What is hepatic synthetic function?

Hepatic Synthetic Function: Definition and Clinical Significance

Hepatic synthetic function refers to the liver's ability to produce essential proteins, coagulation factors, and other molecules necessary for normal physiological processes, and is a critical marker of liver health that directly impacts morbidity and mortality in liver disease.

Key Components of Hepatic Synthetic Function

• The liver synthesizes most blood coagulation factors, including fibrinogen, prothrombin, factors V, VII, IX, X, XI, XII, as well as protein C, protein S, and antithrombin 1
• Albumin production is a major component of hepatic synthetic function, serving as an important marker of liver health 2
• The liver is responsible for producing carrier proteins such as transferrin that are essential for various metabolic processes 3
• Hepatic synthetic function is generally well preserved in many liver conditions until advanced stages of disease 4

Assessment of Hepatic Synthetic Function

• Impaired liver synthetic function is primarily assessed through measurement of:

  • Prothrombin time (PT) and International Normalized Ratio (INR) 4, 5
  • Serum albumin levels 2
  • Other coagulation parameters that reflect the liver's ability to produce clotting factors 5

• Prolonged INR, decreased albumin values, or recurrence of jaundice are considered markers of severe liver disease associated with poor outcomes 4

• These parameters are more reliable indicators of liver function than transaminases (ALT, AST), which primarily reflect hepatocellular injury rather than synthetic function 6, 7

Clinical Significance in Liver Disease

• Impaired synthetic function is a late manifestation of liver disease and indicates more severe hepatic dysfunction than isolated enzyme elevations 4

• In cirrhosis, there is a stage-dependent progressive impairment of protein metabolism characterized by reduced albumin synthetic rate 4

• Liver synthetic function is the key determinant in assessing risk for post-hepatectomy liver failure, with parameters like INR and bilirubin being critical components of the "50-50 criteria" 4

• Signs of impaired synthetic function (prolonged INR, decreased albumin) along with clinical manifestations of portal hypertension (ascites, varices, bleeding, encephalopathy) should trigger consideration for liver transplantation 4

Synthetic Function in Different Liver Conditions

• In acute liver failure, there is severe derangement of protein metabolism with impaired hepatic glucose production and protein catabolism associated with hyper-aminoacidemia and hyper-ammonemia 4

• In hereditary hemorrhagic telangiectasia with liver involvement, synthetic function is generally well preserved despite other liver abnormalities 4

• In alpha-1 antitrypsin deficiency, markers of impaired synthetic function such as prolonged INR and decreased albumin are used to identify severe disease associated with poor outcomes 4

• In chronic liver diseases, the liver's ability to synthesize proteins is progressively impaired, correlating with disease severity 4, 5

Therapeutic Implications

• When synthetic function is compromised, liver support systems may be necessary to substitute the main functions of the liver, including detoxification, synthesis, and regulation 8

• Extracorporeal systems like molecular adsorbent recirculation system (MARS) and Prometheus can temporarily support liver function but cannot fully replace synthetic capacity 8

• Orthotopic liver transplantation remains the definitive treatment for end-stage liver disease with severely impaired synthetic function 4

• Monitoring synthetic function is essential when evaluating the efficacy of treatments for liver disease 4