Bilirubin (bile pigment), a major waste product of hemoglobin metabolism, is excreted by the liver. Normally, erythrocytes have a lifespan of about 120 days. They are then broken down by the reticuloendothelial cells, and the iron (heme) from the worn-out red cells is conserved for reuse in the synthesis of fresh hemoglobin. The remaining iron-free pigment is free (unconjugated) bilirubin, which is continually present in the bloodstream in small quantities. As blood passes through the liver, unconjugated bilirubin is removed. It is then combined (conjugated) with other substances and excreted via the bile ducts; a small amount of conjugated bilirubin returns to the blood [1,7].

Conjugated bilirubin is more soluble and less toxic than unconjugated bilirubin. In the intestines, conjugated bilirubin is converted into a highly soluble substance called urobilinogen, which is excreted primarily in the feces in an oxidized form known as stercobilin. About 5% of urobilinogen is absorbed into the bloodstream and excreted via the kidneys in an oxidized form called urobilin. Because stercobilin gives feces their brownish color, clay-colored stools are a classic sign of biliary tract abnormalities [1,7].

Under normal circumstances, the liver is capable of regeneration following alleviation of an acute condition (e.g., drug toxicity, abscess, inflammation). If the pathogenic influence persists, however, regeneration will be of fibrotic origin [7].

When dead or diseased cells are replaced by fibrous tissue, the liver becomes enlarged (hepatomegaly). Fibrotic scar tissue may impede emptying of blood from the hepatic veins, causing the liver lobules to become engorged. This engorgement leads to further enlargement. Pressure exerted on abdominal nerves by the enlarged liver or displacement of other abdominal organs may cause discomfort or pain. Hepatomegaly may also be related to invasion and multiplication of neoplastic cells [7].

Cholelithiasis (gallstones) occurs in women four to five times as often as it does in men. This increased incidence is thought to be related to the action of estrogen and progesterone, which increase the cholesterol saturation of bile. The higher the cholesterol saturation, the greater the risk that gallstones will form. Pregnant women and those taking oral contraceptives are at even higher risk of developing cholelithiasis, especially those who have had several pregnancies or who have been on oral contraceptives for several years [12].

For dye clearance studies, the patient fasts for 12 hours prior to the test. Dye is injected intravenously (about 5 mg/kg of body weight). Blood is drawn 45 minutes after the injection and inspected for the presence of dye. Normally, less than 5% of the dye will be found in the serum; the presence of a greater proportion of the dye indicates liver cell damage, as the impaired cells cannot absorb the dye from the blood. If hepatic damage is known to exist, lower dosages of dye are administered. The indocyanine green (ICG) clearance test is the most widely used quantitative liver function test [23,28,30].

For pain associated with cholelithiasis, nonsteroidal anti-inflammatory drugs (NSAIDs) provide greater relief of biliary pain and are considered first-line management [38]. NSAIDs have been reported as superior to antispasmodics for pain control. For narcotic management, meperidine is usually the drug of choice; butorphanol or hydromorphone can also be utilized, especially if NSAIDs are contraindicated [39]. Morphine is rarely administered. Nitroglycerin or phenobarbital may promote comfort by relaxing smooth muscle. Nursing measures, such as giving a backrub, assisting the patient in changing position, providing distraction, and offering emotional support, may supplement analgesic medication [27].

Cirrhosis is the end stage of any chronic liver disease. In developed countries, the most common causes include nonalcoholic fatty liver disease, hepatitis infection, and excessive alcohol intake; in developing counties, hepatitis A and B infections are the most likely causes. There are two clinical categories of cirrhosis: compensated and decompensated. Patients who have compensated cirrhosis can be further categorized as:

Alcoholic cirrhosis and malnutrition is the end result of repeated bouts of drinking-related liver injury and designates the onset of end-stage alcoholic liver disease. The gross appearance of the early cirrhotic liver is one of fine, uniform nodules on its surface. The condition has traditionally been called monocular or Laënnec cirrhosis. With more advanced cirrhosis, regenerative processes cause the nodules to become larger and more irregular in size and shape. As this occurs, the nodules cause the liver to become relobulized through the formation of new portal tracts and venous outflow channels. The nodules may compress the hepatic veins, curtailing blood flow out of the liver and producing portal hypertension, extrahepatic portosystemic shunts, and cholestasis [64,65,69].

Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously referred to as nonalcoholic fatty liver disease (NAFLD) but was renamed in 2023 to better reflect the underlying pathophysiology and embrace affirmative, non-stigmatizing terminology [70]. It is caused by metabolic dysfunction that affects the liver. As noted, in the United States, it is the most frequently occurring form of chronic liver disease. The condition can range from simple steatosis (fatty infiltration of the liver) to nonalcoholic steatohepatitis (steatosis with inflammation and hepatocyte necrosis). Although steatosis alone does not appear to be progressive, approximately 10% to 15% of people with nonalcoholic steatohepatitis progress to cirrhosis. Obesity, type 2 diabetes, metabolic syndrome, and hyperlipidemia are coexisting conditions frequently associated with fatty liver disease. The condition is also associated with other nutritional abnormalities, surgical conditions, drugs, and occupational exposure to toxins. Both rapid weight loss and parenteral nutrition may lead to MASLD. Jejunoileal bypass, a surgical procedure historically used for weight loss, has largely been abandoned for this reason [65,71].

Varying patterns of hepatic dysfunction are seen in response to use of other drugs and anesthetic agents. For example, halothane, methyldopa, and isoniazid can produce hepatitis. Chlorpromazine, erythromycin estolate, and methimazole can cause intrahepatic cholestasis with jaundice. Phenylbutazone and the sulfonamides can produce granulomas within the liver [76,78].

Cholangiocarcinoma is not associated with the same risk factors as hepatocellular carcinoma. Instead, most of the risk factors revolve around long-standing inflammation and injury of the bile duct epithelium. Bile duct cancer may occur more frequently in patients with a history of primary sclerosing cholangitis, chronic ulcerative colitis, choledochal cysts, or infections with the liver fluke Clonorchis sinensis [137].