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เชื้อไวรัสตับอักเสบบี พบได้ในสารน้ำและสารคัดหลั่งต่างๆ ของร่างกาย ได้แก่ เลือด น้ำลาย น้ำนม น้ำอสุจิ
 และเมือกในช่องคลอด จึงติดต่อถึงกันได้ทางเข็มฉีดยา หรือของมีคมที่เปื้อนเลือด ทางเพศสัมพันธ์ และการ
ติดต่อจากมารดาสู่ทารกในครรภ์

อาการเริ่มแรกไม่ชัดเจน ไม่รวดเร็ว จะมีไข้ต่ำๆ หรืออาจไม่มี ต่อมาไข้สูง อ่อนเพลีย คลื่นไส้ อาเจียน และค่อยๆ 
ตัวเหลือง ตาเหลือง และเป็นดีซ่าน บางรายไม่มีอาการแสดงให้เห็น กว่าจะรู้ตัวเป็นตับแข็งแล้ว 
โรคตับอักเสบเรื้อรังอาจมีอาการอื่นร่วมอยู่ด้วย เช่น ปวดข้อ หรือไตอักเสบ ส่วนใหญ่ผู้ป่วยจะทุเลาและ
หายสนิท ส่วนน้อยที่จะมีความรุนแรงของโรคถึงแก่ชีวิต หรือทุเลาแล้วกลับรุนแรงขึ้นอีก บางรายกลาย
เป็นพาหนะเรื้อรัง โดยไม่แสดงอาการเจ็บป่วย แต่สะสมเชื้อไว้ภายในร่างกาย

การดูแลรักษา
1. กรณีเป็นโรคชนิดเฉียบพลัน ไม่มีภาวะแทรกซ้อน ให้ผู้ป่วยพักผ่อนประมาณ 4 สัปดาห์ งดออกกำลังกาย
    หลังหายป่วยแล้ว 2-3 เดือน หลีกเลี่ยงอาหารและการกินสารที่เป็นพิษต่อตับ และรักษาโรคตามอาการ
2. กรณีมีภาวะแทรกซ้อน แพทย์จะพิจารณารักษาเป็นรายๆ ไป
3. ผู้ปว่ยโรคตับอักเสบเรื้อรัง ให้รักษาตามอาการ อยู่ในความดูแลของแพทย์
4. ผู้เป็นพาหนะเรื้อรังไม่มีอาการ ให้ตรวจร่างกายเป็นประจำตามแพทย์สั่ง แนะนำให้นำบุตรหลาน และ
    ผู้ใกล้ชิดมาตรวจร่างกาย และฉีดวัคซีนป้องกันก่อนเป็นโรคนี้ 
ผู้เป็นพาหนะห้ามมิให้ใช้ของส่วนตัวที่อาจเปื้อนเลือดร่วมกับผู้อื่น และควรแจ้งทันตแพทย์ แพทย์และ
บุคลาการทางการแพทย์ให้ทราบเพื่อจะได้ระมัดระวังการติดต่อแพร่เชื้อไปสู่ผู้อื่นและเลี่ยงในการสั่งยาที่
จะเป็นพิษต่อตับ

การป้องกัน
1. บุคคลทั่วไป ป้องกันตนเองมิให้ติดโรคนี้ได้โดย ไม่ใช้เข็มฉีดยาร่วมกับผู้ป่วย ใช้ถุงยางอนามัยเมื่อมี
    เพศสัมพันธ์ ตรวจเลือด หากไม่มีภูมิคุ้มกันให้ฉีดวัคซีนป้องกันโรค
2. ทารกแรกเกิด ที่มารดาเป็นโรคหรือเป็นพาหนะ ให้ฉีดวัคซีนหลังคลอดโดยเร็วที่สุด 


Hepatitis B: A Brief History:

In 1965, Dr. Blumberg who was studying haemophilia, found an antibody in two patients which reacted against an antigen from an Australian Aborigine. Later the antigen was found in patients with serum type hepatitis and was initially designated "Australian Antigen". Subsequent study has shown the Australia Antigen to be the hepatitis B surface antigen. Dr. Blumberg was subsequently awarded the Nobel Prize for his discovery. Initially there appeared to be three particles associated with hepatitis B infection: a large "complete" particle called the "Dane particle", a small circular 20nm particle and an oblong 40nm particle. Further research identified the Dane particle as the hepatitis B viron and the other two particles as excess surface protein. This former terminology is no longer used and the virus is referred to according to its structure.

Hepatitis B Virus: A Complex Structure
The hepatitis B viron consists of a surface and a core. The core contains a DNA polymerase and the e antigen. The DNA structure is double stranded and circular. There are four major polypeptide reading frames (genes): the S (surface), the C (core), the P (polymerase) and the X (transcriptional transactivating). The S gene consists of three regions, the pre-S1, pre-S2 and encodes the surface proteins (HBsAg). Very rarely a mutation may occur in the S gene and may abort the HBsAg with the result that a person may be HBsAg negative but still have virus present as determined by HBV DNA. The C gene is divided into two regions, the pre-core and the core, and codes for two different proteins, the Core antigen (HBcAg) and the e antigen (HBeAg). A not uncommon mutant is the pre-core mutant, which may stop production of HBeAg, and these persons will be HBsAg positive, HBV DNA positive, but HBeAg negative. A third mutant which appears to have a mutant in the core has been described and is referred to as HBV2. These patients are HBsAg positive, but lack HBeAg and HBV DNA, thus also anti-HBc. Another mutant, the YMDD mutant, will be described at a later date.

To make it even more complex, the HBsAg particles are antigenically complex and these antigenic determinants have been identified. There is a single common determinant designated a, and four major subdeterminants designated d,y,w and r. Thus, the four major determinants are: adw, adr, ayw and ayr.

Multiple Tests are Available
Because of the complexity and the antigenic differences of the virus, there are a number of tests available for hepatitis B:

Antigens
HBsAg = presence of the virus
HBcAg = not detected in blood
HBeAg = correlates with the viral replication and infectivity

Antibodies
anti-HBs = antibodies to the surface
anti-HBc = antibodies to the core can be either IgM (acute) or IgG (chronic)
anti-HBe = antibodies to e and indicates low infectivity and probable recovery

Other Markers
HBV DNA = indicates virus presence and activity
DNA polymerase = determines the presence of HBV DNA
HBsAg in liver cells (Orcein stain = Shakata cells) = HBsAg inside hepatocytes

Hep B:The Complexities
Carrier Rates Vary Greatly
Carrier rates for hepatitis B vary enormously:

Country and Carrier rate%:

Scandinavia	0.1 %
USA/Canada	0.1%
Spain	2.0%
Southern Italy	3.0%
Greece	5.0%
Hong Kong	15.0%
Taiwan	15.0%
Alaskan Eskimos	45.0%

High Infectivity
Hepatitis B DNA is found in many body fluids including saliva, urine, semen and menstrual blood. It has also been shown that the virus can be transmitted by ingesting contaminated blood. Hence, hepatitis B may be transmitted by:

- mother to infant at the time of birth
- sexually
- horizontally through shared utensils such as razors, toothbrushes, etc.
- through unsterile instruments such as tattoo needles, dental equipment, etc.
- parenteral drug use through shared needles, syringes, etc.
- hospital staff through needle prick
- blood sucking arthropods (usually in the tropics)

Extra-Hepatic Associations
Although uncommon, a number of conditions associated with hepatitis B antigen/antibody complexes have been recognized. These include:

Polyarteritis - usually involves medium and small arteries, appears early
Glomerulonephritis - largely in children, liver disease is usually mild
Polymyalgia rheumatica - usually in older persons
Essential mixed cryoglobulinemia - sometimes only a test tube finding
Guillain-Barre syndrome
Myocarditis

Concentration of Hepatitis B Virus in Various Body Fluids

Notes:
HBV is transmitted by percutaneous or permucosal exposure to infectious blood or body fluids from persons who have either acute or chronic HBV infection. The highest concentrations of virus are in blood and serous fluids; lower concentrations are found in semen, vaginal fluid, and saliva. Therefore, blood exposure and sex contact are relatively efficient modes of transmission. Saliva can be a vehicle of transmission through bites; however, transmission has not been documented to occur as a result of other types of exposure to saliva, including kissing. HBsAg has also been detected in low concentrations in other body fluids, including tears, sweat, urine, feces, breast milk, cerebrospinal fluid, and synovial fluid; however, these fluids have not been associated with transmission.

This original paper   was written by Dr. Florence Wong, Gastroenterologist at The Toronto Hospital in Ontario, Canada.  Hepatitis B is a virus that infects the liver. Is estimated that 350 million people are infected with hepatitis B worldwide, with 50 million new cases diagnosed annually. The carrier rate of hepatitis B varies widely, being uncommon amongst Westerners, but reaching as high as 20% in people from Asia and Africa. Thus, the disease is very common amongst Chinese. With immigration of Chinese into Western countries, hepatitis B is now becoming established in countries where it was previously uncommon. Approximately 10 percent of patients contract hepatitis B as an adult and that is usually the case amongst Westerners. In the Chinese population, hepatitis B is usually transmitted from infected mother to the newborn infant. Because of the immature immune system in these infants, they cannot clear the virus from their bodies. They therefore remain infected for life. Such infected individuals act as potential reservoirs of infection and can transmit the disease through kissing, sharing of toothbrushes, razors and sexual contact. Hepatitis B can also be transmitted through blood transfusion, although the incidence of this happening is very low now since routine screening of blood donations. Intravenous drug users who share needles with others and health-care workers who handle blood samples are also at high risk of contracting hepatitis B. Currently, it is estimated that approximately 20 percent of the Chinese population  are infected with hepatitis B. Many infected individuals cannot remember being ill with hepatitis. The virus may remain dormant and these people are usually a symptomatic and therefore referred to as healthy carriers. However, a significant portion of patience may have ongoing liver damage despite remaining asymptomatic. Occasionally their liver inflammation can be so severe that the patient feels ill with nausea, loss of appetite and becomes jaundiced. Repeat episodes of liver damage will lead to scarring of the liver called cirrhosis which will lead to many complications including the development of liver cancer. Because many patients with liver inflammation remain asymptomatic, they may progress to liver cirrhosis or even liver cancer silently. Therefore it is important for the Chinese population to be screened for hepatitis B. Once hepatitis B is diagnosed, the treating physician will determine from various investigations and abdominal ultrasound the extent of liver inflammation. If the patient has normal liver function tests as well as a normal and abdominal ultrasound, he needs to be followed up regularly by his family physician since it is totally unpredictable when  the virus will become active. Blood tests are recommended every six months and abdominal ultrasound every year. The patient should also be screened for the presence of liver cancer, especially in males older than 40 years of age. Should liver inflammation be detected, patient should be referred for a specialist opinion. The specialist will undertake further investigations which may include a liver biopsy to determine the extent of inflammation and cirrhosis. Treatment is now available for hepatitis B and it should be offered to patients who have persistence inflammation for more than six months. Once cirrhosis is established treatment is less effective. Therefore, patients should be screened and treatment offered before a there is any significant liver damage. Approved treatment for hepatitis B is Interferon given over a period of 16 weeks during which time the patient is closely monitored. Treatment with Interferon is associated with some side effects which tend to settle down after the initial few weeks. The dose of Interferon may be reduced should the side effects become intolerable. Approximately 50 percent of patients treated with Interferon will a favorable response with the virus being converted from the active to be inactive form. Treatments are now being developed for those patients who were unsuitable for Interferon treatments or have failed Interferon treatment. These are still currently being used in investigational studies. Once an index case of viral hepatitis B is identified, the entire family should be screened for hepatitis B. Some members of the family may have been infected but cleared the virus and therefore have become immune. Other members may be chronic carriers, while others may still be unexposed to the virus. those individuals who have cleared the virus do not require further medical attention. Those individuals not yet exposed to the virus should be vaccinated against hepatitis B while chronic carriers need to be cared in the same way as the index case. Vaccination against hepatitis B is very effective and consists of the course of three injections. Vaccination can be arranged with the family physician. Once the course  is completed, the individual is protected for life. Currently various provincial governments have agreed to fund vaccination for children in grades 7. It is recommended that all children in communities with high carrier rates, such the Chinese community, should be vaccinated from birth or as soon as possible once they have been screened and found to be unexposed. Is only with a mass vaccination program that we can hope to eradicate hepatitis B in the next generation.   Viral Hepatitis C Infection Hepatitis C virus is another virus which infects the liver. It is made up of a family of similar viruses and they are structurally different from the hepatitis B virus. The distribution of hepatitis C infection differs from that of hepatitis B in that it is particularly prevalent in certain countries such as Japan, Korea, Vietnam and China. It is mainly transmitted through contact with infected blood. Therefore, patients who required transfusion of blood and blood products are risk, together with patients who have had injections with shared needles. Unlike hepatitis B, infection with hepatitis C usually occurs in adulthood. Once infected, the majority patients will not be able to get rid of the virus, but rather will have ongoing inflammation ultimately leading to cirrhosis. Hepatitis C is a very slow growing virus and this process of smoldering inflammation may take 20 years before symptoms develop. Certain subgroups of patients tend to have a more rapid progression of the disease leading to cirrhosis in a few years and these are usually patients who contracted the disease at an older age, patients who abuse , alcohol and patients who also have hepatitis B infection. Once symptoms develop, the liver disease is usually quite advanced and complications of cirrhosis are usually present. Therefore, it is important to screen patients from high prevalence countries for hepatitis C, even at the asymptomatic stage, so that treatments can be offered before the development of cirrhosis. Once the patient is diagnosed to have hepatitis C infection, investigations including blood test and ultrasound and the liver biopsy will be performed to determine the severity of the inflammation and to assess for the presence of cirrhosis. Screening for liver cancer is also performed since patients infected with hepatitis C also are at higher risk for the development of liver cancer. The currently recommended treatment for hepatitis C infection is Interferon. Like hepatitis, the treatment is more effective before the development of cirrhosis. Our present experience recommends treatment for a period of 12 months. Side effects tend to be less severe since these patients require a lower daily dose than those being treated for hepatitis B. The response rate to Interferon as approximately 30% after one year of treatment. Recently, a new anti-viral agent in the form of an oral medication, has been used in combination with Interferon with improved response rates. Patients being treated with Interferon for hepatitis C with or without the oral agent, need to be monitored regularly. Successful treatment will suppress liver inflammation and convert the patient from an active phase to a dormant phase of the disease. This will slow down progression to cirrhosis and also reduce the risk of the development of liver cancer. Currently, there is no available vaccination against hepatitis C infection. The only effective prevention is to avoid contact with infected blood. Current practices with blood transfusion should make the risk of contracting viral hepatitis C minimal. Patients who are infected should not share their razors toothbrushes, or shavers. Sharing needles should also be avoided. Patients with hepatitis C should not drink alcohol, because the combination of alcohol and hepatitis C will accelerate the progression to cirrhosis and even increase the risk of liver cancer. Currently, Hepatitis C infection is the biggest epidemic worldwide. Active screening and treatment of suitable cases is the only possible means of controlling this problem.

Evaluation of the HBsAg-positive patient

Specific Immunotherapy for the Control of Hepatitis B Virus Multiplication
Christian Bréchot, MD, PhD
Professor Cell Biology/Hepatology  Paris, France

 Key Learning Objectives
At the end of the session, the participants will be able to: 

• define the concept of "specific immunotherapy"
• clearly delineate its potential side effects
• update the literature on data obtained with current vaccines
• define new strategies and, in particular, the concept of "DNA vaccination"
• summarize the data available with DNA vaccines for HBV
• evaluate the potentials and drawbacks of this approach

   

Abstract

Despite significant improvements, the treatment of chronic hepatitis due to HBV infection remains insufficient. Several lines of evidences suggest that tolerance to HBV might be, at least in part, abrogated by a specific immunotherapy. Thus, B lymphocytes of HBV chronic carriers have retained their capacity to synthetize anti-HBsAg antibodies. In addition, injection of HBsAg protein to HBV ­ expressing transgenic mice induces a significant reduction in HBV viremia and HBsAg titers, together with anti-HBs detection.

We have previously suggested in a pilot study that vaccination against HBV using a regular, PreS2/S or S-based vaccine, might abolish or significantly lower HBV multiplication in around 30% of patients with HBV-related chronic hepatitis. We will present recent results from a randomized prospective study which confirms the potential of this approach.

We have indeed comparatively evaluated the efficacy of six injections of the Genevac B (PreS2/S), the Recombivac (S). We were able to demonstrate that three injections of either PreS2/S or S-based vaccines were sufficient to abolish serum HBV DNA detection in 13/84 patients, compared to only 1/37 unvaccinated controls (p=0.04). In addition, anti-HBe seroconversion was only observed after 6-month follow-up in the vaccinated patients.

Finally we were able to demonstrate induction of a PreS/S specific T cell proliferation upon vaccination. Thus, collectively, these data pave the way for the use of immunotherapy for the treatment of HBV infection.

Still, the currently available recombinant vaccines show a too limited efficacy. These results therefore, stimulate the development of new approaches to achieve a more efficient and durable immunotherapy.

Beside the use of PreS1/S2/S-based vaccines which are now evaluated, DNA vaccination shows great promise and is currently being evaluated for HIV. DNA vaccination against HBV is based on the direct in vivo expression of HBsAg from a recombinant plasmid injected intramuscularly. Several studies, performed in mice and primates have demonstrated the capacity of such constructs to induce both humoral and cellular immune (in particular Th1) responses to the viral antigen. This efficacy is due to the neosynthesis of viral peptides from the injected plasmids. The production of anti-HBs has been shown to be stable after an 18 month follow-up and this humoral immune response does mimic that observed during natural infection. On the same line, injection of a 10 microgram dose of HBsAg encoding plasmid to BALB/c mice induces, for at least 12 weeks, a cytotoxic T cell response. Studies in ducks and woodchucks infected with the Hepadnaviruses DHBV and WHV, respectively, have confirmed the potential of this approach by showing protection against viral challenge and induction of specific neutralizing antibodies. Experiments performed in macaques have confirmed the possibility to induce a humoral and immune response to HBV and thus prompt clinical evaluation of this strategy.

There is so far no evidence for side-effects specific to this therapeutic approach and clinical studies are now initiated to thoroughly evaluate the actual clinical relevance of this elegant treatment option in humans.

References 

1. Davis HL, McCluskie MJ, Gerin JL, Purcell RH. DNA vaccine for hepatitis B: evidence for immno-genicity in chimpanzees and comparison with other vaccines. Proc Natl Acad Sci USA 1996;93:7213-8.
2. Davis HL, Michel ML, Mancini M, Schleef M, Whalen RG. Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine 1994;12:1503-9.
3. Geissler M, Tokushige K, Wakita T, Zurawski VR Jr, Wands JR. Differential cellular and humoral immune responses to HCV core and HBV envelope proteins after genetic immunizations using chimeric constructs. Vaccine 1998;16:857-67.
4. Le Borgne S. Mancini M, Le Grand R, Schleef M, Dormont D, Tiollais P, et al. In vivo induction of specific cytotoxic T lymphocytes in mice and rhesus macaques immunized with DNA vector encoding an HIV epitope fused with hepatitis B surface antigen. Virology 1998;240:304-15.
5. Mancini M, Hadchouel M, Davis HL, Whalen RG, Tiollias P, Michel ML. DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state. Proc Natl Acad Sci USA 1996;93:12496-501.

Frequency Asked and Question about Hepatitis B Virus

How do you get hepatitis B?

You get hepatitis B by direct contact with the blood or body fluids of an infected person; for example, you can become infected by having sex or sharing needles with an infected person. A baby can get hepatitis B from an infected mother during childbirth.

Hepatitis B is not spread through food or water or by casual contact.

What does the term "hepatitis B carrier" mean?

Hepatitis B carriers are people who are infected with HBV and never recover fully from the infection; they carry the virus and can infect others for the rest of their lives. In the United States, about one million people carry HBV. 

How do you know if you have hepatitis B?

You may have hepatitis B (and be spreading the disease) and not know it; sometimes a person with HBV infection has no symptoms at all.

If you have symptoms

• your eyes or skin may turn yellow
• you may lose your appetite
• you may have nausea. vomiting, fever, stomach or joint pain
• you may feel extremely tired and not be able to work for weeks or months

Is there a cure for hepatitis B?

There are medications available to treat long-lasting HBV-infection (carrier). These work for some people, but there is no cure for hepatitis B when you first get it. That is why prevention is so important. Hepatitis B vaccine is the best protection against HBV. Three doses are commonly needed for complete protection.

If vaccine was never given, children 0-18 years of age should get hepatitis B vaccine.

If you are pregnant, should you worry about hepatitis B?

If you have HBV in your blood, you can give hepatitis B to your baby. Babies who get HBV at birth may have the virus for the rest of their lives, can spread the disease, and can get cirrhosis of the liver or liver cancer. 

All pregnant women should be tested for HBV early in their pregnancy. If the blood test is positive, the baby should receive vaccine along with another shot, hepatitis B immune globulin (called H-BIG), at birth. The second dose of vaccine should be given at 1-2 months of age and the third dose at 6 months of age.

Who should get vaccinated?

All babies, at birth

• All children 0-18 years of age who have not been vaccinated
• Persons of any age whose behavior puts them at high risk for HBV infection
• Persons whose jobs expose them to human blood

Fact Sheet: Vaccine

• Hepatitis B is a serious disease, responsible for an estimated 4000 to 5000 deaths each year in the United States due to cirrhosis and liver cancer.

• Hepatitis B vaccine prevents hepatitis B disease and its serious consequences. Therefore, this is the first anti-cancer vaccine.

• Use of hepatitis B vaccine and other vaccines is strongly endorsed by the medical, scientific and public health communities as a safe and effective way to prevent disease and death.

• Hepatitis B vaccines have been shown to be very safe when given to infants, children and adults.

• There is no confirmed evidence that indicates that hepatitis B vaccine can cause chronic illnesses.

• Case reports of unusual illnesses following vaccines are most often related to other causes and not related to a vaccine. Whenever large number of vaccines are given, some adverse events will occur coincidentally after vaccination and be falsely attributed to the vaccine.

• To assure a high standard of safety with vaccines, several federal agencies continually assess and research possible or potential health effects that could be associated with vaccines.

• Anyone believing they have had a possible reaction or adverse health effect from a vaccine should report it to their health care provider. The Vaccine Adverse Events Reporting System (1-800-822-7967) receives reports from health care providers and others about vaccine side effect.

INTERFERON TREATMENT FOR HEPATITIS B AND C
What is interferon?
- Interferon is produced by the body's cells in response to viral hepatitis and other infections. There are three types--alpha, beta and gamma. All are proteins. Commercial alpha interferon mixtures consist of the types of interferon produced by the body. Interferon alpha-2b is the only commercial form approved by the U.S. Food and Drug Administration for the treatment of hepatitis B and C. However, other forms of alpha interferon (interferon alpha-2a, lymphoblastoid or "natural" interferon and "consensus" interferon) are being evaluated. Interferons stimulate the body's immune system to fight viral infections and affect the ability of viruses to divide in liver cells. Patients with chronic hepatitis B or C infections also appear to be unable to produce normal amounts of interferon.

Which patients with hepatitis B should take interferon?
- Less than 50% of patients with chronic hepatitis B infection are eligible for interferon therapy. Patients should have infection documented for at least six months, elevated liver enzymes (AST or SGOT, and ALT or SGPT tests) and an actively dividing virus in their blood (hepatitis "e" antigen (HBeAg) and/or hepatitis B virus DNA (HBV DNA) positive tests). Patients with normal liver enzymes are less likely to respond to therapy. Patients with low hepatitis B virus DNA levels and elevated liver enzymes are more likely to benefit than those with high HBV DNA levels. A biopsy, where a needle is inserted into the liver to obtain a small sample of tissue, is helpful to determine liver damage prior to treatment. Patients with acute infection, cirrhosis or other major medical problems should not be treated.

When is it indicated for hepatitis C?
- Patients with elevated liver enzymes for six or more months and who have a detectable antibody (ELISA test) to hepatitis C (anti-HCV) are eligible for therapy. Patients who have a risk factor for hepatitis C (blood transfusion, needle-stick exposure or illegal intravenous drug use) need not have the hepatitis C result confirmed by additional testing. However, patients without such a risk factor should have a second test (RIBA test). Liver biopsy is helpful in the diagnosis of viral hepatitis, assessing liver damage prior to treatment, and at the end of therapy to evaluate the response. Patients with acute infection, complications from cirrhosis, other major medical problems and autoimmune liver disease should not be treated with interferon.

What are the doses used?
- The standard approved dose for hepatitis C is three million units, three times weekly for 24 weeks. Approved treatment for hepatitis B is five million units daily for 16 weeks. Treatment may be modified for significant side effects. However, lower doses may result in lower rates of response. Higher doses or longer therapy are being tested.

What are the side effects of treatment?
- The most common serious side effect is depression, particularly in patients with a prior history. Most patients will have muscle aches, fatigue and low grade fevers. These can be minimized by taking low doses of acetaminophen (e.g. Tylenol) at night. Nausea and diarrhea are common as is irritation of the skin at the injection site. Patients may experience significant weight loss, and if this occurs the dose should be adjusted. Patients often complain of irritability and headaches. A small number of patients may develop thyroid disease. Normal thyroid function should be documented prior to treatment. Hair loss is not uncommon, but usually reversible. Few side effects are severe or persist after treatment.

When is treatment not indicated?
- Patients with chronic hepatitis B or C, with fluid in the abdomen (ascites), bleeding from dilated veins in the esophagus (variceal bleeding), or mental confusion (encephalopathy) should be treated only in a clinical trial. Others not suitable for treatment are those with symptomatic heart, lung or kidney disease, with human immunodeficiency virus (HIV) infection or organ transplant recipients on prednisone, cyclosporine and FK-506 and patients on antidepressants or with a history of suicide attempts. Interferon should not be given to women considering pregnancy, nor to the intended father. Patients with active substance abuse (alcohol or illegal drugs) should not be offered this therapy.

What can be expected from treatment?
- Approximately 40%-50% of patients with chronic hepatitis C receiving full dose therapy will have a normalization of their liver enzymes, usually by the third month. With normal liver tests, the virus may become undetectable in blood. If no response is seen by three months, most researchers advocate stopping therapy. A few patients who respond to therapy may see their liver enzymes rise towards the end of treatment. The reason for this is unknown. When interferon is stopped after six months, more than half of the patients with hepatitis C who have responded will experience a rise in their liver tests. Patients will usually respond again if given further therapy. Therefore, 10%-15% will have a long lasting positive response. Longer treatments will likely result in longer positive responses. However, there is no evidence that this affects the relapse rate when treatment is stopped. Few patients will eradicate the virus.

A positive response to treatment for hepatitis B occurs in about 35% of patients. This is usually associated with a normalization of liver enzymes, and a loss of three "markers" for an active infection. These markers are hepatitis "e" antigen (HBeAg), hepatitis B DNA (indicating that the virus is reproducing) and hepatitis B surface antigen (HBsAg). An estimated 6% to 20% of patients lose these markers after therapy is stopped. A positive response to therapy is preceded by a rise in liver enzymes. Why this happens is not understood. Complete elimination of the virus is seldom achieved.

What happens if interferon is not given?
- The long term prognosis of hepatitis C is poorly understood. However, hepatitis C is generally a slowly progressive disease, with evolution over years if not decades. There is no proof that six months of treatment with interferon alters this. The changes vary from mild chronic hepatitis (least amount of liver damage) to moderate or severely active chronic hepatitis, with or without fibrosis or cirrhosis (most amount of liver scar damage). It is not known who will develop complications of chronic liver disease and liver failure.

In contrast, hepatitis B tends to progress more rapidly over years, although occasionally over decades. Not all patients with either hepatitis B or