Liver Fibrosis / End-stage liver disease (ESLD) / Cirrhosis

Liver cirrhosis is common worldwide and can have various causes:

• Adiposity / obesity,


• non-alcoholic fatty liver disease,


• high alcohol consumption,


• hepatitis B or C infection,


• autoimmune diseases,


• cholestatic diseases, and


• iron or copper overload.

Ginès et al. 2021 The Lancet 398: 1359-1376

Liver fibrosis is the primary determinant of liver dysfunction and mortality in patients with chronic liver disease
Keshavarz Azizi Raftar et al. 2021 Microbiol Spectr 9: e00484-21

Liver cirrhosis leads to a significant change in liver perfusion and extrahepatic hemodynamics.
Sauerbruch et al. 2021 Front. Physiol. 12:718783

These changes increase portal pressure on the one hand and fuel the dysfunction of other organs such as the kidneys (Wong et al. 2020 Clin. Gastroenterol. Hepatol. 19(8): 1661-1669) and the lungs (Goldberg & Fallon 2015 Clin. Gastroenterol. Hepatol. 13: 2118-2127).

The heart can also be involved in the complex of hyperdynamic circulatory disorders or cirrhotic cardiomyopathy.
Sauerbruch et al. 2021 Front. Physiol. 12:718783

There is an overall reduction in the bile acid pool in liver cirrhosis with a relative increase in CDCA.
Sauerbruch et al. 2021 Front. Physiol. 12:718783

At the same time, the concentration of conjugated bile acids in the systemic circulation increases sharply, especially that of CDCA. Chenodeoxycholic Acid (CDCA) is an activating ligand for FXR and also for TGR5 and, in this way, releases Nitrous oxide / Nitric Oxide (NO), i.e., may cause vasodilation
Sauerbruch et al. 2021 Front. Physiol. 12:718783

Liver cirrhosis develops after a prolonged inflammatory phase that leads to the replacement of healthy liver parenchyma with fibrotic tissue and regenerative nodules, resulting in portal hypertension.
Ginès et al. 2021 The Lancet 398: 1359-1376

The disease progresses from an asymptomatic phase (compensated liver cirrhosis) to a symptomatic phase (decompensated liver cirrhosis), the complications of which often lead to hospitalization, reduced quality of life, and high mortality.
Ginès et al. 2021 The Lancet 398: 1359-1376

Progressive portal hypertension, systemic inflammation, and liver failure determine the course of the disease.
Ginès et al. 2021 The Lancet 398: 1359-1376

This can lead to a vicious circle that aids the development of ascites, hepatorenal syndrome, and life-threatening variceal bleeding
Sola & Gines 2015 Dig. Dis. 33: 534-538

Around 20-30% of Non-Alcoholic Fatty Liver Disease (NAFLD) / Metabolic dysfunction-associated fatty liver disease (MAFLD) patients develop Non-Alcoholic Steatohepatitis (NASH / MASH) with only some of them further evolving to fibrosis and then cirrhosis
de Alwis & Day 2008 J Hepatol. 48(Suppl 1): S104-112
Singh et al. 2015 Clin Gastroenterol Hepatol. 13: 643-654

The consequences are serious: formation of collaterals bypassing the liver and splanchnic and peripheral systemic vasodilation with hyperdynamic circulation and central hypovolemia
Schrier et al. 1988 Hepatology 8: 1151-1157
Maroto et al. 1994 Hepatology 20: 839-844
Blendis & Wong 2001 Pharmacol. Ther. 89: 221-231
Moller et al. 2011 Gut 60: 1254-1259

The hemodynamic changes increase with liver dysfunction but are not specific to the particular cause of cirrhosis. They can also be demonstrated in various animal models Heller et al. 2005 Liver Int. 25: 657-666
Hennenberg et al. 2009 Liver Int. 29: 933-941

Cirrhosis is a condition marked by "feminization," which involves low levels of serum testosterone and high levels of serum estrogen. In up to 90% of patients with cirrhosis, serum testosterone is reduced, and this reduction becomes more significant as the severity of liver disease worsens.
Zietz et al. 2003 Eur J Gastroenterol Hepatol 15(5): 495-501

The body reacts to this by activating the renin-angiotensin system (Bosch et al. 1980 Gastroenterology 78: 92-99) and releasing other vasoconstrictors such as catecholamines or vasopressin (Henriksen et al. 1984 Gut 25: 1034-1043).

see also:
Hepatic Stellate Cells (HSC)
Non-Alcoholic Fatty Liver Disease (NAFLD) / Metabolic dysfunction-associated fatty liver disease (MAFLD)
Sexual dysfunction