Hepatitis B overview

# Overview
Chronic Hepatitis B virus (HBV) is a major global health problem, according to the World Health Organization (WHO).
Hepatitis B virus (HBV) is a double-stranded DNA virus belonging to the family Hepadnaviridae. It is responsible for hepatitis B virus infection in humans, which attacks the liver and causes both acute and chronic disease.
During HBV infection, the host's immune response causes both hepatocellular damage and viral clearance. The HBV virion binds to a receptor at the surface of the hepatocyte and enters the cell, where it uses the host's cell mechanisms to replicate its genome and proteins. Transmission occurs from exposure to infectious blood or body fluids. Hepatitis B is often associated with hepatocellular carcinoma. Immune complexes, such as surface antigen-antibody, are important in the pathogenesis of hepatitis B.
Hepatitis B must be differentiated from other diseases that cause fever, nausea, vomiting, jaundice, hepatomegaly, icteric sclera, elevated ALT, and/or elevated AST, such as other viral hepatitis strains, alcoholic hepatitis, and autoimmune hepatitis.
Generally, the highest risk for HBV infection is associated with certain lifestyles, occupations, or environments in which contact with blood from infected persons is frequent.
The diagnosis of hepatitis B is made by biochemical assessment of liver function.
In the majority of patients with acute and chronic hepatitis B (HBV), symptoms may initially be non-specific and physical examination will be normal.
The diagnosis of hepatitis B is made by biochemical assessment of liver function. Initial laboratory evaluation usually reveals increased bilirubin, ALT, AST, and alkaline phosphatase, as well as decreased protein. Prothrombin time may be prolonged in cases of hepatocellular necrosis. Serologic markers, such as Hepatitis B surface antigen (HBsAg); anti-HBsAg; anti-HBc IgM and anti-HBc IgG; hepatitis Be antigen; and anti-HBeAg confirm the diagnosis of hepatitis B.
In the majority of adult patients, the body is able to eliminate the virus without treatment.  Currently, there is no treatment available for acute hepatitis B infection. Early antiviral treatment may only be required in fewer than 1% of patients with fulminant hepatitis. Treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Treatment lasts between six months and a year, depending on the medication and genotype.  Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. These include the antiviral drugs Lamivudine, Adefovir, Tenofovir, Telbivudine, and Entecavir, as well as immune system modulators such as interferon alpha-2a and pegylated interferon-alpha-2a.

# Historical Perspective
The first descriptions of hepatitis (epidemic jaundice) are generally attributed to Hippocrates, who identified the disorder during the 5th century BCE. In 1885, the earliest identifiable occurrence of hepatitis B virus was documented by Lurman. In 1947, the current nomenclature of hepatitis A (so-called "infectious hepatitis") and hepatitis B (so-called "serum hepatitis") was proposed by MacCallum and Bauer.
Throughout the 20th century, advancements in the recognition, isolation, classification, and prevention of hepatitis B were achieved. Today, the focus around HBV remains on the spread of awareness and prevention across the world, especially in endemic areas that would benefit greatly from immunization programs.

# Pathophysiology
The intracellular hepatitis B virus is a non-cytopathic virus that causes little or no damage to the cell. During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. The HBV virion binds to a receptor at the surface of the hepatocyte and enters the cell, where it uses the host cell's mechanisms to replicate its own genome and proteins. Different viral antigens and antibodies are detected in serum throughout the course of the disease, such as: HBsAg, HBcAg, HBeAg, anti-HBs, anti-HBC and anti-HBe. Transmission occurs from exposure to infectious blood or body fluids. Hepatitis B is often associated with hepatocellular carcinoma. Immune complexes, such as surface antigen-antibody, are important in the pathogenesis of hepatitis B.

# Causes
The hepatitis B virus is responsible for causing hepatitis B. HBV is a double-stranded DNA virus belonging to the family Hepadnaviridae. The viral particle consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA. HBV DNA polymerase has reverse transcriptase activity. It shows tropism for hepatocytes.  Humans are the only natural reservoir of the virus.
HBV is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins and ten genotypes (A-J) according to overall nucleotide sequence variation of the genome.

# Differentiating Hepatitis B from other Diseases
Hepatitis B must be differentiated from other diseases that cause fever, nausea, vomiting, jaundice, hepatomegaly, icteric sclera, and/or elevated ALT and AST, such as other forms of viral hepatitis, alcoholic hepatitis, and autoimmune hepatitis.

# Epidemiology and Demographics
Chronic Hepatitis B (HBV) is a major global health problem.  According to the World Health Organization (WHO), more than 2 billion people have been infected with HBV.  It is a major cause of chronic liver disease worldwide, affecting an estimated 1.25 million people in the United States, and more than 240 million people worldwide.

# Risk Factors
Generally, the highest risk for HBV infection is associated with lifestyles, occupations, or environments in which contact with blood from infected patients is frequent. High-risk populations include immigrants/refugees from areas of high HBV endemicity, clients in mental health institutions, injecting drug users, men who have sex with men (MSM), patients receiving hemodialysis, and household contacts of HBV carriers. Perinatal transmission from mother to infant at birth is very efficient. If the mother is positive for both HBsAg and HBeAg, 70%90% of infants will become infected in the absence of post-exposure prophylaxis.

# Screening
High-risk groups should be tested for HBV infection. These include immigrants/refugees from areas of intermediate or high endemicity, patients with chronically elevated aminotransferases, immunocompromised individuals, and people with a history of injection drug use (IDU).
Additionally, screening for hepatocellular carcinoma should extend to any HBV carrier over 40 years of age with persistent or intermittent ALT elevation and/or high HBV DNA levels (>2,000 IU/mL).

# Natural History, Complications and Prognosis
The course of hepatitis B is extremely variable. Hepatitis B has different clinical manifestations depending on the patients age at infection, immune status, and the stage at which the disease is recognized. During the incubation period, patients may experience flu-like symptoms such as nausea, vomiting, and headaches. A person infected with hepatitis B virus may recover completely, become an asymptomatic carrier of the virus, develop chronic disease, or develop fulminant hepatitis. In acute hepatitis B, the incubation period may range from 45 to 120 days, depending on the amount of virus in the inoculum, host factors, and the mode of transmission. These patients may experience the following symptoms: fatigue, nausea, vomiting, anorexia, abdominal pain, and jaundice. In most cases, no special diet or treatment are necessary. The risk of developing chronic hepatitis decreases with age, with infants having the highest risk. Chronic hepatitis may progress to cirrhosis,  liver failure, or hepatocellular carcinoma. In most cases the prognosis of acute hepatitis is good, with symptoms lasting 2 to 3 weeks. However, in infants and immunocompromised patients, the risk of developing chronic disease is increased.

# Diagnosis

## Diagnostic criteria
The diagnosis of hepatitis is made by biochemical assessment of liver function. A diagnosis is confirmed by the presence of specific antigens and/or antibodies in sera. Three clinically useful antigen-antibody systems have been identified for hepatitis B. These include hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs); antibody (anti-HBc IgM and anti-HBc IgG) to hepatitis B core antigen (HBcAg); and hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe).

## History and symptom
50% of adult patients and the majority of infants and children with acute HBV do not present with symptoms.  Symptoms may initially be non-specific. It is critical to obtain an accurate and thorough history in cases of both acute and chronic HBV infections in order to determine modes of infection transmission, as well as to assess risk factors for the progression of HBV-related liver disease.

## Physical examination
For the majority of patients with acute and chronic hepatitis B (HBV), the physical examination is normal.

## Laboratory tests
The diagnosis of hepatitis is made by the biochemical assessment of liver function. An initial laboratory evaluation usually reveals increased bilirubin levels; increased ALT, AST, and alkaline phosphatase; and decreased protein. Prothrombin time may be prolonged in cases of hepatocellular necrosis and hemoglobin may be low. Initial lymphopenia and neutropenia may be followed by lymphocytosis. Serologic markers, such as Hepatitis B surface antigen (HBsAg); anti-HBsAg; anti-HBc IgM and anti-HBc IgG; hepatitis B e antigen and anti-HBeAg confirm the diagnosis of hepatitis B. These levels fluctuate throughout the course of the disease.

## CT
CT scans may diagnose and/or monitor biliary obstruction, cirrhosis, and hepatocellular carcinoma in hepatitis B patients.:

## MRI
An MRI may be used to diagnose/monitor biliary obstruction, cirrhosis, and hepatocellular carcinoma in hepatitis B patients. MRI findings in these patients may include nodular appearance and signs of portal hypertension, such as ascites and splenomegaly.

## Ultrasound
Ultrasounds may be used as a screening tool in patients with chronic hepatitis for the early detection of hepatic cirrhosis. HBsAg carriers with cirrhosis should be echographically evaluated every 6 months.

# Treatment

## Medical therapy
The majority of adults are able to eliminate the virus without treatment.  Currently, there is no treatment available for acute hepatitis B infection. Symptomatic treatment may be indicated. Early antiviral treatment may only be required in fewer than 1% of patients, whose hepatitis B takes a very aggressive course, such as in cases of fulminant hepatitis. Treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer.  Chronically infected patients with persistently elevated serum alanine aminotransferase and HBV DNA levels are candidates for therapy.  Treatment lasts from six months to a year, depending on the medication and genotype.  Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. These include antiviral drugs (e.g., Lamivudine, Adefovir, Tenofovir, Telbivudine and Entecavir) and immune system modulators, including interferon alpha-2a and pegylated interferon-alpha-2a.

## Surgery
Surgery is usually not indicated for the treatment of hepatitis B. However, for patients with advanced liver damage secondary to HBV infection or liver failure in fulminant hepatitis, liver transplantation may be beneficial.

## Primary Prevention
The risk of transmission of hepatitis B may be diminished by following measures proposed by the WHO. These include vaccination of all infants within 24 hours of birth; vaccination of members of certain risk groups, such as travelers to endemic areas and healthcare workers (if they have not been vaccinated yet); avoidance of sexual contact with a person who has acute or chronic hepatitis B; and avoiding sharing personal items such as razors or toothbrushes. The HBV vaccine is effective in preventing HBV infections when it is administered either before or shortly after exposure.

### Vaccination
The Hepatitis B vaccine is the most effective tool in preventing the transmission of HBV and HDV. Vaccines are composed of the surface antigen of HBV (HBsAg) and are produced by two different methods, including plasma-derived and recombinant DNA.
The primary hepatitis B immunization series conventionally consists of three doses of vaccine. Vaccination of infants and, in particular, delivery of hepatitis B vaccine within 24 hours of birth is 9095% effective in preventing infection with HBV, as well as decreasing HBV transmission if followed by at least two other doses. WHO recommends universal hepatitis B vaccination for all infants, and further advises that the first dose should be given as soon as possible after birth. This strategy has resulted in a dramatic decrease in the prevalence of CHB among young children in regions of the world where universal infant vaccination programs have been implemented. A small proportion of vaccinated children (510%) have a poor response to vaccination, and will remain susceptible as adults to acquisition of HBV infection.

### Vertical transmission
Hepatitis B virus (HBV) infection in a pregnant woman poses a serious risk to the fetus. Without postexposure immunoprophylaxis, approximately 40% of infants born to HBV-infected mothers in the United States will develop chronic HBV infection, approximately one-fourth of whom will eventually die from chronic liver disease.

## Secondary Prevention
Hepatitis B Immunoglobulin (HBIG) is a form of passive immunization when given shortly before or soon after exposure to hepatitis B virus. It is also administered in combination with HBV vaccines to newborns of HBsAg-positive mothers.