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Figure 58-7. Hepatic schistosomiasis. A hepatic granuloma surrounds a degenerating egg of Schistosoma mansoni. (Reproduced with

permission from Rubin E, Farber JL. Pathology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999.)

Preferred treatment of schistosomiasis is praziquantel, with cure efficacy around 90%. Treated

patients should also undergo evaluation and management of any esophageal varices that may have

developed.17,18

VIRAL HEPATITIDES

3 Viral hepatitis represents an important cause of chronic liver disease, cirrhosis, and hepatocellular

cancer. Infection is pandemic in the United States and worldwide. Hepatitis C has become the most

common indication for liver transplant in the United States and its recurrence has been the most

common cause for graft loss after transplant. Liver transplant for hepatitis B has shown greatly

improved results in recent years due to improved antiviral treatment. Hepatitis C is now following the

same trajectory with the advent of effective antivirals.

The mechanism of liver injury is largely a host inflammatory response to virus. Table 58-1

summarizes current understanding of the characteristics of the five viruses most commonly associated

with clinical hepatitis, their modes of transmission, and the consequences of infection.

GB Virus, formerly known as hepatitis G virus (HGV) does not appear to be deleterious to the liver.

Other viral infections can produce acute hepatitis, particularly in immunocompromised hosts (e.g.,

Epstein–Barr virus, cytomegalovirus, herpes simplex virus, and varicella zoster virus). In some cases the

hepatitis caused by these viruses in association with systemic symptoms can be severe and liver

involvement may be the dominant manifestation of the patient’s illness.

HEPATITIS A VIRUS

Molecular Structure

Hepatitis A virus (HAV) was identified in 197327 and belongs to the Picornaviridae family, genus

Hepatovirus. Four distinct genotypes have been identified and all four genotypes belong to a single

serotype.28 HAV is a single-stranded RNA virus that is 27 nm in diameter and is nonenveloped. The viral

genome is 7,474 nucleotides in length and is divided into 5- and 3-in untranslated regions and a single

long open reading frame that encodes a 2,227 amino acid polypeptide. Upon processing this peptide

yields four structural and seven nonstructural proteins.

Epidemiology/Risk Factors for Transmission

Hepatitis A has been long known (epidemic jaundice, catarrhal jaundice, campaign jaundice) and

continues to occur worldwide. The incidence in the United States has declined with effective vaccination

but remains around 1.2 per 100,000.29

The major mode of transmission is fecal–oral and it is more common in lower socioeconomic areas

where sanitation is poor. Common risk factors in the United States are international travel, especially to

Mexico or Central/South America; household contact with an infected family member; homosexual

activity in men; ingestion of contaminated foods (shellfish, green onions, frozen strawberries) or

waterborne outbreaks; children in daycare centers; and injection drug use.30 Humans are the only host

for HAV and the liver is the only affected tissue.

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Clinical Features

Hepatitis A infection almost universally results in an acute, self-limited illness and can produce either

icteric or anicteric syndromes (Fig. 58-8). The incubation period is 28 days. The anicteric prodrome lasts

from 2 days to 3 weeks and typically consists of fatigue, malaise, nausea, vomiting, anorexia, fever, and

right upper quadrant pain. The diagnosis may be missed in cases without jaundice. In cases where

jaundice becomes manifest, it persists for 1 to 6 weeks. Transaminase levels are typically above 1,000

IU/mL, serum bilirubin above 10 mg/dL, and alkaline phosphatase values are elevated as well. Serum

IgM antibodies are detected in 95% of patients and are the gold standard of diagnosis. IgG antibodies

become elevated as jaundice subsides and may persist for years.

Table 58-1 Classification of Viral Hepatitis

HAV leads to fulminant liver failure in 0.01% to 0.35% of cases of acute HAV infection. This rare

event mostly occurs in patients with underlying liver disease, especially chronic hepatitis C infection

and less commonly hepatitis B infection or alcoholic liver disease. The risk of fulminant failure is also

higher in people over 40 years of age, intravenous drug abusers, men who have sex with men, and in

inhabitants of endemic areas.31

Figure 58-8. Clinical course of hepatitis A infection.

Treatment

Most patients with HAV infection recover with supportive care; approximately 20% require

hospitalization in large outbreaks. Infection control measures such as hand washing and isolation should

be a top priority to prevent spread of virus. Fecal shedding of virus occurs even prior to onset of

symptoms and jaundice. Spontaneous recovery and survival even in cases of acute liver failure (ALF)

may be as high as 50%. Liver transplantation is indicated in cases in which recovery seems unlikely.

Recurrence of HAV in the allograft may be encountered and administration of immunoglobulin may be

beneficial in such instances.31,32

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A formalin-inactivated HAV vaccine is safe and effective in almost all recipients after two doses.

Vaccination is recommended by the CDC for children 2 years of age or older in states or countries with

high rates of infection (20 or more cases per year per 100,000 population) as well as in individuals at

high risk such as persons infected with hepatitis B or C. Immune globulin administered within the first

14 days of exposure prevents disease in more than 85% of cases. Close contacts of patients with recent

onset of the illness, people exposed to contaminated foods, and selected travelers to endemic areas

benefit the most.33

HEPATITIS B VIRUS

Molecular Structure

Hepatitis B Virus (HBV) is a DNA virus that belongs to the hepadnavirus family. It is the smallest DNA

virus with the ability to infect humans. HBV virions are 40 to 42 nm in diameter, with a double shell

and an outer lipoprotein envelope. The viral nucleocapsid, or core, contains a 3.2-kb partially duplex

DNA and a polymerase. Replication resembles that of retroviruses, in which the viral DNA polymerase

acts as a reverse transcriptase. The HBV polymerase lacks proofreading activity. This is associated with

an estimated 105 to 106 mutations per nucleotide per year and the resultant development of mutant

forms of the virus.34–36

Epidemiology/Risk Factors for Transmission

It is estimated that over 350 million people worldwide are infected by HBV. In the developing world,

perinatal infection is the most common mode of transmission. In the United States, transmission is

primarily sexual as the virus is present in semen and vaginal fluids in addition to blood. Infection from

intravenous drug use and occupational infections due to percutaneous exposure also occur. There are no

known animal reservoirs or evidence that insects are involved in transmission of HBV. The hepatitis B

virus replicates mainly in hepatocytes but is not itself cytotoxic. Liver injury is due to the resultant host

immune response.

Clinical Features

The incubation period for HBV is 8 weeks. The presence of serum hepatitis B surface antigen (HBsAg)

may precede jaundice. Acute infection is associated with detectable serum HBV DNA, hepatitis B early

antigen (HBeAg), and IgM to hepatitis B core. HBeAg is a useful marker of viral replication except in

patients with mutant viruses where it may be undetectable despite active replication (Fig. 58-9). In such

cases detection of HBV DNA is diagnostic. Serum anti-HBc IgM becomes detectable with the onset of

jaundice. In most patients, when HBV does not develop into chronic hepatitis, anti-HBc IgM becomes

undetectable after 6 months. On occasion, however, it may persist for years after the acute infection or

may recur as an amnestic phenomenon in reactivating chronic hepatitis B, thus limiting its usefulness as

a marker of acute HBV infection.

Although HBV accounts for 40% of ALF in developing countries, it is estimated that the incidence in

the United States is about 10%. Hepatitis B becomes fulminant in about 1% of acute infections. Women,

elderly individuals, and those who sustain superinfection with another virus (such as HCV) seem to be

at greater risk. Furthermore, the risk of ALF seems to be proportional to antibody titers of HBcAg and

HBsAg. Some cases of ALF may be due to reactivation of HBV in patients with chronic infection. In cases

of reactivation, reappearance of HBc IgM antibodies aids in the diagnosis. Spontaneous survival after

HBV ALF is in the 25% range.37,38

Most patients with acute HBV infection in the Western world recover completely. Approximately 25%

of these patients will develop jaundice but do not become HBV carriers. They will usually retain HBcAb

and HBsAb markers with no detectable HBsAg or HBV DNA. Approximately 10% of Western adults with

HBV infection do progress to become chronic carriers, as determined by the presence of HBsAg in serum

for more than 6 months (Fig. 58-10). Most HBV carriers have a benign state with HBV DNA integrating

into their native genome. The remainder of HBV carriers develop ongoing liver injury and usually have

detectable HBeAg or HBV DNA and have free episomal HBV sequences in addition to the ones integrated

into their native genomes.

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