11
Gastroenterology

Kathleen Rooney¹ and Gerry MacQuillan²

¹ Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Australia

² UWA Medical School, University of Western Australia, Nedlands, Australia

Hepatology is a subspecialty of gastroenterology, and as such, most gastroenterologists are familiar and experienced with interpreting a blood panel that suggests a sick liver. Acknowledging that this book is not a liver medicine textbook, that most hepatologists are by trade also gastroenterologists, and that gastroenterologists are well versed in liver conditions, the content provided here is aimed mostly toward those practicing internal medicine, to whom gastroenterological conditions frequently first come to attention.

Abnormal Liver Tests in Gastroenterological Disease

Routine initial workup of any patient with gastrointestinal (GI) symptoms invariably includes standard liver blood tests. With the organs being so intimately connected, it is unsurprising that abnormal liver tests are overwhelmingly common in gastroenterological disease, often raising unnecessary concern of a primary liver disorder. These can be thought of in two main categories:

Pancreatobiliary conditions.

Luminal conditions.

Table 11.1 Liver test abnormality patterns in gastroenterological conditions.

Indication	Acute	Chronic
Hepatocellular	Choledocholithiasis	Inflammatory bowel disease
↑ ALT, AST	Pancreatitis	Celiac disease
Cholestatic	Choledocholithiasis	Malignant obstruction
↑ ALP ± GGT	Malignant obstruction	Chronic pancreatitis
↑ ALP ± GGT	Malignant obstruction	Inflammatory bowel disease
Mixed	Choledocholithiasis	Malignant obstruction

ALP, alkaline phosphatase; AST, aspartate amino transferase; GGT, gamma‐glutamyl transferase.

These disorders can also be broadly considered according to the “pattern” of liver test abnormality they typically cause, and whether they present acutely or chronically (Table 11.1). Bear in mind that the pattern of abnormality does not always stand true; it can be dynamic, and should be interpreted in the context of the clinical picture. Diseases have not read medical textbooks and are not always aware of the strict expectations placed upon them.

Pancreatobiliary Conditions

The distinction between pancreatobiliary medicine and hepatology is sometimes blurred, but the concepts behind disease process and impact on liver biochemistry are the same. These conditions cause an abnormality in liver enzymes via biliary obstruction and resulting cholestasis; and depending on where this obstruction occurs, they are considered to be either intrahepatic or extrahepatic (Figure 11.1). Although the terms “obstruction” and “cholestasis” are often used synonymously in this setting, this use is not accurate. Indeed, intrahepatic biliary obstruction is perhaps better thought of only as intrahepatic cholestasis and further defined by its cause, as bile stasis can occur in the presence or absence of mechanical bile duct obstruction; it may be due to a functional impairment of hepatocytes in the excretion of bile constituents.

Conditions causing intrahepatic cholestasis range from any cause of acute or chronic hepatocyte injury, such as drug‐induced liver injury (including alcohol), biliary conditions such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis, and infiltrative diseases (sarcoidosis, amyloidosis, secondary malignancies).

Diseases that result in biliary obstruction (both intrahepatic and extrahepatic) are also frequently considered according to the site of obstruction, with specific reference to the bile duct wall (Box 11.1). Note that the conditions resulting from abnormalities of the biliary wall are, for the most part, also those generally considered to be primary liver disorders. This seems logical, given that the surface area of the intrahepatic biliary tree is far greater than the extrahepatic system; it follows, then, that any intrinsic disease of the bile duct wall has greater potential to affect the much smaller intrahepatic ducts and ductules, a process that tends to be more insidious and causes gradual destruction to the liver parenchyma.

Schematic illustration of biliary drainage system. — **Figure 11.1** Biliary drainage system.

Source: Modified from Terese Winslow LLC.

Pancreatobiliary conditions managed by gastroenterologists (and associated with abnormal liver tests), generally refer to those that cause mechanical obstruction and blockage of the extrahepatic biliary tree.

Unfortunately, elevation in cholestatic liver enzymes (ALP, gamma‐glutamyl transferase, GGT) does not differentiate whether the disruption of bile flow is secondary to disease of the intrahepatic or extrahepatic biliary tree (or both), nor etiology. This can, however, be further delineated on imaging. Ultrasound is the first step in investigating cholestatic liver blood tests but may not always be diagnostic. Depending on clinical suspicion of malignancy versus stone, computed tomography (CT) of the abdomen, and magnetic resonance cholangiopancreatography (MRCP; or CT cholangiogram) are the most useful imaging modalities, respectively. Note that CT cholangiogram requires a normal serum bilirubin, as impaired contrast excretion in the bile will reduce opacification of the biliary tree and potentially result in a non‐diagnostic study.

Biliary obstruction can have varied clinical presentations depending on the underlying etiology and degree of obstruction, but frequently presents with abdominal pain, jaundice, pale stools, dark urine, and pruritus. Fever may be present in the setting of infection.

Liver test derangement will frequently show a cholestatic pattern with variable degrees of conjugated hyperbilirubinemia. There will typically also be elevation of serum aminotransferases in cases of acute obstruction.

Of note, prothrombin time may be prolonged in the setting of biliary obstruction due to vitamin K‐dependent clotting factor deficiency (factors II, VII, IX, X), as there is impaired absorption of fat‐soluble vitamins (A, D, E, and K) in the absence of bile. This may initially raise concern for coagulopathy resulting from injured hepatocytes; however, the rapid normalization of prothrombin time with administration of parenteral vitamin K will reassure that hepatocyte function is normal.

Box 11.1 Causes of Intrahepatic and Extrahepatic Biliary Obstruction with Respect to Bile Duct Wall

Within the bile duct lumen:

Stone
- Gallstone
- In situ ductal stone formation
Sludge
Parasite
- Ascariasis
- Liver flukes

Intrinsic: disease of the bile duct wall

Non‐malignant:

Primary sclerosing cholangitis
Primary biliary cholangitis
Secondary sclerosing cholangitis:
- Iatrogenic – trauma, surgical anastomosis
- Ischemia
- AIDS cholangiopathy
- Chronic or recurrent infective cholangitis
IgG4‐related disease