Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV).

It is estimated that 350 million individuals worldwide are infected with the virus, which causes 620,000 deaths worldwide each year. According to the Centers for Disease Control (CDC), approximately 46,000 new cases of hepatitis B occurred in the United States in 2006. In the United States, rates of new infection were highest among people aged 25 to 44 years (3.1 cases per 100,000 population) and lowest among those younger than 15 years of age (0.02 per 100,000). This reflects the major modes of transmission of hepatitis B (sexual transmission, illicit drug use, exposure to infected blood) and the effect of universal vaccination of infants. In the United States, there has been a 75% decrease in newly diagnosed cases of hepatitis B during the past decade. This decrease is attributed to increased vaccination and to heightened public awareness of HIV/AIDS and the resulting safer sexual practices. When a person first gets hepatitis B, they are said to have an 'acute' infection. Most people are able to eliminate the virus and are cured of the infection. Some are not able to clear the virus and have 'chronic' infection with hepatitis B that is usually life-long (see below). In the United States an estimated 800,000 to 1.4 million people are chronically infected with hepatitis B. Hepatitis B is found throughout the world. Some countries have much higher rates of infection than the United States; for example, in Southeast Asia and Sub-Saharan Africa, as many as 15% to 20% of adults are chronically infected with hepatitis B. What kind of a virus is hepatitis B? The hepatitis B virus is a DNA virus, meaning that its genetic material is made up of deoxyribonucleic acids. It belongs to a family of viruses known as Hepadnaviridae. The virus is primarily found in the liver but is also present in the blood and certain body fluids. Hepatitis B virus consists of a core particle (central portion) and a surrounding envelope (outer coat). The core is made up of DNA and the core antigen (HBcAg). The envelope contains the surface antigen (HBsAg). These antigens are present in the blood and are markers that are used in the diagnosis and evaluation of patients with suspected viral hepatitis. How does hepatitis B virus cause liver injury? The hepatitis B virus reproduces in liver cells, but the virus itself is not the direct cause of damage to the liver. Rather, the presence of the virus triggers an immune response from the body as the body tries to eliminate the virus and recover from the infection. This immune response causes inflammation and may seriously injure liver calls. Therefore, there is a balance between the protective and destructive effects of the immune response to the hepatitis B virus.

How is the hepatitis B virus spread (transmitted)?

Hepatitis B is spread mainly by exposure to infected blood or body secretions. In infected individuals, the virus can be found in the blood, semen, vaginal discharge, breast milk, and saliva. Hepatitis B is not spread through food, water, or by casual contact. In the United States, sexual contact is the most common means of transmission, followed by using contaminated needles for injecting illicit drugs, tattooing, body piercing, or acupuncture. Additionally, hepatitis B can be transmitted through sharing toothbrushes and razors contaminated with infected fluids or blood. Hepatitis B also may be spread from infected mothers to their babies at birth (so-called 'vertical' transmission). This is the most prevalent means of transmission in regions of the world where hepatitis B rates are high. The rate of transmission of hepatitis B from mother to newborn is very high, and almost all infected infants will develop chronic hepatitis B. Fortunately, transmission can be significantly reduced through immunoprophylaxis (see below). Rarely, hepatitis B can be transmitted through transfused blood products, donated livers and other organs. However, blood and organ donors are routinely screened for hepatitis which typically prevents this type of transmission.

What are the symptoms of acute hepatitis B?

Acute hepatitis B is the period of illness that occurs during the first one to four months after acquiring the virus. Only 30% to 50% of adults develop significant symptoms during acute infection. Early symptoms may be non-specific, including fever, a flu-like illness, and joint pains. Symptoms of acute hepatitis may include:

fatigue, loss of appetite, nausea, jaundice (yellowing of the skin and eyes), and pain in the upper right abdomen (due to the inflamed liver).

Rarely, acute hepatitis damages the liver so badly it can no longer function. This lifethreatening condition is called "fulminant hepatitis." Patients with fulminant hepatitis are at risk of developing bleeding problems and coma resulting from the failure of the liver. Patients with fulminant hepatitis should be evaluated for liver transplantation. Small studies suggest that the drug lamivudine (Epivir), may be of limited assistance in these cases (see below). What determines the outcome of acute hepatitis B? The body's immune response is the major determinant of the outcome in acute hepatitis B. Individuals who develop a strong immune response to the infection are more likely to

clear the virus and recover. However, these patients also are more likely to develop more severe liver injury and symptoms due to the strong immune response that is trying to eliminate the virus. On the other hand, a weaker immune response results in less liver injury and fewer symptoms but a higher risk of developing chronic hepatitis B. People who recover and eliminate the virus will develop life-long immunity, that is, protection from subsequent infection from hepatitis B. Most infants and children who acquire acute hepatitis B viral infection have no symptoms. In these individuals, the immune system fails to mount a vigorous response to the virus. Consequently, the risk of an infected infant developing chronic hepatitis B is greater than 95%. In contrast, only 5% of adults who have acute hepatitis B develop chronic hepatitis B.

What are the symptoms of chronic hepatitis B?

The liver is a vital organ that has many functions. These include a role in the immune system, production of clotting factors, producing bile for digestion, and breaking down toxic substances, etc. Patients with chronic hepatitis B develop symptoms in proportion to the degree of abnormalities in these functions. The signs and symptoms of chronic hepatitis B vary widely depending on the severity of the liver damage. They range from few and relatively mild signs and symptoms to signs and symptoms of severe liver disease such as cirrhosis or liver failure. Most individuals with chronic hepatitis B remain symptom free for many years or decades. During this time, the patient's blood tests usually are normal or only mildly abnormal. Some patients may deteriorate and develop inflammation or symptoms, putting them at risk for developing cirrhosis. Cirrhosis of the liver due to hepatitis B Inflammation from chronic hepatitis B can progress to cirrhosis (severe scarring) of the liver. Significant amounts of scarring and cirrhosis lead to liver dysfunction. Symptoms may include:

weakness, fatigue, loss of appetite, weight loss, breast enlargement in men, a rash on the palms, difficulty with blood clotting, and spider-like blood vessels on the skin.

Decreased absorption of vitamins A and D can cause impaired vision at night and thinning of bones (osteoporosis). Patients with liver cirrhosis also are at risk of infections because the liver plays an important role in the immune system. Advanced cirrhosis of the liver due to hepatitis B In patients with advanced cirrhosis, the liver begins to fail. This is life-threatening condition. Several complications occur in advanced cirrhosis:

Confusion and even coma (encephalopathy) results from the inability of the liver to detoxify certain toxic substances. Increased pressure in the blood vessels of the liver (portal hypertension) causes fluid to build up in the abdominal cavity (ascites) and may result in engorged veins in the swallowing tube (esophageal varices) that tear easily and may cause massive bleeding. Portal hypertension can also cause kidney failure or an enlarged spleen resulting in a decrease of blood cells and the development of anemia, increased risk of infection and bleeding. In advanced cirrhosis, liver failure also results in decreased production of clotting factors. This causes abnormalities in blood clotting and sometimes spontaneous bleeding. Patients with advanced cirrhosis often develop jaundice because the damaged liver is unable to eliminate a yellow compound, called bilirubin.

Hepatitis B virus and primary liver cancer (hepatocellular carcinoma) Patients with chronic hepatitis B are at risk of developing liver cancer. The way in which the cancer develops is not fully understood. Symptoms of liver cancer are nonspecific. Patients may have no symptoms, or they may experience abdominal pain and swelling, an enlarged liver, weight loss, and fever. The most useful diagnostic screening tests for liver cancer are a blood test for a protein produced by the cancer called alpha-fetoprotein and an ultrasound imaging study of the liver. These two tests are used to screen patients with chronic hepatitis B, especially if they have cirrhosis or a family history of liver cancer. Hepatitis B virus involvement of organs outside of the liver (extra-hepatic) Rarely, chronic hepatitis B infection can lead to disorders that affect organs other than the liver. These conditions are caused when the normal immune response to hepatitis B mistakenly attacks uninfected organs. Among these conditions are:

Polyarteritis nodosa: a disease characterized by inflammation of the small blood vessels throughout the body. This condition can cause a wide range of symptoms,

including muscle weakness, nerve damage, deep skin ulcers, kidney problems, high blood pressure, unexplained fevers, and abdominal pain. Glomerulonephritis: another rare condition, which is inflammation of the small filtering units of the kidney.

How is hepatitis B diagnosed?

Infection with hepatitis B is suspected when the medical history and the physical examination reveal risk factors for the infection or symptoms and signs that are suggestive of hepatitis B. Abnormalities in the liver tests (blood tests) also can raise suspicion; however, abnormal liver tests can result from many conditions that affect the liver. The diagnosis of hepatitis B can be made only with specific hepatitis B virus blood tests. These tests are known as hepatitis 'markers' or 'serology.' Markers found in the blood can confirm hepatitis B infection and differentiate acute from chronic infection. These markers are substances produced by the hepatitis B virus (antigens) and antibodies produced by the immune system to fight the virus. Hepatitis B virus has three antigens for which there are commonly-used tests - the surface antigen (HBsAg), the core antigen (HBcAg) and the e antigen (HBeAg). HBsAg and anti-HBs The presence of hepatitis B surface antigen (HBsAg) in the blood indicates that the patient is currently infected with the virus. HBsAg appears an average of four weeks after initial exposure to the virus. Individuals who recover from acute hepatitis B infections clear the blood of HBsAg within approximately four months after the onset of symptoms. These individuals develop antibodies to HBsAg (anti-HBs). Anti-HBs provides complete immunity to subsequent hepatitis B viral infection. Similarly, individuals who are successfully vaccinated against hepatitis B produce anti-HBs in the blood. Patients who fail to clear the virus during an acute episode develop chronic hepatitis B. The diagnosis of chronic hepatitis B is made when the HBsAg is present in the blood for at least six months. In chronic hepatitis B, HBsAg can be detected for many years, and anti-HBs does not appear. Anti-HBc In acute hepatitis, a specific class of early antibodies (IgM) appears that is directed against the hepatitis B core antigen (anti-HBc IgM). Later, another class of antibody, anti-HBc IgG, develops and persists for life, regardless of whether the individual recovers or develops chronic infection. Only anti-HBc IgM can be used to diagnose an acute hepatitis B infection. HBeAg, anti-HBe, and pre-core mutations

Hepatitis B e antigen (HBeAg) is present when the hepatitis B virus is actively multiplying, whereas the production of the antibody, anti-HBe, (also called HBeAg seroconversion) signifies a more inactive state of the virus and a lower risk of transmission. In some individuals infected with hepatitis B virus, the genetic material for the virus has undergone a structural change, called a pre-core mutation. This mutation results in an inability of the hepatitis B virus to produce HBeAg, even though the virus is actively reproducing. This means that even though no HBeAg is detected in the blood of people with the mutation, the hepatitis B virus is still active in these persons and they can infect others. Hepatitis B virus DNA The best marker of hepatitis B virus reproduction is the level of hepatitis B virus DNA in the blood. Detection of hepatitis B virus DNA in a blood sample signals that the virus is actively multiplying. In acute hepatitis, HBV DNA is present soon after infection, but is eliminated over time in patients' who clear the infection. In chronic hepatitis, levels of HBV DNA often continue to be elevated for many years and then decrease as the immune system controls the virus. HBV DNA levels are sometimes referred to as the 'viral load'. How are the hepatitis B blood tests interpreted? The following table gives the usual interpretation for sets of results from hepatitis B blood (serological) tests. Most Likely Status* Susceptible, not infected, not immune Tests HBsAg anti-HBc anti-HBs HBsAg anti-HBc anti-HBs HBsAg anti-HBc anti-HBS HBsAg anti-HBc IgM anti-HBc anti-HBs HBsAg anti-HBc IgM anti-HBc Results negative negative negative negative positive positive negative negative positive positive positive positive negative positive positive negative

Immune due to natural infection

Immune do to hepatitis B vaccination

Acutely infected Chronically infected

anti-HBs

negative

*Interpretation of the hepatitis B virus blood tests should always be made by an experienced clinician with knowledge of the patient's medical history, physical examination, and results of the standard liver blood tests.

What is the role of a liver biopsy in chronic hepatitis B?

During a liver biopsy, a small sample of liver tissue is collected and examined under the microscope. This test is valuable because this sample reflects the health of the liver. It can show the amount of liver injury (inflammation or cirrhosis). Liver biopsy is not routinely needed to diagnose hepatitis B, but it is used for monitoring the progression of liver damage in people with chronic hepatitis and helping to choose or evaluate treatment options.

What is the natural course of chronic hepatitis B?

The course of chronic hepatitis B is variable and depends on several factors. These factors are the patient's age at which the infection began, the extent of viral multiplication, and the immune system's ability to control the infection. The infection can progress from an:

immune tolerant phase (in which the immune system ignores the virus) immune clearance phase (in which the immune system attempts to eliminate the virus) quiescent phase (in which the virus is less active)

Immune tolerant phase For individuals infected at birth or at a young age, the immune system initially does not react to the hepatitis B virus. This phase of the infection is known as the immune tolerant phase. Despite high levels of virus in the body, there may be little evidence of inflammation and no symptoms. This phase typically lasts for years, even up to two or three decades. It is important to know that the immune tolerant phase is generally not seen in individuals who become infected during adulthood. Immune clearance phase During the third to fourth decade of chronic hepatitis B acquired in childhood, the immune system may start to react to the virus. This is known as the immune clearance phase. In contrast, an infection acquired in adulthood usually begins with the immune clearance phase. In the immune clearance phase, the immune system attacks the hepatitis B virus-infected liver cells in an attempt to clear the virus. This causes inflammation, liver injury, and the development of scar tissue. Standard liver blood tests are abnormal,

and the liver biopsy shows inflammation and/or formation of scar tissue (fibrosis). The severity of liver cell destruction, the degree of fibrosis, and the duration of the immune clearance phase determine the outcome of chronic hepatitis B. The more severe the destruction and fibrosis and the longer the phase, the more likely it is that cirrhosis will develop. Quiescent phase Following the immune clearance phase, the viral infection may enter a less active phase known as the quiescent phase. During this phase, there are no symptoms, the levels of hepatitis B virus become very low, and the standard liver blood tests become normal or nearly normal. Advanced scaring or cirrhosis that may have developed earlier, however, remains. Occasionally, during the quiescent phase, the virus becomes active again. This is known as a "flare," and often is associated with symptoms, abnormal liver blood tests, and further injury to the liver. The flares are caused by reactivation of the immune system against the virus. Flares can be very severe and result in further scarring of the liver. The disease in many of these individuals will progress to cirrhosis and eventually to advanced or end-stage cirrhosis with its associated complications, including liver cancer. Infected individuals who experience a mild immune clearance phase and move into the quiescent phase are known as healthy carriers of hepatitis B virus. These individuals usually have normal liver tests and do not have symptoms; however, they can still transmit the hepatitis B viral infection to others. The risk of hepatitis B virus carriers developing cirrhosis and liver cell cancer is small although the risk is higher as compared to people without chronic hepatitis B.

What medications are used to treat hepatitis B?

Acute infection Acute infection with hepatitis B usually does not require treatment. In rare cases, however, the infection may cause life-threatening liver failure. Patients with liver failure due to acute hepatitis B should be evaluated for liver transplantation. Small studies suggest that the drug lamivudine (Epivir) may be effective in this setting. Chronic infection If a person is chronically infected with hepatitis B and has few signs or symptoms of complications, medications usually are not used. These patients are watched carefully and given periodic blood tests. One test measures the 'viral load,' that is, the amount of viral DNA in the blood. Doctors will recommend treatment if there are signs that the virus is beginning to cause damage or if the viral load is high. Another reason to prescribe medication is if the patient has a positive test for the Hepatitis B e-antigen (HBeAg) in the blood. HBeAg is associated with an increased risk of progression of liver disease and its complications.

In chronic hepatitis B, the goal of treatment is to reduce the risk of complications including cirrhosis and liver failure. However, it takes decades for complications to occur, which makes it difficult to study the effect of medications. As a substitute for waiting years to find out what happens, scientists have used tests like the viral load or liver function tests to evaluate if medicines are working. This is logical because it is known that people who have large amounts of the virus in their blood are at highest risk to get cirrhosis. Up to one-third of people with very high viral loads (more than one million viral copies per milliliter of blood) will develop cirrhosis over a decade, compared to only 4.5% of those with low viral loads (fewer than 300 viral copies per milliliter). Medications can reduce the number of viruses in the body and may be able to eliminate the virus from the bloodstream. Logically, this should lead to them having a low rate of progression to cirrhosis (<1% per year), although large, long-term studies have not been done. Even in people who clear the virus from their blood, low numbers of viruses still live in the liver and other cells. Thus, the medications do not cure the disease, but they can prevent or delay complications and symptoms. People who have a good response to treatment can still transmit the virus. Doctors follow blood tests that measure viral load and liver function and they may recommend liver biopsies to evaluate if the medications are working. The medications in current use for chronic hepatitis B include the interferons and nucleoside/nucleotide analogues. New agents are being developed although they are still under investigation and considered experimental. There are no accepted guidelines that tell how every patient should be treated. As a result, treatment is individualized. Interferon Interferon-alpha has been used to treat hepatitis B for more than 20 years. Interferonalpha is a naturally occurring protein that is made in the body by white blood cells to combat viral infections. In addition to its direct anti-viral effects, interferon works against the hepatitis B virus by stimulating the body's immune system to clear the virus. Compared to older interferon alpha agents, pegylated interferon alpha, marketed as Pegasys or Pegintron, has a more convenient dosing schedule, may be slightly more effective and suppresses the virus for a longer period of time. Pegylated interferon alpha is given once a week for 48 weeks.

A significant reduction in the viral load or elimination of detectable viral DNA from the blood occurs in two-thirds of persons during treatment. Blood tests for liver functions normalize in approximately 40% people treated with interferon. People who have significant abnormalities in liver function before therapy are more likely to respond to treatment. Those who have normal liver blood tests before treatment are less likely to respond to interferon therapy. Liver biopsy results show improvement in about one-third of patients.

Only 27%-32% of persons who have Hepatitis B e-antigen (HBeAg) in their blood will be able to eliminate HBeAg and produce antibodies against the HBe antigen after treatment with interferon. Relapse may occur after treatment is stopped. Sustained response (undetectable viral load in the blood, normal liver function tests) occurs in approximately 15% to 30% of patients after the drug is stopped. Although this is not a cure (some virus still lives in the liver and elsewhere), people with sustained response are at low risk for complications of liver disease. If the responder's immune system is compromised, for example through the use of steroids or acquiring HIV, the disease can recur. Periodic monitoring of blood tests can help confirm that the response continues to be sustained. Interferon side effects Interferon causes several side effects including:

fatigue, generalized muscle aches, fever, chills and loss of appetite. These flu-like symptoms occur in approximately 80% of treated patients; mood swings, depression, anxiety and other neuropsychiatric effects may occur; and thyroid gland abnormalities resulting in hypothyroidism (too little thyroid hormone); significant suppression of the bone marrow and production of blood cells; infection; or hair loss may occur.

The side effects may be severe enough that the patient is unable to continue treatment. During treatment, the normal immune response to the virus is stimulated and may cause worsening inflammation in the liver. This is normally a good sign showing that the interferon is working, but more extreme responses may in rare cases cause liver failure. Thus, physicians will monitor blood tests closely during therapy. Persons with unstable liver disease due to cirrhosis usually should not take interferon because of the increased risk of liver failure. Nucleoside/nucleotide analogues Nucleoside/nucleotide analogues (NAs) are man-made chemicals that mimic the nucleosides and nucleotides that are used for making DNA. When the virus tries to use the analogues to make its own DNA, it is unable to make the DNA and, therefore, cannot reproduce. Examples of these agents include adefovir (Hepsera), entecavir (Baraclude), lamivudine (Epivir-HBV, Heptovir, Heptodin), telbivudine (Tyzeka) and tenofovir (Viread).

In patients who have HBeAg in their blood, NAs reduce the viral load, causing the virus to become undetectable in 21% to 67% of patients.

Normalization of blood liver tests occurs in 40% to 77%, and loss of HBeAg occurs in approximately 12% to 22% of cases after one year of treatment. Results are better in patients who do not have HBeAg in their blood, with 50% to 90% having non-detectable virus and 60% to 80% having normalization of liver function tests.

In a 2004 study in people who already had cirrhosis from hepatitis B, treatment with lamivudine cut the risk of liver cancer and progressive liver failure by more than 50%. Newer NAs such as entecavir (Baraclude) and telbivudine (Tyzeka) appear to have higher response rates than older agents such as lamivudine (Epivir-HBV, Heptovir, Heptodin), but there is less experience with these NAs. Unfortunately, the hepatitis B virus may become resistant to NAs over time (see below). Adefovir may be effective against strains of virus that have become resistant to lamivudine and may be added to lamivudine when resistance appears. Simply switching from one NA to another is not recommended because this leads to virus strains that are resistant to multiple medications. Currently, the optimal duration of treatment with nucleoside/nucleotide analogues is uncertain. Persons with HBeAg may be treated until six months after the HBeAg disappears from the blood and is replaced by antibodies (anti-HBe), if this occurs. In persons without HBeAg, the endpoints are less clear. Some experts advocate treating until the viral load (viral DNA) is undetectable and the surface antigen (HbsAg) has been cleared from the blood. Others suggest continuing medications for prolonged periods to suppress the virus. All of these strategies are hampered by the risk of the virus becoming resistant to the medications. Patients who discontinue treatment with NAs should be monitored carefully for recurrent hepatitis, which may be severe. Why does hepatitis B virus become resistant to nucleoside/nucleotide analogues? The major challenge associated with long-term therapy with NAs is the development of viral resistance to the NAs. This resistance results from a change (mutation) in the genetic material of the virus.

For lamivudine (Epivir-HBV, Heptovir, Heptodin), the incidence of resistance is 25% after one year and as high as 50% after three years of treatment. With telbivudine (Tyzeka), resistance rates are 5% to 11% after one year.

Therefore, some guidelines do not recommended lamivudine or telbivudine alone as the first treatment for chronic hepatitis B. For other NAs such as adefovir (Hepsera), resistance is less common after one year of therapy but rises to 30% after five years. Early results with entecavir (Baraclude) suggest that resistance may be uncommon with this agent. When resistance occurs, the viral load may rise or blood liver tests may become abnormal.

Is there a preferred treatment for chronic hepatitis B? There are no clear guidelines to recommend which agent to use first in treating chronic hepatitis B. Interferon is given for a defined period of time and may have a more prolonged response after the medication is discontinued than NAs. However, interferon is given as an injection, and side effects often are troublesome. NAs are given as a pill and have few side effects, but the duration of treatment is unclear, and prolonged therapy may be required. NAs may be preferred in patients with unstable disease and cirrhosis because they are thought to be less likely to cause serious flares of hepatitis with more severe liver disease.

What are the effects of alcohol on hepatitis B virus?

Agents that damage the liver are particularly harmful in patients who already have hepatitis B. For this reason, it is recommended that persons with hepatitis B avoid drinking alcohol.

What are the effects of immunosuppressive medications on hepatitis B virus?

Even in people with chronic hepatitis B, the immune system is working to suppress the virus. Medications that suppress the immune system allow the virus to reproduce in large numbers and may cause the hepatitis to flare. Examples of medications that suppress the immune system are:

prednisone: used to treat many diseases, including asthma, inflammatory bowel disease, and certain types of skin disease and arthritis methotrexate (Rheumatrex, Trexall): used to treat certain types of skin disease, arthritis, and cancer; cyclophosphamide (Cytoxan): used to treat some cancers.

If an immunosuppressant drug is stopped, the body's immune system's activity may rebound and cause severe inflammation of the liver.

What is delta hepatitis?

Delta hepatitis is caused by a virus that only infects people who already have hepatitis B. The delta hepatitis virus (also known as hepatitis D or HDV) is an RNA virus, meaning that its genetic material is made up of ribonucleic acid. It is spread through exposure to contaminated blood, especially with illicit, intravenous drug use, and by sexual contact. Delta hepatitis can be acquired at the same time as acute hepatitis B. When this happens, infected people are quite sick but more than 95% are eventually able to eliminate the viruses from their bodies. People who already have chronic hepatitis B can acquire delta hepatitis as well. This often causes severe inflammation of the liver, and the viruses are less likely to be cleared.

Delta hepatitis makes chronic hepatitis B much worse. It increases the risk of complications, especially cirrhosis, which occurs in up to two-thirds of patients. There is no vaccine against delta hepatitis. Interferon treatment may cause improvement in the hepatitis, but relapse is common after therapy is stopped. Prevention includes avoiding contaminated needles and practicing safer sex (abstaining or limiting the number of partners, using barrier methods of contraception). Universal vaccination of newborns with hepatitis B vaccine effectively prevents delta hepatitis because the delta hepatitis virus only causes disease in the presence of hepatitis B virus.

What about co-infection with hepatitis B virus and hepatitis C virus?

Hepatitis C is caused by a virus that is spread through contaminated needles or blood products and, less commonly, through sexual intercourse. About 10% of patients with chronic hepatitis B also are co-infected chronically with hepatitis C virus (HCV). The two viruses interfere with each other and one usually predominates. If hepatitis C is the predominant infection, treatment is directed against the hepatitis C. Patients infected with both viruses are at higher risk for complications of liver disease. There is no effective vaccine against hepatitis C. Persons with hepatitis C should be vaccinated against hepatitis B to prevent co-infection.

What happens in co-infection with hepatitis B virus and HIV?

The human immunodeficiency virus (HIV) and hepatitis B virus are transmitted in similar ways, and it is not uncommon for an individual to have both infections. Persons with HIV who acquire hepatitis B are more likely to become chronically infected with hepatitis B than persons who do not have HIV. The reason for this is thought to be that HIV suppresses the immune system and impairs the ability of the body to eliminate the hepatitis B virus. Some nucleoside/nucleotide analogues (a class of antiretroviral drugs) are used to treat both HIV and hepatitis B, although dosages may vary in the two different infections. Stopping one of these agents when the HIV regimen is adjusted may cause hepatitis to flare.

What is the role of liver transplantation in hepatitis B infection?

Liver transplantation has been successful in patients who have irreversible, lifethreatening complications of hepatitis B. This includes patients with liver failure due to end-stage cirrhosis or unusually severe (fulminant) hepatitis. Liver transplantation does not cure hepatitis B, and hepatitis may occur in the new liver. The incidence of recurrent hepatitis has been reduced to less than 10% through use of lamivudine and HBIG in transplant recipients. Use of these agents has also improved long-term survival, with 75% to 85% of patients alive after five years.

What can be done to prevent hepatitis B?

Hepatitis B is a preventable disease. Vaccination and post-exposure prophylaxis have significantly reduced rates of infection. Risk can also be reduced by avoiding unprotected sex, contaminated needles, and other sources of infection. How effective is vaccination for hepatitis B? The hepatitis B vaccine contains a protein (antigen) that stimulates the body to make protective antibodies. Examples of hepatitis B vaccines available in the United States include hepatitis b vaccine-injection (Engerix-B, Recombivax-HB). Three doses (given at 0, 1, and 6 months) are necessary to assure protection. There are also combination vaccines on the market that provide protection against hepatitis B and other diseases. Examples include:

Hepatitis-b-hepatitis-a vaccine - injection (Twinrix), which provides protection against both hepatitis A and hepatitis B. Haemophilus B/hepatitis B vaccine - injection (Comvax) provides protection against hepatitis B and Haemophilus influenzae type b (a cause of meningitis). Pediarix provides protection against hepatitis B, tetanus, pertussis (whooping cough), and polio.

Hepatitis B vaccines are effective and safe. Up to 95% of vaccinated individuals form effective antibodies when they get the vaccine and are protected from hepatitis B. In healthcare workers, high-risk public safety workers, dialysis patients, and sexual partners of infected persons, a blood test for antibodies is recommended after vaccination to ensure that the person produced antibodies. For the few who do not form antibodies, revaccination may improve response, especially in infants. However, a small proportion of individuals will never respond to hepatitis B vaccination. Side effects from the vaccine are usually mild and include soreness at the site of injection. The risk of serious allergic reactions (anaphylaxis) is less than one per million doses. Vaccination has reduced the number of new cases of hepatitis B by more than 75% in the United States. In the United States, hepatitis B vaccination is recommended for all infants at birth. Older children and adolescents should receive the vaccine if they did not do so at birth. Adults in high risk situations also are advised to receive hepatitis B vaccine. This includes:

health care workers dentists intimate and household contacts of patients with chronic hepatitis B infection public safety workers who may be exposed to blood men who have sex with men individuals with multiple sexual partners dialysis patients injection drug users

persons with chronic liver disease residents and staff in institutions that care for persons with developmental disabilities persons infected with HIV persons who require repeated transfusions or blood products.

Centers that serve high-risk individuals are encouraged to provide the vaccine to their clients. Such centers include dialysis units, drug treatment facilities, sexually transmitted diseases clinics and correctional facilities. Some countries have a high prevalence of hepatitis B in their population. Travelers who visit these countries for a prolonged period of time (usually six months) and those who may be exposed to blood or semen should consider vaccination. How effective is hepatitis B immune globulin (HBIG) in preventing hepatitis B? HBIG is a product that contains antibodies against hepatitis B. When injected, it provides temporary protection against hepatitis B. HBIG is used when people have had significant exposure to the virus. An example would be an accidental needle stick in an unvaccinated health care worker from a needle contaminated with blood from a person with hepatitis B. HBIG should be given as soon as possible after exposure, preferably within seven days. Persons who need HBIG should also receive hepatitis B vaccine. HBIG also is given to patients with hepatitis B following liver transplantation to suppress the hepatitis B virus in the transplanted liver. What is post-exposure immunoprophylaxis for hepatitis B virus? Unvaccinated individuals who are exposed to a known case of hepatitis B or to a person at high risk for hepatitis B should be evaluated by a physician. Examples of such exposures include needle stick injuries in health care workers or sexual intercourse with an infected person. If the exposure is significant, the physician will recommend vaccination and also may recommend an injection of hepatitis B immune globulin (HBIG). HBIG is prepared from the plasma of blood donors and contains antibodies to hepatitis B. Vaccination and HBIG can substantially reduce the risk of disease in persons exposed to hepatitis B if given within one week of a needle stick or two weeks of sexual intercourse. Vaccination provides long-term immunity in people who respond to the vaccine. There is no need for HBIG if an exposure occurs to a vaccinated person who is known to respond to the vaccine; however, a blood test might be drawn to verify that the person did respond to the vaccine. How is transmission of hepatitis B virus from mother to newborn infant prevented? Infected mothers can pass hepatitis B to their newborn infants. All pregnant women should have blood tested to determine if they are infected. Infants born to infected

mothers should receive HBIG and hepatitis B vaccine at birth. This is 85% to 95% effective in eliminating the risk of hepatitis B in the infant.

What is new in the treatment of hepatitis B virus?

New agents are under development to treat hepatitis B. Many of these are nucleoside/nucleotide analogues that investigators hope will be more effective than older agents. Experts also are working on treatment guidelines and the use of multi-drug therapy. Vaccination remains the key to preventing hepatitis B and holds the most promise for reducing disease burden.

Hepatitis B At A Glance

The hepatitis B virus is a DNA virus belonging to the Hepadnaviridae family of viruses. Hepatitis B virus is not related to the hepatitis A virus or the hepatitis C virus. Some people with hepatitis B never clear the virus and are chronically infected. Approximately 350 million individuals in the world and one million in the United States are chronically infected with hepatitis B. Many of these people appear healthy but can spread the virus to others. Hepatitis B infection is transmitted through sexual contact, contact with contaminated blood (for example, through shared needles used for illicit, intravenous drugs), and from mother to child. Hepatitis B is not spread through food, water, or casual contact. Serologic (blood) markers specifically for hepatitis B virus are used to diagnose hepatitis B viral infection. The blood tests can also identify people who are at highest risk for complications. Injury to the liver by hepatitis B virus is caused by the body's immune response as the body attempts to eliminate the virus. In the United States, 95% of adults who get hepatitis B are able to clear the virus and cure themselves of infection. The remaining 5% of adults with acute hepatitis B go on to develop chronic hepatitis B. Those who acquire the infection in childhood are much more likely to have chronic infection. Chronic hepatitis B may lead to cirrhosis or liver failure. Approximately 15% to 25% of persons with chronic infection will die prematurely as a result of the infection. Progression of chronic hepatitis B viral infection occurs insidiously (subtly and gradually), usually over several decades. The course is determined primarily by the age at which the hepatitis B viral infection is acquired and the interaction between the virus and the body's immune system. Treatment with interferons or nucleoside/nucleotide analogues suppresses viral reproduction in about 40% to 90% of patients with chronic hepatitis B. The medications are also effective in reducing inflammation and improving blood tests. This can delay or reduce complications such as cirrhosis. However, most people do not have a permanent response and relapse is common. The medications do not cure the infection.

Liver transplantation should be considered for patients with impending liver failure due to acute (initial) infection or advanced cirrhosis. Hepatitis B is preventable through vaccination. All children should receive the vaccine. In addition, adults at high risk for hepatitis B should be vaccinated. Unvaccinated people who are exposed to hepatitis B should be evaluated by a physician to determine if they need specific immune globulin (HBIG).

Reference: Centers for Disease Control and Prevention, "Viral Hepatitis FAQs for the Public," January 15, 2009 Previous contributing medical author and editor: Tse-Ling Fong, MD and Leslie J. Schoenfield, M.D., Ph.D. http://www.medicinenet.com/hepatitis_b/discussion-175.htm

One of the most common complications of chronic hepatitis is cirrhosis. This is a scarring of the liver that can be detected with a biopsy. Cirrhosis makes it difficult for the liver to do its job and can lead to liver failure, a life-threatening condition. Symptoms include fatigue, nausea, weight loss, and swelling in the belly and legs. In severe cases, patients may experience jaundice and confusion.

Viral hepatitis is the top cause of liver cancer, so people with chronic hepatitis B or C need monitoring even if you feel fine. Blood tests can detect proteins that suggest the presence of liver cancer. Ultrasounds, CT scans, and MRIs can reveal abnormal lesions in the liver (seen here in green). A biopsy is needed to determine if these areas are cancerous. Tumors that are found early may be surgically removed. But most liver cancers are difficult to treat.

There are vaccines to protect against hepatitis A and B. The CDC recommends hepatitis A vaccination for all children ages 12 to 23 months and for adults who plan to travel or work in areas with hepatitis A outbreaks. People with chronic hepatitis B or C should also get the hepatitis A vaccine if they don't already have immunity to hepatitis A. The hepatitis B vaccine is recommended for all infants at birth and for adults who have any of the risk factors we discussed earlier. There is no vaccine for hepatitis C.

Lyme disease is a bacterial illness caused by a bacterium called a "spirochete," which may be transmitted to humans by the bite of infected ticks (Ixodes scapularis and Ixodes pacificus). The actual name of the bacterium in the United States is Borrelia burgdorferi. In Europe, another bacterium, Borrelia afzelii, also causes Lyme disease.

What causes Lyme disease?

Certain ticks, found on deer, harbor the bacterium in their stomachs. Lyme disease is spread by these ticks when they bite the skin, which permits the bacterium to infect the body. Lyme disease is not contagious from an infected person to someone else. Lyme disease can cause abnormalities in the skin, joints, heart, and nervous system.

What is the history of Lyme disease?

Interestingly, the disease only became apparent in 1975, when mothers of a group of children who lived near each other in Lyme, Connecticut, made researchers aware that their children all were diagnosed with rheumatoid arthritis. This unusual grouping of illness that appeared "rheumatoid" eventually led researchers to the identification of the bacterial cause of the children's condition, what was then called "Lyme disease

The number of cases of the disease in an area depends on the amount of ticks in an area and how many are infected with the Lyme bacteria. In certain areas of New York, where Lyme disease is common, over half of the ticks are infected. Lyme disease has been reported most often in the northeastern United States, but it has been reported in all 50 states, as well as China, Europe, Japan, Australia, and parts of the former Soviet Union.

What are the symptoms and signs of Lyme disease?

Lyme disease affects different areas of the body in varying degrees as it progresses and is medically described in three phases: (1) early localized disease with skin inflammation; (2) early disseminated disease with heart and nervoussystem involvement, including palsies and meningitis; and (3) late disease featuring motor and sensory-nerve damage and brain inflammation and arthritis. Let's take a look at each phase.

Phase 1: Early localized disease

The site where the tick bites the body is where the bacteria enter through the skin. Within days to weeks of the tick bite, the local skin around the bite develops an expanding ring of flat redness. There may be an outer ring of brighter redness and a central area of clearing, leading to a bull's-eye or target appearance. This classic initial rash is called "erythema migrans." Multiple secondary lesions can occur that are a reaction to the infection and are not due to multiple tick bites. Patients often can't recall the tick bite (the ticks can be as small as the periods in this paragraph). Also, they may not have the identifying rash to signal the doctor. More than one in four patients never develops a rash. The redness of the skin is often accompanied by generalized fatigue, muscle and joint stiffness, swollen glands, and headache resembling symptoms of a viral infection. Later, it can produce abnormalities in the joints, heart, and nervous

Phase 2: Early disseminated disease

The redness resolves, without treatment, in about a month. Weeks to months after the initial redness of the skin, the bacterium and its effects can spread throughout the body, subsequently causing disease in the joints, heart, and nervous system.

Phase 3: Late disease

The later phases of Lyme disease can affect the heart, causing inflammation of the heart muscle. This can result in abnormal heart rhythm and heart failure. The nervous system can develop facial-muscle paralysis (Bell's palsy), abnormal sensation due to disease of peripheral nerves (peripheral neuropathy), meningitis, and confusion. Arthritis, or inflammation in the joints, begins with swelling, stiffness, and pain. Usually, only one or a few joints become affected, most commonly the knees. The arthritis of Lyme disease can look like many other types of inflammatory arthritis and can become chronic.

How is Lyme disease diagnosed?

In early Lyme disease, doctors can sometimes make a diagnosis simply by finding the classic red rash, particularly in people who have recently been in regions in which Lyme disease is common. The doctor might review the patient's history and examine the patient in order to exclude diseases with similar findings in the joints, heart, and nervous system. Blood testing for antibodies to Lyme bacteria is generally not necessary or helpful in early stage disease, but it can help with diagnosis in later stages. Antibodies are produced by the body to attack the bacteria and can be evidence of exposure to the bacteria. These antibodies can be detected using a laboratory method called an ELISA assay. Antibodies, however, can be false indicators of disease, since they can remain for years after the disease is cured. Currently, the confirmatory test that is most reliable is referred to as the Western blot assay.

What is the treatment for Lyme disease?

Most Lyme disease is curable with antibiotics. The type of antibiotic depends on the stage of the disease (early or late) and what areas of the body are affected. Early illness is usually treated with oral medicines, for example, doxycycline (Vibramycin), amoxicillin (Amoxil), or cefuroxime axetil (Ceftin). Therefore, if a person finds a typical bull's-eye skin rash (as described on a previous slide) developing in an area of a tick bite, they should seek medical attention as soon as possible. Generally, antibiotic treatment resolves the rash within one or two weeks. Later illness such as nervous-system disease might require intravenous drugs, for example, ceftriaxone (Rocephin).

What's the treatment for later-stage joint pain of Lyme disease?

For the relief of symptoms, pain-relieving medicines might be given. Swollen joints can be reduced by the doctor removing fluid from them (arthrocentesis). An arthrocentesis is a procedure whereby fluid is removed from a joint using a needle and syringe under sterile conditions. It is usually performed in a doctor's office. Rarely, even with appropriate antibiotics, the arthritis continues. It has been suggested by researchers that sometimes joint inflammation can persist even after eradication of the Lyme bacterium. The doctor also can use oral medications, such as ibuprofen (Motrin, Nuprin) to reduce inflammation and improve function.

How can Lyme disease be prevented?

Because Lyme disease is transmitted by ticks attaching to the body, it is important to use tick-bite avoidance techniques when visiting known tick areas. Spraying insect repellant containing DEET onto exposed skin can help. Wearing long clothing can protect the skin. Clothing, children, and pets should be examined for ticks. Ticks can be removed gently with tweezers and saved in a jar for later identification. Bathing the skin and scalp and washing clothing upon returning home might prevent the bite and transmission of the

Is there a vaccine for Lyme disease?

Vaccines were on the market, however, on Feb. 25, 2002, the manufacturer announced that the LYMErix Lyme disease vaccine would no longer be commercially available. Further studies of vaccines are needed. For now, ideal prevention focuses on the recommendations of the preceding slide.

Virusul hepatitic B se transmite de la o persoana infectata prin sange si produse din sange, saliva, sperma, secretii vaginale, lichid amniotic, alte fluide corporale. Exista mai multe moduri de transmitere: - verticale sau perinatale, de la mama infectata la copil, in timpul sarcinii sau nasterii - contacte intime (sarut, contact sexual) - prin contact apropiat intrafamilial cu un purtator de virus (de exemplu, prin utilizarea aceleiasi periute de dinti, aparat de ras, vesela) - prin intermediul sangelui sau materialelor contaminate (transfuzii de sange, inoculari cu seringi ace, instrumente medicale nesterilizate, etc.) Purtatorii cronici reprezinta o serioasa problema de sanatate publica, fiind un rezervor de transmitere continua a virusului. Virusul hepatitic B este de aproximativ 1000 de ori mai infectios decat HIV !!! Perioada de contagioziate este de 2 saptamani inaintea debutului bolii si dureaza pana la disparitia portajului de AgHBs. Prezenta prelungita in sange a virusului B si cea a antigenelor acestuia face ca sangele bolnavilor de hepatita B sa fie foarte infectios (timp de cateva saptamani, luni sau chiar toata viata).

Simptome
Sus Perioada de incubatie este de 6 saptamani pana la 6 luni, fiind in medie 120 de zile. Debutul (perioada preicterica) poate fi pseudo-gripal, cu febra, dureri de cap, dureri musculare, pierderea apetitului, astenie (oboseala) marcata dar si alte simptome inselatoare (dureri reumatice, astenie, eruptii cutanate). Dupa 3-4 zile, 50% din persoanele infectate vor prezenta semne caracteristice de hepatita: icter, urini hipercrome (inchise la culoare) si scaune decolorate. Evolutia este lunga si dificila, iar vindecarea survine lent la numai 70-80% dintre bolnavi. Ceilalti raman cu o infectie persistenta (hepatita cronica, ciroza sau pot fi purtatori cronici de virus). Cele mai grave complicatii sunt: hepatita fulminanta, ciroza, cancerul hepatic. Riscul de hepatita cronica (prezenta cronica a virusului in sange) este cu atat mai mare cu cat infectarea s-a produs la o varsta mai mica. 90% dintre copii infectati la nastere devin purtatori cronici. Cronicizarea apare mai ales ca urmare a formelor inaparente de boala. La 25% din purtatorii cronici apar complicatii majore in timp (ciroza, cancer hepatic primar).

Tratament
Sus Nu exista un tratament specific contra bolii acute. Anumite medicamente pot sa stopeze evolutia bolii la purtatorii cronici de virus. Tratamentul este complex, costisitor si doar partial eficient. Convalescenta este marcata de o lunga perioada de astenie. Dupa perioada de spitalizare obligatorie este necesar un control al vindecarii cu o durata intre 6-12 luni.

Hepatita B este o problema de sanatate publica, fiind una dintre cele mai raspandite boli infectioase. Vaccinarea este singura metoda eficienta de protectie bolii.

Ce este hepatita B?
Hepatita B este o infectie a ficatului cauzata de un virus de tip ADN care este transmis sange sau derivati ai sangelui contaminat in timpul transfuziilor, prin contact sexual cu o persoana infectata, prin utilizarea unor ace sau instrumente similare contaminate. Spre deosebire de virusul hepatic A, virusul B poate cauza atat o forma acuta de hepatita, cat si una cronica. Hepatita B este cea mai frecventa afectiune cronica din lume.

Infectia acuta cu hepatita B

In faza acuta a hepatitei B, inflamatia evolueaza rapid si dureaza o perioada scurta de timp (de obicei, o recuperare totala poate aparea in maxim cateva luni). In aproximativ 6 luni, cea mai mare parte a adultilor care sufera de hepatita B acuta se vor vindeca si vor dezvolta anticorpi care ii vor proteja de o noua infectare pentru toata viata. Hepatita cronica B apare atunci cand ficatul esueaza recuperarea totala dupa forma activa a hepatitei si poate evolua multi ani fara a genera simptome. Statisticile arata ca in cazul adultilor, peste 85% dintre adultii si 10% dintre copiii afectati de hepatita acuta B se vor reface complet, devenind imuni la o potentiala viitoare infectie.

Teste de laborator:

valorile transaminazelor sunt foarte ridicate; AgHBs este pozitiv; Viremie foarte mare (1000000000-1000000000 virioni/ml)

Infectia cronica cu Hepatita B

Majoritatea copiilor infectati cu virusul hepatic B vor dezvolta forma cronica a hepatitei B. Riscul cronicizarii depinde de varsta la care acestia sunt infectati. Mai mult de 90% dintre nou-nascutii infectati, 50% dintre copiii si 5% dintre adultii infectati cu virusul hepatic B vor dezvolta hepatita cronica. Hepatita B cronica cunoaste 4 faze: 1. Faza de toleran imun (replicativ) caracterizata de valori normale ale transaminazelor (TGP si TGO), antigen HBs pozitic si de o viremie ridicata. La persoanele infectate in copilarie, aceasta faza poate dura intre 15 si 30 de ani. 2. Faza de clearance imun (imunoreactiv, hepatit cronic) cel mai frecvent intalnita, poate dura ani de zile. Este caracterizata de transaminaze ridicate, AgHBe pozitiv si replicare virala inalta.

3. Faza de replicare viral joas (purttor inactiv de VHB) se caracterizeaza prin prezenta AgHBs, prin absenta AgHBe, viremie nedetectabila sau foarte joasa si valori normale ale transaminazelor. 4. Faza de reactivare este caracterizata prin valori ridicate ale transaminazelor, de replicare virala si de o posibila reaparitie a AgHBe. Aceasta faza poate fi spontana sau se poate datora unor mutatii sau unor coinfectii virale.

Hepatita B o scurta istorie

Desi hepatita este cunoscuta de secole, nimeni nu a stiut care e cauza pana in anii 40, cand doctorii au inceput sa suspecteze ca responsabil pentru aceasta afectiune hepatica era un virus transportat prin sangele uman. Primul pas in descoperirea virusului hepatic B a fost facut in 1963 cand Dr. Baruch Blumberg si colegii sai au identificat o proteina (antigenul Australia) care a avut o reactie neobisnuita la anticorpii pacientilor care fusesera supusi la transfuzii de sange. Asocierea antigenului si infectia hepatica a fost facuta 3 ani mai tarziu, iar specialistii au inteles ca pentru a reduce riscul infectiei cu hepatita B trebuie sa testeze sangele inainte de transfuzii.

Hepatita B perioada de incubatie

Virusul hepatic B are o perioada de incubatie cuprinsa intre 45 si 160 de zile (in medie 100 de zile). De obicei, simptomele apar la 30-180 de zile de la expunerea la virusul hepatic B, dar trebuie spus ca jumatate din persoanele infectate cu acest virus nu vor prezenta nici un semn de infectie. Faza acuta a hepatitei B genereaza un set de simptome, acest fapt insa nu este valabil in cazul infectiei cronice, care, cel mai frecvent, este asimptomatica. Persoanele care sufera de hepatita acuta B pot experimenta simptome de gripa accentuate de greata, anorexie, indispozitie fizica si oboseala, durere in zona ficatului si icter. Simptomele hepatitei acute dureaza, in medie, intre 1-3 luni. In aceasta perioada, persoana infectata este foarte contagioasa. Virusul nu este foarte rezistent in mediu normal se considera ca apa fierbinte utilizata in masina de spalat in mod normal este capabila sa omoare virusul de pe haine, si de asemenea detergentul de vase si apa calda ii vor elimina pe cei de pe tacamuri.

Hepatita B simptome
In faza acuta, hepatita B genereaza simptome de o severitate ce variaza de la una minima, asimptomatica pana la manifestari fatale. Statisticile sugereaza ca peste o treime din persoanele infectate nu prezinta simptome, la acestia infectia considerandu-se tacuta. O alta treime a persoanelor infectate cu virusul hepatic B prezinta simptome similare cu cele generate de o gripa: slabiciune fizica, dureri, cefalee, febra, lipsa poftei de mancare, diaree, icter, greata si varsaturi.

O a treia parte a persoanelor infectate vor prezenta simptome mai severe, care se vor manifesta perioade mai lungi de timp. Pe langa simptomele asemanatoare celor provocate de gripa, mai pot aparea dureri abdominale puternice si icter accentuat. Icterul apare ca si consecinta a faptului ca ficatul se afla in incapacitate de a elimina bilirubina (un pigment care, in parametri mai ridicati decat cei normali, cauzeaza ingalbenirea pielii si a albului ochilor) din sange.

Hepatita B transmitere
Infectia cu hepatita B apare cand sange infectat intra in organismul unei persoane neinfectate. Este de asemenea transmis prin sex neprotejat (fara prezervativ) si, foarte frecvent, de la o mama infectata la copil in timpul nasterii. Exista cateva grupuri care sunt prezinta un risc ridicat de a contacta hepatita B:

persoane cu parteneri sexuali multipli sau diagnosticate cu boli cu transmitere sexuala; copii nascuti din mame infectate; personal al spitalelor sau pacienti internati pe perioada lungi in spitale; persoane care au contact prelungit cu persoane infectate (familii, prieteni); receptori ai transfuziilor de sange; utilizatori ale drogurilor injectate; persoane care lucreaza in sau sunt incarcerate in inchisori; persoane ale caror sange ar fi putut intra in contact cu saliva unei persoane infectate cu virusul hepatic B; persoane care calatoresc in tari cu prevalenta ridicata de hepatita B; pacienti dializati;

Hepatita B tratament
Evolutia naturala a hepatitei cronice B este catre ciroza hepatica si cancer, prin urmare, principalul scop al tratamentului este de a stopa aceasta evolutie, eradicarea virusului fiind un tel foarte dificil de obtinut. Pe termen scurt, tratamentul se orienteaza catre obtinerea urmatoarelor:

inhibitia replicarii virale; normalizarea valorilor transaminazelor; seroconversia AgHBe si aparitia Ac anti HBe; incetinirea/regresia fibroze.

In prezent, in Romania se folosesc in tratarea infectiei cu virus hepatic B:

A) medicamente cu efect antiviral si imunomodulator:

A.1. IFN (interferon) standard

Schema de tratament: 5-10MU de trei ori pe saptamana timp de 6-12 luni

A.2. IFN (interferon) pegilat

Este mai eficient decat interferonul standard. Schema de tratament pentru infectie cu AgHBe negativ: 180 g pe saptamana timp de 48 de saptamani Reactii adverse ale tratamentului cu interferon: Nonsevere Anorexie, vrsturi, diaree, dureri abdominale lips de concentrare, insomnie, instabilitate psihica Tuse, dispnee de efort, faringit Eruptii cutanate, prurit, inflamatie la locul injectiei Anemie, leucopenie, trombocitopenie Severe Tiroidit, hipotiroidie, hipertiroidie Depresie, suicid, delir, psihoze Tulburari cardiace Psoriazis, lichen plan, vitiligo Epilepsie, neuropatie, polimiozit

B) medicamente cu efect antiviral

B.1. Lamivudina
administrata oral, este tolerata destul de bine de catre pacienti; Schema de tratament: 100mg la 24h, timp de 52 de saptamani; Rezultate ce se pot obtine:

AgHBe pozitiv:

In cazul pacientilor cu AgHBe pozitiv, seroconversia HBe la un an de zile este de 15%. Aceasta creste la 30% in cazul tratamentului ce dureaza 3 ani si la 50% la cel de 5 ani. Administrarea prelungita (intre 2 si 5 ani) creste atat rata seroconversiei, cat si efectul antifibrotic. La oprirea tratamentului, seroconversia se mentine la jumatate din pacienti peste 3 ani.

AgHBe negativ:

La pacientii cu AgHBe negativ, raspunsul durabil dupa oprirea tratamentului este de 10%, 90% dintre ei recidivand. Efecte adverse ale tratamentului cu lamivudina:

oboseala, cefalee, ameteli; eruptii cutanate; greata, disconfort abdominal, diaree.

B.2 Adefovir
Schema de tratament: Doza este de10 mg/zi, insa durata optima nu este bine definita, tratamentul fiind necesar de regula, cel putin un an. Dupa incetarea lui, beneficiile se pierd. Efecte adverse:

cefalee, astenie, ameteli; inapetenta; simptome asemanatoare gripei; dureri abdominale, greata, diaree;

B.3. Entecavir
Schema de tratament: Doza este de 0,5mg/zi in cazul in care este prima optiune de tratament si de 1mg/zi in cazul tratamentului virusilor rezistenti la lamivudina. Este eficient in incetarea replicarii virale, in negativarea AgHBe si in scaderea valorilor transaminazelor.

Hepatita B - preventie
Vaccinarea impotriva hepatitei B este cea mai eficienta metoda impotriva infectarii cu acest virus hepatic. Vaccinul este disponibil din 1982 si preintampina infectarea cu virusul hepatic B si a celorlalte infectii aseciate cu acesta. Persoanele care se vaccineaza

sunt protejate atat impotriva formelor acute de hepatita B, cat si a consecintelor mai grave pe care forma cronica le poate genera: ciroza sau cancerul hepatic. Vaccinul impotriva hepatitei B produce niveluri eficiente de anticorpi impotriva virusului hepatic B la majoritatea acultilor, copiilor si nou-nascutilor. Schema de vaccinare cel mai frecvent utilizata este de 3 injectii intramusculare administrate astfel: prima doza, a doua doza la o luna de la cea precedenta, si a cea de a treia doza la 6 luna de la prima. Vaccinul antihepatic este foarte bine tolerat de majoritatea persoanelor, inclusiv nou-nascuti, copii si femei insarcinate sau care alapteaza. Exista exceptii foarte rare de alergii severe la unul din componentele vaccinului. Studiile recente indica faptul ca memoria imunologica ramane intacta pentru o perioada de cel putin 25 de ani si confera protectia impotriva imbolnavirii de hepatita B chiar daca numarul anticorpilor scade sub limita detectabila.

Alte cai de prevenire:

utilizarea corespunzatoare a prezervativelor de fiecare data cand faceti sex cu un partener instabil; administrarea imunoglobulinei antihepatita B (HBIG) nou-nascutilor din mame infectate si vaccinarea acestora la 12 ore dupa nastere; evitarea drogurilor injectate (a acelor sau a seringilor folosite); evitarea utilizarii de catre mai multe persoane are unor intrumente care ar putea avea sange pe ele: aparate de ras, periute de dinti etc.; evitarea efectuarii de tatuaje sau piercinguri in locatii dubioase, care nu prezinta incredere.

Legislatie - Eligibilitate Tratament Hepatita

Criteriile de eligibilitate pentru includerea in tratamentul antiviral si alegerea schemei terapeutice la pacientii cu hepatita cronica virala B,C,D.

1. HEPATITA CRONICA CU VIRUS B

Interferon - conventional sau pegylat, Lamivudina pot fi utilizate ca terapie initiala

1.1. Hepatita cronica cu Virus B cu AgHBe pozitiv

Criterii de includere in tratament:

biochimic: ALT = 2X N = 6 luni virusologic: AgHBs pozitiv = 6 luni AgHBe pozitiv si anti Hbe negativ ADNVHB = 100 000copii/ml IgG anti-VHD negativ morfologic - hepatita cronica: ANI = 4 (Knodell) varsta = 65 ani

Scheme terapeutice utilizate:

Interferon conventional 4,5-5MU/zi sau 9-10MUx3/sapt, 4-6 luni Interferon pegylat pe o durata de 6 luni.

Pacientii cu contraindicatie sau nonresponderi la Interferon pot primi Lamivudina

Lamivudina - 100mg/zi.

Evaluarea raspunsului initial se face la 6 luni de terapie prin determinarea ALT. Daca nu s-a obtinut normalizarea ALT se recomanda efectuarea ADN-VHB. Daca aceasta nu a scazut cu mai mult de 2log10 se considera rezistenta primara la Lamivudina si se opreste tratamentul. Ulterior, se vor verifica periodic, la interval de 6 luni, ALT, Ag HBe si Ac anti Hbe. In functie de raspunsul biochimic si virusologic tratamentul se va opri sau se va putea continua pana la maximum 5 ani. Cresterea transaminazelor pe parcursul tratamentului impune efectuarea viremiei iar cresterea viremiei sub tratament se considera rezistenta si lipsa de raspuns terapeutic Rezistenta si lipsa de raspuns impun reevaluarea pacientului si luarea unei noi decizii terapeutice. In cazul responderilor tratamentul se continua 6 luni dupa seroconversia AgHBe (verificata la 3 si 6 luni).

1.2. Hepatita cronica cu Virus B cu AgHBe negativ

Criteriile de includere in tratament:

Aceleasi ca si la forma AgHBe pozitiva, AgHBe negativ si anti-HBe pozitiv La pacientii cu incarcatura virala intre 10.000 si 100.000 copii/ml, in luarea deciziei terapeutice primeaza rezultatul histologic.

Scheme terapeutice utilizate:

Interferon conventional: 4,5-5 MUx 3/sapt 12 luni Interferon pegylat: 12 luni Lamivudina: 100mg/zi. Evaluarea raspunsului initial se face la 6 luni de terapie prin determinarea ALT. Daca nu s-a obtinut normalizarea ALT se recomanda efectuarea ADN-VHB. Daca aceasta nu a scazut cu mai mult de 2log10 se considera rezistenta primara la Lamivudina si se opreste tratamentul. Ulterior, se vor verifica periodic, la interval de 6 luni, ALT, Ag HBe si Ac antiHbe. In functie de raspunsul biochimic si virusologic tratamentul se va opri sau se va putea continua pana la maximum 5 ani. Cresterea transaminazelor pe parcursul tratamentului impune efectuarea viremiei iar cresterea viremiei sub tratament se considera rezistenta si lipsa de raspuns terapeutic Rezistenta si lipsa de raspuns impun reevaluarea pacientului si luarea unei noi decizii terapeutice.

1.3.Infectia cronica VHB - alte situatii

Ciroza VHB clasele Child A,B,C cu ADN-VHB = 103 copii/ml, indiferent de statusul HBe:
amivudina - 100mg/zi. Se vor verifica periodic, la interval de 6 luni, ALT. In functie de raspunsul biochimic si virusologic tratamentul se va opri sau se va putea continua. Cresterea transaminazelor pe parcursul tratamentului impune efectuarea viremiei iar cresterea viremiei sub tratament se considera rezistenta si lipsa de raspuns terapeutic Rezistenta si lipsa de raspuns impun reevaluarea pacientului si luarea unei noi decizii terapeutice.

Hepatita recurenta in ficatul transplantat:

profilaxie Lamivudina+ globulina umana terapie: Lamivudina =12 luni? cit timp exista beneficiu

1.4. HEPATITA CRONICA asociata cu:

1.4.1. Glomerulonefrita 1.4.2. PNA 1.4.3. Vasculita de hipersensibilitate (crioglobulinemica)+lomerulonefrita 1.4.4. Imunodepresie (terapie imunosupresiva, antineoplazica) cu Ag HBs pozitiv
Lamivudina (odata cu terapia imunosupresiva si 3-6 luni dupa sistarea acesteia)

1.4.5. Hemodializa:
Pacientii pot primi tratament cu IFN, Lamivudina in doze adaptate functiei renale.

1.4.6. Hepatita cronica VHB+VHC

se trateaza cu Interferon (sau de preferat Interferon pegylat) activ asupra ambelor virusuri se trateaza virusul care este replicativ daca ambele virusuri sunt replicative: se trateaza VHC (cu Interferon pegylat+Ribavirina) daca persista ADN-VHB se continua cu Lamivudina

1.4.7. Hepatita cronica cu VHB+VHD

Criterii de includere in tratament:

biochimic: ALT = 2X N = 6 luni virusologic: AgHBs pozitiv = 6 luni anti Hbe pozitiv sau AgHBe negativ IgG anti-VHD pozitiv, ADN-VHB pozitiv sau negativ morfologic - hepatita cronica: ANI = 4 (Knodell) varsta = 65 ani

Se vor efectua ADN-VHB, ARN-VHD (optional). Pacientii vor fi tratati in functie de virusul replicativ. In cazul replicarii VHD: Interferon conventional 9/10 MU x 3 /saptamana timp de 12 luni

Heplisav - un nou vaccin impotriva hepatitei B, mai aproape de aprobare

Faza a treia a studiului (HBV-16) a incercat sa determine daca imunogenetica a doua doze de Heplisav era inferioara/superioara unui tratament alcatuit din trei doze de Engerix-B comparand datele privind seroprotectia la opt saptamani de la primirea ultimei doze. Rezultatele raportate de catre ICAAC demonstreaza capacitatea Heplisav de a genera un raspuns mai rapid, mai puternic si de o mai lunga durata decat Engerix-B, astfel: HEPLISAV a indus un raspuns imun superior celui indus de Engerix, pe tot parcursul studiului. Seroprotectia si concentratia geometrica medie (CGM) in grupul Heplisav au fost semnificativ mai mari decat cele din grupul Engerix-B, la fiecare control, incepand cu saptamana 4 pana in saptamana 52. Heplisav a asigurat o seroprotectie mai devreme decat Engerix-B. La ultimul control, care s-a efectuat in saptamana 12 pentru Heplisav si saptamana 32 pentru Engerix-B, seroprotectia in grupul Heplisav era de 90% comparativ cu 71% in grupul Engerix-B. De fapt, in saptamana 8, seroprotectia in grupul Heplisav era mai mare (77%) fata de maximul la care a ajuns grupul Engerix-B pana la sfarsitul tratamentului. si in cazul CGM rezultatele au aratat un raspuns mai prompt in cazul grupului Heplisav - 93 mIU/mL (in saptamana 12), comparativ cu 61 mIU/mL (in saptamana 32). Heplisav a furnizat rate mai mari de seroprotectie fata de Engerix-B. Rata maxima de seroprotectie in cazul Heplisav a fost de 95% in saptamana 24, fata de 73% in saptamana 28 in cazul Engerix-B. Rata maxima a concentratiei geometrice medii pentru Heplisav a fost de 233 mIU/mL in saptamana 24, iar in cazul Engerix-B de 89 mIU/mL in saptamana 28. Heplisav a oferit anticorpi pentru o durata mai lunga de timp fata de Engerix-B. Siguranta Heplisav a fost similara cu cea a Engerix-B. Ratele de reactii post-imunizare locale si sistemice, efectele adverse si efectele adverse autoimune au fost similare in ambele grupuri.

Datele indica in mod clar faptul ca Heplisav produce un raspuns imunitar mai rapid, mai mare si mai durabil decat cel produs de Engerix-B si cu efecte adverse similare. (Tyler Martin, M.D.) Engerix-B este marca inregistrata a GlaxoSmithKline Despre Heplisav Heplisav este un vaccin experimental impotriva Hepatitei B. In studiile efectuate cu acest medicament s-a demonstrat o protectie mai rapida si mai eficienta cu doze mai mici fata de celelalte medicamente aflate in folosinta. Despre Dynavax Dynavax Technologies Corporation este o companie biofarmaceutica care descopera si dezvolta produse noi pentru prevenirea si tratarea bolilor infectioase si inflamatorii. Sursa: Therapeuticsdaily

19 Mai - Ziua Mondiala a Hepatitei

Ziua mondiala a hepatitei are loc in fiecare an la 19 mai. In tari precum Statele Unite ale Americii, Canada, Australia intreaga luna mai a fost declarata luna constientizarii pericolului hepatitei. In aceasta perioada au loc manifestari ale specialistilor si campanii de informare a publicului, inclusiv in Romania. Sursa: HepatitisFoundation.org

Numar crescut de imbolnaviri cu hepatita B si C in judetul Botosani

Situatie alarmanta n judetul Botosani, unde numarul bolnavilor de hepatita B si C s-a dublat n mai putin de un an de zile. Autoritatile sanitare sustin ca una dintre cauze este aceea ca n mediul rural oamenii se adreseaza pentru diferite tratamente unor vraci de ocazie si nu medicilor.