Physical Examination

The physical examination is invaluable in establishing a diagnosis of cirrhosis. The liver may be enlarged in early stages or shrunken and firm in more advanced cirrhosis. Abdominal ascites with a fluid wave might be present.

There may be evidence of temporal muscle wasting in a decompensated cirrhotic patient. Jaundice and scleral icterus are usually detected at total bilirubin levels above 3 to 4 mg/dL. Spider angiomas—visible small arterioles—are common, particularly on the upper arms and chest.

Several findings are noted on examination of the hand. Palmar erythema is characterized by redness of the ball of the palm with the thenar and hypothenar eminences. Dupuytren’s contracture may be a nonspecific finding but is often seen in alcoholic liver disease; it involves the fourth and fifth fingers because of thickening of the palmar fascia. White nails and clubbing are often present. Asterixis (flapping tremor) may also be noted in decompensated patients with hepatic encephalopathy.

Gynecomastia, testicular atrophy, and pectoral alopecia are also commonly present. Xanthelasma, xanthomas, and calcinosis can be seen in patients with biliary cirrhosis. Xanthelasmas usually occur below the inner canthal fold of the eye and the eyelid. Xanthomas are most commonly found in the creases of the hands, arms, and legs. Calcinoses typically occur at pressure points such as the elbow and the ulnar surface of the forearm. Ascites, peripheral edema, splenomegaly, umbilical hernia, and caput medusae are seen in patients with advanced cirrhosis.

Disease Course

Patients with cirrhosis may live productive lives, but their disease may cause complications and death. Complications of cirrhosis include portal hypertension, often associated with the development of esophageal varices, hepatic encephalopathy, ascites, and spontaneous bacterial peritonitis. Furthermore, cirrhosis can lead to the development of hepatocellular carcinoma. Once a cirrhotic patient experiences a complication of portal hypertension with evidence of decreased hepatic synthetic function, or develops a hepatocellular tumor, the overall prognosis is very poor, and the patient should be evaluated for liver transplantation.

DIAGNOSTIC STUDIES

The evaluation, diagnosis, and treatment of patients with cirrhosis are expensive endeavors. Duplicate workups, such as performing a liver and spleen nuclear scan in a patient scheduled for a liver biopsy, add little to the diagnosis and should be minimized. However, much of the cost is incurred during evaluation and symptomatic treatment of various complications of chronic liver disease, and optimal therapy without unnecessary costs can be obtained only with accurate diagnosis and evaluation.

Laboratory Tests

Routine laboratory tests play a crucial role in recognizing chronic liver disease and subsequently delineating the etiology, particularly in healthy, asymptomatic persons. Rather than a single specific test, the combination of several tests assessing different aspects of hepatic physiology, measured over a period of time, can lead to the diagnosis.

Serum aminotransferase levels are a sensitive indicator of liver cell injury and hepatocellular necrosis. Alanine aminotransferase (ALT; or serum glutamic puruvic transaminase [SGPT]) and aspartate aminotransferase (AST; or serum glutamic oxaloacetic transaminase [SGOT]) are two such enzymes commonly measured in the routine assessment of liver dysfunction. ALT is thought to be more sensitive and specific for liver injury because it is present in highest concentration there, whereas AST is found in the liver, cardiac, and skeletal muscles; the kidneys; the brain; and elsewhere. Aminotransferase levels are usually elevated in all liver disorders. However, in cirrhosis, the degree of elevation is less than that in acute hepatitis and rarely rises above eight times the upper limit of normal except during flare-ups of chronic viral and autoimmune hepatitis. The AST:ALT ratio is of little diagnostic value except in the recognition of alcoholic liver disease, in which the AST: ALT ratio is often >2. It should be noted that the AST:ALT ratio can also be >2 in the presence of cirrhosis from any etiology.

The serum bilirubin level depends on a balance between the rate of production and removal from the liver. Unconjugated (indirect) hyperbilirubinemia results from overproduction (e.g., hemolysis) or impaired hepatic uptake or conjugation, as in Gilbert’s syndrome, which is a benign hereditary condition of mildly increased levels of serum unconjugated bilirubin. Conjugated (direct) hyperbilirubinemia results from decreased hepatic excretion or leakage of the conjugated bilirubin from diffuse liver injury or damaged bile ducts. Detection of bilirubin on a routine urinalysis indicates the presence of hepatobiliary disease because the unconjugated bilirubin is not excreted by the kidney.

The biosynthetic capacity of the liver is assessed by serum albumin and prothrombin time. Albumin is synthesized exclusively by the liver, and hypoalbuminemia is common in cirrhosis. A serum albumin level below 3 g/dL usually reflects severe liver damage. The liver is the most important site of synthesis for most blood coagulation proteins, and various components of the clotting cascade may be abnormal in cirrhosis. The prothrombin time is a most useful test in predicting the severity of hepatocellular damage. On a complete blood count, thrombocytopenia or leukopenia may be found (from hypersplenism secondary to portal hypertension), and microcytic anemia (from chronic gastrointestinal blood loss) or macrocytic anemia (e.g., alcoholic liver disease) is commonly present.

Imaging

Noninvasive radiologic imaging studies such as abdominal ultrasound with Doppler, computed tomography scanning, or magnetic resonance imaging can be suggestive of cirrhosis if there is caudate lobe hypertrophy or the liver appears morphologically nodular, especially amid radiographic findings of portal hypertension such as splenomegaly and ascites. In most cases, abdominal ultrasound is sufficient, unless the patient’s body habitus precludes an accurate study. If findings of cirrhosis appear incidentally on abdominal imaging, the laboratory tests mentioned earlier should be collected and the patient referred to a gastroenterologist for further evaluation.

Liver Biopsy

Although not a routine study, a liver biopsy is sometimes necessary to diagnose cirrhosis and confirm the etiology. The biopsy, often done via a percutaneous approach in an outpatient setting, should be done only after clotting factors are assessed and a complete blood count, including platelet count, is done. If ascites or severe coagulopathy and/or thrombocytopenia are present, a transjugular approach is preferred. This method has the added benefit of being able to measure estimated portal pressure. The results of a biopsy are not always conclusive, and further testing may have to be done.

Specific Findings

Detection of hepatitis B surface antigen in cirrhotic patients typically establishes the diagnosis of hepatitis B cirrhosis, whereas HCV infection is diagnosed by testing for anti-HCV antibody. If a test for anti-HCV by second-generation enzyme linked immunosorbent assay (ELISA) is positive, HCV RNA by polymerase chain reaction should be performed to confirm active HCV infection (as opposed to cleared), especially if antiviral therapy is being considered.

Autoimmune hepatitis is characteristically associated with hyperglobulinemia and circulating autoantibodies such as anti-nuclear and anti–smooth muscle antibodies. Often, one clue to its diagnosis is the coexistence of other diseases with immune or autoimmune features, such as thyroiditis (Krawitt, 2008). The diagnosis of primary biliary cirrhosis is made by a combination of positive antimitochondrial antibodies and increased immunoglobulin M on immune protein electrophoresis, in addition to characteristic histological findings on liver biopsy (Lindor et al., 2009). Primary sclerosing cholangitis is diagnosed when endoscopic retrograde cholangiopancreatography demonstrates the characteristic beaded bile duct appearance.

Hemochromatosis is an autosomal recessive metabolic disorder in which there is increased iron absorption over many years. Elevated serum ferritin levels and an increased percentage of transferrin saturation are typical biochemical findings. However, the best method of confirming the diagnosis is to measure quantitative hepatic iron content through liver biopsy. Alpha-1-antitrypsin deficiency is an inherited condition in which early-onset emphysema and a variable spectrum of liver disease can be found. About 1% of adult patients with cirrhosis are homozygous deficient. An adult with diagnosis of cryptogenic cirrhosis should be evaluated for this disease, and serum alpha-1-antitrypsin level should be measured and Pi typing carried out.

Another hereditary condition, Wilson’s disease, is an autosomal recessive disorder resulting in abnormalities in copper metabolism. Deficiency of the plasma copper protein ceruloplasmin, because of its impaired synthesis, is seen in more than 95% of these homozygote patients.

TREATMENT OPTIONS, EXPECTED OUTCOMES, AND COMPREHENSIVE MANAGEMENT