Chapter 12 Clinical investigation of hepatopancreaticobiliary disease

Despite the rapid increase in diagnostic modalities available to the clinician dealing with hepatobiliary disease, a detailed history and clinical examination are crucial if an accurate overall assessment is to be made. With advances in technology, an array of diagnostic modalities is at the disposal of the physician. These include better availability of tumor markers and more sensitive and specific imaging. A systematic approach is important to rationalize the use of these techniques. Multidisciplinary assessment allows more accurate diagnosis and disease staging, while avoiding unnecessary and expensive investigations. This chapter addresses the specific features in the history and clinical examination that are of particular importance in hepatobiliary and pancreatic disease.

Clinical History and Physical Examination

The clinical investigation of patients with hepatobiliary and pancreatic disease begins with a detailed history and physical examination that will direct the sequence of subsequent investigations. The history should begin with the presenting complaint and then proceed with a systematic inquiry into hepatopancreatobiliary symptoms. The history should include details of gastrointestinal symptoms including anorexia, nausea, vomiting, and any alteration of bowel habit, because this may indicate the source of a liver mass (e.g., colorectal metastasis to the liver). The history also should include a careful assessment of pain, itching, or jaundice and a comprehensive past medical history, family history, foreign travel history, and drug history, including alcohol intake and smoking. The general symptoms of liver dysfunction include weakness, fatigue, anorexia, nausea and vomiting, weight loss or gain (related to ascites), disordered taste and smell, muscle cramps, and impotence. Specific symptoms of liver dysfunction relate to ascites (abdominal distension and oliguria), coagulopathy (excessive bruising or bleeding), cholestasis (itching), and jaundice.

Examination should assess the presence or absence of the stigmata of chronic liver and biliary disease (see Chapter 7), including jaundice, pruritus, spider nevi (Fig. 12.1), hepatosplenomegaly (Fig. 12.2), ascites (Fig. 12.3), and caput medusae. Abnormal abdominal masses should also be noted. The circulation in patients with liver failure is hyperdynamic with flushed extremities and a bounding pulse, and peripheral cyanosis may be evident. Fetor hepaticus—a sweet, musty odor of the breath—is associated with hepatocellular failure and is thought to be related to changes in the gut flora (Challenger & Walsh, 1995). Spider nevi are angiomata that occur in the vasculature of the superior vena cava, and their disappearance and reappearance vary with liver function and are thought to be associated with estrogen excess (Bean, 1959). Palmar erythema (Fig. 12.4) affects the thenar and hypothenar eminences and is associated with the hyperdynamic state. Other changes include loss of axillary and pubic hair and whitening of the nails (Lloyd & Williams, 1948). Gynecomastia (Fig. 12.5) and testicular atrophy can also occur.

FIGURE 12.1 Spider nevus in a patient with cirrhosis.

FIGURE 12.2 Hepatomegaly and Dupuytren contracture in a patient with extensive cirrhosis.

FIGURE 12.3 Ascites with an everted umbilicus and venous distension in a patient with cirrhosis.

FIGURE 12.4 Palmar erythema affecting the thenar and hypothenar eminences.

FIGURE 12.5 Bilateral gynecomastia in a patient with alcoholic liver disease.

Chronic encephalopathy associated with portal hypertension and portosystemic shunting varies in severity, producing symptoms that range from mild confusion and a shortened attention span to marked intellectual deterioration that may end in coma. Psychomotor tests have been devised to quantify the intellectual deterioration and allow monitoring (Sherlock & Dooley, 2002). A flapping tremor of the extended wrist (“liver flap”) and later cogwheel rigidity and ankle clonus may be present. Acute liver failure is associated with jaundice, confusion, delirium, and renal failure. These features may occur on a background of cirrhosis, and the precipitating cause may be treatable (e.g., infection).

Patients also may be seen with acute abdominal pain or jaundice. Examination may reveal localized peritonism in the right upper quadrant or epigastrium with a tender mass or generalized peritonitis in cases of gallbladder perforation or severe pancreatitis. A Murphy sign is a “catch” in the breath elicited by gently pressing on the right upper quadrant and asking the patient to take a deep breath. A Boas sign is hyperesthesia of the skin over the lower right ribs posteriorly. One or both of these signs may be found in acute cholecystitis. Erythema ab igne is caused by prolonged local application of heat and may be evident in the right upper quadrant in patients with chronic gallbladder disease or, more commonly, on the back in patients with chronic pancreatitis (Fig. 12.6). In Asia, bleeding from a ruptured hepatocellular carcinoma is a common acute presentation. Patients with severe acute pancreatitis may develop a bluish discoloration of the flanks as a result of retroperitoneal bleeding (Turner sign) or in the periumbilical area (Cullen sign; Fig. 12.7).

FIGURE 12.6 This patient has long-standing chronic pancreatitis that affects the entire length of the pancreas with severe flank and back pain on the left side. Prolonged application of local heat has resulted in marked rash of erythema ab igne.

FIGURE 12.7 Turner sign (A) and Cullen sign (B) in patients with acute pancreatitis.

Examination of the Liver

The liver is examined using a combination of palpation and percussion from above and below to delineate its borders. Dullness to percussion of the upper border extends as far as the fifth intercostal space. Auscultation is also important, because a venous hum may be heard with portal hypertension, and a bruit may be heard in association with hepatocellular carcinomas. The normal liver is usually impalpable; however, in asthenic individuals, the anterior edge may be palpable. Enlargement of the liver occurs in many pathologic states, although a tonguelike extension from the right lobe—a Riedel lobe, which is of no pathologic significance—may be mistaken for a tumor (Fig. 12.8). Causes of hepatomegaly are listed in Table 12.1. A lobe may undergo hypertrophy and become palpable, and this may occur in the presence of liver atrophy or after liver resection. Reduction in liver size also is important, because this may occur in cirrhosis and certain types of hepatitis. Consistency also is relevant; a hard, knobbly liver often represents the presence of metastases, whereas smooth enlargement may be due to cirrhosis.

FIGURE 12.8 Coronal magnetic resonance image of a Riedel lobe of liver. This normal variant, a tonguelike extension from the right lobe, may be mistaken for a mass or an enlarged liver on physical examination.

Table 12.1 Causes of Hepatomegaly

Variant Anatomy

Riedel lobe

Low-lying diaphragm

Inflammatory

Hepatitis

Abscesses, amebic and pyogenic

Schistosomiasis

Cirrhosis, early

Sarcoid

Biliary obstruction, especially extrahepatic

Metabolic

Amyloid

Steatohepatitis

Glycogen storage disease

Hematologic

Leukemias

Lymphomas

Myeloproliferative disorders

Sickle cell disease

Porphyrias

Tumors

Primary, benign and malignant

Secondary

Cardiovascular

Cardiac failure

Hepatic vein obstruction

Examination of the Spleen

Examination of the spleen should begin in the right iliac fossa and proceed toward the left subcostal region, because this is the direction in which splenomegaly occurs. Rotation of the patient 45 degrees to the right may aid palpation, because the spleen then falls onto the examining right hand. During this maneuver, the left hand should support the rib cage and relax the skin and abdominal musculature by drawing these down to the right. Percussion may be useful, and if ascites is present, the spleen may be ballotable. If the spleen is sufficiently enlarged, the notch on its anterior border may become palpable. Causes of splenomegaly are listed in Table 12.2.

Table 12.2 Causes of Splenomegaly

Infection

Acute: viral, bacterial

Chronic: tuberculosis, brucellosis

Parasitic: malaria, schistosomiasis

Hematologic

Leukemias

Hemolytic anemias

Hemoglobinopathies

Portal hypertension, especially extrahepatic

Neoplastic

Lymphomas

Myeloproliferative disorders

Inflammatory

Signs of Portal Hypertension

Portal hypertension (see Chapter 70A, 74 ) is due to either intrahepatic or extrahepatic portal venous obstruction. Intrahepatic portal hypertension usually is associated with hepatomegaly and may be accompanied by splenomegaly and ascites. Dilated abdominal wall veins also may be found secondary to portosystemic anastomosis, giving rise to a caput medusae. The more common clinical site of portosystemic anastomosis is at the gastroesophageal junction, leading to esophageal varices; any evidence of upper gastrointestinal blood loss, whether hematemesis or melena, should be investigated with urgent endoscopy (see Chapter 75A). Rarely, these patients may develop hemorrhoidal varices around the anus as a result of portosystemic anastomosis.

Extrahepatic portal hypertension is usually due to portal vein thrombosis, and as such it is important to identify any history of neonatal infection around the umbilicus, major intraabdominal sepsis, pancreatic cancer, or a blood disorder that might lead to hypercoagulability. These patients almost invariably have splenomegaly, often associated with pancytopenia. In such cases, the liver is normal, but ascites may be present. A palpable spleen in the upper left abdomen associated with portal hypertension may be found in the event of splenic occlusion caused by tumor or chronic pancreatitis.

Clinical Features of Alcoholic Liver Disease

The symptoms and signs of alcoholic liver disease may be related directly to alcoholism or to secondary hepatocellular dysfunction. Patients commonly experience repeated falls while inebriated and may have signs of trauma and bruising. Multiple “old” rib fractures are common findings on chest radiographs and are related to such behavior. Alcoholic neuropathy also may be present, especially given the malnourished state of many patients. Acute alcoholic hepatitis usually occurs after a bout of drinking and may be associated with liver tenderness, jaundice, pyrexia, and leukocytosis. Advanced alcoholic liver disease may be associated with other manifestations of hepatic impairment (e.g., portal hypertension, ascites, hepatomegaly, liver failure).

Clinical Features of Other Types of Liver Disease

Primary Biliary Cirrhosis

Primary biliary cirrhosis, or chronic nonsuppurative destructive cholangitis, usually affects middle-aged women. Asymptomatic individuals may be diagnosed during routine examination, where they are found to have hepatomegaly, elevated autoantibodies, or elevated plasma alkaline phosphatase. The earliest symptom is usually pruritus, even before clinical jaundice is apparent, but later the patient may develop overt jaundice; hepatosplenomegaly; xanthelasma, especially in the palms and around the eyes; vitiligo; and arthritis. Primary biliary cirrhosis often is found in association with connective tissue disease.

Ulcerative Colitis and Crohn Disease

Ulcerative colitis and Crohn disease are associated with hepatobiliary disorders, especially primary sclerosing cholangitis (see Chapter 41). It is important to include a detailed gastrointestinal systems review and investigations in any patient with unexplained liver disease.

Budd-Chiari Syndrome

This syndrome is characterized by venous outflow obstruction to the liver, which could be intrahepatic or extrahepatic (see Chapter 77). Acute venous obstruction is usually secondary to another pathologic process and presents with abdominal pain, vomiting, hepatomegaly, ascites, and jaundice, which may be mild. Hepatocellular failure leading to death is usually rapid. Chronic venous obstruction of the liver usually presents with ascites and hepatomegaly. If the inferior vena cava (IVC) is blocked with tumor or thrombus, gross edema of the legs and superficial venous distension of the abdominal veins is apparent. Diagnosis is made on imaging.

Hemochromatosis

Hemachromatosis is an iron overload state in which the liver is usually affected. Excess iron deposition leads to fibrosis and cirrhosis with an increased risk of developing hepatocellular carcinoma. Clinically, hemochromatosis usually presents between the ages of 40 and 60 years. Symptoms are usually nonspecific with lethargy, increased pigmentation, loss of body hair, loss of libido, arthralgia, and diabetes, usually due to the involvement of the pancreas. Clinical examination may show hepatomegaly and hyperpigmentation in the axillae, groins, and genitalia as well as testicular atrophy. Diagnosis is made by hematologic tests including serum iron, serum ferritin, and serum transferrin; liver damage can be assessed with a liver biopsy.

Polycystic Disease

Symptoms of polycystic disease are usually caused by the mass effect of the enlarged liver (see Chapter 69A). Abdominal distention and breathlessness are common. Early satiety and vomiting can occur because of pressure on the stomach. Acute abdominal pain is usually due to infection or bleeding into a cyst.

Acute Liver Failure

Acute liver failure (ALF) is characterized by massive cellular injury to a previously healthy liver, and it is associated with the development of hepatic encephalopathy (see Chapter 72). This can occur as a result of paracetamol (acetaminophen) toxicity, usually caused by overdosage, or from a massive viral infection. ALF is associated with a high mortality and requires careful monitoring. Orthotopic liver transplantation is the only effective treatment for this condition, although some cases of ALF can recover spontaneously. Donor organ shortage has dictated the development of criteria that can help to predict whether a patient with ALF has a potential to recover or whether a liver transplant is required. More recently, these criteria have also been used to predict the prognosis of patients with cirrhosis undergoing surgery for hepatocellular carcinoma (Kuang et al, 2009). Various sets of criteria have been proposed, of which the Model for End-Stage Liver Disease (MELD) and the King’s College Hospital (KCH) criteria are the best known. Most criteria utilize prothrombin time/INR, serum bilirubin, serum creatinine, arterial blood pH, and hepatic encephalopathy in categorizing patients’ disease severity.