Hepatic Insufficiency: Causes

Pathogenesis (development of disease)

Liver failure (liver insufficiency) can be divided into the following forms:

  • Acute liver failure (ALV; ALF), causes:
    • Acute viral hepatitis (HBV) or other hepatotropic viruses (EBV, CMV, HSV).
    • Toxic induced ALV (due toe.g. ethyl toxic liver cirrhosis. i.e. due toalcohol abuse).
    • Cryptogenic ALV (30-50% of the cause of acute liver failure is unclear; a large proportion will be autoimmunological).
  • Subacute liver failure (SALV; SALF).
  • Chronic liver failure (CLV; CLF)

Cellular damage to hepatocytes (liver cells) occurs, leading to massive cell death. This in turn leads to the restriction of liver function.

Etiology (causes)

Biographic causes

  • Genetic burden
    • Genetic diseases
      • Alpha-1-antitrypsin deficiency (AATD; α1-antitrypsin deficiency; synonyms: Laurell-Eriksson syndrome, protease inhibitor deficiency, AAT deficiency) – relatively common genetic disorder with autosomal recessive inheritance in which too little alpha-1-antitrypsin is produced because of a polymorphism (occurrence of multiple gene variants). A deficiency of protease inhibitors is manifested by a lack of inhibition of elastase, which causes the elastin of the pulmonary alveoli to degrade. As a result, chronic obstructive bronchitis with emphysema (COPD, progressive airway obstruction that is not fully reversible) occurs. In the liver, the lack of protease inhibitors leads to chronic hepatitis (liver inflammation) with transition to liver cirrhosis (non-reversible damage to the liver with pronounced remodeling of the liver tissue). The prevalence (disease frequency) of homozygous alpha-1 antitrypsin deficiency is estimated at 0.01-0.02 percent in the European population.
      • Hemochromatosis (iron storage disease) – genetic disease with autosomal recessive inheritance with increased deposition of iron as a result of increased iron concentration in the blood with tissue damage.
      • Wilson’s disease (copper storage disease) – autosomal recessive inherited disease in which copper metabolism in the liver is disturbed by one or more gene mutations.
      • Storage diseases

Behavioral causes

  • Consumption of stimulants
    • Alcohol
  • Drug use
    • Ecstasy (also XTC, Molly, etc.) – methylenedioxymethylamphetamine (MDMA); dosage on average 80 mg (1-700 mg); structurally belongs to the group of amphetamines.
    • Cocaine

Disease-related causes

Cardiovascular system (I00-I99)

  • Budd-Chiari syndrome – thrombotic occlusion of the hepatic veins.
  • Ischemia (decreased or abolished blood flow to a tissue due to lack of arterial blood supply) of the liver/shock
  • Veno-occlusive disease (occlusion of the hepatic veins).

Infectious and parasitic diseases (A00-B99).

  • Acute viral hepatitis (HBV; acute liver inflammation caused by hepatitis B virus) or other hepatotropic viruses (EBV, CMV, HSV).
  • Bacterial infections – triggers for acute-on-chronic liver failure (ACLF).

Liver, gallbladder and bile ducts – Pancreas (pancreas) (K70-K77; K80-K87).

Pregnancy, childbirth and puerperium (O00-O99)

Injuries, poisonings, and other sequelae of external causes (S00-T98).

  • Graft-versus-host disease (graft-host reaction).
  • Shock liver

Drugs (hepatotoxic) → drug-induced liver damage.

Researchers at the University of Iceland in Reykjavik had analyzed all cases of drug-induced liver injury over two years in their study. They found that, on average, 19 out of every 100,000 residents suffered liver damage from medications each year. The drugs that frequently affected the liver included paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as antibiotics. For example, the combination of amoxicillin and clavulanic acid was responsible for 22% of damage

Environmental exposures – intoxications

  • Tuber leaf fungus intoxication (amanitins).
  • Carbon tetrachloride