Hepatitis B: A Cross-sectional Study

DE LA SALLE UNIVERSITY DASMARINAS

HEPATITIS – B A Cross-sectional Study Roque, Jason R. Bencito, Dennise Marie Estacio, Anna Lorraine HUB-42

Mr. Norbel Tabo Professor, Microbiology – Lecture

August 2012

TABLE OF CONTENTS

I.

Introduction Brief Description of the Disease Brief History and Facts Classical Signs and Symptoms Etiology

II.

Epidemiology World Distribution Southeast Asia Distribution Philippines Distribution Ten Leadin Causes of Morbidity and Mortality Gender Distribution Age Group Distribution Patterns, Severity and Occurrence Recent (2005 – 2010)

III.

Updates on Diagnosis Classical Diagnosis Recent Diagnosis Advanced Diagnosis New Technologies

IV.

Prevention and Control Programs of DOH Methods

V.

Intervention and Strategies

VI.

Issues and Problems

VII.

References

INTRODUCTION

A. Brief Description of the Disease Hepatitis B is a potentially serious form of liver inflammation due to infection caused by the hepatitis B virus (HBV). It occurs in both rapidly developing (acute) and long-lasting (chronic) forms, and is one of the most common chronic infectious diseases worldwide. An effective vaccine is available that will prevent the disease in those who are later exposed.

Hepatitis B is originally known as serum hepatitis. Hepatitis B has only been recognized as such since World War II, and has caused current epidemics in parts of Asia and Africa.

Hepatitis B is recognized as endemic in China and various other parts of Asia. Over one-third of the world's population has been or is actively infected by hepatitis B.

Hepatitis B is largely transmitted through exposure to bodily fluids containing the virus.

This includes unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, vertical transmission from mother to child during childbirth, and so on. The primary method of transmission depends on the prevalence of the disease in a given area. In low prevalence areas, such as the continental United States, IV drug abuse and unprotected sex are the primary method. In high prevalence countries, such as China, vertical transmission is most common. In moderate prevalence areas, the disease is predominantly spread among children.

The virus that causes hepatitis B is a member of the Hepadnavirus family and it is composed of an icosahedral nucleocapsid (core) enclosing a circular, double-stranded DNA

genome. The virus is unique amongst the DNA viruses; in that it uses a reverse transcriptase to generate the genomic DNA to deliver to its progeny. Additionally, the DNA genome is incomplete on one strand.

Hepatitis B infection may lead to a chronic inflammation of the liver, leading to cirrhosis.

This type of infection dramatically increases the incidence of liver cancer.

B. Brief History and Facts Hepatitis has been known for centuries, and until recently referred simply to an inflammation of the liver. It was not until the 1940’s however, that doctors began to realize that a virus was possibly responsible for it. A conclusion would have to wait until the 1970’s when doctors finally made a clear link between what was then called protein AA and hepatitis. This protein is now called Hepatitis B Surface Antigen, or HBsA, and scientists have discovered Hepatitis strains from A to G.

A disease correlating to Hepatitis was known over 1,800 years ago in China. The prescribed treatment was a decoction of herbs which is still used today in many Asian countries, including Japan, China, and Vietnam. Many of the herbs used in this decoction would be familiar to westerners, and included licorice, rhubarb, and cinnamon. Many Western trained Asian doctors prescribe this decoction for Hepatitis B over any Western medicine, citing that it is more effective than modern drugs.

Milk thistle, or the extract of this plant, has been an herbal remedy for Hepatitis for many years. It is believed that the extract of the milk thistle plant will flush toxins and viruses from the liver, leaving it cleaner and functioning better. Many tests have been run, most placebo controlled studies and no improvement was found in any participants using the milk thistle extract.

Studies have also been performed on Aryurvedic Medicine, the Indian words meaning “Science of Life�. In the history of Hepatitis B, many herbal remedies have come into vogue, but this one actually shows some results. In a placebo controlled test the herbal remedy was proven to enhance liver function by a great deal over placebo. The results are still not completely clear, but it seems that there may be some promise in at least one ancient remedy.

C. Classical Signs and Symptoms (as defined by WHO) Nausea and vomiting have been listed by the World Health Organization (WHO) as symptoms associated with the hepatitis B virus. Many viral diseases cause some nausea and vomiting, but the hepatitis B virus also damages the liver. Without the liver, bile is not produced and without bile, normal digestion of fat is hindered. This process may add to the nausea and vomiting experienced by the patient.

The stools of patients with hepatitis B can become light or pale in color, according to the WHO. The normal dark color of stools is due to the presence of bile and bilirubin in the stool. In a patient with a damaged liver (like a hepatitis B patient), there is less bile and bilirubin being secreted into the colon. Therefore, these substances cannot be incorporated into the stool.

As the disease ravages the liver, the organ becomes inflamed. This inflammation leads to abdominal pain, which is a symptom of hepatitis B. The abdominal pain is usually located in the area of the liver, which is in the right upper portion of the abdomen.

Patients who contract hepatitis B often complain of a yellowing of their skin and sclera (white part of the eye). This yellow discoloration is a condition called jaundice. The virus replicates in the liver and has been reported to cause severe damage to the organ. This liver damage, or cirrhosis, causes a yellowish pigment called bilirubin to leak from the ruptured liver cells. The pigment then gets stored in the skin and this leads to jaundice.

D. Etiology Hepatitis B is a liver disease caused by infection with the hepatitis B virus (HBV).

Hepatitis B is one of the most common forms of viral hepatitis, which includes hepatitis A, B, C, D, and E. But hepatitis has many other causes, including some medicines, long-term alcohol use, fatty deposits in the liver, and exposure to certain industrial chemicals.

HBV is spread when blood, semen, or vaginal fluids (including menstrual blood) from an infected person enter another person's body, usually in one of the following ways:

•

Sexual contact. The hepatitis B virus can enter the body through a break in the lining of the rectum, vagina, urethra, or mouth.

•

Sharing needles. People who share needles and other equipment (such as cotton, spoons, and water) used for injecting illegal drugs may inject HBV-infected blood into their veins.

•

Work-related exposure. People who handle blood or instruments used to draw blood may become infected with the virus. Health care workers are at risk of becoming infected with the virus if they are accidentally stuck with a used needle or other sharp instrument contaminated with an infected person's blood. Infection also can occur if blood splashes onto an exposed surface, such as the eyes, mouth, or a cut in the skin.

•

Childbirth. A newborn baby can get the virus from his or her mother during delivery when the baby comes in contact with the mother's body fluids in the birth canal (prenatal transmission). But breast-feeding does not transmit the virus from a woman with HBV to her child.

•

Body piercings and tattoos. HBV may be spread when needles used for body piercing or tattooing are not properly cleaned (sterilized) and HBV-infected blood enters a person's skin.

•

Toiletries. Grooming items such as razors and toothbrushes can spread HBV if they carry blood from a person who is infected with the virus.

EPIDEMIOLOGY

A. World Distribution Hepatitis B virus (HBV) infection remains a major global public health problem, despite the availability of a highly effective vaccine and improvements in antiviral therapy. Globally, of the two billion people previously infected, more than 350 million people have developed chronic HBV infection, causing one million HBV-related deaths each year. HBV infection varies according to geography, with chronic HBV prevalence ranging from 0.2% to 20%.

Approximately 45% of the world’s population lives in highly endemic areas, such as Africa and the Asia-Pacific region (excluding Japan, Australia and New Zealand).

Figure 1. Geographic distribution of chronic hepatitis B (HBV) infection worldwide 2006*

Source: CDC. Travelers’ health; yellow book. Atlanta, GA: US Department of Health and Human Services, CDC; 2008. Available at http://wwwn.cdc.gov/travel/yellowbookch4 HepB.aspx.

Table 1. Prevalence of Hapatitis B in Various Areas % of population positive for Area

Infection

HBsAg

Anti-HBS

Neonatal

Childhood

0.2-0.5

4-6

rare

Infrequent

2-7

20-55

frequent

Frequent

8-20

70-95

very frequent

very frequent

Northern, Western, and Central Europe,North America,Australia

Eastern Europe, theMediterranean,Russia and theRussian Federation,Southwest Asia, Central and South America

Parts of China, Southeast Asia, tropical Africa

Source: Zuckerman AJ. Hepatitis Viruses. In: Baron S, eds. Medical Microbiology, 4th ed.

Galveston, TX, The University of Texas Medical Branch at Galveston, 1996:849863,52 with permission.

B. Southeast Asia Distribution Approximately 100 million hepatitis B carriers, more than 5.6% of the total population, live in the Member countries of the WHO South-East Asia Region. More than 300 000 people

are estimated to die each year due to the chronic consequences of hepatitis B, particularly cirrhosis and liver cancer.

Since 1976, Member States of the Region have identified liver diseases as one of the leading health priorities in the Region and requested WHO to provide technical support in conducting epidemiological studies on viral hepatitis, development of diagnostic reagents and tests as well as development and production of the hepatitis B vaccine.

A hepatitis B control programme is multi-faceted and may involve immunization, blood screening, injection safety, public health awareness and education, sexual health programmes, surveillance, drug and alcohol services, and blood testing and access to treatment. Strategic planning and coordination are therefore essential.

All countries in the WHO South-East Asia Region consider hepatitis B an urgent public health issue and have a policies, goals and plans, but in most countries implementation is not adequate, sometimes following a series of uncoordinated programmes rather than a cohesive strategic approach.

However, in all countries of the Region, much progress has been made in protecting the next generation from hepatitis B, and to date more than 130 million infants have received three doses of the HBV vaccine. The limited availability of the hepatitis B vaccine for national immunization programmes, largely due to cost, has been an obstacle. Following the launch of the Global Alliance for Vaccines and Immunization (GAVI) to intensify national immunization programmes in developing countries worldwide, most countries in this Region have taken

advantage of the support it provided to introduce hepatitis B vaccine into their national immunization programmes (NIPs). Currently, all Member States in the Region have introduced the hepatitis B vaccine into their routine NIPs. However, India with the largest birth cohort in the world, is yet to complete the introduction of hepatitis B vaccine coverage to all parts of the country. In all countries where HepB (the hepatitis B vaccine) has been introduced, it has been accepted well both by the community as well as health workers, and coverage is 71.5%.

Table 2. Number of Children immunized in different countries and year

Source: http://www.searo.who.int/LinkFiles/Diarrhoea,_ARI_and_hepatitis_SEA-CD-232.pdf

Graph 1.

Source: http://www.searo.who.int/LinkFiles/Diarrhoea,_ARI_and_hepatitis_SEA-CD-232.pdf

The lack of accurate prevalence data for viral hepatitis is an obstacle which links directly to limited access to testing — more than half the population in the Region lives in countries with no provision for free testing. Further, some countries have not been able to implement the mandatory HBsAg screening of blood and blood products, and blood transfusion without screening is still practiced. Currently, there is no government funding for treatment of chronic hepatitis B patients. In addition to access to testing, improving diagnosis requires awareness of the risks and routes of transmission among those who may have been exposed to the hepatitis B virus. This is also crucial for prevention. However, government-funded public awareness work is not regular and more effort and resources are required.

In addition to the governments’ efforts, civil society and non-governmental organizations are involved in promotion of HBV vaccination. Their participation is crucial for the control of hepatitis B infection and spread, and better coordination with the national health authorities is needed.

C. Philippine Distribution Hepatitis B virus (HBV) infection is a majorpublic health problem in the Philippines. The impact of this infection is primarily on the considerable number of disability adjusted life years lost from the chronic sequelae of HBV infection. These include chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), the last of these ranking as one of the leading causes of cancer deaths among Filipino males.

A case control study of HCC conducted by Lingao et al showed that the odds ratio for HCC among hepatitis B surface antigen (HBsAg) positive Filipinos was 11.07 (95% CI 4.88 to 25.30), with the crude odds being slightly higher among men than women.

Figure 2. HBsAg Positivity Rates in Various Surveys in the Philippines

The Figure shows the prevalence of HBsAg positivity among various groups that have been surveyed in the Philippines. The prevalence ranges from a relatively low rate of 2째/o among medical students who have not yet been exposed to direct patient care, to a high of 16-5% among prisoners 2-5 (and EB Dy, unpublished data). In a survey of four villages in different provinces of the Philippines, the HBsAg prevalence ranged from 9-15%, with an average rate of 12%.

These rural villagers generally belonged to the lower socioeconomic class.4 Some variability in the age specific rates was observed between the four villages, but two distinct patterns emerged: in two villages, an early peak in HBsAg rates occurred at around 5 years of age, while, in the other two villages, there was a late peak in HBsAg positivity at around 35 years of age. As yet, there are no explanations for these differences, which would require prospective follow up studies to observe possible differences in behaviour and hygienic practices.

D. Gender and Age Group Distribution Table 3. Viral Hepatitis by Age Group, Sex and Province / City

G. Recent (2005 – 2010)

Figure 3. Viral Hepatitis Morbidity Rate By Year (1997 – 2010)

UPDATES on DIAGNOSIS

The diagnosis of hepatitis B virus (HBV) infection was initiated by the discovery of Australia antigen (hepatitis B surface antigen, HBsAg). During the following decades, serologic assays were established for HBsAg and other HBV antigens and antibodies. Advances in molecular biology techniques led to the development of polymerase chain reaction (PCR) assays for direct determination of hepatitis B virus DNA (HBV DNA).

Diagnosis of Hepatitis B Virus (HBV) infection tests for a series of serological markers of HBV and excludes alternative etiological agents such as hepatitis A, C, and D viruses.

Serological tests are used to distinguish acute, self-limited infections from chronic HBV infections and to monitor vaccine-induced immunity. These tests are also performed to determine if the patient should be considered for antiviral therapy. Nucleic acid testing for HBV DNA is used as the standard to quantify HBV viral load and measure the effectiveness of therapeutic agents.

Serological tests for viral antigens like Hepatitis B can be performed on serum or plasma.

Its diagnosis can also be made by the detection of Hepatitis B core or surface antigen (HBcAg or HBsAg) in liver tissues or by HBV DNA hybridization or PCR.

A. Detection of Hepatitis B Core Antigen HBcAg is an intracellular antigen that is expressed in infected hepatocytes. It is not detectable in serum but is detected by immunohistochemical staining. Moreover, anti-HBc can

be detected throughout the course of Hepatitis B virus infection in the serum. It is made up predominantly of IgM class.

During acute infections, IgM anti-HBc is the important marker of HBV infection. It may be detectable up to two years after acute infection. However, levels of these detectors may present incorrect diagnosis. When their level increases, it might suggest chronic Hepatitis B, or Hepatitis D or C infection rather than acute Hepatitis B. The evaluation of individuals with isolated anti-HBc should include repeat testing for anti-HBc, HBsAg, and anti-HBs. Those who remain isolated anti-HBc positive should be tested for the presence of IgM anti-HBc to rule out recent HBV infection.

B. Detection of Hepatitis B Surface Antigen HBsAg is a serologic hallmark or HBV infection. It can be detected by radioimmunoassay or enzyme immunoassays. It appears in the serum 1 to 10 weeks after acute exposure to HBV. It is usually undetectable after four to six months in patients who recover from Hepatitis B. Its persistence in the body for more than six months indicates chronic infection. Its disappearance might be followed by the appearance of anti-HBsAg. This might confer long term immunity but if not, vaccination must be administered.

C. Serum Hepatitis B Viral DNA Assays Qualitative and quantitative tests for HBV DNA in serum have been developed to assess HBV replication. Recovery from acute Hepatitis B is usually accompanied by the disappearance of HBV DNA in serum. However, HBV DNA may remain detectable in serum for many years if

tested by polymerase chain reaction assays suggesting that the virus persists but is controlled by the immune system.

PREVENTION and CONTROL

Hepatitis B is a serious public health problem that affects humans of all ages around the world. We have learned that it is passed from person to person through bodily fluids (blood, semen, and vaginal secretions). It is most often it is transmitted through sexual contact or from an infected mother to her infant during birth. Its infection can lead to severe illness like liver cirrhosis, liver damage, and in worst cases, death. Thus, prevention and control of Hepatitis B is necessary. Prevention refers to the act of preventing the spread of the disease from one person to another to promote health. Control, on the other hand, means reducing the severity of the disease.

Prevention and control includes disease risk assessment, application of prescribed measures, vaccination, and health teaching.

A. Disease risk assessment It is designed to determine an individual’s risk for viral hepatitis by asking questions based on CDC’s guidelines for testing and vaccination. The assessment allows individuals to answer questions privately and print their recommendations to discuss with their doctor. Some of the questions asked are the following: •

Gender

•

Age

•

Were born to an HBV-infected mother

•

Have ever worked with or come in contact with infected bodily fluids

•

Have ever had unprotected sex with an HBV-infected person

•

Have ever had multiple sexual partners

•

Have ever had a sexually transmitted disease

•

Are a man who has sex with men

•

Have ever injected or inhaled drugs (even if it was only once or many years ago)

•

Have ever received hemodialysis (used equipment that cleans blood)

•

Have ever worked or been housed in a prison

•

Have ever traveled to countries where HBV is common

•

Have ever had tattoos or body piercings

B. Preventive measures This involves go after certain procedures or recommendations in order to avoid being infected. These procedures are the following: 1. Use of use condoms.

Use a new latex or polyurethane condom every time you have sex. If you don't know the health status of your partner, use a new latex condom every time you have sexual contact. Remember that although condoms can reduce your risk of contracting HBV, they don't eliminate the risk entirely. Condoms can break or develop small tears, and people don't always use them properly.

2. Wear gloves when touching or cleaning up blood on personal items.

Our skin is our first line of defense and in order to protect it, we must use protective gears such as gloves when we are exposed to bodily fluids present in tissues, tampons or in other items.

3. Practice antiseptic technique.

In cleaning areas with blood or other bodily fluids on it, using mixture of one part bleach and 10 parts water must be applied. This is an effective antimicrobial agent.

4. Stop using prohibited drugs.

If you use illicit drugs, get help to stop. If you can't stop, use a sterile needle each time you inject illicit drugs. Never share needles.

5. Be cautious about body piercing and tattooing.

If you choose to undergo piercing or tattooing, look for a reputable shop. Ask questions beforehand about how the equipment is cleaned or sterilized. Make sure the employees use sterile needles. If the staff won't answer your questions, look for another shop.

6. Do not share personal belongings with anyone.

Avoid sharing stuffs like razors, toothbrushes or pierced earrings because these things might be a carrier of the virus.

Note; we must remember that Hepatitis B is not spread by casual contact like holding hands, kissing on the cheek, eating food prepared by a carrier, visiting an infected person, and playing or talking to a carrier.

C. Vaccination You can protect yourself from Hepatitis B through vaccination. The vaccine for this disease contains one of the viral envelope proteins, Hepatitis B surface antigen (HBsAg). This is produced by yeast cells (Saccharomyces cerevisiae), into which the genetic code for HBsAg is inserted. It is typically administered in a series of three injections. The second injection is given at least one month after the first dose while the third one is given six months after the first dose.

After exposure to the vaccine, the body develops immune system antibody to HBsAg in the bloodstream. This antibody is known as anti-HBsAg. This antibody and immune system memory then provide immunity to Hepatitis B infection. The effectivity of the vaccine lasts for at least five years or longer depending on the reaction of the host’s immune system.

Aside from Hepatitis B vaccine, Hepatitis B immune globulin is also administered to prevent infection. It provides passively acquired anti-Hepatitis B and temporary protection (usually 3-6 months) when administered in standard doses. It is used as an adjunct to Hepatitis B vaccine for post exposure immunoprophylaxis (Measures of preventing health). It is prepared from plasma of donors with high concentrations of anti-Hepatitis B.

Hepatitis B Vaccine is recommended for: •

All infants beginning at birth

•

All children and adolescents who weren't vaccinated at birth

•

Health care workers, emergency workers and other people who come into contact with blood on the job

•

Men who have sex with men

•

People who have multiple sexual partners

•

People who inject illicit drugs

•

People who live with someone who has hepatitis B

•

Sexual partners of someone who has hepatitis B

•

Travelers planning to go to an area of the world with a high hepatitis B infection rate

Vaccination for infants, children and adolescents Babies who are born to carrier mothers are at risk. Generally, the baby doesn’t encounter the Hepatitis B virus in the womb as the placenta pars the virus. During delivery, the baby usually first encounter the virus upon entering the birth canal. The virus present in the blood and vaginal fluids of the mother readily expose the baby to the disease. Following birth, nursing infants via breast feeding can be a source of infection. In order to break this chain, prompt administration of Hepatitis B immunoglobulin and Hepatitis B vaccine must be done.

Due to this fact, the Advisory Committee on Immunization Practices (ACIP) recommends that all children receive their first dose of Hepatitis B vaccine at birth and complete the vaccine series by age 6–18 months. Older children and adolescents who did not previously receive the Hepatitis B vaccine should also be vaccinated.

Vaccination for Adults Adults are highly susceptible to Hepatitis B infection as it is the stage where travelling is predominant, and sexual encounters occur.

D. Health Teaching Educating people regarding the causes and risk of Hepatitis B is an essential step in preventing the spread of the infection. One way to do this is to promote education campaign initiative to decrease the burden of Hepatitis B. by doing so, there will be increased awareness about this epidemic and thus encourages people who may be infected to get tested.

E. Treatment of Hepatitis B There are four medications currently approved by the Food and Drug Administration (FDA) for treatment of active hepatitis B infection.

Alfa Interferon (Brand names: INTRON A, INFERGEN, ROFERON): Interferon is an antiviral agent with antiproliferative and immunomodulatory agent that is administered by subcutaneous injection daily or three times per week, for 12-16 weeks or longer. With adequate teaching, the injections can easily be administered at home by patients. High pretreatment ALT and lower levels of HBV DNA are the most important predictors of response to alfa interferon therapy. Virologic response to alfa interferon occurs in less than 10 percent of patients with normal ALT. A sustained response can be seen in 15 - 30 percent of patients with HBeAgnegative chronic hepatitis B and less than half of the responders show sustained clearance of HBsAg.

Side Effects: Depression – this is more commonly seen in patients with a prior history of depression. Muscle aches, fatigue, and low grade fevers are common and may be minimized by taking Tylenol (acetaminophen). Occasionally, patients may develop low white blood cell count,

headaches, irritability, and thyroid dysfunction. Underlying autoimmune disorders may also be unmasked.

Lamivudine (Epivir-HBV, 3TC): inhibits hepatitis B viral DNA synthesis. It should be taken orally, once daily. It is approved for use in adults and children and is usually tolerated well.

Occasionally, it may cause a rise in the liver enzyme ALT. Pretreatment ALT is an important predictor of response, with HBeAg conversion occurring in over a third of patients when the ALT is greater than five times normal. While Lamivudine benefits patients with HBeAg-negative chronic hepatitis B, the vast majority of patients relapse once treatment is stopped.

Adefovir dipivoxil (Hepsera): inhibits DNA polymerase activity and reverse transcriptase. This drug is administered orally on a daily basis and is typically well tolerated. It can be associated with kidney dysfunction, particularly if used in high doses. The optimal duration of therapy is not yet clear. About 50 - 60 percent of HBeAg positive and negative hepatitis B patients respond to this medication; data regarding the durability of response is awaited.

Baraclude (Entecavir): is the latest drug approved by the FDA for treatment of chronic hepatitis B. It works by inhibiting the function of Hepatitis B virus polymerase. Side effects include headache, fatigue, dizziness, nausea, and transient elevation in liver enzymes. This drug is taken orally, once daily and the optimal duration of therapy is not yet established.

In patients with severe liver dysfunction, a liver transplant may be required.

INTERVENTION STRATEGIES

Hepatitis B vaccination is the most effective measure to prevent HBV infection. Since they were first issued in 1982, recommendations for hepatitis B vaccination have evolved into a comprehensive strategy to eliminate HBV transmission in the United States. A primary focus of this strategy is universal vaccination of infants to prevent early childhood HBV infection and to eventually protect adolescents and adults from infection. Other components include routine screening of all pregnant women for hepatitis B surface antigen (HBsAg) and post exposure immunoprophylaxis of infants born to HBsAg-positive women, vaccination of children and adolescents who were not previously vaccinated, and vaccination of unvaccinated adults at increased risk for infection.

ISSUES and PROBLEMS

Hepatitis B virus (HBV) infection remains a global health concern. It is estimated that 2 billion individuals worldwide have been infected with this virus; 350 million are chronically infected, and 50 million new cases are diagnosed annually. Implementation of HBV vaccination programs has led to significant reductions in the HBV infection rate among children and healthcare workers. However, in highly endemic areas, this virus remains the leading cause of cirrhosis and hepatocellular carcinoma. Among those individuals who are chronically infected, 15% to 25% will die of sequelae related to HBV infection.

The clinical spectrum of HBV infection is broad, ranging from asymptomatic chronic carriers to fulminant hepatitis, with many factors influencing the natural history of the disease, including age at initial time of infection, viral characteristics, and exogenous factors, such as coinfection or alcohol. This report discusses clinical issues in the diagnosis and management of hepatitis B, including the management of the increasingly recognized hepatitis B e antigen (HBeAg-negative) chronic hepatitis, viral resistance patterns, and new therapeutic strategies and medications, as based on key presentations at this year's Digestive Disease Week meeting.

HBeAg-negative chronic hepatitis is increasingly recognized worldwide. Patients are at risk for sequelae of chronic infection, including cirrhosis and hepatocellular carcinoma.

Awareness and testing for HBeAg-negative chronic hepatitis B is important, and treatment options should be fully evaluated, taking into consideration viral resistance patterns and side effects.

All of the currently available medications for hepatitis B have both advantages and disadvantages. Careful evaluation of the individual patient's replication status, likelihood of response, age, associated cost, and disease severity should all play a role in the decision regarding choice of treatment strategy. New oral nucleoside/nucleotide analogs are currently in development and will soon add to the therapeutic armamentarium.

Vaccination for hepatitis B is safe and efficacious, and in patients at high risk for acute infection or for those with known chronic liver disease, implementation of early vaccination is important because it may affect response to the therapy.

REFERENCES

Beers, M.H., Fletcher,A.J., Jones, T.V, et al. 2003. Merck manual of medical information 2nd home edition. Chapter 137: Hepatitis. New York: Merck and co., inc. 729-733.

Mayo clinic staff. Prevention. September 11, 2011. http://www.mayoclinic.com/health/hepatitisb/DS00398/DSECTION=prevention. Retrieved August 26, 2012.

Hepetitis B information to the public. March 12, 2009. http://www.cdc.gov/hepatitis/B/index.htm. Retrieved August 26, 2012.

Hepatitis B vaccination. July 6 2012. http://www.cdc.gov/vaccines/vpd-vac/hepb/default.

Retrieved August 26, 2012.

Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP). http://www.cdc.gov/MMWr/preview/mmwrhtml/00033405.htm. Retrieved August 26, 2012.

Hepatitis B. April 1, 2009. http://www.healthscout.com/ency/1/513/main.html. Retrieved August 26, 2012.

Current Issues on Hepatitis B. http://www.medscape.org/viewarticle/480259 Retrieved August 28, 2012.

History of Hepatitis B. Retrieved on August 26, 2012 at http://www.hepatitisbvirus.net/thehistory-hepatitis-b.php

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http://www.thebody.com/content/art43531.html?ic=2004 Causes. Retrieved on August 26, 2012 at http://www.webmd.com/hepatitis/hepb-guide/hepatitisb-cause Hepatitis B. Retrieved on August 26, 2012 at http://www.wordiq.com/definition/Hepatitis_B