18 - SECTION 3 Liver and Biliary Tract Disease

SECTION 3 Liver and Biliary Tract Disease

Jensen GL et al: GLIM criteria for the diagnosis of malnutrition: A con­ sensus report from the global clinical nutrition community. JPEN J Parenter Enteral Nutr 43:32, 2019. Singer P et al: ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit. Clin Nutr 42:1671, 2023. Wischmeyer PE et al: Personalized nutrition therapy in critical care: 10 expert recommendations. Crit Care 27:261, 2023. Section 3 Liver and Biliary Tract Disease Marc G. Ghany, Jay H. Hoofnagle

Approach to the Patient

with Liver Disease A diagnosis of liver disease usually can be made accurately by careful elicitation of the patient’s history, physical examination, and applica­ tion of a few laboratory tests. In some circumstances, radiologic exami­ nations are helpful or, indeed, diagnostic. Liver biopsy is considered the criterion standard in evaluation of liver disease but is now needed less for diagnosis than for grading (activity) and staging (fibrosis) of disease. Noninvasive means of assessing fibrosis stage have become increasingly helpful and may allow for avoidance of biopsy in an increasing proportion of patients. This chapter provides an introduc­ tion to diagnosis and management of liver disease, briefly reviewing the structure and function of the liver; the major clinical manifestations of liver disease; and the use of clinical history, physical examination, laboratory tests, imaging studies, and liver biopsy. LIVER STRUCTURE AND FUNCTION The liver is the largest organ of the body, weighing 1–1.5 kg and rep­ resenting 1.5–2.5% of the lean body mass. The size and shape of the liver vary and generally match the general body shape—long and lean or squat and square. This organ is located in the right upper quadrant of the abdomen under the right lower rib cage against the diaphragm and projects for a variable extent into the left upper quadrant. It is held in place by ligamentous attachments to the diaphragm, peritoneum, great vessels, and upper gastrointestinal organs. The liver receives a dual blood supply; ~20% of the blood flow is oxygen-rich blood from the hepatic artery, and 80% is nutrient-rich blood from the portal vein arising from the stomach, intestines, pancreas, and spleen. The majority of cells in the liver are hepatocytes, which constitute two-thirds of the organ’s mass. The remaining cell types are Kupffer cells (members of the reticuloendothelial system), stellate (Ito or fatstoring) cells, endothelial and blood vessel cells, bile ductular cells, and cells of supporting structures. Viewed by light microscopy, the liver appears to be organized in lobules, with portal areas at the periphery and central veins in the center of each lobule. However, from a func­ tional point of view, the liver is organized into acini, with both hepatic arterial and portal venous blood entering the acinus from the portal areas (zone 1) and then flowing through the sinusoids to the terminal hepatic veins (zone 3); the intervening hepatocytes constitute zone 2. The advantage of viewing the acinus as the physiologic unit of the liver is that this perspective helps to explain the morphologic patterns and zonality of many vascular and biliary diseases not explained by the lobular arrangement. Portal areas of the liver consist of small veins, arteries, bile ducts, and lymphatics organized in a loose stroma of supporting matrix and small amounts of collagen. Blood flowing into the portal areas is distributed through the sinusoids, passing from zone 1 to zone 3 of the acinus and

draining into the terminal hepatic veins (“central veins”). Secreted bile flows in the opposite direction—that is, in a countercurrent pattern from zone 3 to zone 1. The sinusoids are lined by unique endothelial cells that have prominent fenestrae of variable sizes, allowing the free flow of plasma but not of cellular elements. The plasma is thus in direct contact with hepatocytes in the subendothelial space of Disse.

Hepatocytes have distinct polarity. The basolateral side of the hepa­ tocyte lines the space of Disse and is richly lined with microvilli; it exhibits endocytotic and pinocytotic activity, with passive and active uptake of nutrients, proteins, and other molecules. The apical pole of the hepatocyte forms the canalicular membranes through which bile components are secreted. The canaliculi of hepatocytes form a fine network, which fuses into the bile ductular elements near the portal areas. Kupffer cells usually lie within the sinusoidal vascular space and represent the largest group of fixed macrophages in the body. The stel­ late cells are located in the space of Disse but are not usually prominent unless activated, whereupon they produce collagen and matrix. Red blood cells stay in the sinusoidal space as blood flows through the lob­ ules, but white blood cells can migrate through or around endothelial cells into the space of Disse and from there to portal areas, where they can return to the circulation through lymphatics. Hepatocytes perform numerous and vital roles in maintaining homeostasis and health. These functions include the synthesis of most essential serum proteins (albumin, carrier proteins, coagulation fac­ tors, many hormonal and growth factors), the production of bile and its carriers (bile acids, cholesterol, lecithin, phospholipids), the regulation of nutrients (glucose, glycogen, lipids, cholesterol, amino acids), and the metabolism and conjugation of lipophilic compounds (bilirubin, anions, cations, drugs) for excretion in the bile or urine. Measurement of these activities to assess liver function is complicated by the multi­ plicity and variability of these functions. Commonly used liver “function” tests are measurements of serum bilirubin, serum albumin, and pro­ thrombin time. The serum bilirubin level is a measure of hepatic con­ jugation and excretion; the serum albumin level and prothrombin time are measures of protein synthesis. Abnormalities of bilirubin, albumin, and prothrombin time are typical of hepatic dysfunction. Frank liver failure is incompatible with life, and the functions of the liver are too complex and diverse to be subserved by a mechanical pump; a dialysis membrane; or a concoction of infused hormones, proteins, and growth factors. CHAPTER 347 Approach to the Patient with Liver Disease LIVER DISEASES While there are many causes of liver disease (Table 347-1), these disor­ ders generally present clinically in a few distinct patterns and are usu­ ally classified as hepatocellular, cholestatic (obstructive), or mixed. In hepatocellular diseases (such as viral hepatitis and alcoholic liver dis­ ease), features of liver injury, inflammation, and necrosis predominate. In cholestatic diseases, such as gallstone or malignant obstruction, primary biliary cholangitis (previously referred to as primary biliary cirrhosis), and some drug-induced liver diseases, features of inhibition of bile flow predominate. In a mixed pattern, features of both hepato­ cellular and cholestatic injury are present (such as in cholestatic forms of viral hepatitis and many drug-induced liver diseases). The pattern of onset and prominence of symptoms can rapidly suggest a diagnosis, particularly if major risk factors are considered, such as the age and sex of the patient and a history of exposure or risk behaviors. Typical presenting symptoms of liver disease include jaundice, fatigue, itching, right-upper-quadrant pain, nausea, poor appetite, abdominal distention, and intestinal bleeding. At present, however, many patients are diagnosed with liver disease who have no symptoms and who have been found to have abnormalities in biochemical liver tests as a part of a routine physical examination or screening for blood donation or for insurance or employment. The wide availability of bat­ teries of liver tests makes it relatively simple to demonstrate the pres­ ence of liver injury as well as to rule it out in someone in whom liver disease is suspected. Evaluation of patients with liver disease should be directed at deter­ mining (1) the etiologic diagnosis, (2) disease severity (grading), and (3) disease stage (staging). Diagnosis should focus on the pattern of