Albumin  (3.5 – 5.5 g/dL or  25-55g/L)

Albumin, the most important plasma protein, accounts for 75% of plasma colloid oncotic pressure and is synthesized solely by hepatocytes.   The liver can double albumin production in response to rapid loss or dilution in the blood. Albumin has a half-life of 14 to 21 days. Its synthesis is influenced by nutrition, osmotic pressure, inflammation, and hormones. 

Albumin is a transpoter protein. Ligands transported by serum albumin include endogenous ligands such as bilirubin, ions, fatty acids, thyroxine (T4)  and exogenous ligands such as drugs. The list of drugs transported by albumin includes   propranolol, thiopental, furosemide, warfarin, methotrexate, alfentanil, and many others.

Severe liver disease can result in hypoalbuminemia, which leads to fewer available binding sites for exogenous drugs. This results in larger amounts of unbound exogenous drugs, which can lead to increased drug sensitivity. This sensitivity manifests when patients have serum albumin concentrations lower than 2.5 g/dL.

 Serum albumin (hypoalbuminemia) can result from liver dysfunction, malnutrition, protein-losing conditions (e.g., enteropathy, nephrotic syndrome), inflammation, or hormonal issues.

However, due to its long half-life, albumin is not the most reliable marker for acute liver injury or nutrition, but is useful for assessing liver function in chronic liver disease and cirrhosis.  However, in cirrhosis with ascites, albumin levels may appear low despite normal or increased production due to expanded distribution.  

Clotting- Protombin Time (9.4 to 12.5 seconds)

Clotting is the result of a complex enzymatic process involving clotting factors, most of which are produced in the liver, except for factor VIII, made by vascular endothelial cells. The prothrombin time (PT) measures the conversion of prothrombin to thrombin, reflecting the extrinsic clotting pathway and involving factors II, V, VII, and X. The INR (International Normalized Ratio) is used to express PT, particularly for patients on warfarin, and adjusts for differences in laboratory reagents using the international sensitivity index (ISI). However, the ISI, designed for patients on vitamin K antagonists, may not accurately calculate the INR in patients with liver disease, and studies suggest liver-specific ISI measures may be needed.

Prolonged PT can result from conditions beyond liver dysfunction, including clotting factor deficiencies, vitamin K deficiency (which affects factors II, VII, IX, and X), and disseminated intravascular coagulation (DIC). DIC can be distinguished from liver disease by measuring factor VIII levels (decreased in DIC but normal or elevated in liver disease). Vitamin K deficiency can be confirmed if PT improves by 30% or more after intravenous vitamin K administration.

Unlike serum albumin, PT is useful for assessing current liver function, particularly in acute liver disease, as factor VII has a short half-life (6 hours). PT and INR are key prognostic markers for acute liver failure and alcoholic hepatitis and are part of the MELD score, which predicts survival in decompensated cirrhosis and helps allocate donor organs for liver transplantation.

However, PT alone does not fully assess bleeding risk in cirrhosis, as it only measures procoagulant factors and not anticoagulants like protein C and antithrombin, which are also reduced. The partial thromboplastin time (PTT) assesses the intrinsic coagulation pathway and can also be prolonged in advanced cirrhosis, though PT is more sensitive in detecting coagulopathy.

In summary , these test are a direct reflect of liver function.  PT (short half life) and albumin are direct indicators of normal liver synthetis . Bilirubin, despite not being produced in liver, can guide us (If elevated in blood, that can translate inability of the hepatocytes to conjugate it or to excrete bilirubin to bile).  The last thing for  assessment in liver function would be looking for any signs of hepatic encephalopathy due to inhability of the liver to metabolize ammonia and this builds up in the brain can cross the blood-brain barrier and enter the brain causing disturbances