Handbook of Liver Disease E-Book

Lawrence S. Friedman, Paul Martin

• Publisher: Elsevier
• Year: 2017
• ISBN:
  9780323478823
• Edition: 4
• Topic: Medicine
• Subtopic: Gastroenterology & Hepatology

Well-organized and vibrantly illustrated throughout, Handbook of Liver Disease is a comprehensive yet concise handbook providing authoritative guidance on key clinical issues in liver disease. The quick-reference outline format ensures that you'll find answers when you need them, and cover-to-cover updates keep you abreast of the recent rapid changes in the field. Written by leading international experts in hepatology, this reference is ideal for hepatologists, gastroenterologists, internists, family practitioners, trainees, and others who diagnose and manage patients with liver disorders.

• Uses a highly templated outline format, key points in each chapter, alert symbols, and highlighted review points to provide a "just the facts" approach to daily clinical questions on liver disease.

• Features expanded hepatitis chapters, including completely updated coverage of new, safe, and effective oral regimens for the treatment of hepatitis C.
• Provides completely updated coverage of: alcoholic liver disease * autoimmune hepatitis * portal hypertension * primary biliary cholangitis * hepatic tumors * cirrhosis * nonalcoholic liver disease * liver transplantation * and more.
• Includes the latest information on adolescents with liver disease moving into adult care.
• Covers the revised criteria for prioritizing liver transplantation using the MELDNa score, new options for the treatment of hepatocellular carcinoma, and improved management of hepatorenal syndrome.

Chapter 1

Assessment of Liver Function and Diagnostic Studies

Paul Martin, MD, FRCP, FRCPI, and Lawrence S. Friedman, MD

Abstract

The detection of abnormal liver biochemical test levels is often the first indication of the presence of liver disease. The pattern of abnormalities can provide clues to the etiology of hepatic dysfunction; for example, elevated serum aminotransferase levels are typical of viral hepatitis, whereas a predominant elevation of the alkaline phosphatase level is more typical of cholestatic disorders such as primary biliary cholangitis and primary sclerosing cholangitis. Precise diagnosis of hepatic dysfunction requires additional workup, including serologic tests and imaging studies. For some causes of liver disease, such as drug-induced liver disease and nonalcoholic fatty liver disease, specific testing is not available, and diagnosis is by exclusion of other etiologies. Liver biopsy is increasingly reserved for hepatic dysfunction of unknown cause. The severity of liver disease is best assessed with tests of hepatic function, specifically the serum total bilirubin level, albumin level, and international normalized ratio.

Keywords

alanine aminotransferase; alkaline phosphatase; aspartate aminotransferasebilirubin; hepatic imaging; liver biochemical tests; liver fibrosis tests; liver function tests

Key Points

1 Reflecting the liver’s diverse functions, the colloquial term liver function tests (LFTs) includes true tests of hepatic synthetic function (e.g., serum albumin), tests of excretory function (e.g., serum bilirubin), and tests that reflect hepatic necroinflammatory activity (e.g., serum aminotransferases) or cholestasis (e.g., alkaline phosphatase [ALP]).

2 Abnormal liver biochemical test results are often the first clues to liver disease. The widespread inclusion of these tests in routine blood chemistry panels uncovers many patients with unrecognized hepatic dysfunction.

3 Normal or minimally abnormal liver biochemical test levels do not preclude significant liver disease, even cirrhosis.

4 Laboratory testing can assess the severity of liver disease and its prognosis; sequential testing may allow assessment of the effectiveness of therapy.

5 Although liver biopsy had been the gold standard for assessing the severity of liver disease, as well as for confirming the diagnosis for some causes, fibrosis is increasingly assessed by noninvasive means, most notably by ultrasound elastography, especially in chronic viral hepatitis.

6 Various imaging studies are useful in detecting focal hepatic defects, the presence of portal hypertension, and abnormalities of the biliary tract.

Routine Liver Biochemical Tests

Serum Bilirubin

1. Jaundice

▪ Often the first evidence of liver disease

▪ Clinically apparent when serum bilirubin exceeds 3 mg/dL; patient may notice dark urine or pale stool before conjunctival icterus

2. Metabolism

▪ Bilirubin is a breakdown product of hemoglobin and, to a lesser extent, heme-containing enzymes; 95% of bilirubin is derived from senescent red blood cells.

▪ After red blood cell breakdown in the reticuloendothelial system, heme is degraded by the enzyme heme oxygenase in the endoplasmic reticulum.

▪ Bilirubin is released into blood and tightly bound to albumin; free or unconjugated bilirubin is lipid soluble, is not filtered by the glomerulus, and does not appear in urine.

▪ Unconjugated bilirubin is taken up by the liver by a carrier-mediated process, attaches to intracellular storage proteins (ligands), and is conjugated by the enzyme uridine diphosphate (UDP)–glucuronyl transferase to form a diglucuronide and, to a lesser extent, a monoglucuronide.

▪ Conjugated bilirubin is water soluble and thus appears in urine.

▪ When serum levels of bilirubin glucuronides are elevated, some binding to albumin occurs (delta bilirubin), leading to absence of bilirubinuria despite conjugated hyperbilirubinemia; this phenomenon explains delayed resolution of jaundice during recovery from acute liver disease until albumin-bound bilirubin is catabolized.

▪ Conjugated bilirubin is excreted by active transport across the canalicular membrane into bile.

▪ Bilirubin in bile enters the small intestine; in the distal ileum and colon, bilirubin is hydrolyzed by beta-glucuronidases to form unconjugated bilirubin, which is then reduced by intestinal bacteria to colorless urobilinogens; a small amount of urobilinogen is reabsorbed by the enterohepatic circulation and mostly excreted in the bile, with a smaller proportion undergoing urinary excretion.

▪ Urobilinogens or their colored derivatives urobilins are excreted in feces.

3. Measurement of serum bilirubin

a. van den Bergh reaction

▪ Total serum bilirubin represents all bilirubin that reacts with diazotized sulfanilic acid to form chromogenic pyrroles within 30 minutes in the presence of alcohol (an accelerating agent).

▪ Direct serum bilirubin is the fraction that reacts with the diazo reagent in an aqueous medium within 1 minute and corresponds to conjugated bilirubin.

▪ Indirect serum bilirubin represents unconjugated bilirubin and is determined by subtracting the direct reacting fraction from the total bilirubin level.

b. More specific methods (e.g., high-pressure liquid chromatography) demonstrate that the van den Bergh reaction often overestimates the amount of conjugated bilirubin; ...