Liver Shrinkage (Cirrhosis): Causes

Pathogenesis (development of disease)

The pathohistology of liver cirrhosis includes the following signs:

  • Hepatocellular necrosis (death of liver cells).
  • Proliferation of connective tissue

The above changes lead to:

  • Irreversible connective tissue remodeling due to activation of fibrocytes (connective tissue cells) by Ito cells (contain vitamin A and serve to store fat; they are also considered producers of connective tissue fibers).
  • Formation of regenerative nodules (this consist of coarse connective tissue, which harden the liver tissue and thus produce the typical nodular surface).

This leads collectively to an increasing limitation of function and to portal hypertension (also portal hypertension, portal hypertension).

Etiology (causes)

Biographic causes

  • Genetic burden
    • By parents, grandparents – e.g. alpha-1 antitrypsin deficiency (see below “Genetic disorders”).
    • Risk variants in the PNPLA3, MBOAT7, and TM6SF2 genes:
      • PNPLA3 contains information for a lipase that degrades triglycerides in the liver cell. (responsible for 20.6-27.3% of all liver cirrhosis).
        • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
          • Genes: PNPLA3
          • SNP: rs738409 in the gene PNPLA3
            • Allele constellation: CC (3.2-fold; increased risk of alcoholic fatty liver; increased liver fat)
            • Allele constellation: CG (1.79-fold; increased liver fat, risk of alcoholic fatty liver).
            • Allele constellation: GG (low risk of fatty liver).
      • MBOAT7 interferes with the transport of fats (responsible for 7.4-17.2% of all liver cirrhosis)
      • TM6SF2 is likely involved in the release of lipoproteins (responsible for 2.5-5.2% of all liver cirrhosis)
    • 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 due to 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.
      • Cystic fibrosis (ZF) – genetic disease with autosomal recessive inheritance.
  • Anatomical variants – such as biliary atresia (bile duct not created).

Behavioral causes

  • Consumption of stimulants
    • Alcohol (woman: > 40 g/day; man: > 60 g/day).
    • Tobacco (smoking, secondhand smoke) – smoking promotes fibrosis of the liver in the presence of liver cirrhosis
  • 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

Causes related to disease

  • Alcohol abuse (alcohol dependence) (about 50% of cases).
  • Autoimmune hepatitis (AIH; autoimmune hepatitis) – acute or chronic inflammatory autoimmune disease of the liver.
  • Bilharzia (schistosomiasis) – worm disease (tropical infectious disease) caused by trematodes (sucking worms) of the genus Schistosoma (couple flukes).
  • Budd-Chiari syndrome (thrombotic occlusion of the hepatic veins).
  • Choledocholithiasis (gallstones).
  • Chronic bile duct obstruction
  • Chronic right heart failure (right ventricular failure → chronic congestive heart failure/cardiac cirrhosis)
  • Graft-versus-host disease (graft rejection reaction).
  • Fatty liver hepatitis – liver inflammation due to a fatty liver.
  • Hepatitis (liver inflammation) B and C (chronic viral hepatitis: about 45% of cases).
  • Infectious diseases such as toxoplasmosis (transmission by the parasite Toxoplasma gondii in raw meat or cat feces).
  • Jejunoileal bypass – short-circuit connection between the jejunum (jejunum) and ileum (ileum).
  • Liver fluke
  • Metabolic syndrome (due topossible sequelae: Fatty liver hepatitis (non-alcoholic steatohepatitis; NASH), liver fibrosis, portal hypertension (portal hypertension; portal hypertension), steatosis hepatis (fatty liver)).
  • Wilson’s disease (copper storage disease).
  • Parasitoses (infestation with parasites; eg, schistosomiasis, liver fluke).
  • Pericarditis constrictiva – chronic pericarditis with shrinkage of the pericardium and thereby limiting cardiac function.
  • Primary biliary cholangitis (PBC, synonyms: non-purulent destructive cholangitis; formerly primary biliary cirrhosis) – relatively rare autoimmune disease of the liver (affects women in about 90% of cases); begins primarily biliary, i.e., at the intra- and extrahepatic (“inside and outside the liver”) bile ducts, which are destroyed by inflammation (= chronic non-purulent destructive cholangitis). In the longer course, the inflammation spreads to the entire liver tissue and eventually leads to scarring and even cirrhosis; detection of antimitochondrial antibodies (AMA); PBC is often associated with autoimmune diseases (autoimmune thyroiditis, polymyositis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis); Associated with ulcerative colitis (inflammatory bowel disease) in 80% of cases; long-term risk of cholangiocellular carcinoma (CCC; bile duct carcinoma, bile duct cancer) is 7-15%.
  • Sarcoidosis – chronic disease with the formation of granulomas, which are found preferentially in the lungs, skin and lymph nodes.
  • Steatosis hepatis/fatty liver (alcoholic and non-alcoholic); non-alcoholic fatty liver disease (NAFL): 10-20% of cases; non-alcoholic steatohepatitis (NASH): 20% of cases.
  • Viral infections – such as Epstein-Barr virus (EBV) infection.
  • Cystic fibrosis (cystic fibrosis) – hereditary disease in which the sufferer forms viscous secretions in the lungs, pancreas, etc., which can lead to functional disorders of various kinds.

Drugs (hepatotoxic: hepatotoxic drugs/hepatoxic drugs) [list does not claim to be exhaustive].

Environmental pollution – intoxications (poisonings).

  • Arsenic
  • Formaldehyde
  • Carbon tetrachloride