Hepatitis E

Outbreaks of hepatitis E have occurred in resource-constrained countries, but nosocomial transmission has not been described in the West. Increasing reports of liver transplant patients with chronic hepatitis E suggest that the infection is not transmitted at transplant but rather is latent among certain patients with exposure to pig and swine.²⁸ In Pakistan, an outbreak of hepatitis E affected up to 18 people (7 confirmed and 11 possible cases). Assessment of the outbreak suggested that spread occurred due to improper sharing of intravenous equipment sets among patients.²⁹

Incidence after Exposure

The risk of transmission from a single needlestick exposure varies according to the hepatitis B e antigen (HBeAg) status of the source case. It ranges from 1% to 6% for HBeAg-negative blood to 22% to 31% for HBeAg-positive blood (see Table 305-1).³⁸ In addition, transmission from an HBsAg-negative patient may occur.

Over the past several decades, dozens of episodes involving HCW-to-patient transmission of hepatitis B have been described, resulting in hundreds of secondary cases (range, 1 to 55 secondary cases per source case).^{11,12,39–43} In a series of 10 clusters reported from the United Kingdom, the transmission rate ranged from 0.3% to 9%.^12,42 At least 42 of the 47 HCWs involved were dentists or surgeons. No cases of transmission from dentists to others have been reported since 1987, suggesting the effectiveness of Universal Precautions,⁴² although lack of case clustering may prevent recognition of transmission.⁴³ In response to these concerns, in 1991, the CDC promulgated recommendations for preventing transmission of HIV and HBV to patients during exposure-prone invasive procedures, which were modified by non-CDC experts in 2012.^44,45 These and other guidelines addressing infected HCWs have been sought to balance patient safety against a worker’s right to privacy.⁴⁵ Most U.S. and European guidelines now recommend that workers performing exposure-prone procedures maintain a low HBV DNA level, usually less than 1000 IU/mL.⁴⁵

In a classic outbreak from the 1990s, 19 (13%) of 144 susceptible patients operated on by an HBeAg-positive thoracic surgery resident developed acute hepatitis B infection despite appropriate infection control.¹¹ Thirteen available isolates, including the surgeon’s, were identical when compared by molecular analysis. Examination of the resident’s surgical technique suggested that small cuts in his fingers, sustained by tying sutures, resulted in entry of his blood into patients’ wounds. Ironically, the surgeon had declined hepatitis B vaccine 2 years earlier and then had become infected as the result of an occupational exposure.

In most but not all of the reported instances, the source worker was HBeAg positive. However, in one series, four HBeAg-negative surgeons each transmitted disease.¹² The cases occurred in England, where restriction of HBeAg-positive surgeons (principally cardiothoracic, gynecologic, orthopedic, and abdominal) is strictly enforced. Confirmation of transmission was aided by HBV DNA sequencing of both the putative source and secondary cases.

Recently, hepatitis B transmission occurred in at least 2 of 232 exposed, tested patients in the United States.⁴⁶ The source was an orthopedic surgeon with previously undetected HBV and an HBV DNA level of almost 18 million IU/mL. Of note, he had twice received a three-dose HBV vaccination series but had not been evaluated for chronic HBV infection, despite failing to respond to the vaccine.

Interventions and Management

Management in exposed or susceptible workers has been well summarized elsewhere^20,38,59 (see Table 305-1 and Chapter 146). Treatment should be given within 24 hours after exposure. Intramuscular hepatitis B immune globulin (HBIG) was the original intervention for postexposure prophylaxis.⁶⁰ It is still used, in conjunction with initiation of a vaccine series, for management after exposure in unvaccinated HCWs and vaccine nonresponders. Vaccine nonresponders should receive a second dose 1 month later (HBIG dose, 0.06 mL/kg).²⁰ Vaccine and HBIG may be given at the same time but should be administered with separate needles and syringes and at different anatomic sites. Plain immune globulin does not contain sufficient titers of HBIG and should not be given.²⁰ The role of antiviral agents such as lamivudine, entecavir, and tenofovir in the management of nosocomial exposure has not been determined.

The durability of hepatitis B vaccine–induced immunity is not known.⁶¹ Vaccine-induced antibody predictably wanes in many initial responders. However, in longitudinal reports, persons with waning antibody (to <10 mIU/mL) have not developed clinical hepatitis.⁶² Rather, those newly infected typically develop core antibody (HBcAb) with subclinical disease. Therefore, the CDC does not recommend routine revaccination of HCWs or patients, except for dialysis patients. Dialysis patients should have their antibody level determined annually and be revaccinated when the level drops to less than 10 mIU/mL.⁶³

Because of the cost, determination of antibody to HBV before vaccination is not recommended.²⁰ Postvaccination testing should be routinely provided to all HCWs with an anticipated risk of occupational exposure. Knowledge of serostatus assists management of subsequent exposures.^20,37 For vaccine responders, no postexposure intervention is required, regardless of the HBsAg or HBeAg status of the source. Vaccinated HCWs with an unknown response to vaccine should have their antibody titer checked immediately after exposure and be treated according to the result (see Table 305-1). Vaccine is generally well tolerated.

The best long-term management for the hepatitis B vaccine nonresponder is not known. This is of particular importance because up to 10% of vaccinated persons do not seroconvert.⁶⁴ All nonresponders must be tested for evidence of HBsAg. Risk factors for a suboptimal response include cigarette smoking, increasing age, obesity, and, in some series, male sex.⁶⁴ Persons who do not seroconvert after the initial three-dose series should be evaluated for HBsAg carrier state and, if negative, receive a second three-dose series.²⁰ Among those receiving a second course, up to half seroconvert. A third series for nonresponders is not recommended. Many studies have examined strategies to increase vaccine response rates, including intradermal vaccination,⁶⁵ but none have been approved.