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Risk Factors of Liver Diseases

Abbreviation Used

AIH - Autoimmune hepatitis
ALD - Alcoholic Liver Disease

HAV - Hepatitis A
HBV - Hepatitis B
HCV - Hepatitis C
HCC - Hepatocellular Carcinoma
NAFLD - Nonalcoholic fatty liver disease
NASH - Nonalcoholic Steatohepatitis
PLC - Primary Liver Cancer
Risk Factors for Liver Diseases
  • Aflatoxin
    • A byproduct of aspergillus flavus, acts as cocarcinogen.
    • Dietary ingestion of high levels of aflatoxins presents a significant environmental hazard, particularly in the context of coexisting chronic HBV infection which leads to a more than 50-fold increase in the risk of developing HCC.[13]
  • Contraceptives
    • Women who take oral contraceptives have an increased risk of benign liver tumors, but the relationship between oral contraceptive use and malignant liver tumors is less clear.[10]
    • Overall, the risks of endometrial and ovarian cancer appear to be reduced with the use of oral contraceptives, whereas the risks of breast, cervical, and liver cancer appear to be increased.[11]
  • Cigarettes
    • Smokers tend to develop liver cancer slightly faster than nonsmokers
  • Diabetes
    • Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors.[8,9]
  • Dietary Supplements
    • Dietary supplements account for nearly 20 percent of drug-related liver injuries that turn up in hospitals, up from 7 percent a decade ago, according to an analysis by a national network of liver specialists.[18]
  • Excessive drinking
    • Regular daily consumption of > 50g ethanol in females or > 80g in males is generally considered sufficient to induce liver cirrhosis, although individual susceptibility can vary considerably.
      • Women has a lower alcohol tolerance than men do. Perhaps because of this, women often contract ALD and cirrhosis at a younger age than men do.
      • Drinking two more cups of coffee each day has been linked to a dramatically lowered odds of the liver damage caused by excessive alcohol, a recent study found.[28]
    • Alcohol toxicity levels can be affected by the interaction between drugs and alcohol. In an ALD patient who is actively drinking, ingesting as little as 4 grams (only 8 extra-strength tablets) of acetaminophen (Tylenol)[15] in one 24-hour period may cause serious liver damage.
    • Mixing alcohol and any pain reliever or medication, even over-the-counter pills, can be dangerous.
  • Heredity
    • Genetic predisposition assisted with some events such as infection or the use of medications is suggested to have triggered autoimmune hepatitis. 
      • AIH strikes women 70% of the time.  
      • AIH may occur in any ethnic group and at any age, but is most often diagnosed in patients between age 40 and 50.[19]
    • In Wilson disease, a disorder of copper metabolism caused by abnormal genes, excessive accumulation of copper in the body can rise to dangerous levels, causing cirrhosis and psychiatric problems.
    • Asian or African descent, or have a history of liver cancer in their family.
  • HIV-positive
    • Chronic HCV occurs in persons who are HIV-positive
  • Iron overload[7,25].
    • Because liver is the body's primary location for storing iron, it suffers the most damage when we have iron overload, a disease called hemochromatosis.
    • Hemochromatosis is also the most common genetic disease in the United States-especially among individuals with northern European ancestors such as the Irish, Celtic, British, Scottish, or Nordic peoples.
    • Those with NASH who also show iron overload may at higher risk for scarring and consequently cirrhosis.
    • See more details from a companion article:
  • Liver cirrhosis
    • Approximately 70–90% of HCCs develop in patients with macronodular cirrhosis which is characterised by the presence of large nodules.[4]
    • Macronodular and mixed macro-micro-nodular cirrhosis are typically caused by or associated with viral hepatitis, metabolic disorders, and toxic liver injury.
    • People with the metabolic syndrome generally also have NAFLD, which in some cases will have progressed to NASH.
    • Insulin resistance poses another major risk of NAFLD. Almost all people with NAFLD are insulin resistant.
    • Drug-induced fatty liver which can be caused by medications such as prednisone (a steroid), tamoxifen (used in treating breast cancer), estrogen (a female hormone), methotrexate (used to treat cancer and autoimmune conditions), amiodarone (used to treat heart conditions), or Arimidex (used to treat breast cancer).
  • Obesity
    • Studies show that an increased incidence of cirrhosis and liver cancer in obese patients.
    • NAFLD most often found in people who are obese.
    • NAFLD is found in every demographic group, though its primary targets are women in their middle years who carry too much weight and who also may have high cholesterol and triglyceride levels.
    • Fatty liver may also occur in people who lose weight too quickly. The liver may not be able to handle the huge task of breaking down all that fat in the tissues, so it simply accumulates it.
    • Central obesity (visceral fat), the accumulation of a disproportionate amount of weight in the abdomen, puts the individual at high risk for serious liver and heart diseases.
  • Parasites[4]
    • Hepatic cholangiocarcinoma has peak incidences in Northern Thailand. 
      • Here, it is caused by chronic infection with the liver fluke, Opisthorchis Viverrini, which is ingested through infected raw fish.
  • Virus infection
    • Poor bathroom hygiene in day-care centers for toddlers (HAV).
    • Poor sanitation and food preparation (HAV) .
    • HBV transferred from its carriers through blood (for example, blood transfusion) and semen.
    • Shares a razor or nail clippers, or exposes another person through a bleeding skin condition. (HBV).
    • If immune systems become deeply suppressed, as happens following chemotherapy or an organ transplant, chronic HBV can reemerge.
    • Patients with chronic HBV[2,5,6] or HCV[9] have a high risk of developing liver cancer
      • A high incidence of HCC is associated with an increase in serum HBV DNA concentrations, which provides the evidence of HBV mediating HCC.
      • In [5,6], it also shows why there are higher incidences of HBV-induced HCC in male than in female.
      • HCV appears to be a major cause of HCC in Japan, Italy, and Spain, but it seems to play a less important role in South Africa and Taiwan.[12]
      • HCV-associated HCCs typically develop after 20-30 years of infection and are generally preceded by liver cirrhosis.[4]

  • Harmful substances (see table)

Harmful Substances

  • Black cohosh
  • Buckthorn
  • Chaparral, also known as greasewood and creosote bush
  • Comfrey, germander
  • Kava kava
  • Kombucha
  • Lobelia
  • Ma huang, or ephedra
  • Mate[14]
  • Mistletoe
  • Nutmeg

  • Pennyroyal
  • Pokeweed
  • Ragwort
  • Sarsaparilla
  • Sassafras
  • Saw palmetto
  • Skullcap
  • Sweet clover
  • Tansy
  • Valerian
  • Woodruff

Photo Credits

  1. "Liver Disorders" by Nizar N. Zein, M.D., and Kevin M. Edwards, M.S.N., C.N.P.
  2. 早期肝癌治療找到新方法
  3. 睡覺與肝的保健
  4. Tumours of the Liver and Intrahepatic Bile Ducts
  5. 醫學新發現—治療肝癌的新方法
  6. Androgen Receptor Promotes Hepatitis B Virus–Induced Hepatocarcinogenesis Through Modulation of Hepatitis B Virus RNA Transcription
  7. Mandishona E, MacPhail AP, Gordeuk VR, Kedda MA, Paterson AC, Rouault TA, Kew MC (1998). Dietary iron overload as a risk factor for hepatocellular carcinoma in Black Africans.  Hepatology 27: 1563-1566.
  8. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005;54:533–539.
  9. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study.
  10. Oral Contraceptives and Cancer Risk (National Cancer Institute)
  11. Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. American Journal of Obstetrics and Gynecology 2004; 190(4 Suppl):S5–22.
  12. Cohen J (1999). The scientific challenge of hepatitis C. Science 285: 26-30.
  13. Sun Z, Lu P, Gail MH, Pee D, Zhang Q, Ming L, Wang J, Wu Y, Liu G, Zhu Y (1999). Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology 30: 379-383.
  15. Acute liver failure in a metropolitan area in Germany: a retrospective study (2002 - 2008)
  16. Oncofetal Gene SALL4 in Aggressive Hepatocellular Carcinoma
  17. CDC Testing Recommendations for Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965
  18. Spike in Harm to Liver Is Tied to Dietary Aids
  19. Manns, MP; Czaja, AJ; Gorham, JD; Krawitt, EL; Mieli-Vergani, G; Vergani, D; Vierling, JM; American Association for the Study of Liver, Diseases (June 2010). "Diagnosis and management of autoimmune hepatitis.". Hepatology (Baltimore, Md.) 51 (6): 2193–213.
  20. New AbbVie hepatitis C regimen shows high cure rates: studies (04/16/2016)
  21. Hepatitis C By The Numbers Infographic
  22. Quiz: Myths and Facts About Hepatitis C
    • Baby boomers -- people born from 1945 to 1965 -- have the highest rates of hepatitis C. It may be that they became infected in the '70s and '80s when hepatitis C rates were high and blood wasn't screened as well as it is now.
  23. Vitamin E and Non-alcoholic Fatty Liver Disease
  24. 10 Foods & Supplements That Reverse Liver Disease
  25. Heath Effects of Iron Overload and Benefits of Blood Donation (Travel to Health)
  26. Higher Esophageal Cancer Risk — If You Blush Easily With Drinking (Travel and Health)
  27. Dietary Iron Overload as a Risk Factor for HepatocellularCarcinoma in Black Africans
    • Among 24 patients, the risk of developing HCC in the iron-loaded subjects was 10.6-fold relative to individuals with normal iron status.
  28. Can More Coffee Lead to Less Liver Damage? Study Finds Link