, it is vital that you be aware of the signs and symptoms of liver damage so that you can seek medical attention immediately.
Symptoms of liver damage include 5, 18:
- Dark Urine.
- Pain in the abdomen.
- White stools.
- Build-up of fluid in the abdominal cavity.
- Jaundice (yellowing of eyes and skin).
- Enlarged liver.
- Weight loss.
- Loss of appetite.
Preventing Liver Damage
There are many different things you can do in order to prevent liver damage. Be mindful of the following tips 5, 7:
- Don’t take more than the recommended dose of acetaminophen or other non-prescription medications.
- Don’t take the maximum recommended dose for an extended period of time.
- Follow your doctor’s prescribing instructions carefully.
- Avoid drinking alcohol while taking medication.
- Inform your physician of the drugs and supplements that you are currently taking.
- If you suffer from liver disease, avoid taking drugs containing acetaminophen or phenytoin (Dilantin), and consult with your doctor about any other contraindicated pharmaceuticals.
- If you abuse drugs or alcohol, seek addiction treatment to help you get clean.
- U.S. National Library of Medicine. (2015). How does the liver work?
- University of Rochester Medical Center. (2016, May 05). Retrieved May 05, 2016, from https://www.urmc.rochester.edu/Encyclopedia/Content.aspx?ContentTypeID=85
- Herrine, S. K. (n.d.). Effects of Drugs on the Liver.
- The most common period of appearance of DILI is within the first three months of starting the drug5 , although the latency period can vary from a few hours to as long as up to a year
- MedlinePlus. (2014). Drug-induced hepatitis: MedlinePlus Medical Encyclopedia.
- Chalasani, N., & Björnsson, E. (2010). Risk Factors for Idiosyncratic Drug-Induced Liver Injury. Gastroenterology, 138(7), 2246-2259. doi:10.1053/j.gastro.2010.04.001
- Herrera, J. L. (2012). Medications and the Liver.
- Maher, J. J. (1997). Exploring Alcohol’s Effects on Liver Function. Alcohol Health and Research World, 21(1), 5-12.
- University of Maryland Medical Center. (2016). Cirrhosis.
- Basra, G. (2011). Symptoms and Signs of Acute Alcoholic Hepatitis. WJH World Journal of Hepatology5: 118.
- Cohen, S. M., and J. Ahn. (2009). Review Article: The Diagnosis and Management of Alcoholic Hepatitis. Alimentary Pharmacology & Therapeutics1: 3-13.
- Stickel, F., & Seitz, H. K. (2013). Update on the Management of Alcoholic Steatohepatitis. Gastrointestinal Liver Disease, 22(2), 189-197.
- National Institute on Drug Abuse. (2014). What are the medical complications of chronic heroin use?
- U.S. National Library of Medicine. (2016). Cocaine
- Campbell, G. A., & Rosner, M. H. (2008). The Agony of Ecstasy: MDMA (3,4-Methylenedioxymethamphetamine) and the Kidney. Clinical Journal of the American Society of Nephrology, 3(6), 1852-1860. doi:10.2215/cjn.02080508
- Halpin, L. E., Gunning, W. T., & Yamamoto, B. K. (2013). Methamphetamine causes acute hyperthermia-dependent liver damage. Pharmacol Res Perspect Pharmacology Research & Perspectives, 1(1). doi:10.1002/prp2.8
- Herrine, S. K. (n.d.). Overview of Liver Disease.
- U.S. Department of Veterans Affairs. (2205). Viral Hepatitis.
- National Institute of Diabetes and Digestive and Kidney Diseases. (2012.) What I need to know about Hepatitis C.