hepatic disorders

HCC dx

A hepatitis panel can confirm the presence of viral hepatitis. Screening for hepatic carcinoma with ultrasound and AFP testing every 6 months is recommended in patients with chronic HBV or cirrhosis secondary to HBV, HCV, or alcohol. AFP levels may be used as a diagnostic test in conjunction with CT or MRI imaging. Multiphasic helical CT and MRI with contrast are used to determine the location and vascularity of hepatic carcinomas. A liver biopsy should be obtained for definitive diagnosis.

What are some causes of cirrhosis?

Alcoholic liver disease, nonalcoholic steatohepatitis, hepatitis B, hepatitis C, and schistosomiasis.

The diagnostic evaluation is targeted at ruling out other causes of encephalopathy.

Ammonia levels play a controversial role. Ammonia should not be used to screen for hepatic encephalopathy, and hepatic encephalopathy can be diagnosed without checking an ammonium level. CT of the head without contrast is indicated if traumatic injuries, such as subdural hematomas, are on the differential. There is often a trigger to an exacerbation of hepatic encephalopathy in patients with liver disease.

What is the only life-saving medication in the acute management of esophageal variceal hemorrhage?

Answer: Ceftriaxone is the only medication proven to increase survival.

What congenital condition are decreased alpha-fetoprotein, decreased estriol, and increased human chorionic gonadotropin associated with?

Answer: Down syndrome.

What does an elevated international normalized ratio (INR) that corrects with vitamin K administration suggest in the setting of obstructive jaundice?

Answer: Impaired intestinal absorption of fat-soluble vitamins

What is the mechanism of action of lactulose?

Answer: Reduces absorption of ammonium from the gastrointestinal tract.

Which enzyme is reduced or completely absent in patients with Crigler-Najjar syndrome?

Answer: UDP-glucuronosyltransferase.

management of esophageal variceal bleeding

Balloon tamponade should be initiated in all patients with esophageal variceal hemorrhage who fail initial endoscopic management. Esophageal varices are enlarged veins that functionally decompress the hepatic portal vein in the setting of elevated portal venous pressure. Comorbid conditions include cirrhosis of the liver and, less commonly, portal vein thrombosis (Budd-Chiari syndrome). Half of patients with cirrhosis have esophageal varices, and one-third will develop variceal hemorrhage. Esophageal variceal hemorrhage may cause hematemesis, melena, hematochezia, fever, tachycardia, hypotension, or altered mental status. Endoscopy is the diagnostic test of choice and should be performed within 12 hours for patients with suspected variceal hemorrhage. Before endoscopy, management focuses on hemodynamic stabilization, decreasing portal venous pressure, and preventing infection. Intravascular volume depletion may be replaced with IV fluids or blood products, however, aggressive over resuscitation can reverse the splanchnic vasoconstriction induced by hypovolemia, and thus worsen variceal hemorrhage. Portal venous pressure is decreased using IV octreotide, a somatostatin analogue that decreases splanchnic blood flow. Hemodynamically unstable patients refractory to volume repletion and octreotide may require IV vasopressin. IV ceftriaxone is given for spontaneous bacterial peritonitis prophylaxis, and erythromycin is given for prophylaxis with invasive endoscopic procedures. Endoscopic band ligation or endoscopic sclerotherapy is recommended as a first-line intervention. If initial endoscopic intervention fails, balloon tamponade is recommended for no more than 24 hours. Prophylaxis with nonselective beta-blockers (e.g., nadolol, propranolol) is indicated for patients with small esophageal varices and for patients with medium to large esophageal varices as an alternative to prophylactic band ligation.

Esophageal Varices Caused by ___ Associated with ____ Diagnosis is made by ____ Treatment: Prophylaxis:

Caused by portal hypertension, history of chronic liver disease or alcohol use Associated with massive UGIB Diagnosis is made by upper endoscopy: dilated submucosal esophageal or gastric veins Treatment: hemodynamic support, endoscopy with banding, octreotide, prophylactic ceftriaxone, balloon tamponade for temporary hemostasis Prophylaxis: nonselective beta-blockers (nadolol, propranolol), endoscopic ligation, TIPS for select patients

esophageal varices

Esophageal varices, complications of portal hypertension, are a cause of upper gastrointestinal bleeding and hemorrhage.

Causes of unconjugated bilirubinemia include

Gilbert syndrome, drugs (sulfonamides, penicillin, rifampin, radiocontrast agents), hemolysis (hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency), and Crigler-Najjar syndrome.

Hepatic encephalopathy is graded on a severity scale from I-IV.

Grade I consists of mild confusion and sleep disturbances without asterixis. Grade II consists of moderate confusion and lethargy with asterixis. Grade III consists of severe confusion, incoherent speech, and asterixis. Grade IV is marked by patients being comatose and unresponsive.

Most common complication of portal hypertension

Hemorrhage of the varices is the most common complication of portal hypertension, with mortality being significant from the amount of blood loss.

Hepatic Encephalopathy History of Presents with PE will show Most commonly caused by Treatment is ____ correlates with severity

History of infection, dehydration, medications, GI bleed, hypoxia, hypoglycemia Presents with confusion PE will show scleral icterus and asterixis Most commonly caused by toxin accumulation due to liver dysfunction Treatment is lactulose, rifaximin CSF glutamine correlates with severity

prehepatic and posthepatic phases

In the prehepatic phase, bilirubin is bound to albumin, as it is not water soluble, and then brought to the liver for conjugation. In the liver, bilirubin is conjugated via the enzyme UGT, where it is now water soluble and ready to be excreted. In the posthepatic phase, conjugated bilirubin is stored in the gallbladder or enters the intestine, where it is converted to urobilinogen. Urobilinogen is then converted to stercobilin (which gives a brown color to stools), urobilin (which gives urine its characteristic yellowish color), or is recycled into the enterohepatic circulation.

HCC risk factors

Men are affected more than women, although the reason for this is not completely understood. Older patients are more likely to develop hepatocellular carcinoma because the majority of cases occur with cirrhosis or chronic liver disease, and it takes many years to get to this stage of disease. A number of risk factors for developing hepatocellular carcinoma exist and are important to consider when determining which patients merit screening. These risk factors include nonalcoholic fatty liver disease, hepatitis B and C infections, hereditary hemochromatosis, alcohol use, and cirrhosis of the liver. High-risk patients should be screened at regular intervals, typically every 6 months, with abdominal ultrasound.

Hepatocellular Carcinoma

Most common primary liver cancer Most common cause: chronic HBV or HCV cirrhosis Rapidly ↑ ascites Bloody ascitic fluid ↑ AFP

esophageal varices pt presentation

Patients with varices will usually present with signs and symptoms of advanced liver disease, portal hypertension, and upper gastrointestinal bleeding. Symptoms of liver disease include fatigue, anorexia, nausea, weight loss, abdominal pain, jaundice, dark urine, edema, pruritus, easy bruising, and mental status changes. Hematemesis or melena may indicate upper gastrointestinal bleeding from the varices, and physical exam may reveal ascites, jaundice, muscle wasting, and splenomegaly. Pallor, dyspnea, and tachypnea may be seen in patients with acute bleeding.

portal hypertension

Portal hypertension occurs when there is an elevated pressure in the portal vein (which carries blood from the bowels, spleen, and stomach to the liver) due to increased venous flow through the vein or obstruction of that flow. Over time, collateral circulation develops to alleviate the pressure, resulting in the formation of esophageal varices, which are very prone to hemorrhage. Increased pressure on the collateral veins causes thinning of the vascular walls due to increased tension, which can lead to rupture.

jaundice diagnosis

The diagnosis of jaundice starts with measuring serum total, indirect, and direct bilirubin, as well as urinary bilirubin. Elevated serum indirect bilirubin should warrant additional testing (such as CBC, reticulocyte count, haptoglobin, LDH, and a peripheral smear), which may aid in the diagnosis of hemolysis as a cause of jaundice. Elevated urinary bilirubin indicates conjugated hyperbilirubinemia and can be confirmed by an elevated direct (conjugated) bilirubin in the blood. An abdominal ultrasound or CT scan may be performed to assess for biliary obstruction or anatomic changes. Liver function tests and biopsy may reveal hepatocellular injury as a potential cause of hyperbilirubinemia.

HCC protective factors

The hepatitis B vaccine helps prevent hepatitis B infection, which is a risk factor. Treating known hepatitis B or C infection reduces the risk of developing hepatocellular carcinoma. Medications such as statins and aspirin have been found in some studies to be protective factors. Dietary consumption of white meat, fish, omega-3 fatty acids, coffee, and vegetables has also been found to be protective in reducing the risk of hepatocellular carcinoma.

hepatic encephalopathy s/sx

The symptoms and signs vary from subtle to patients presenting in a coma. Hepatic encephalopathy may cause cognitive deficits (impairment in attention, impairment in reaction time, and decreased working memory), impaired neuromuscular function (bradykinesia, hyperreflexia, rigidity, and myoclonus), or disturbances in sleep pattern (hypersomnia or insomnia). Disturbance in sleep pattern is a common initial manifestation.

HCC tx

Treatment for hepatic carcinoma depends on multiple factors including staging, spread, and presence of comorbidities. Laparoscopic or open surgical resection is appropriate for solitary tumors if liver function is preserved and there is no evidence of portal vein thrombosis. Liver transplantation is indicated in certain patients with advanced cirrhosis who have unresectable tumors.

esophageal varices tx

Treatment is aimed at preventing variceal hemorrhage. Nonselective beta-blockers (e.g., propranolol) are first-line agents for primary prophylaxis due to their role in decreasing portal and collateral blood flow and reducing cardiac output, which decreases the risk of bleeding. Vasodilators (e.g., isosorbide mononitrate) can also be used as second-line agents. Active variceal bleeding is most commonly treated endoscopically. Endoscopic sclerotherapy and endoscopic variceal ligation can be used to prevent recurrence of hemorrhage. Pharmacotherapy agents, such as vasopressin and nitroglycerin, can be used to stop acute bleeds as well as to decrease portal resistance. Surgical measures, such as implementation of decompressive shunts (e.g., total portal systemic shunts), devascularization procedures, and splenectomy, are reserved for more severe cases, with liver transplantation being reserved for those with end-stage liver disease.

esophageal varices dx

Ultrasonography can be used to evaluate portal hypertension and esophageal varices in the upper abdomen. Computed tomography scanning and magnetic resonance imaging can also be used as second- and third-line modalities. For patients with esophageal varices, an esophagogastroduodenoscopy (EGD) is the diagnostic and therapeutic tool of choice. Visualization of the varices and their condition can be used in the development of a management plan. Any active bleeding can also be addressed and treated at the time of endoscopy

which varices are most likely to hemorrhage?

Varices that are closest to the gastroesophageal junction are the thinnest and most likely to hemorrhage. Other risk factors for hemorrhage include varix size (the larger the vein, the higher the risk of rupture), the presence of ascites, endoscopic evidence of red color signs (e.g., cherry red spots), active alcohol use in patients with existing liver disease, and bacterial infection.

A 52-year-old man with a history of alcoholic cirrhosis presents with altered mental status and hematemesis. The patient was intubated in the ED, and ICU treatment included blood transfusions, ceftriaxone, octreotide, and, prior to endoscopy four hours after admission, a dose of erythromycin. During endoscopy, a 4 mm esophageal varix with spurting blood is identified and cannot be controlled with band ligation. Which of the following is the best next step?

balloon tamponade

If there is suspected biliary obstruction,

biliary imaging is warranted with MRI or CT scan.

Conjugated bilirubinemia is caused by

biliary obstruction, hepatitis, certain drugs or toxins, and some inherited disorders.

An elevation in both GGT and alkaline phosphatase suggests

cholestasis

hepatic carcinoma risk factors

chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, chronic alcoholic cirrhosis, nonalcoholic fatty liver disease, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson disease, and hemochromatosis. Patients of Hispanic or Asian descent or with decompensated cirrhosis have a worse prognosis.

Hepatic encephalopathy

consists of a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction. The pathogenesis is multifactorial, but the accumulation of ammonium and other toxins plays an important role

A 56-year-old man presents with epigastric pain, accompanied by yellowing of the whites of his eyes and intense itching. He also reports dark urine and gray stools. On exam, he is noted to have generalized jaundice, scleral icterus, and pallor. Elevated bilirubin is seen on urinalysis. Laboratory studies demonstrate an elevated total bilirubin. Transabdominal ultrasound reveals common bile duct stones and common bile duct dilation. Which of the following history and physical exam findings is specific to the type of hyperbilirubinemia the patient is experiencing?

dark urine

Clinical manifestations of jaundice may include

dark urine and pale stools (only seen with conjugated hyperbilirubinemia), scleral icterus, and pruritus.

Causes of conjugated hyperbilirubinemia include

decreased intrahepatic excretion of bilirubin (hepatocellular disease, Dubin-Johnson syndrome, rotor syndrome, drug-induced, primary biliary cholangitis, primary sclerosing cholangitis) and extrahepatic biliary obstruction (gallstones, choledocholithiasis, carcinoma of the head of the pancreas, cholangiocarcinoma, periampullary tumors, extrahepatic biliary atresia)

The first step in treating hepatic encephalopathy is

determining the appropriate care setting. Patients with grade I and sometimes grade II hepatic encephalopathy may be discharged if there is a proper caregiver at home. Patients with grade III or IV must be admitted to the hospital and often to the intensive care unit. Lactulose is a synthetic disaccharide used to treat hepatic encephalopathy. Lactulose is titrated to a dose that gives patients two or three loose bowel movements per day. Rifaximin is a nonabsorbable antibiotic that can be administered in addition to lactulose for patients who do not improve with lactulose alone. Patients with recurrent hepatic encephalopathy can be treated with lactulose and rifaximin on a maintenance dose to prevent hepatic encephalopathy.

A 66-year-old man presents to his primary care provider with complaints of fatigue and decreased appetite for the past 3 months. He reports an unintentional 20-pound weight loss in the past 3 months. He has a history of chronic hepatitis C. Which of the following tumor markers is associated with the most likely diagnosis?

elevated alpha fetoprotein

Precipitating causes include

gastrointestinal bleeding, infection, constipation, medication noncompliance, kidney injury, or metabolic derangements.

A 72-year-old man with a history of cirrhosis presents to the emergency department with acute confusion. His wife reports he ran out of his lactulose 3 days ago. On exam, the patient is lethargic but arousable and has asterixis. Laboratory findings reveal a normal basic chemistry panel, and CT of the head shows no acute abnormalities. What is the most likely diagnosis?

grade II hepatic encephalopathy

Normal alkaline phosphatase with normal aminotransferase levels in the setting of jaundice suggests

hemolysis or Gilbert or Crigler-Najjar syndrome

Unconjugated causes of hyperbilirubinemia include

hemolysis, impaired bilirubin conjugation, or impaired bilirubin uptake

Predominant elevation of serum alkaline phosphatase in relation to the serum aminotransferases suggests

intrahepatic cholestasis or biliary obstruction (potentially caused by a tumor) instead of acute hepatic injury.

Conjugated (direct) bilirubin

is loosely bound to albumin and thus is water-soluble, making it more likely to be excreted via urine when it is present in excess. Therefore, dark urine (as well as pale stools) is only seen with conjugated hyperbilirubinemia.

Unconjugated (indirect) bilirubin

is tightly bound to albumin and is not water-soluble. Excess production of unconjugated bilirubin cannot be excreted in the urine.

An accumulation of bilirubin caused by abnormalities in transport, metabolism, or excretion causes

jaundice or icterus

The most common cause of esophageal varices in adults is

liver cirrhosis, with alcoholic and viral cirrhosis being the leading causes in the United States.

A 45-year-old obese man presents to your office for his annual physical exam. He has questions about risk factors for the development of hepatocellular carcinoma given his weight. Which of the following is a risk factor?

non alcoholic fatty liver disease

Jaundice results from

overproduction or underexcretion of bilirubin and is characterized by the yellow coloration of the skin, mucous membranes, and sclerae.

A 72-year-old man with a history of pancreatic cancer presents with jaundice. He states that he is otherwise feeling well and reports no nausea, vomiting, or bowel changes. Physical exam reveals mild epigastric tenderness, scleral icterus, and jaundice. Laboratory studies are completed. Which of the following would be most consistent with the suspected diagnosis?

predominant alkaline phosphatase elevation

Elevated alkaline phosphatase can be normal in

pregnancy and healthy children.

Bilirubin is metabolized in three phases:

prehepatic, intrahepatic, and posthepatic.

A 55-year-old man with alcoholic liver disease presents to the office with upper abdominal pain, weight loss, and anemia. An endoscopy reveals the presence of small- to medium-sized esophageal varices. Which of the following medications is used as primary prophylaxis for the prevention of variceal hemorrhage?

propranolol

jaundice dx

testing bilirubin levels, measuring aminotransferases, and measuring alkaline phosphatase. In addition, gamma-glutamyl transpeptidase (GGT) should be measured when investigating jaundice

hepatic carcinoma signs and symptoms

weakness, fatigue, unintentional weight loss, decreased appetite, right upper quadrant pain, abdominal distension, ascites, hepatomegaly, jaundice, or white, chalky stools.