Hepatitis B is still alive and kicking; know all about it


Muhammad Naeem, MD, FACP, FACG (USA)

"Hepatitis" is used to describe a common form of liver injury. Hepatitis means "inflammation of the liver" ("itis" means inflammation and "hepa" means liver). There are many causes of hepatitis; examples include alcohol, certain drugs, poisonous mushrooms, and viruses. Hepatitis B was the first hepatitis virus identified by scientists. Since then, a tremendous amount has been learned about the virus.

 

Infection with the hepatitis B virus can lead to a range of clinical illnesses. Infected people may not have any symptoms at all or they can develop an illness characterized by fever, nausea, abdominal pain, lack of appetite and yellowing of the skin (acute hepatitis). Acute hepatitis can be severe, with symptoms lasting for many weeks or months, and is much less commonly life-threatening or "fulminant," in which the liver is so badly damaged that it can no longer function. The only treatment for fulminant hepatitis is liver transplantation.

It is important to emphasize that most people with acute hepatitis B recover uneventfully. However, in about 5 percent of adults (1 in 20) the virus makes itself at home in the liver, where it continues to make copies of itself for many years. People who continue to harbor the virus are referred to as "carriers" while liver damage associated with longstanding infection is referred to as "chronic hepatitis." Chronic hepatitis B develops more commonly in people who are infected with the virus at an early age, such as at birth. Unfortunately, this is a common event in some parts of the world such as in southeast Asia, China, and sub-Saharan Africa where as many as 1 in 10 people have chronic infection.

During its residence in the liver, the hepatitis B virus is capable of causing damage to the liver, but the amount of damage is variable, and in part depends upon the liver's ability to repair itself and the body's ability to control the infection. Some people may have little or no damage to the liver at all, but are still infected and capable of transmitting the virus to others.

Most infected patients, even those with progressing disease, have no specific symptoms for many years. However, the absence of symptoms does not necessarily mean that the infection is under control. All people who have chronic infection with hepatitis B are at increased risk for developing complications that include the development of liver scarring (which in its advanced stage is termed cirrhosis) and liver cancer. It is estimated that there are more than 300 million carriers of the hepatitis B virus in the world, of whom over 250,000 die annually from HBV-related liver disease.

Fortunately, treatments for chronic hepatitis B are available, and many new treatments are in development. Furthermore, highly effective vaccines have been developed that

can prevent infection. Hepatitis B vaccination is now given routinely to children in the

United States and in many other countries and is highly recommended for adults who are at risk for acquiring the infection.

Because the course of hepatitis B can vary widely from person to person, the treatment of this condition is individualized. It is important to learn as much as you can about hepatitis B and to carefully discuss the diagnostic and treatment options with your doctor.

SYMPTOMS OF HEPATITIS B? — The symptoms of hepatitis B differ during acute (new) hepatitis and chronic (long-standing) hepatitis. Within these categories, the symptoms can also vary widely from person to person.

WHAT IS Acute hepatitis B — The symptoms of acute hepatitis B usually appear after a one- to four-month incubation period. The first symptoms may be non-specific, including fever, skin rash, and joint pain and inflammation. Although many people have no symptoms at all, symptoms of acute hepatitis may include fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), and pain in the upper right abdomen.

The symptoms of acute hepatitis B usually resolve within three months as the body eliminates the virus or brings the virus under control. People with acute hepatitis can rarely experience complications in other organs and tissues, and a very small percentage of people (0.1 to 0.5 percent) develop severe liver failure.

 

 

 

 

 

Chronic hepatitis B — The symptoms of chronic hepatitis B can last for many years and vary widely. Many people who carry the virus have no symptoms at all; other people have symptoms of ongoing liver inflammation, such as fatigue and loss of appetite. Some people with chronic hepatitis B also experience sudden, short-lived exacerbations of their symptoms.

About 10 to 20 percent of people with chronic hepatitis B develop complications in other organs and tissues outside the liver; vascular inflammation and kidney disease are the two most common complications. People with chronic hepatitis B who develop cirrhosis or liver cancer may experience symptoms such as fatigue, weight loss, fluid accumulation in the abdomen and legs and abdominal pain.

HOW IS IT TRANSMITTED? — The hepatitis B virus can be transmitted in a variety of ways. In the United States, the virus is most commonly transmitted by needle sharing during intravenous drug use or by unprotected sexual intercourse; in regions of the world where hepatitis B is prevalent, perinatal transmission (transmission from a mother to her baby) is the most common type of transmission.

Transmission by contaminated needles — Any activity that transfers blood or body fluids beneath the skin can transmit the hepatitis B virus. These include tattooing, acupuncture, and ear piercing if these procedures are performed with contaminated instruments, and needle sharing among intravenous drug users.

Sexual transmission — Transmission by unprotected sexual intercourse is the most common type of transmission of hepatitis B in developed countries. Sexual transmission accounts for about 30 percent of acute (new) cases of hepatitis B virus infection in the United States.

Perinatal transmission — Perinatal transmission refers to transmission from a mother to her baby near the time of birth. Transmission usually occurs during delivery, but it can also result from close mother-baby contact shortly after birth. Babies who are infected around the time of birth have a 90 percent chance of developing chronic infection.

Transmission by close contact — Hepatitis B transmission can occur through close personal contact. Infection most likely occurs when body fluids containing the virus enter tiny breaks in the skin or the membranes of the eyes and mouth. This type of transmission often occurs between children. Because the virus can survive outside the body for long periods of time, transmission can also occur by sharing household items that carry the virus, including toys, toothbrushes, and razors.

Blood transfusion — Blood transfusion is now an extremely uncommon route for the transmission of hepatitis B virus. Blood donors are carefully screened, and all donated blood is tested for markers of hepatitis infection. These procedures detect most contaminated units of blood, but a very small percentage of these units go undetected. As a result, people who require many blood transfusions during their lifetime (for conditions such as hemophilia or thalassemia) have an increased risk of hepatitis B.

Transmission in the hospital setting — In the hospital setting, hepatitis B virus can be transmitted from patient to patient or from patient to health care provider by contaminated needles or instruments. Transmission from health care providers to patients is extremely rare.

Organ transplantation — Hepatitis B virus can be transmitted in donated livers and other organs. However, organ donors are routinely screened for hepatitis markers, and screening usually prevents this type of transmission.

HOW IS IT DIAGNOSED? — The diagnosis of hepatitis B is based upon a careful review of a person's medical history, the signs and symptoms noted during a physical examination, and the results of specific diagnostic tests.

Medical History — A detailed medical history may suggest the presence of hepatitis B and the likely route of infection. Your doctor will ask about the common risk factors for hepatitis B, including unprotected sexual intercourse and intravenous drug use, your country of birth and any family history of hepatitis B. He or she will also ask about the onset, nature, and severity of any symptoms that you may have noticed.

Physical Examination — The results of a physical examination in patients with hepatitis B vary widely. As mentioned above, some people with acute hepatitis B have no symptoms, and may also lack findings on physical examination. In others, acute hepatitis can be accompanied by fever, yellowing of the eyes and skin (jaundice), a tender, slightly enlarged liver, and a skin rash. Symptoms in patients with chronic hepatitis B are also variable. Most patients with chronic hepatitis B do not have any abnormal findings on examination. However, patients with advanced disease (such as those who have developed cirrhosis) can have a number of findings on physical examination reflecting the underlying liver problem. These include:

  bullet Jaundice                                          

  bullet  Confusion                 

  bullet A distended, fluid-filled abdomen (ascites)

                                   

Liver cancer from hepatitis B

  bullet An enlarged spleen

  bullet Edema of the legs

  bullet Enlarged breast tissue (in men)

  bullet Redness of the palms (palmar erythema)

  bullet Small, spider-like veins, usually on the chest and back (spider angiomas)

  bullet Muscle wasting

  bullet Atrophy of the testes

  bullet Asterixis (spontaneous flapping of the hands when outstretched with the palms facing forward)

Liver tests — Liver tests are blood tests that provide information about the presence of liver damage and help determine the severity of damage and whether it has stopped or is ongoing.

  Alanine and aspartate aminotransferase — During acute hepatitis B, blood levels of two liver enzymes, alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT), are usually elevated. High levels of these enzymes signal ongoing liver inflammation. In most people with acute hepatitis, levels return to normal within one to four months. The persistence of high ALT levels after six months suggests that a person is developing chronic hepatitis. Liver enzyme levels may be more than 1000 IU/L during acute hepatitis but may vary from normal (less than 40 IU/L) to a few hundred in patients with chronic infection. Liver enzyme levels may fluctuate during the course of chronic infection.

  Bilirubin — High blood levels of bilirubin (a substance produced mostly from red blood cells and metabolized by the liver) often signal more severe liver damage. High bilirubin levels give rise to jaundice, which is yellowing of the skin and eyes and darkening of the urine.

  Albumin — Low blood levels of albumin, a protein synthesized by the liver, often signal chronic liver damage.

  Prothrombin time — An abnormally long prothrombin time (a measure of the time required for blood clotting) suggests more severe liver damage. The results of a prothrombin time are the best predictor of prognosis in acute hepatitis B.

Blood levels of hepatitis markers — Blood levels of several hepatitis markers can confirm hepatitis B infection and differentiate acute from chronic infection. These markers include substances produced by the hepatitis B virus (called antigens) and substances produced by the immune system to control and eliminate the virus (called antibodies).

The diagnosis of acute hepatitis B is based upon the presence of the hepatitis B surface antigen (HBsAg) and hepatitis B core IgM antibody. The diagnosis of chronic hepatitis B is based on the presence of the HBsAg marker for at least six months.

  Hepatitis B surface antigen — In acute hepatitis, HBsAg can be detected soon after infection; falling levels of this marker and the appearance of hepatitis B surface antibodies (HBsAb) signal recovery. In chronic hepatitis, HBsAg can be detected for many years, and HBsAb may never appear.

  Hepatitis B e antigen — Hepatitis B e antigen (HBeAg) is present when the hepatitis B virus is actively multiplying. In acute hepatitis, HBeAg can be detected soon after infection; falling levels of this marker and the appearance of hepatitis B e antibodies (HBeAb) signal recovery. In most patients with chronic hepatitis, HBeAg can be detected for many years. With time, the immune system may suppress the virus to such low levels that HBeAg is no longer detected and HBeAb is present. Loss of HBeAg and appearance of HBeAb is usually an indication that the virus is suppressed and the liver disease becomes inactive. However, some HBV mutants that cannot make HBeAg have been described (precore mutants). In this case, patients may be HBeAg negative but still have high levels of virus and active liver disease.

  Hepatitis B virus DNA — Detection of hepatitis B virus DNA in a blood sample signals that the virus is actively multiplying. In acute hepatitis, DNA can be detected soon after infection; falling levels of DNA signal recovery, and levels usually become undetectable over time. In chronic hepatitis, levels of DNA often remain high for many years and then decrease as the immune system gains control over the virus.

  Antibodies to Hepatitis B core antigen — In acute hepatitis, a specific class of antibodies directed against the hepatitis B core antigen (anti-HBc) appears early in infection. There are two classes of this antibody (core IgG and core IgM). The IgM class appears first during the acute phase of hepatitis and then gradually switches to the IgG type.

Liver Biopsy — During a liver biopsy, a small sample of liver tissue is collected for microscopic examination. A liver biopsy is not routinely needed to diagnose hepatitis. However, this test may be useful if other tests are inconclusive. Liver biopsy is also useful for monitoring the progression of liver damage in people with chronic hepatitis, helping to decide upon the best treatment, and for detecting cirrhosis or liver cancer.

HOW IS IT TREATED? — There is no specific treatment for acute hepatitis B; in 95 percent of adults, the immune system controls the infection and eliminates the virus within about six months. In people who develop chronic hepatitis, the goals of treatment are to stop the virus from multiplying while liver damage is still reversible.

General measures — All people infected with chronic hepatitis B should be vaccinated against hepatitis A unless they are already known to be immune. Pneumococcal vaccine and yearly influenza vaccination should be considered in patients who have developed cirrhosis.

Regular screening for liver cancer is also recommended, particularly for older individuals, those with cirrhosis, and patients with family history of liver cancer. In general, this entails an annual or biannual ultrasound examination and blood test for serum alpha fetoprotein level (a protein frequently produced by liver tumors, which is detectable in blood). The best approach to screening for liver cancer has not been determined.

Antiviral Therapy — Three currently available drugs slow or stop multiplication of the hepatitis B virus: lamivudine, adefovir, and interferon-alpha. The physician and the patient should discuss treatment options after a careful assessment of the individual's conditions.

  Lamivudine — Lamivudine (Epivir-HBV) is a good first treatment for people with chronic hepatitis B who have detectable virus activity and ongoing liver inflammation. Lamivudine is also appropriate for people who have had a poor response to interferon-alpha, people who have worsening cirrhosis, and people who experience sudden liver failure.

Studies suggest that long-term treatment with lamivudine (treatment for at least one year) promotes favorable changes in the blood markers for hepatitis and reduces inflammation of the liver.

Lamivudine is taken orally, usually at a dosage of 100 mg/day, for at least one year. Although it is very safe, the drug can trigger a flare of hepatitis in some people and can also be associated with uncommon but serious side effects that you should discuss with your doctor. The major problem with lamivudine is that a resistant form of hepatitis B virus (referred to as a YMDD mutant) frequently develops in patients on long-term treatment. Despite the development of resistance, continued treatment may be beneficial since the resistant strains appear to cause less damage than the natural form of the virus. However, the long-term effect of these mutants is not yet known.

  Adefovir — Adefovir (Hepsera) is also a reasonable initial choice for people who have detectable virus activity and ongoing liver inflammation. It is a relatively new drug, so its benefits and safety compared to other therapies is still being determined. An advantage of adefovir compared to lamivudine is that the YMDD resistant mutants do not appear to develop. Adefovir has been associated with kidney problems, so kidney function needs to be checked before and during treatment.

  Interferon-alpha — Interferon-alpha is an appropriate treatment for people with chronic hepatitis B infection who have detectable virus activity and ongoing liver inflammation. It is also safe and effective for people who have early cirrhosis. Interferon-alpha is not appropriate for people with cirrhosis who have liver failure or for people who have a recurrence of hepatitis after liver transplantation.

Studies suggest that three to six months of treatment with interferon-alpha produces favorable changes in the blood markers for hepatitis (decrease in serum HBV DNA levels and loss of HBeAg) in about 30 to 40 percent of people and halts liver inflammation; in people who have a good response to the drug, it also reduces the risk of liver failure and liver cancer, and reduces the risk of dying from liver disease.

Interferon-alpha must be taken by injection for 16 weeks. The drug triggers a flare of hepatitis in 30 to 50 percent of people. The major downside of interferon-alpha is that it has many side effects, which you should discuss with your doctor.

Liver transplantation — Liver transplantation may be the only option in those who have developed advanced cirrhosis. The transplantation process is elaborate, involving an extensive screening process for eligibility. Thus, not all patients with cirrhosis are eligible, and only those with the most advanced cirrhosis and otherwise good medical and social conditions will be put on the transplant waiting list.

WHAT IS THE PROGNOSIS?— As discussed above, the clinical course of hepatitis B can vary widely. Certain factors help predict prognosis.

Likelihood of developing chronic hepatitis — The likelihood of acute hepatitis progressing to chronic hepatitis largely depends on a person's age at the time of infection. Chronic hepatitis develops in about 90 percent of children who are infected at birth, in 20 to 50 percent of children who are infected between the ages of 1 and 5 years, and in less than 5 percent of people infected during adulthood.

Factors that influence prognosis — Several factors affect the prognosis of hepatitis. Prognosis is largely influenced by the extent of viral multiplication and the immune system's ability to control the infection. Other factors that appear to worsen the course of hepatitis include male gender, habitual alcohol consumption, and coinfection with other hepatitis viruses.

I HAVE CHRONIC HEPATITIS B, WHAT CAN I DO TO HELP MY LIVER? — As discussed above, the majority of people with acute hepatitis B spontaneously clear the infection. Those who develop chronic infection should be evaluated by a physician with expertise in liver disease (usually a gastroenterologist or hepatologist) who can discuss treatment options. In addition to the routine vaccinations discussed above and possibly screening for liver cancer, a number of other issues are commonly discussed:

Diet — No specific diet has been shown to improve the outcome in patients with hepatitis B. The best advice is to eat a normal healthy and balanced diet. Alcohol should be avoided.

Exercise — Exercise is good for your overall health and is encouraged, but has no effect on the virus.

Prescription and nonprescription drugs — Many drugs require metabolism by the liver. Thus, it is always best to check with your doctor or pharmacist before starting a new prescription. As a general rule, unless your liver is already scarred, most drugs are as safe as for people without hepatitis B. An important possible exception is acetaminophen (Tylenol), the maximum dose of which should not be more than 2 grams (in divided doses) per 24 hours.

Herbal medications — Although many claims about herbal medications have been made (particularly on the internet) please beware. None has been proven to improve outcomes in patients with hepatitis B, and some have been associated with serious liver toxicity.

Support — Do not underestimate the value of sharing your concerns with other people with hepatitis B. Ask your doctor about support groups.

IMPLICATIONS FOR YOUR FAMILY — Acute and chronic hepatitis B are contagious. Thus, you should discuss with your doctor the proper measures needed to reduce the risk of infecting others. This usually entails counseling on ways to minimize blood and fluid contacts while testing and vaccinating those at risk for acquiring the infection or who may have already acquired the infection.

FOR MORE INFORMATION —

  bullet National Library of Medicine

      (http://www.nlm.nih.gov/medlineplus)

  bullet Centers for Disease Control

      (http://www.cdc.gov/ncidod/diseases/hepatitis/index.htm)

  bullet National Institute of Diabetes and Digestive and Kidney Diseases

      (http://www.niddk.nih.gov)

  bullet National Institute of Allergy and Infectious Diseases

      (http://www.niaid.nih.gov/)

  bullet National Foundation for Infectious Diseases

      (http://www.nfid.org/)

  bullet American Gastroenterological Association

      (http://www.gastro.org/)

  bullet American Liver Foundation

      (http://www.liverfoundation.org/)