Hepatitis B Virus

Hepatitis B virus (HBV) is a partially double-stranded DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. The virus can cause potentially life-threatening liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, leading to liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases ( HCC HCC Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases). Management of acute hepatitis is typically supportive. Administration of antivirals or liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation may be necessary in fulminant and chronic cases.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Classification

Dna virus classification flowchart

Identification of DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure viruses:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure or RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. Viruses with a DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure genome can be further characterized as single or double stranded. “Enveloped” viruses are covered by a thin coat of cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane, which is usually taken from the host cell. If the coat is absent, however, the viruses are called “naked” viruses. Some enveloped viruses translate DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure into RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure before incorporating into the genome of the host cell.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Structure

  • Taxonomy: Hepadnaviridae family, Orthohepadnavirus genus
  • DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure: circular (icosahedral) and partially double stranded
  • Small (30–42 nm)
  • 8 different genotypes are known.
Structure of hepatitis b virus

Structure of hepatitis B virus (HBV):
The virus particle (virion) is made up of an outer lipid envelope. The nucleocapsid (core) encloses the viral DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure and a DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure polymerase, which has reverse transcriptase activity. The outer envelope contains proteins, which help the virus bind to and enter target cells.

Image: “Hepatitis B Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview (HBV)” by Mansouri, N., et al. License: CC BY 3.0, edited by Lecturio.

Features

  • Causes acute and chronic hepatitis
  • Infection is preventable by vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination (95% efficiency).
  • One of the most common causes of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
Electron micrograph of the hepatitis b virus

Electron micrograph of the hepatitis B virus (HBV)

Image: “Hepatitis-B virions” by CDC. License: Public Domain

Epidemiology and Pathogenesis

Epidemiology

  • Hepatitis B virus (HBV) is the most common viral hepatitis worldwide.
  • Highest prevalence: Asia, sub-Saharan Africa, South America, and the Middle East
  • In the United States: 
    • Approximately 2 million people have chronic HBV. 
    • Very low prevalence in children < 12 years of age

Transmission

  • The only reservoir for HBV: humans
  • Unprotected sexual intercourse: ⅔ of cases
  • Parenteral: e.g., shared IV drug needles, accidental needle sticks
  • Mother to child: most common in high-prevalence areas

Host risk factors

  • Persons who inject drugs (PWIDs)
  • Unprotected sex with multiple partners
  • Men who have sex with men (MSM)
  • HIV infection HIV infection Human immunodeficiency virus (HIV), a single-stranded RNA virus belonging to the Retroviridae family, is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus is a sexually transmitted or blood-borne infection that attacks CD4+ T lymphocyte cells, macrophages, and dendritic cells, leading to eventual immunodeficiency. HIV Infection and AIDS
  • Hemodialysis
  • Infants born to HBV-positive mothers
  • Professions with exposure to human blood or seminal/vaginal fluids 
  • Individuals on hemodialysis or recipients of organ/blood transfusion

Pathophysiology

  • HBV infects liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver cells expressing viral peptides on the surface → peptides activate lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes (CD8+ cytotoxic T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells) → WBCs mount a cellular immune response against infected liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver cells → destruction of hepatocytes → liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
  • Primary replication:
    • Exposure to infectious bodily fluids → replication in the mucosa → bloodstream (1st viremia)
    • Reaches the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver due to tissue tropism (hepatotropic due to receptor recognition)
    • Viral uptake by hepatocytes via a receptor on the plasma membrane
    • Replication occurs in hepatocytes and Kupffer cells (hepatic macrophages):
      • After cell entry → a double-stranded relaxed circular DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure (rcDNA) positive strand is completed by the viral polymerase
      • The RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase of the host transcribes DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure into viral mRNA.
      • Viral mRNA is reverse transcribed into viral rcDNA → viral mRNA and reverse transcriptase are packaged into a capsid → new viral DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure genomes are enveloped
    • Newly enveloped virus particles are excreted into the bloodstream and infect bodily fluids.
    • Hepatic injury is immune related (no viral cytotoxicity):
      • Immunologic response to infection
      • Accompanied by portal and periportal lymphocytic infiltration→ varying degree of necrosis
Hepatitis b virus (hbv) replication

Hepatitis B virus (HBV) replication:
The HBV is phagocytosed to replicate by utilizing the replication machinery of the host cell.

Image: “HBV replication” by Graham Beards. License: Public Domains

Clinical Presentation

Acute infection

  • Incubation time: 1–6 months 
  • ⅔ of individuals with acute infection are asymptomatic.
  • ⅓ of individuals develop symptoms of acute hepatitis: 
    • Nausea and vomiting
    • Jaundice
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Tiredness
    • Dark urine
    • Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain 
    • Myalgias and arthralgias
  • Symptom duration: often only a few weeks
  • Death is rare.

Chronic infection

  • Approximately 5% of cases show persistent viral infection.
  • Only 30% of the cases with persistent viral infection develop chronic hepatitis.
  • Can lead to acute-on-chronic exacerbation
  • Acute reactivation:
    • Asymptomatic
    • May mimic the course of acute infection 
    • May develop liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure 
  • Cirrhosis
  • Hepatocellular carcinoma ( HCC HCC Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases)
  • Extrahepatic manifestations:
    • Vasculitis: 
      • Panarteritis nodosa
      • Sicca syndrome
      • Raynaud syndrome
      • Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
    • Neuritis and polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy
    • Glomerulonephritis
    • Skin rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes

Diagnosis

Viral markers

  • Hepatitis B surface antigen (HBsAg): 
    • Increased in acute hepatitis B, chronic hepatitis B, and asymptomatic carriers
    • Detectable 4 weeks after exposure → false negative results possible
  • Hepatitis B surface antibody (anti-HBs):
    • Corresponding antibody to HBsAg
    • Marker for recovery from infection
  • Hepatitis B core antigen (HBcAg): not routinely used in HBV testing
  • Hepatitis B core antibody (anti-HBc):
    • Corresponding antibody to HBcAg
    • Common screening parameter indicating contact to HBV
    • Total Anti-HBc: does not differentiate between acute, chronic, or past infection
    • Anti–HBc-IgM: acute HBV infection
    • Anti–HBc-IgG: always detectable after contact to HBV (unspecific)
  • Hepatitis B envelope antigen (HBeAG): indicator of active viral replication
  • Hepatitis B e antibody (anti-HBe):
    • Corresponding antibody to HBeAg
    • Indicates the transition to recovery from HBV infection 
  • HBV DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure:
    • Measure of viral load
    • Used to monitor efficacy of antiviral therapy
    • > 20 IU/mL indicates replication of the virus → individual is contagious

Laboratory evaluation

Screening for HBV infection:

  • Perform in the following cases: symptoms of acute hepatitis, high risk of exposure, and/or increased risk for severe disease course
  • HBsAg:
    • Detectable 1–6 months after infection
    • Early infection may not be discovered.
  • Anti-HBc: IgM and IgG
  • If both positive → acute or chronic HBV infection

Acute hepatitis B:

  • ↑ HBsAg anti–HBc-IgM
  • ↑ Transaminases 

HBV-vaccinated individuals:

  • Anti-HBs positive
  • Anti-HBc negative

Chronic hepatitis B:

  • ↑ HBsAg for > 6 months
  • Anti-HBe and Anti-HB not elevated!
  • HBeAg may be elevated.
  • ↑ HBV DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure 

Additional parameters

  • Hallmark of early acute disease is ↑ transaminases:
    • ALT and AST: 1000–2000 IU/mL
    • ALT > AST
  • Gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP): usually ↑ but < 3x the upper limit of normal
  • Erythrocyte sedimentation rate (ESR): may be ↑
  • Signs of severe disease: 
    • Hemolysis
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
    • ↑ INR
Laboratory parameters of hbv infection

Laboratory parameters of hepatitis B virus (HBV) infection:
The chart shows the typical course of important markers in diagnosis of HBV infection after viral exposure.

Image by Lecturio.

Management and Prevention

Management

Acute hepatitis B:

  • No specific therapy available
  • Treatment is supportive.

Chronic hepatitis B:

  • 1st-line treatment: 
    • Pegylated interferon alfa (PEG-IFN-α)
    • Entecavir (ETV)
    • Tenofovir disoproxil fumarate (TDF) 
    • Indications: 
      • HBV DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure positivity with clinical complications
      • Cirrhosis
      • Acute liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure
      • Reactivation of chronic HBV during or after chemotherapy
      • Immunosuppression
    • Treatment goals:
      • Reversal of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease 
      • DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure levels of HBV
      • Seroconversion to anti-HBe
    • Contraindications:
      • Mental illness
      • Decompensated cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis (e.g., ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, encephalopathy)
      • Autoimmune conditions
      • Leukopenia or thrombocytopenia
      • Kidney dysfunction
  • Liver transplantation: the only curative treatment option in cases of end-stage liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease 

Prevention

Screening:

Screening for HBV infection is recommended by the CDC for the following groups:

  • Individuals from areas with medium-to-high HBV prevalence
  • Needle injuries (e.g., medical staff, IV drug users)
  • Pregnant individuals
  • Newborns of mothers with known, active HBV infection

Vaccination:

  • HBV vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination: active, leads to long-term immunity
  • For infants:
    • 3-dose series
    • Administered at 0, 1, and 6 months
  • For adults: 2-dose series (1 month apart) 
  • Hepatitis A Hepatitis A Hepatitis A is caused by the hepatitis A virus (HAV), a nonenveloped virus of the Picornaviridae family with single-stranded RNA. HAV causes an acute, highly contagious hepatitis with unspecific prodromal symptoms such as fever and malaise followed by jaundice and elevated liver transaminases. Hepatitis A Virus + B combination vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination is also available as 3-dose series.

Postexposure prophylaxis (PEP):

Options dependent on immunization status:

  • Active immunization (hepatitis B vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination)
  • Passive immunization (hepatitis B immune globulin)
  • Combined active and passive immunization
  • No immunization

Hepatitis Viruses Comparative Table

Comparison table of hepatitis viruses

Anti-HBc: hepatitis B core antibody
Anti-HBs: hepatitis B surface antibody
HBcAg: hepatitis B core antigen
HBsAg: hepatitis B surface antigen
HBV: hepatitis B virus
HCC HCC Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases: hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases
HCV HCV Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C Virus: hepatitis C virus Hepatitis C Virus Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C Virus
HDV HDV Hepatitis D virus (HDV) is a small enveloped, single-stranded RNA virus. Hepatitis D virus is considered a satellite virus, as it requires the presence of hepatitis B virus (HBV) for assembly and secretion. Therefore, in order for an individual to contract hepatitis D, coinfection or superinfection with HBV is required. Hepatitis D Virus: hepatitis D virus Hepatitis D virus Hepatitis D virus (HDV) is a small enveloped, single-stranded RNA virus. Hepatitis D virus is considered a satellite virus, as it requires the presence of hepatitis B virus (HBV) for assembly and secretion. Therefore, in order for an individual to contract hepatitis D, coinfection or superinfection with HBV is required. Hepatitis D Virus

Image by Lecturio. License: CC BY-NC-SA 4.0

Differential Diagnosis

  • Alcoholic liver disease Alcoholic Liver Disease Alcoholic liver disease is a spectrum of disorders ranging from fatty liver to cirrhosis secondary to chronic alcohol abuse. Excessive and prolonged consumption of alcohol results in impairment of the lipolysis pathway, causing inflammatory changes within the hepatocytes. Patients typically present during the hepatitis stage with jaundice, fever, and abdominal pain. Alcoholic Liver Disease (ALD): liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver pathology occurring due to prolonged, excessive alcohol consumption. The 1st stage is asymptomatic fatty liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, which is reversible. The 2nd stage is alcoholic hepatitis, which most commonly presents with jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, fever, and RUQ pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Liver cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis occurs in the 3rd stage. Diagnosis is established by history, liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests, and imaging studies. 
  • Drug-induced liver injury Drug-induced liver injury Drug-induced liver injury (DILI) is the most common cause of acute liver failure (ALF). Hepatotoxic drugs can cause injury to the hepatocytes directly in a predictable dose-dependent way or through idiosyncratic reactions. The injury mechanisms can have the following effects: hepatitis, cholestasis, vascular lesions, or overlapping changes. Drug-induced Liver Injury (DILI): occurs when ingested drugs directly injure the hepatocytes in a predictable, dose-dependent way, or through idiosyncratic reactions. The presentation can be acute or chronic. Severe toxicity manifests as fulminant liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure. The diagnosis of DILI requires a thorough history and laboratory tests. Management consists of early diagnosis, discontinuation of the drug, and supportive therapy.
  • Autoimmune hepatitis Autoimmune hepatitis Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis (AIH): liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation occurring when the immune system attacks the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver cells. Clinical presentation may range from asymptomatic to symptoms of acute liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure. Diagnosis is established via blood testing for the characteristic autoantibodies (especially anti-smooth muscle antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins) and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver biopsy. Management includes corticosteroids and azathioprine. 
  • Wilson disease: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancedisorder from a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Neuropsychiatric manifestations differentiate Wilson disease from other causes of hepatitis. In early stages, Wilson disease may be confused with hepatic encephalopathy Hepatic Encephalopathy Hepatic encephalopathy is a reversible condition in which elevated ammonia levels cause impaired brain function in patients with advanced liver disease. Hepatic encephalopathy can be precipitated by conditions that affect the normal absorption, metabolism, or clearance of ammonia, including dehydration, renal failure, infections, and gastrointestinal bleeding. Hepatic Encephalopathy. Kayser-Fleischer rings and low ceruloplasmin levels help separate Wilson disease from other causes of hepatitis.
  • Nonalcoholic fatty liver disease Nonalcoholic Fatty Liver Disease Nonalcoholic fatty liver disease is a spectrum of liver pathology that arises due to accumulation of triglycerides in hepatocytes. Risk factors include diabetes mellitus, insulin resistance, obesity, and hypertension, among others. Nonalcoholic fatty liver disease ranges from fatty liver or hepatic steatosis but can lead to nonalcoholic steatohepatitis (NASH), which features fatty deposits and inflammation. Nonalcoholic Fatty Liver Disease (NAFLD): a spectrum of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver pathology arising from accumulation of triglycerides in hepatocytes. The disease ranges from fatty liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver/hepatic steatosis to nonalcoholic steatohepatitis, which has fatty deposits and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation. Progressive liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver injury and fibrosis irreversibly develop into cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and, possibly, primary liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver cancer. Management is through lifestyle modifications (e.g., diet, exercise).

References

  1. Sorrell, M.F., Belongia, E.A., Costa, J., et al. (2009). National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med. 150(2), 104–10. https://pubmed.ncbi.nlm.nih.gov/19124811/
  2. Centers for Disease Control and Prevention. (2020). Hepatitis B information for health professionals: hepatitis B FAQs for health professionals. Retrieved January 27, 2021, from https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm#overview
  3. Te, H.S., Jensen, D.M. (2010). Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis. 14(1), 1–21, vii. https://pubmed.ncbi.nlm.nih.gov/20123436/
  4. World Health Organization. (2011). Weekly epidemiological record (WER): global routine vaccination coverage. 86(46), 509–20. http://www.who.int/wer/2011/wer8646/en/index.html
  5. Pyrsopoulos, N. (2020). Hepatitis B. Emedicine. Retrieved January 28, 2021, from https://emedicine.medscape.com/article/177632-overview#a3
  6. Lok, A. (2020). Hepatitis B virus: Overview of management. Retrieved January 27, 2021, from https://www.uptodate.com/contents/hepatitis-b-virus-overview-of-management

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