Diseases of the liver and biliary tract

Liver anatomy

The liver receives the highest proportion of cardiac output of all the organs in the body: approximately 25% via the portal vein and hepatic artery. The portal vein, which is formed by the confluence of the splenic and superior mesenteric veins, provides 75% of blood flow to the liver. However, it accounts for only 50% of oxygen delivery given the portal venous blood’s deoxygenated state after perfusing organs such as the stomach, intestines, spleen, and pancreas. The hepatic artery provides the remaining 25% of liver blood flow and 50% of oxygen delivery due to its higher oxygen content. Fig. 16.1 describes the pressure gradient of blood flow to the liver. Anatomically, the liver is divided into eight segments ( Fig. 16.2 ).

Blood flow to the liver is regulated by intrinsic and extrinsic mediators. Hepatic arterial flow has an inverse relationship with changes in portal venous flow. Mediated by adenosine, hepatic artery dilation occurs as portal venous flow decreases. This helps maintain blood flow and oxygen content in the liver. This autoregulation is a one-way mechanism as the portal vein cannot dilate in response to decreased hepatic artery flow. Extrinsic factors, such as sympathetic innervation, regulate blood flow through the portal vein indirectly by modulating arterial tone in the splanchnic vessels. Portal venous pressure therefore reflects both splanchnic arterial tone and intrahepatic resistance to flow. When portal venous pressure is elevated, portosystemic shunts are formed from tributaries that allow portal venous blood to bypass the liver and flow directly to the systemic circulation, leading to the development of esophageal and gastric varices. Portal hypertension is considered present when the hepatic venous pressure gradient (HVPG [difference between wedged hepatic venous pressure and free hepatic venous pressure]) exceeds 10 mm Hg. HVPG is commonly used to predict the risk and severity of portal hypertension ( Fig. 16.3 ).

Assessment of liver function

Evaluation of liver function should be guided by a careful history that considers risk factors for liver disease, severity of clinical findings, and presence of comorbidities. Risk factors for liver disease include family history, heavy alcohol usage, lifestyle, diabetes, obesity, intravenous drug use, tattoos, prior transfusion, and use of medications that can cause hepatotoxicity. Specific questions regarding chronic fatigue, pruritis, easy bleeding/bruising, volume overload, changes in weight, and dark urine should be asked. The physical exam findings may reveal jaundice, ascites, asterixis, hepatomegaly, splenomegaly, or spider nevi. Patients may present without any physical exam findings.

When liver dysfunction is suspected, laboratory workup begins with a liver chemistry panel, complete blood count, and prothrombin time (PT)/international normalized ratio (INR). These tests help confirm clinical suspicion and include biomarkers of hepatobiliary disease that can be divided into three different groups: markers of hepatocellular injury or inflammation, cholestasis, and synthetic function. Table 16.2 lists common causes of hepatic dysfunction and correlating test results.

Hepatocellular injury and inflammation are reflected by increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), found in high concentrations in hepatocytes. Since AST and ALT are also present in skeletal and cardiac muscle, correlation with creatine kinase can be useful for discriminating extrahepatic causes. Liver disease processes can have distinctive patterns of enzyme elevations. Acute liver failure (ALF) secondary to medication use often results in AST and ALT levels more than 25 times greater than normal. ALD will usually have an AST:ALT ratio of at least 2:1, while nonalcoholic steatohepatitis will often have an AST:ALT ratio of 1:1. Although liver chemistry elevations can be suggestive of certain disease processes, they are not always specific.

Alkaline phosphatase, γ-glutamyltransferase (GGT), and bilirubin are used to assess for cholestasis. Alkaline phosphatase is an enzyme found in the biliary system and within bone, intestines, and the placenta. Elevation can indicate issues with the bile duct, pregnancy, or bone disease, thus clinical correlation is needed to assist with the appropriate diagnosis. GGT is an enzyme highly concentrated in the liver that is more specific for biliary disease compared to alkaline phosphatase. The level of bilirubin, the end product of heme catabolism, is a function of uptake, conjugation, and excretion by the liver. Bilirubin that is bound to albumin in the blood is known as indirect bilirubin. It is transported to the liver where it is conjugated to a water-soluble form, known as direct bilirubin, before secretion into the small intestine as bile. Elevated indirect bilirubin can be caused by prehepatic disorders such as hemolysis, ineffective erythropoiesis, medications, and portosystemic shunts. Elevated direct bilirubin can be caused by biliary obstruction, cholestasis, hepatocellular injury, and disorders such as Dubin-Johnson syndrome.

Synthetic function of the liver is indicated by albumin and PT/INR. Albumin is a plasma protein synthesized in the liver that acts as a primary modulator of plasma oncotic pressure and as a transporter for drugs. Synthesis of albumin is reduced with liver disease. PT is a test that evaluates the extrinsic and common pathway of the coagulation cascade to measure how long it takes for a thrombus to form. PT requires factors II, V, VII, and X, and therefore is prolonged with advanced liver disease due to any etiologic factor.

Liver imaging includes a variety of techniques. Imaging usually begins with ultrasound evaluation. Ultrasound can be used to assess liver size and nodularity, biliary tree anatomy, spleen size, and presence of hepatic masses. It can also detect ascites in its earliest stages (≥100 mL). Doppler ultrasound imaging can be used for assessment of portal venous patency and direction of portal flow. Computed tomography (CT) scan or magnetic resonance imaging (MRI) can be used for further evaluation of hepatobiliary anatomy and for exclusion of other intraabdominal processes.

Biliary tract anatomy

The biliary system consists of the gallbladder, bile ducts, and structures involved in the production, storage, and transport of bile. Hepatocytes secrete bile (composed of water, bilirubin, bile salts, and cholesterol) into small ducts that form the common hepatic duct. Between meals, secreted bile is stored in the gallbladder. During a meal, the gallbladder contracts to secrete bile into the duodenum and aid in digestion of fats. Fig. 16.4 shows anatomy of the biliary tree.

Cholelithiasis

Cholelithiasis occurs when substances in bile become hardened within the gallbladder. This can occur for several reasons: cholesterol oversecretion, excess bilirubin, or gallbladder hypomotility. Risk factors for gallstones include obesity, hyperlipidemia, diabetes, pregnancy, family history, and female gender. Nearly 80% of patients with cholelithiasis are asymptomatic. Symptomatic patients may have right upper quadrant pain or referred pain to the shoulders, nausea, vomiting, and indigestion. Acute cholecystitis occurs when a gallstone obstructs the cystic duct causing the gallbladder to become distended and inflamed. The patient may present with fever, pain in the right upper quadrant, and tenderness over the gallbladder. Management of these patients initially includes intravenous (IV) fluids, antibiotics, and pain management. Laparoscopic cholecystectomy is performed once the patient is medically optimized and stable. If the patient develops septic shock, a percutaneous cholecystostomy may be warranted, given the tenuous preoperative status. Anesthetic considerations should include the risk of opioid use and resultant sphincter of Oddi spasm. The risk of opioid-induced sphincter of Oddi spasm is low and can be antagonized using drugs such as glucagon, naloxone, or nitrate drugs.

Choledocholithiasis

Choledocholithiasis is a complication of cholelithiasis in which a gallstone obstructs the common bile duct impeding the flow of bile from the liver to the duodenum. Patients often present with symptoms of biliary colic suggested by intermittent episodes of nausea, vomiting, and crampy right upper quadrant pain. Common bile duct obstruction can lead to cholangitis, which is associated with fever, rigors, and jaundice in addition to the abovementioned symptoms. Treatment involves surgical or endoscopic removal of the obstruction. The most common method is preoperative endoscopic retrograde cholangiopancreatography (ERCP) to identify the stone followed by endoscopic sphincterotomy to remove it. Laparoscopic exploration of the common bile duct may also be performed concurrently with cholecystectomy.

Gilbert syndrome

Gilbert syndrome is a benign, autosomal dominant inherited disorder that results in unconjugated hyperbilirubinemia. Activity of the enzyme, uridine diphosphoglucuronate glucuronosyltransferase (UGT1A1), is decreased, resulting in mildly elevated indirect bilirubin levels. Patients may report jaundice, fatigue, or abdominal discomfort that is precipitated by dehydration, exercise, fasting, or stress. Symptoms typically resolve spontaneously. Plasma indirect bilirubin is only mildly elevated.

Crigler-Najjar syndrome

Crigler-Najjar syndrome is one of the most severe, albeit rare, forms of inherited unconjugated hyperbilirubinemia. It is inherited in an autosomal recessive pattern and characterized by either no or very little expression of the enzyme UGT1A1. Shortly after birth, affected infants develop signs of severe jaundice, fever, and vomiting. If untreated, the hyperbilirubinemia can result in severe brain damage. Diagnosis is made by high serum concentrations of indirect bilirubin. Treatment includes daily exchange transfusions, 12 hours /day phototherapy, and heme oxygenase inhibitors. Oral calcium phosphate is often used to bind bilirubin in the gut. Phenobarbital can be used in specific forms of the syndrome. Curative treatment is liver transplantation before the onset of brain damage.

Benign postoperative intrahepatic cholestasis

Benign postoperative intrahepatic cholestasis is postoperative jaundice in which there is no hepatic inflammation or cell necrosis. The cause is often multifactorial and associated with hypotension, significant blood loss, multiple transfusions, or hypoxemia. Bilirubin and alkaline phosphatase levels can increase two- to fourfold within the first 7 to 10 days following surgery. The diagnosis is made after excluding other causes. Although the jaundice may appear severe and dramatic, the condition is generally self-limited.

Viral hepatitis

Viral hepatitis is most commonly caused by hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) viruses. Each of these can cause acute infections with the potential for substantial morbidity. HBV and HCV are associated with significant chronic sequelae, while HAV lacks a chronic stage and contributes only to acute infection. Table 16.4 lists characteristic features of the various viral hepatitides. Of those, HAV and HEV rarely result in chronic liver disease and infrequently lead to liver transplantation. Both HBV and HCV remain a common reason for liver transplantation in developing countries, while HCV remains the most common viral hepatitis leading to liver transplantation in the United States. Advances in antiviral therapies over the last decade have revolutionized management of HCV disease. Current treatment regimens typically include two direct-acting antiviral drugs that target specific steps within the HCV replication cycle with or without interferon for a duration of 8 to 12 weeks. Antiviral drug choice and treatment duration are based on the genotype of HCV, stage of liver disease, presence of cirrhosis, and previous response to interferon. Genotype 1 is the most common, accounting for 70% to 75% of all HCV infections in the United States. One of the recommended medication regimens for genotype 1 is a 12-week course of sofosbuvir/velpatasvir, which has been found to provide a rate of infection clearance of 98% in genotype 1A and 99% in genotype 1B. Duration of drug therapy is heavily dependent on history of prior therapy and severity of liver disease.