LIVER DISEASE

WHY IS LIVER FUNCTION IMPORTANT TO THE HUMAN BODY?

The liver is located just below the diaphragm and is the largest organ in the human body.  When it functions properly, few of us give it a second thought.  Because it can function even after sustaining significant damaged, even some people with liver disease rarely think about it.  The truth is, however, that the liver plays over 500 roles that are essential to overall health and life (1).  The main function of the liver is to act as a filter for the blood, cleansing it of toxins before returning it to the circulatory system.  The toxins removed from the blood by the liver include substances found in industrial chemicals (including pesticides, cleaners, and solvents), medicines and other drugs, alcohol, and preservatives.  The liver also removes byproducts of the natural metabolism of fats, sugars, and proteins, which can be toxic if their concentrations in the blood become too high.  When the liver is diseased or otherwise dysfunctional, toxins can accumulate within the body and disrupt the functions of other body systems.

The liver also regulates the supply of essential nutrients, synthesizes the proteins necessary for the formation of new red blood cells and for blood clotting, converts excess glucose into glycogen and stores it for when energy/glucose levels are low, produces bile to aid digestion and the elimination of toxins, and produces and metabolizes cholesterol (2,3).

RISK FACTORS FOR LIVER DISEASE

There are over 100 different forms of liver disease.  Risk factors for liver disease vary depending on the specific disease, but some common factors generally associated with the development of liver disease include:

• Family history of liver disease (4)
• History of liver cancer or liver adenoma (5)
• Obesity, leading to fat accumulation on the liver
• Excessive exposure to toxins or use of toxin-containing substances like drugs and alcohol (6)

Some medications can also lead to drug-induced liver injury.  Common medications in this category include: acetaminophen, isoniazid, amoxicillin, chlorpromazine, and phenytoin (7).  Some herbal supplements may also harm the liver.  Common supplements in this category include: artemesia, comfrey, kava, germander, ma huang/ephedra (1).

Infection with Hepatitis virus A, B, or C (8) cause liver disease, which may be acute or chronic.  The Hepatitis A virus is transmitted via contact with an infected individual’s stool or through sexual intercourse.  The Hepatitis B and C viruses are transmitted via direct contact with an infected individual’s blood or bodily fluids (9).

SYMPTOMS OF LIVER DISEASE

In some cases, a person with liver disease may experience no symptoms until late in the progression of the disease (1).  In other cases, as the liver becomes inflamed in the early stages of the disease, an affected individual will experience pain just under the right ribcage.  The pain may also radiate to the back of the right flank.  Some people with liver disease also report non-specific symptoms including nausea, vomiting, light-colored stools, weakness, and loss of appetite.

If liver inflammation persists for more than a short time, healthy liver tissue will become replaced by scar tissue, a condition known as fibrosis (10).  Fibrosis, in turn, causes the liver to lose its proper functionality.  Left untreated, fibrosis can advance to cirrhosis, a condition in which large amounts of healthy liver tissue is replaced by hard scar tissue (11). Symptoms and complications associated with cirrhosis include:

• Swelling of the ankles and legs
• Itchy skin
• Easy bruising
• Jaundice
• Type 2 diabetes
• Blocked blood vessels
• Buildup of toxins in the body, including the brain (12,13)

For more information on liver disease and diagnosis:  1. Talk to your doctor  2. Visit the American Liver Foundation website  3. Visit the Canadian Liver Foundation website

LIVER DISEASE FACTS AND STATISTICS

Over 3 million people in the United States live with some form of liver disease (14).  Deaths due to liver disease have been on the rise in the past several years, increasing by 31% from 2000-2015.  Liver disease was the 12th leading cause of death in the United States in 2015 (15).

MEDICAL TREATMENT AND PREVENTION OF LIVER DISEASE

• Vaccination against Hepatitis A and B
• Lactulose, marketed as Cephulac or Enulose.  Side-effects include nausea, cramps, and bloating.
• Beta-blockers, marketed as Inderide or Corgard.  Side-effects include fatigue and dizziness.
• Obeticholic acid, marketed as Ocaliva.  Side-effects include rapid weight gain, bloating, swelling of the face or limbs, and severe skin itching.
• Ursodiol, marketed as Actigall, Urso, Urso Forte, or Urso DS.  Side-effects include indigestion, vomiting, bloody or cloudy urine, difficult or painful urination, bladder pain, lower back pain, and weakness (16).

NATURAL WAYS TO SUPPORT LIVER HEALTH

Everyday Practices to Support Liver Health:

• Wash hands, fruits, and vegetables to prevent exposure to hepatitis viruses.
• Avoid direct contact with blood or bodily fluids to prevent exposure to hepatitis viruses.
• Ensure proper sterilization of equipment when getting piercings or tattoos to prevent accidental exposure to hepatitis viruses.
• Avoid excessive alcohol consumption.
• Take precaution with over-the-counter medicines (especially acetaminophen) and some herbal supplements (e.g. comfrey, kava, and germander).  Consult your doctor about your current medications.
• Use “green” environmentally friendly or organic household cleaners and lawn/garden products to minimize exposure to toxic chemicals (1).

Natural Supplements That Support Liver Health:

• Artichoke leaf (17,18,19)
• Barberry root (20,21)
• Chicory leaf (22,23)
• Dandelion root (24,25,26)
• Milk thistle seed (27,28)
• Selenium (29,30)
• Turmeric root (31,32)
• Resveratrol (Polygonum cuspidatum root) (33,34)
• N-Acetyl cysteine (35,36)
• Long pepper (37)
• Holy basil (37)
• Phyllanthus amarus (38)
• Licorice root extract (glycyrrhizic acid) (39,40)

REFERENCES

1. Your liver is essential to your life. The Canadian Liver Foundation. 2018. https://www.liver.ca/your-liver/. Accessed February 1, 2018.
2. Rui L. Energy metabolism in the liver. Compr Physiol. 2014;4(1):177-197. doi:10.1002/cphy.c130024.
3. Boyer JL. Bile formation and secretion. Compr Physiol. 2013;3(3):1035-1078. doi:10.1002/cphy.c120027.
4. Day CP. Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease. Liver Int. 2006;26(9):1021-1028. doi:10.1111/j.1478-3231.2006.01323.x.
5. Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109(4):542-553. doi:10.1038/ajg.2014.11.
6. John U and Hanke M. Liver cirrhosis mortality, alcohol consumption and tobacco consumption over a 62 year period in a high alcohol consumption country: A trend analysis. BMC Res Notes. 2015;8(1). doi:10.1186/s13104-015-1808-2.
7. Liver injury caused by drugs – hepatic and biliary disorders. Merck Manuals Professional Edition. 2018. http://www.merckmanuals.com/professional/hepatic-and biliary-disorders/drugs-and-the-liver/liver-injury-caused-by drugs#v27709308. Accessed February 2, 2018.
8. Zuckerman AJ. Chapter 70 hepatitis viruses. Med Microbiol 4th Ed. 1996:1-16.
9. Liver disease. Medlineplusgov. 2018. https://medlineplus.gov/liverdiseases.html. Accessed February 2, 2018
10. Czaja AJ. Hepatic inflammation and progressive liver fibrosis in chronic liver disease. World J Gastroenterol. 2014;20(10):2515-2532. doi:10.3748/wjg.v20.i10.2515.
11. Kang W, Kim SU, Ahn SH. Non-invasive prediction of forthcoming cirrhosis-related complications. World J Gastroenterol. 2014;20(10):2613-2623. doi:10.3748/wjg.v20.i10.2613
12. Cirrhosis | NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases. 2018. https://www.niddk.nih.gov/health-information/liver-disease/cirrhosis.  Accessed February 1, 2018.
13. The stages of liver disease. American Liver Foundation. 2018. https://liverfoundation.org/for-patients/about-the-liver/the-progression-of-liver-disease/. Accessed February 2, 2018.
14. FastStats. (2018). Cdc.gov. https://www.cdc.gov/nchs/fastats/liver-disease.htm. Retrieved February 2, 2018.
15. QuickStats: Death rates for chronic liver disease and cirrhosis, by sex and age group – national vital statistics system, United States, 2000 and 2015. (2018). https://www.cdc.gov/mmwr/volumes/66/wr/mm6638a9.htm. Retrieved February 1, 2018.
16. List of liver disease medications. Drugs.com. 2018. https://www.drugs.com/condition/liver-disease.html. Accessed February 2, 2018.
17. Frank K, Patel K, Lopez G, Willis B. Artichoke extract research analysis. Examine.com. 2018. https://examine.com/supplements/artichoke-extract/. Accessed February 2, 2018.
18. Salem M Ben, Affes H, Ksouda K, et al. Pharmacological studies of artichoke leaf extract and their health benefits. Plant Foods Hum Nutr. 2015;70(4):441-453. doi:10.1007/s11130-015-0503-8.
19. Englisch W, Beckers C, Unkauf M, Ruepp M, Zinserling V. Efficacy of artichoke dry extract in patients with hyperlipoproteinemia. Arzneimittelforschung. 2011;50(3):260265. doi:10.1055/s-0031-1300196.
20. Barberry. University of Maryland Medical Center. 2018. https://www.umm.edu/health/medical/altmed/herb/barberry. Accessed February 1, 2018.
21. Zarei A, Changizi-Ashtiyani S, Taheri S, Ramezani M. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L. Avicenna J Phytomedicine. 2015;5(6):485-497.
22. Chicory: uses, side effects, interactions and warnings. Webmdcom. 2018. https://www.webmd.com/vitamins/ai/ingredientmono-92/chicory. Accessed February 1, 2018.
23. Elgengaihi S, Mossa A-TH, Refaie AA, Aboubaker D. Hepatoprotective efficacy of Cichorium intybus L. extract against carbon tetrachloride-induced liver damage in rats. J Diet Suppl. 2016:1-15. doi:10.3109/19390211.2016.1144230.
24. Callahan C. Nutritional information on dandelion root. LIVESTRONGCOM. 2018. https://www.livestrong.com/article/174470-nutritional-information-on-dandelion-root/. Accessed February 1, 2018.
25. Cai L, Wan D, Yi F, Luan L. Purification, preliminary characterization and hepatoprotective effects of polysaccharides from dandelion root. Molecules. 2017;22(9). doi:10.3390/molecules22091409.
26. Domitrović R, Jakovac H, Romić Ž, Rahelić D, Tadić Ž. Antifibrotic activity of Taraxacum officinale root in carbon tetrachloride-induced liver damage in mice. J Ethnopharmacol. 2010;130(3):569-577. doi:10.1016/j.jep.2010.05.046.
27. Milk thistle. Mayo Clinic. 2018. https://www.mayoclinic.org/drugs-supplements-milkthistle/art-20362885. Accessed February 1, 2018.
28. Milk Thistle. NCCIH. 2018. https://nccih.nih.gov/health/milkthistle/ataglance.htm#hed1. Accessed February 1, 2018.
29. Selenium. WebMD. 2018. https://www.webmd.com/a-to-z-guides/supplement-guide-selenium#2. Accessed February 1, 2018.
30. Selenium. National Institute of Health Office of Dietary Supplements. 2018. https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/. Accessed February 1, 2018.
31. Turmeric. NCCIH. 2018. https://nccih.nih.gov/health/turmeric/ataglance.htm#hed4. Accessed February 1, 2018.
32. Yiu WF, Kwan PL, Wong CY, et al. Attenuation of fatty liver and prevention of hypercholesterolemia by extract of Curcuma longa through regulating the expression of CYP7A1, LDL receptor, HO-1, and HMG-CoA reductase. J Food Sci. 2011;76(3). doi:10.1111/j.1750-3841.2011.02042.x.
33. Faghihzadeh F, Hekmatdoost A, Adibi P. Resveratrol and liver: A systematic review. J Res Med Sci. 2015;20(8):797-810. doi:10.4103/1735-1995.168405.
34. Resveratrol. Linus Pauling Institute. 2018. http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resveratrol#metabolism-bioavailability. Accessed February 1, 2018.
35. Algren A. Review of N-acetylcysteine for the treatment of Acetaminophen (paracetamol) toxicity in pediatrics. 2018. http://www.who.int/selection_medicines/committees/subcommittee/2/acetylcysteine_rev.pdf?ua=1. Accessed February 2, 2018.
36. Your liver is essential to your life. The Canadian Liver Foundation. 2018. https://www.liver.ca/your-liver/#risk-prevention. Accessed February 2, 2018.
37. Xiong F and Guan YS. Cautiously using natural medicine to treat liver problems. World J Gastroenterol. 2017;23(19): 3388-3395. doi:10.3748/wjg.v23.i19.3388.
38. Naaz F, Javed S, and Abdin MZ. Hepatoprotective effect of ethanolic extract of Phyllanthus amarus Schum. et Thonn. on aflatoxin B1-induced liver damage in mice. J of Ethnophar. 2007;113(3):503-509. doi:10.1016/j.jep.2007.07.017.
39. Li J, Coa H, Liu P, Cheng G, Sun M. Glycyrrhizic acid in the treatment of liver diseases: literature review. BioMed Res Int. 2014:1-15. doi:10.1155/2014/872139.
40. Jung JC, Lee YH, Kim SH, Kim KJ, Kim KM, OH S, Jung YS. Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fisher, in alcohol-induced fatty liver disease. BMC Comp Alt Med. 2016;16(1). doi:10.1186/s12906-016-0997-0.