Managing Hepatitis B in the Community: Infection Prevention and Control

Introduction to Hepatitis B as a Public Health Challenge

One of the key public health issues impacting innumerable individuals worldwide is viral hepatitis. This virus leads to substantial human mortality and morbidity from severe infection as well as chronic sequelae — including cirrhosis and chronic active hepatitis (with regard to Hepatitis B, C, and D). One among the ten most common cancers to emerge globally, hepatocellular carcinoma, has been found to be closely linked to Hepatitis B and, in some regions of the world, to Hepatitis C (Zuckerman, 2003).

HBV (Hepatitis B virus), which belongs to the hepadnavirus cluster, is a double-stranded DNA virus that, atypically, reproduces via reverse transcription. HBV is endemic among humans and hyper-endemic in several regions across the globe. Researchers have delineated various variants of the HBV virus. Natural infections by the hepadnavirus are also found to occur in beechy ground squirrels, woodchucks, ducks, and other mammals. Initially, HBV was identified as the causative factor of "serum hepatitis," which represents the most common type of parenterally transferred hepatitis viral infection, as well as a major contributor to lasting and severe liver disease. HBV's incubation period varies from one to six months. The clinical characteristics of severe hepatitis infection are similar to those of other viral hepatitides. Often, severe Hepatitis B presents as asymptomatic and anicteric. However, serious jaundice may occur, and severe liver failure might also arise in some cases (Zuckerman, 2003).

Distinctive Properties and Pathogenesis of HBV

HBV is found to exist in five to ten percent of immune-competent adult humans, and in approximately ninety percent of babies infected perinatally. Continued HBV carriage — described as the presence of HBsAg (hepatitis B surface antigen) within blood serum for more than six months — is estimated to affect roughly 350 million individuals worldwide. Its pathology is facilitated by the host's cellular immune responses to infected hepatocytes. Chronic, continuous viral replication can result in evolution toward hepatocellular carcinoma and cirrhosis (Zuckerman, 2003).

Within the primary chronicity stage, the virus continually replicates within the liver. The replicative intermediates of the viral genome can be identified in DNA (deoxyribonucleic acid) isolated from liver biopsy samples. HBV DNA, pre-S1 proteins, and HBeAg (the hepatitis B e antigen) — a soluble antigen produced by HBV-infected hepatocytes — serve as indicators of serum viral replication. In individuals infected at a young age, this stage can continue throughout life. However, more often, viral levels reduce over time. Ultimately, in most persons, immune clearance of infected hepatocytes is achieved, linked to seroconversion from HBeAg to anti-HBe (Zuckerman, 2003).

During the replication stage, the viral genome may integrate with chromosomal DNA in some hepatocytes; such cells can then persist and expand clonally. Seroconversion to anti-HBs rarely follows clearance of viral replication. Typically, HBsAg persists into a second chronicity stage owing to expression of integrated viral DNA (Zuckerman, 2003).

The antiviral and pathogenic capacity of the HBV-linked cytotoxic T-lymphocyte (CTL) response has been corroborated through the emergence of acute necroinflammatory liver disease following adoptive transfer of hepatitis B surface antigen-specific CTLs to an HBV transgenic mouse population. Notably, CTLs also expel HBV replicative intermediaries from the liver through secretion of type-1 inflammatory cytokines, thereby restricting transmission of the virus to unaffected cells and reducing the degree of immunopathology needed to terminate infection (Chisari, Isogawa, & Wieland, 2011).

Continuing HBV infection has been characterized by inadequate adaptive immune reactions, believed to stem from ineffective CD4+ T-cell priming during the infection's initial phases and the resulting qualitatively and quantitatively weak CD8+ T-cell response. Other factors that may contribute to viral persistence include immunological tolerance, T-cell receptor anergy, mutational epitope silencing, infection of immunologically privileged tissues, and partial downregulation of viral replication. These pathways, however, become evident only in the context of an inefficient immune response, which constitutes the chief underlying cause of disease in the community. Chronic infection is marked by ongoing hepatocyte injury, inflammation, regeneration, insertional deregulation of cell-cycle control genes, and extensive DNA damage — all of which together give rise to hepatocellular carcinoma and liver cirrhosis (Chisari, Isogawa, & Wieland, 2011).

Microbiology and Genome Organization

HBV is a 42-nanometer particle consisting of a nucleocapsid (electron-dense core) with a diameter of 27 nanometers, enclosed by an external HBsAg envelope embedded within a membranous lipid derived from host cells. HBsAg is secreted in large quantities by infected hepatocytes as 22-nanometer tubular structures and spherical particles (Zuckerman, 2003).

These 22-nanometer units comprise the dominant surface protein in both glycosylated (gp27) and non-glycosylated (p24) forms in roughly equimolar quantities, along with secondary elements — the so-called middle proteins (gp36 and gp33) — that include a pre-S2 domain, a glycosylated 55-amino-acid N-terminal extension. HBV's surface composition is similar, differing only in that it includes large surface proteins (gp42 and p39) encompassing both pre-S1 and pre-S2 regions. These large surface proteins do not appear in spherical 22-nanometer particles (though they may be present in tubular forms in highly viremic individuals), and their detection in serum is associated with viremia. The domain responsible for binding to a specific hepatocyte HBV receptor is considered to reside within the pre-S1 region (Zuckerman, 2003).

The nucleocapsid of the HBV virion contains the viral genome surrounded by the core antigen (HBcAg). This genome, approximately 3.2 kilobases in length, has a unique structure comprising two linear DNA strands maintained by base-pairing at their 5′ ends in a circular arrangement. One strand is incomplete. The 3′ extremity is linked to a DNA polymerase molecule capable of completing the strand when deoxyribonucleoside triphosphates are provided (Zuckerman, 2003).

Over twelve HBV isolate genomes have been sequenced in full to determine the complete nucleotide sequence. Examination of genome coding capacity reveals four open reading frames (ORFs) conserved across isolates (Zuckerman, 2003).

The first of these four ORFs encodes the various surface protein variants and contains three in-frame methionine codons used to initiate translation. An additional promoter upstream of the pre-S1 initiation codon directs the production of a 2.4-kb messenger RNA (ribonucleic acid) co-terminal with the other surface messages; this is translated to generate the large surface proteins (pre-S1) (Zuckerman, 2003).

The core ORF contains two in-frame initiation codons. The "precore" region is well conserved, possesses the characteristics of a signal sequence, and is responsible for HBeAg production (Zuckerman, 2003).

Another ORF — the largest, overlapping the remaining three — encodes the viral polymerase. This appears to be an alternative translation product of the 3.5-kb RNA, apparently arising through internal ribosomal initiation. The amino-terminal domain is believed to act as a protein primer during minus-strand synthesis, followed by a spacer region and then the DNA- and RNA-dependent DNA polymerase (Zuckerman, 2003).

The final ORF has been designated "x," as the function of its small gene product was initially unknown. It is now established, however, that the "x" protein is a transcriptional transactivator (Zuckerman, 2003).

Standard Precautions and Infection Control Policies

Standard precautions integrate key elements of body substance isolation (BSI) and universal precautions (UP), and are grounded in the premise that all body fluids, secretions, blood, and excretions (with the exception of sweat), as well as mucous membranes and broken skin, can harbor transmissible infectious agents. Standard precautions encompass a set of infection-prevention practices applicable to every patient regardless of confirmed or suspected infection status, across all healthcare settings. They include hand hygiene; use of personal protective equipment such as masks, gloves, gowns, and face shields or eye protectors based on anticipated exposure; and safe injection practices. Additionally, patient care items, tools, or equipment that may have been contaminated with HBV-infected body fluids should be handled carefully in a manner that prevents the spread of infectious agents — for instance, wearing gloves during direct contact, properly containing heavily contaminated instruments, and performing appropriate disinfection and sterilization of reusable equipment before use on other patients (WHO, 2009).

Adherence to standard precautions during patient care is guided by the nature of the provider–patient interaction and the degree of anticipated exposure to infected blood, pathogens, or body fluids. In some interactions — such as performing venipuncture — gloves alone may suffice, whereas in others — such as intubation — the provider must use a gown, gloves, goggles, and a face mask or shield. Standard precautions are also designed to protect patients by ensuring that healthcare providers do not transmit infectious agents via their hands or equipment used in patient care (WHO, 2009).

Since a Hepatitis B vaccine was first introduced in the early 1980s, the incidence of severe HBV has declined sharply within the general population in the United States. According to the Centers for Disease Control and Prevention (CDC), the occurrence of new HBV infections fell fivefold — from approximately 208,000 new infections per year in 1980 to 38,000 in 2010 (Lewis, Enfield, & Sifri, 2015).

The CDC's 2012 guidelines recommend that all individuals working in the healthcare sector be vaccinated against HBV and subsequently tested for antibody response (i.e., hepatitis B surface antibody status). Re-vaccination is advised for those whose immune systems did not respond to the initial vaccine series (CDC, 2012). Healthcare providers who fail to achieve protective anti-HBs levels following a second three-dose HBV vaccine series should be tested for HBsAg and anti-HBc (hepatitis B core antibody) to determine whether they have a chronic or prior infection. Healthcare providers whose mothers originate from endemic countries, sexually active men who have sex with men, and those who perform exposure-prone procedures (EPPs) should have pre-vaccination serology conducted (CDC, 2012).

The CDC's chronic Hepatitis B infection management guidelines apply specifically to healthcare workers who perform EPPs. It is recommended that HBV-positive healthcare providers whose duties include EPPs continue to do so only if they maintain an undetectable or low viral load (<1,000 IU/mL / 5,000 GE/mL), confirmed every six months. If a provider's viral load exceeds this threshold, EPP performance should be restricted until reassessment is completed (CDC, 2012). The CDC also advises healthcare facilities to implement written policies and procedures for the management of HBV-diagnosed healthcare workers, including the formation of a specialist review panel to assist in that management (CDC, 2012).

Most governing bodies recommend the establishment of a specialist review committee to facilitate monitoring and management of HBV-diagnosed providers, as well as providers diagnosed with other bloodborne diseases. Recommended panel members typically include specialists in the affected providers' clinical field, communicable disease experts, hepatologists, healthcare epidemiologists, occupational medicine physicians, the provider's primary care physician, human resources staff, and hospital administrators. An ethics specialist, a public health officer (for state-level matters), and legal counsel are also recommended participants (Lewis, Enfield, & Sifri, 2015).

Conclusion

HBV, which belongs to the Hepadnaviridae virus family, affects over 300 million individuals worldwide and represents a leading cause of liver cancer and liver disease. This small DNA virus shares unique characteristics with retroviruses: it replicates via an RNA intermediary and may integrate into host genomes. The distinctive features of its replication cycle enable it to persist within infected cells. Serological and virological investigations have been developed to diagnose different types of HBV-related illness and to guide treatment of chronic HBV infection. This infection produces a broad spectrum of liver diseases, including acute and chronic hepatitis (encompassing fulminant hepatic failure), hepatocellular carcinoma, and cirrhosis (Liang, 2009).

Acute HBV infection may be either asymptomatic or present with symptomatic acute hepatitis. The majority of HBV-infected adults recover fully; however, between 5% and 10% fail to clear the virus and develop chronic infection. Many chronically infected individuals experience mild liver disease with little or no long-term morbidity or mortality. Others with chronic HBV may develop active disease that can progress to cirrhosis and liver cancer. Such patients must be carefully monitored and provided with appropriate therapeutic interventions. Extra-hepatic manifestations of HBV occur infrequently but may be difficult to identify and manage. Key challenges in HBV-related disease include an incomplete understanding of factors predicting HBV progression and outcome, and an unfulfilled need to elucidate the cellular, molecular, genetic, and immunological bases of the diverse manifestations of HBV-linked disease (Liang, 2009).

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