Understanding Acute Hepatitis B: Transmission, Risks, and Vaccination- pharmacyteach

ACUTE HEPATITIS B

 

ESSENTIALS OF DIAGNOSIS

o   Prodrome of anorexia, nausea, vomiting, malaise, aversion to smoking.

o   Fever, enlarged and tender liver, jaundice.

o   Normal to low white blood cell count; markedly elevated aminotransferases early in the course.

o   Liver biopsy shows hepatocellular necrosis and mononuclear infiltrate but is rarely indicated.

 

General Considerations

Hepatitis B virus (HBV) is classified as a 42-nm hepadnavirus, possessing a partially double-stranded DNA genome, an inner core protein known as hepatitis B core antigen (HBcAg), and an outer surface coat called hepatitis B surface antigen (HBsAg). There exist eight different genotypes (A-H) that may affect the infection's progression and the response to antiviral treatments. The transmission of HBV typically occurs through the inoculation of infected blood or blood products, as well as through sexual intercourse, and it can be found in saliva, semen, and vaginal secretions. HBsAg-positive mothers can transmit HBV during delivery, with the infant's risk of chronic infection potentially reaching as high as 90%.

Since 1990, the rate of HBV infection in the United States has declined from 8.5 to 1.5 cases per 100,000 individuals. The prevalence among those aged 6 and older stands at 0.27%. Due to the implementation of universal vaccination in 1992, exposure to HBV is now significantly low in individuals aged 18 and under [1]. HBV is particularly common among men who have sex with men and individuals who inject drugs, with approximately 7% of HIV-positive individuals also being co-infected with HBV; however, the majority of cases arise from heterosexual transmission. Other susceptible groups include hemodialysis patients and staff, doctors, dentists, nurses, and employees of blood banks, clinical and pathological labs, and other healthcare facilities. In the US, 50% of people with acute hepatitis B have previously received treatment for a sexually transmitted disease or been in detention. In the United States, there is a 1 in 350,000 chance of contracting HBV from a blood transfusion. The US Preventive Services Task Force recommends screening for HBV infection in high-risk categories [2].

The incubation period of hepatitis B is 6 weeks to 6 months (average 12-14 weeks). The onset of hepatitis B is more insidious, and the aminotransferase levels are higher on average than in HAV infection. Fulminant hepatitis occurs in less than 1%, with a mortality rate of up to 60%. Following acute hepatitis B, HBV infection persists in 1-2% of immunocompetent adults but in a higher percentage of children and immunocompromised adults. There are as many as 2.2 million persons (including an estimated 1.32 million foreign-born persons from endemic areas) with chronic hepatitis B in the United States. Persons with chronic hepatitis B, particularly when HBV infection is acquired early in life and viral replication persists, are at substantial risk for cirrhosis and hepatocellular carcinoma (up to 25-40%); men are at greater risk than women [1].

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Clinical Findings

 

A. Symptoms and Signs

The clinical picture of viral hepatitis is extremely variable, ranging from asymptomatic infection without jaundice to a fulminating disease and death in a few days. The onset may be abrupt or insidious, and the clinical features are similar to those for acute hepatitis A. Serum sickness may be seen early in acute hepatitis B. Fever is generally present and is low-grade. Defervescence and a fall in pulse rate often coincide with the onset of jaundice. Infection caused by HBV may be associated with glomerulonephritis and polyarteritis nodosa.

 

The acute illness usually subsides over 2-3 weeks, with complete clinical and laboratory recovery by 16 weeks. In 5-10% of cases, the course may be more protracted, but less than 1% will have a fulminant course. Hepatitis B may become chronic.

B. Laboratory Findings

The laboratory features are similar to those for acute hepatitis A, although serum aminotransferase levels are higher on average in acute hepatitis B, and marked cholestasis is not a feature. Marked prolongation of the prothrombin time in severe hepatitis correlates with increased mortality.

There are several antigens and antibodies, as well as HBV DNA, that relate to HBV infection and that are useful in diagnosis. Interpretation of common serologic patterns is shown in.

 

1. HBsAg

The appearance of HBsAg (Hepatitis B surface antigen) in serum is the first evidence of infection, appearing before biochemical evidence of liver disease, and persisting throughout the clinical illness. Persistence of HBsAg more than 6 months after the acute illness signifies chronic hepatitis B.

 

2. Anti-HBs

Specific antibody to HBsAg (anti-HBs) appears in most individuals after clearance of HBsAg and after successful vaccination against hepatitis B. Disappearance of HBsAg and the appearance of anti-HBs signal recovery from HBV infection, noninfectivity, and immunity.

 

3.  Anti-HBc-IgM

Anti-HBc is detected shortly after the presence of HBsAg. (HBcAg is not found in serum.) In cases of acute hepatitis, the presence of IgM anti-HBc confirms a diagnosis of acute hepatitis B, bridging the serological gap in rare instances where HBsAg has been cleared but anti-HBs is not yet detectable. IgM anti-HBc can remain in the system for 3 to 6 months, and in some cases, even longer. Additionally, IgM anti-HBc may reemerge during episodes of previously inactive chronic hepatitis B. IgG anti-HBc is observed during acute hepatitis B and continues indefinitely, whether the patient recovers (with anti-HBs appearing in serum) or transitions to chronic hepatitis B (with HBsAg remaining). In asymptomatic blood donors, the presence of isolated anti-HBc without other positive HBV serological results may reflect a false positive or a latent infection, where HBV DNA is detectable in serum solely via polymerase chain reaction (PCR) testing.

4. HBeAg

HBeAg represents a secretory variant of HBcAg that can be detected in serum during the incubation period, shortly following the identification of HBsAg. The presence of HBeAg is indicative of ongoing viral replication and the risk of infectivity. If HBeAg persists for over three months, it raises the likelihood of developing chronic hepatitis B. The subsequent disappearance of HBeAg is often accompanied by the rise of anti-HBe, which generally reflects a decrease in viral replication and infectivity.

5. HBV DNA

The detection of HBV DNA in serum typically corresponds with the presence of HBeAg; however, HBV DNA serves as a more sensitive and accurate indicator of viral replication and infectivity. Extremely low concentrations of HBV DNA, which can only be identified through PCR testing, may remain in the serum and liver for an extended period following a patient's recovery from acute hepatitis B, although the HBV DNA in serum is associated with IgG and is infrequently infectious. Some patients with chronic hepatitis B exhibit elevated levels of HBV DNA in their serum without detectable HBeAg, which is attributed to mutations in the core promoter or pre-core region of the gene responsible for HBcAg; these alterations hinder the synthesis of HBeAg in the hepatocytes affected by the virus. Additionally, when further mutations in the core gene are present, the pre-core mutant can worsen the severity of the HBV infection and heighten the likelihood of cirrhosis.

Differential Diagnosis

The differential diagnosis includes hepatitis A and the same disorders listed for the differential diagnosis of acute hepatitis A. In addition, coinfection with HDV must be considered.

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Prevention

Complete isolation of patients is not required. Medical personnel must perform thorough hand hygiene when dealing with potentially contaminated utensils, bedding, or clothing. Medical staff must exercise caution when handling disposable needles and should avoid recapping them. The screening of donated blood for HBsAg, anti-HBc, and anti-HCV has significantly decreased the risk of hepatitis associated with transfusions. It is essential for all pregnant women to be tested for HBsAg. Individuals infected with HBV should engage in safer sexual practices. A cesarean section, along with immunoprophylaxis for the newborn, significantly lowers the risk of perinatal HBV transmission when the mother's serum HBV DNA level is at least 200,000 international units/ml. alternatively; initiating antiviral treatment for the mother during the third trimester is a viable option. Furthermore, HBV-infected healthcare professionals may continue to practice medicine or dentistry provided they adhere to CDC guidelines.

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The administration of Hepatitis B immune globulin (HBIG) may offer protective benefits or lessen the severity of the illness when given within a week following exposure (the adult dosage is 0.06 ml/kg of body weight), in conjunction with the initiation of the HBV vaccination series. This method is currently recommended for individuals exposed to HBsAg-contaminated substances via mucous membranes or skin injuries, and for those who have had sexual contact with an HBV-infected person, regardless of the HBeAg status of the source. HBIG is also indicated for newborn infants of HBsAg-positive mothers followed by initiation of the vaccine series.

 

The Centers for Disease Control and Prevention (CDC) advises that all infants and children in the United States, as well as adults at risk for hepatitis B including individuals under 60 with diabetes mellitus should receive the HBV vaccination, or those who seek vaccination. More than 90% of individuals who receive the vaccine develop protective antibodies against hepatitis B; however, immunocompromised individuals, particularly those undergoing dialysis (especially those with diabetes), tend to have a poor response (refer to Table). In certain instances, a genetic predisposition may contribute to a diminished response to the vaccine, which has also been linked to individuals over 40 years of age and those with celiac disease.

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The recommended dosage for adults ranges from 10 to 20 mcg, depending on the specific formulation, with subsequent doses administered at 1 and 6 months. However, alternative dosing schedules have been authorized, including accelerated regimens of 0, 1, 2, and 12 months, as well as 0, 7, and 21 days followed by 12 months. To ensure optimal absorption, the deltoid muscle is the preferred site for vaccination. Infants under 6 months of age receive vaccine formulations that do not contain the mercury-based preservative thimerosal. If verification of seroconversion is necessary, anti-HBs titers may be assessed following immunization.

The level of protection remains strong for at least 20 years, even if the titer decreases; while booster vaccinations are not generally recommended, they are suggested for immunocompromised individuals whose anti-HBs titers drop below 10 million international units/ml. For those who do not respond to the vaccine, administering three additional doses may result in seroprotective anti-HBs levels in 30-50% of individuals. Increasing the standard dose may also prove beneficial. In countries where HBV is endemic, the universal vaccination of newborns has led to a decrease in the occurrence of hepatocellular carcinoma. Incomplete immunization is the most important predictor of liver disease among vaccines.

 

Treatment

Treatment of acute hepatitis B is the same as that for acute hepatitis A. Encephalopathy or severe coagulopathy indicates acute liver failure, and hospitalization at a liver, Biliary tract and pancreas transplant center is mandatory.

A. Acute

(1) No medication is available

(2) Provide supportive care

B. Chronic

(1) Goal of treatment is amelioration of hepatic dysfunction and seroconversion of HBsAg-positive (surface antigen) to HBsAg-negative and production of HBs antibodies.

(2) Treatment is indicated for chronic HBV infection with high pretreatment ALT level, detectable serum HBV DNA, and moderately active necroinflammation with or without fibrosis on liver biopsy.

Antiviral therapy is generally unnecessary in patients with acute hepatitis B but is usually prescribed in cases of fulminant hepatitis B as well as in spontaneous reactivation of chronic hepatitis B presenting as acute-on-chronic liver failure.

(3) First-line drugs

(a) Pegylated interferon-alfa 2a (Pegasys)

(i) Class: Interferon

(ii) Dose: 180 mcg SQ weekly

(iii) Duration: 48 weeks

 

(b) Entecavir (Baraclude")

(i) Class: reverse transcriptase inhibitor (nucleoside)

(ii) Dose: 0.5 mg daily

(iii) Duration for HBeAg+ (antigen is a marker for active replication): treat for more than 1 year until HBeAg seroconversion and undetectable serum HBV DNA; continue treatment for more than 6 months after HBeAg seroconversion

(iv) Duration for HBeAg negative: treat for more than 1 year until HBsAg (surface antigen) clearance

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(c) Tenofovir (Viread")

(i) Class: Reverse transcriptase inhibitor (nucleotide)

(ii) Dose: 300 mg daily

(iii) Duration for HBeAg+: treat for more than 1 year until HBeAg seroconversion and undetectable serum HBV DNA; continue treatment for more than 6 months after HBeAg seroconversion

(iv) Duration for HBeAg negative: treat for more than 1 year until HBsAg clearance.

 

Prognosis

In most patients, clinical recovery is complete in 3-6 months. Laboratory evidence of liver dysfunction may persist for a longer period, but most patients recover completely. The mortality rate for acute hepatitis B is 0.1-1% but is higher with superimposed hepatitis D.

Chronic hepatitis is marked by elevated aminotransferase levels lasting more than six months and occurs in 1-2% of immunocompetent adults who experience acute hepatitis B. In contrast, it affects nearly 90% of infected neonates and infants, along with a considerable number of immunocompromised adults. Cirrhosis can develop in up to 40% of those with chronic hepatitis B, with an even greater risk present in HBV-infected patients who are also infected with hepatitis C or HIV. Patients with cirrhosis have a 3-5% annual risk of developing hepatocellular carcinoma. Furthermore, individuals with chronic hepatitis B, particularly those with ongoing viral replication, are at an increased risk for hepatocellular carcinoma, even in the absence of cirrhosis.

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When to Refer

Refer patients with acute hepatitis who require liver biopsy for diagnosis.

When to Admit

Encephalopathy is present.

INR greater than 1.6.

The patient is unable to maintain hydration.

References

1.     Chien YC et al. Incomplete hepatitis B immunization, maternal carrier status, and increased risk of liver diseases: a 20-year cohort study of 3.8 million vaccinees. Hepatology. 2014 Jul;60(1):125-32. [PMID: 24497203]

2.     Chou R et al. Screening for hepatitis B virus infection in adoles-cents and adults: a systematic review to update the U.S. Pre ventive Services Task Force recommendation. Ann Intern Med. 2014 Jul 1;161(1):31-45. [PMID: 24861032]

3.     LeFevre ML. et al. Screening for hepatitis B virus infection in nonpregnant adolescents and adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014 Jul 1;161(1):58-66. [PMID: 24863637]

4.     Trépo C et al. Hepatitis B virus infection. Lancet. 2014 Dec 6:384(9959):2053-63. [PMID: 24954675]