Hepatitis A

Background: One of the more common causes of acute hepatitis is hepatitis A virus (HAV). The virus was isolated by Purcell in 1973. Since the application of accurate serologic investigations in the 1980s, the epidemiology, clinical manifestations, and natural history of hepatitis A have become apparent.

The relative frequency of HAV as a cause of acute hepatitis has declined in Western societies, while in contrast, notification of individual cases has increased, primarily as a result of improved reporting and diagnostic techniques. The nadir of reported cases was in 1987.

Improvements in hygiene, public health policies, and sanitation have had the greatest impact on this disease, and vaccination and passive immunization have successfully led to some reduction in illness in high-risk groups. Reduced encounters with HAV at a young age have resulted in both a decline in herd immunity and a change to the epidemiology of the illness, with increases in the mean age of occurrence of illness attributed to acute HAV infection in Western societies. Although this phenomenon may lay a framework for potential epidemics in the future, public health policies and newly implemented immunization practices are likely to reduce this potential.

Humans appear to be the only reservoir for HAV.

Pathophysiology: HAV is a single-stranded, positive-sense, linear RNA enterovirus and a member of the Picornaviridae family. In humans, viral replication depends on hepatocyte uptake and synthesis, and assembly occurs exclusively in liver cells. Acquisition results almost exclusively from ingestion (ie, fecal-oral transmission), although isolated cases of parenteral transmission have been reported.

HAV is an icosahedral nonenveloped virus measuring approximately 28 nm in diameter. Its resilience is demonstrated by its resistance to denaturation by ether, acid (pH 3.0), drying, and temperatures as high as 56°C and as low as -20°C. HAV can remain viable for many years. Boiling water is an effective means of destroying it, and chlorine and iodine are similarly effective (see Image 1).

Various genotypes of the virus exist; however, there appears to be only 1 serotype. Virion proteins 1 and 3 are the primary sites of antibody recognition and subsequent neutralization. No antibody cross-reactivity has been identified with other viruses causing acute hepatitis.

Hepatocyte uptake involves a receptor, recently identified by Kaplan et al, on the plasma membrane of the cell, and viral replication is believed to occur exclusively in hepatocytes. The recent demonstration of HAV in saliva has raised questions about this exclusivity. After entry into the cell, viral RNA is uncoated, and host ribosomes bind to form polysomes. Viral proteins are synthesized, and the viral genome is copied by a viral RNA polymerase. Assembled virus particles are shed into the biliary tree and excreted in the feces. Minimal cellular morphologic changes result from hepatocyte infection. The development of an immunologic response to infection is accompanied by a predominantly portal and periportal lymphocytic infiltrate and varying degree of necrosis (see Image 2).

Person-to-person contact is the most common means of transmission and is generally limited to close contacts. Transmission through blood products has been described. The period of greatest shedding of virus is during the anicteric prodrome (14-21 d) of infection and corresponds to the time when transmission is highest. Recognizing that active virus is shed after the development of jaundice is important, although amounts fall rapidly.

Outbreaks of acute hepatitis A have received international attention. The most notable report of transmission is that which appeared in The New England Journal of Medicine. Here was described a point source epidemic of HAV infection at a Pennsylvania restaurant where the vehicle for transmission was green onions used to make a mild salsa. The contamination of the onions occurred prior to the vegetable arriving in the United States.

Many authorities believe that hepatocyte injury is secondary to the host's immunologic response. This hypothesis is supported by the lack of cytotoxic activity in tissue culture and correlations between immunologic response and manifestations of hepatocyte injury.

The incubation period usually lasts 2-6 weeks, and the time to onset of symptoms may be dose related. The presence of disease manifestations and the severity of symptoms following infection directly correlate with patient age. In developing nations, the age of acquisition is before age 2 years; in Western societies, acquisition is most frequent in persons aged 5-17 years. In this age range, the illness is more often mild or subclinical; however, severe disease, including fulminant hepatic failure does occur

History: Along with outlining the presenting complaint and its severity and sequelae, the history should also initiate a search for the source of exposure (eg, overseas travel, lack of immunization, intravenous drug use) along with excluding other possible causes for acute hepatitis (eg, accidental Tylenol overdose). The incubation period is 2-6 weeks, with a mean of 4 weeks. Shorter incubation periods may result from higher total dose of viral inoculum.

• Discussion focusing on excluding other etiologies should be undertaken early in order to guide further investigation. Not every patient with fever, hepatomegaly, and jaundice has HAV infection. Some of the important differential diagnoses for acute hepatitis warrant early and specific management.

• Prodrome

• Patients may have mild flulike symptoms of anorexia, nausea and vomiting, fatigue, malaise, low-grade fever (usually <39.5°C), myalgia, and mild headache.

• Smokers often lose their taste for tobacco, similar to those presenting with appendicitis.

• Icteric phase

• Dark urine appears first (bilirubinuria).

• Pale stool soon follows, although this is not universal.

• Jaundice occurs in most (70-85%) adults with acute HAV infection. Jaundice is less likely in children and is uncommon in infants. The degree of icterus also increases with age.

• Abdominal pain occurs in approximately 40% of patients.

• Itch (pruritus), although less common than jaundice, is generally accompanied by jaundice.

• Arthralgias and skin rash, although associated, are less frequent than the above symptoms. Rash more often occurs on the lower limbs and may have a vasculitic appearance.

• Relapsing hepatitis A: This is an uncommon sequela of acute infection, is more common in elderly persons, and is characterized by a protracted course of symptoms of the disease and a relapse of symptoms and signs following apparent resolution. This phenomenon is further discussed in Complications, along with some of the less commonly associated features of the disease.

Physical: The physical examination focuses on detecting features to support a diagnosis of acute hepatitis and should include assessment for features of chronic liver disease or similarly assessment for evidence of decompensation.

• Hepatomegaly is common.

• Jaundice or scleral icterus may occur.

• Patients may have a fever with temperatures of up to 40°C.

Causes: Most patients have no defined risk factors. Risk factors for acquisition include the following:

• Personal contacts

• Institutionalization

• Occupation (eg, daycare)

• Foreign travel

• Male homosexuality

• Illicit parenteral drug use

Lab Studies:

• Anti–hepatitis A virus immunoglobulin M

• The diagnosis of acute HAV infection is based on serologic testing for IgM antibody to HAV. Test results for anti-HAV IgM are positive at the time of onset of symptoms and usually accompany the first rise in alanine aminotransferase (ALT) level. This test is sensitive and specific, and results remain positive for 3-6 months after the primary infection and for as long as 12 months in 25% of patients.

• False-positive results are uncommon and should be considered in the event that anti-HAV IgM persists.

• IgM persists in patients with relapsing hepatitis for the duration of this pattern of disease.

• Anti–hepatitis A virus immunoglobulin G

• Anti-HAV IgG appears soon after IgM and generally persists for many years.

• The presence of anti-HAV IgG in the absence of IgM indicates past infection or vaccination rather than acute infection.

• IgG provides protective immunity.

• Liver enzymes

• Rises of levels in ALT and aspartate aminotransferase (AST) assays are sensitive for this disease. Levels may exceed values of 10,000 mIU/mL, with ALT levels generally greater than AST levels. Levels usually return to reference ranges over 5-20 weeks.

• Rises in alkaline phosphatase accompany the acute disease and may progress during the cholestatic phase of the illness following the rises in transaminase levels.

• Hepatic synthetic function

• Bilirubin level rises soon after the onset of bilirubinuria and follows rises in ALT and AST levels. Levels may be impressively high and can remain elevated for several months; persistence beyond 3 months indicates cholestatic HAV infection.

• Older individuals have higher bilirubin levels.

• Both direct and indirect fractions increase because of hemolysis, which often occurs in acute HAV infection.

• Modest falls in serum albumin level may accompany the illness.

• Prothrombin time

• Prothrombin time usually remains within or near the reference range. Significant rises should raise concern and support closer monitoring.
• In the presence of encephalopathy, an elevated prothrombin time has ominous implications (eg, fulminant hepatic failure).

• CBC count

• Mild lymphocytosis is not uncommon. Pure red cell aplasia and pancytopenia may rarely accompany infection.
• Indices of low-grade hemolysis are not uncommon.

Imaging Studies:

• Imaging studies are usually not indicated.

• An ultrasound scan may be required when alternative diagnoses warrant exclusion and should assess vessel patency and evaluate any evidence supporting unsuspected underlying chronic liver disease. Ultrasound scanning is essential in patients with fulminant hepatic failure.

Other Tests:

• Molecular diagnostic techniques performed on blood and feces for HAV RNA are purely research tools.

• Other investigations (eg, serum acetaminophen) may be necessary as suggested by history and clinical examination findings.

Procedures:

• Liver biopsy has a minimal role in acute HAV infection. This procedure may play a part in chronic relapsing HAV infection or when the diagnosis is uncertain.

Histologic Findings: Histopathology reveals pronounced portal inflammation early in the illness, which is consistent with viral hepatitis. Focal necrosis and acidophilic bodies are less pronounced than with infections of hepatitis B virus (HBV) and hepatitis C virus (HCV). In fulminant hepatic failure, biopsy findings may show extensive cell loss with ballooning in many of the remaining hepatocytes. Immunofluorescent stains for HAV antigen provide positive results.

	TREATMENT	Section 6 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Medical Care: For acute cases, therapy is generally supportive, with no specific treatment for acute uncomplicated illness. Locating the primary source and preventing further outbreaks are paramount. Initial therapy often consists of bed rest. The patient should probably not work during the acute phase of the illness.

• Nausea and vomiting are treated with antiemetics.

• Dehydration may require hospital admission and intravenous fluids.

• In most instances, hospitalization is unnecessary. Most children have minimal symptoms; adults are more likely to require more intensive care, including hospitalization.

• Between 3-8% of cases of fulminant hepatic failure are caused by HAV; however, only 1-2% of HAV infections in adults lead to fulminant hepatic failure.

• Tylenol may be cautiously administered but is strictly limited to a maximum dose of 3-4 g/d in adults.

• Other treatments are directed by specific complications.

Surgical Care: Consider patients with fulminant hepatic failure for referral for liver transplantation. Recurrent disease after transplantation has not been reported. Selection of patients who require transplantation may be difficult because 60% of them recover from fulminant failure without a need for transplantation (similar to acetaminophen toxicity), and predicting who needs this life-saving procedure is difficult. Late referral has ominous implications, with the accompanying comorbidities (eg, renal failure, coagulopathy, cerebral edema) and waiting times contributing to poor outcomes.

Consultations: Consider liver transplantation in patients with fulminant hepatic failure. Transplantation for chronic relapsing HAV infection has occurred in the context of decompensation with good results; however, there is a report of clinical recurrence after transplantation.

Diet: Encourage an adequate diet. Patients should avoid alcohol and medications that may accumulate in liver disease. Otherwise, no specific dietary restrictions are necessary.

Activity: Bed rest during the acute illness may be important, although data to support this practice are lacking. Restricting transmission is important, especially

Drug Category: Analgesic agents -- Pain control is essential to quality patient care. Acetaminophen is useful. Acetaminophen (Tylenol, Tempra, Feverall) -- Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of

Drug Category: Antiemetics -- Used to treat nausea and vomitingbody heat via vasodilation and sweating. Relieves mild to moderate pain. Metoclopramide (Reglan) -- Dopamine antagonist that stimulates acetylcholine release in the myenteric plexus. Acts centrally on chemoreceptor triggers in the floor of the fourth ventricle, which provides important antiemetic activity

Drug Category: Vaccines, viral -- Hepatitis A vaccine is used for active immunization against disease caused by HAV. Hepatitis A vaccine, inactivated (Havrix, Vaqta) -- May be administered with immunoglobulin injections without affecting efficacy

Drug Category: Immune globulins -- Purified preparation of gamma globulin. Derived from large pools of human plasma and is composed of 4 subclasses of antibodies, approximating the distribution of human serum. Used for postexposure prophylaxis or when inadequate time is available for immunization to be effective before potential exposureImmune globulin, intramuscular (BayGam 15-18%) -- Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Effective when administered within 14 d of exposure.
If likely to be returning to areas of high endemicity, concurrent vaccination is recommended. For situations in which exposure is likely to occur before vaccination would be effective, both may be administered without reducing the efficacy of HAV vaccine.

Дата добавления: 2015-10-29