The liver, the largest organ in the body, plays a central role in many essential physiological processes, including glucose homeostasis, plasma protein synthesis, lipid and lipoprotein synthesis, bile acid synthesis and secretion and vitamin storage (B12, A, D, E and K) as well as biotransformation, detoxification and excretion of a vast array of endogenous and exogenous compounds. The clinical manifestations of liver disease are likewise, varied and may be quite subtle. Clues to the existence, severity and etiology of liver disease may be obtained from a careful history and physical examination or by routine laboratory screening tests.
Clinical approach to liver disease
Table 1 outlines useful clinical clues to the presence of liver disease that may be elicited from the history and physical examination. Other important information to be obtained includes a history of jaundice or liver disease in family members, recent travel, exposure to individuals or animals with liver or parasitic disease, sexual promiscuity, use of intravenous drugs and exposure to alcohol, toxins or drugs.
Table 1. Clinical manifestations of liver disease
Laboratory tests of liver function and disease
Unlike tests used to asses function of other organ systems (e.g., arterial blood gas, creatinine clearance), “liver function” tests often do not measure liver function, nor do they accurately reflect etiology or severity of a disease process. Nevertheless, if their limitations are understood, they can be very useful. In general, the tests currently available can be divided into two categories: (1) tests of hepatic function or capacity, and (2) screening tests that suggest the presence and/or type of liver disease.
Tests of hepatic function
Although the liver performs a great variety of presumably testable functions, it has proved difficult to devise a test that is simple, cheap, reproducible and non-invasive and that accurately reflects hepatic capacity for all functions. Instead, currently available tests of liver function are indirect, static measurements of serum levels of compounds that are synthesized, metabolized, and/or excreted by the liver. The liver has a large reserve capacity and therefore “function” tests may remain relatively normal until liver dysfunction is serve. Table 2 outlines the most widely available and useful liver function tests. The serum albumin level and prothrombin time both reflect the hepatic capacity for protein synthesis. The prothrombin time responds rapidly to altered hepatic function because the serum half-lives of factors II and VII are short (hours). In contrast, the serum half-life of albumin is 14 to 20 days and serum levels fall only with prolonged liver dysfunction.
Serum bile acid levels, particularly when measured two hours after a meal, have proved to be the most sensitive test of liver disease, and this due to the high efficiency with which the liver normally extracts bile acids from portal blood. Small changes in hepatic blood flow, portosystemic shunting, or liver function all result in a substantial elevation of serum bile acid levels, while terminal ileal dysfunction (e.g., Crohn’ s disease) leads to fecal loss of bile acids and decreased serum levels. Although exquisitely sensitive, bile acid levels are nonspecific and fail to reflect accurately overall liver function.
The 14C-aminopyrine breath test was originally developed as a test of liver function. It measures the rate at which the liver metabolizes 14C-labled aminopyrine to 14CO2, which is collected and measured in exhaled breath. This test is performed only in some academic centers.
Table 2. Clinical test of hepatic function
Dr. Afsaneh Jeddi