Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (180 page)

•   Hypokalemia (early), with metabolic alkalosis

•   Respiratory alkalosis

•   Lactic acidosis

•   Hyponatremia, hypophosphatemia

•   Hypoglycemia in approximately 5% of patients

   Renal function tests may be abnormal. Hepatorenal syndrome may develop.

   Postacute Hepatitis Phase

In uncomplicated viral hepatitis, symptoms of the acute phase should resolve within 1 to 6 months, depending on the virus, with correction of the biochemical abnormalities in the subsequent months. Persistence of clinical or biochemical abnormalities suggests progression to chronic hepatitis in hepatitis B, C, or D infections.

   Resolution: During recovery, systemic symptoms abate. Liver tenderness and biochemical abnormalities may persist. Complete clinical and biochemical recovery occurs 1–2 months after HAV and HEV infections and 3–6 months after uncomplicated HBV. HAV and HEV infections are not associated with progression to chronic infection. HBV, HCV, and HDV may progress to chronic infection. Recovery from acute HBV infection is more likely after clinically apparent (icteric) versus subclinical infection

   Chronic infection

   The persistence of clinical and laboratory abnormalities for >6 months after acute hepatitis is characteristic of chronic infection. Chronic liver infection may develop with HCV, HBV, or HBV plus HDV infections. The clinical presentation varies from asymptomatic disease through progression to end-stage liver failure. Signs and symptoms may be fairly constant or marked by flares in severity, increasing the progression of liver injury. Cirrhosis may develop. Liver damage is influenced by virus factors, as discussed later, and host factors. Host factors include coexisting diseases, especially liver disease, the host immune response, and alcohol consumption or exposure to other hepatotoxins.

   The degree of laboratory abnormalities may not accurately reflect the degree of histologic changes. Aminotransferase elevation may be variable. In mild disease, ALT elevation is typically greater than the degree of AST elevation. Marked elevation of bilirubin levels is associated with advanced liver damage and cirrhosis. In advanced cirrhosis, the pattern of aminotransferase elevation is usually reversed, with the degree of AST elevation exceeding that of ALT elevation. The synthetic function of the liver decreases with advanced chronic disease and cirrhosis, with resulting clinical manifestations of coagulopathy, metabolic derangements, and so on.

   
Hepatocellular carcinoma
: Hepatocellular carcinoma (HCC) may occur as a complication of chronic viral hepatitis. In HBV infection, HCC may occur in patients with or without cirrhosis. Risk factors for the development of HCC in HBV-infected patients include infection early in life, coexisting immunocompromising diseases, and HDV coinfection. HCC may also complicate HCV infection but occurs only in patients with cirrhosis.

HEPATITIS VIRUSES

Most cases of acute viral hepatitis in the United States are caused by HAV, HBV, and HCV. In a CDC surveillance survey in 2012, there were an estimated 69,000 new cases of acute hepatitis caused by these agents (50% HBV; 25% HAV; 25% HCV).

   The acute hepatitis panel (HBsAg, total anti-HBc, IgM anti-HBc, IgM anti-HAV, and total anti-HVC) is recommended for evaluation of patients with suspected acute infectious hepatitis. Repeat testing to confirm negative results may be considered in patients at high risk for viral hepatitis. In addition, testing for rheumatoid factor may be considered if false-positive antibody tests are suspected. Further testing is determined by results of the initial screening tests. Repeat screening after negative results should be considered for patients with a high clinical suspicion or prior risk in order to rule out false-negative results due to a window period. Window periods represent intervals prior to immune response or during a transition from phases of antigen predominance to antibody predominance (e.g., HBsAg positive → anti-HBs positive). There are no FDA-approved diagnostic tests for HDV or HEV; diagnostic testing, when indicated, may be pursued through the CDC/Public Health Laboratory or Reference Laboratories. Specific testing for HDV is not necessary if HBV infection has been ruled out. Testing for HEV is usually unneeded unless a patient has recently traveled to an area where HEV infection is endemic. Specific hepatitis viruses and diagnostic testing are presented in subsequent text of this Chapter.

   Hepatitis Viruses Transmitted by Enteric Routes (HAV and HEV)