Mary D. Nettleman, MD, MS, MACP is the Chair of the Department of Medicine at Michigan State University. She is a graduate of Vanderbilt Medical School, and completed her residency in Internal Medicine and a fellowship in Infectious Diseases at Indiana University.
Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
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.
Interferon-alpha 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;
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.
Liver cancer is the fifth most common cancer in the world and the majority of patients with liver cancer will die within one year as a result. Patients with associated cirrhosis caused by chronic hepatitis B or C infections, alcohol, and hemochromatosis are at the greatest risk of developing liver cancer. Many patients with liver cancer do not develop symptoms until the advanced stages of the tumor which usually makes prognosis poor. The combination of an imaging study (ultrasound, CT, or MRI scans) and an elevated blood level of alpha-fetoprotein will most effectively diagnose liver cancer, while a liver biopsy can make a definitive diagnosis. Medical treatments, including chemotherapy, chemoembolization, ablation, and proton beam therapy, are not very effective. Surgical removal of the tumor or a liver transplant may be most effective in certain cases.
Cirrhosis of the liver refers to a disease in which normal liver cells are replaced by scar tissue caused by alcohol and viral hepatitis B and C. This disease leads to abnormalities in the liver's ability to handle toxins and blood flow, causing internal bleeding, kidney failure, mental confusion, coma, body fluid accumulation, and frequent infections. Symptoms include yellowing of the skin, itching, and fatigue.
Pancreatic cancer is a malignant tumor of the pancreas. Pancreatic cancer has been called a "silent" disease because early pancreatic cancer usually does not cause symptoms.
Liver disease can be cause by a variety of things including infection (hepatitis), diseases such as gallstones, high cholesterol or triglycerides, blood flow obstruction to the liver, and toxins (medications and chemicals). Symptoms of liver disease depends upon the cause; however, common symptoms may include nausea, vomiting, upper right abdominal pain, and jaundice. Treatment depends upon the cause of the liver disease.
Sexually transmitted diseases, or STDs,
are infections that are transmitted during any type of sexual exposure,
including intercourse (vaginal or anal), oral sex, and the sharing of sexual
devices, such as vibrators. Women can contract all of the STDs, but may have no symptoms, or have different symptoms than men do.
Hepatitis C is an inflammation of the liver due to the hepatitis C virus (HCV), which is usually spread by
blood transfusion, hemodialysis, and needle sticks, especially with intravenous
drug abuse. Chronic hepatitis C may be treated with interferon, usually in combination with anti-virals.
Jaundice is a yellowish staining of the skin and whites of the eyes (sclerae) with bilirubin, the pigment found in bile. Jaundice can be an indicator of liver or gallbladder disease, or it may result from the rupture of red blood cells (hemolysis).
Drug-induced liver diseases are diseases of the liver that are caused by physician-prescribed medications, OTC medications, vitamins, hormones, herbs, illicit (“recreational”) drugs, and environmental toxins. There are three types of liver toxicity; dose-dependent toxicity, idiosyncratic toxicity, and drug allergy. The types of liver disease drugs cause include: mild elevations of blood levels of liver enzymes, hepatitis, necrosis, cholestasis, steatosis, cirrhosis, mixed disease, fulminant hepatitis, and blood clots.
Ascites, the accumulation of fluid in the abdominal cavity is most commonly caused by cirrhosis of the liver. Some of the other causes of ascites include portal hypertension, congestive heart failure, blood clots, and pancreatitis. The most common symptoms include increased abdominal girth and size, abdominal bloating, and abdominal pain. Treatment depends on the cause of ascites.
Sexually transmitted diseases, or STDs, are infections that are transmitted during any
type of sexual exposure, including intercourse (vaginal or anal), oral sex, and
the sharing of sexual devices, such as vibrators. Although treatment exists for many STDs, others currently are
usually incurable, such as those caused by HIV, HPV, hepatitis B and C, and HHV-8.
Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis (irreversible, advanced scarring of the liver). All of the stages of NAFLD have in common the accumulation of fat (fatty infiltration) in the liver cells (hepatocytes).
Thrombocytopenia refers to a decreased number of platelets in the blood. There are many causes of thrombocytopenia such as decreased platelet production (viral infections for example rubella, mumps, chickenpox, hepatitis C, and HIV); increased platelet destruction or consumption (for example sulfonamide antibiotics, heparin, blood transfusions, and lupus); or increased splenic sequestration (enlarged spleen due to conditions for example liver disease, blood cancers, and more). Treatment of thrombocytopenia depends on the cause.
Vasculitis is a general term for a group of uncommon diseases which feature inflammation of the blood vessels. Each form of vasculitis has its own characteristic pattern of symptoms. The diagnosis of vasculitis is definitively established after a biopsy of involved tissue demonstrates the pattern of blood vessel inflammation. Treatment is directed toward decreasing the inflammation of the arteries and improving the function of affected organs.
Drug addiction is a chronic disease that causes drug-seeking behavior and drug use despite negative consequences to the user and those around him. Though the initial decision to use drugs is voluntary, changes in the brain caused by repeated drug abuse can affect a person's self-control and ability to make the right decisions and increase the urge to take drugs. Drug abuse and addiction are preventable.
Hepatitis is most often viral, due to infection with one of the hepatitis viruses (A, B, C, D, E, F (not confirmed), and G) or another virus (such as those that cause infectious mononucleosis, cytomegalovirus disease). The main nonviral causes of hepatitis are alcohol and drugs. Many patients infected with hepatitis A, B, and C have few or no symptoms of illness. For those who do develop symptoms of viral hepatitis, the most common are flu- like symptoms including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, and aching in the abdomen. Treatment of viral hepatitis is dependant on the type of hepatitis.
Encephalopathy means brain disease, damage, or malfunction. Causes of encephalopathy are varied and numerous. The main symptom of encephalopathy is an altered mental state. Other symptoms include lethargy, dementia, seizures, tremors, and coma. Treatment of encephalopathy depends on the type of encephalopathy (anoxia, diabetic, Hashimoto's, hepatic, hyper - hypotensive, infectious, metabolic, infections, uremic, or Wernicke's) are examples of types of encephalopathy.
The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
Optic neuritis is inflammation of the optic nerve, the structure that connects the eye to the brain. The precise cause of optic neuritis is unknown, but it is thought to be a type of autoimmune disorder. Optic neuritis most commonly develops due to an autoimmune disorder that may be triggered by a viral infection.
Fatigue can be described in various ways. Sometimes fatigue is described as feeling a lack of energy and motivation (both mental and physical). The causes of fatigue are generally related to a variety of conditions or diseases for example, anemia, mono, medications, sleep problems, cancer, anxiety, heart disease, drug abuse, and more. Treatment of fatigue is generally directed toward the condition or disease that is causing the fatigue.
Travelers should prepare for their trip by visiting their physician to get the proper vaccinations and obtain the necessary medication if they have a medical condition or chronic disease. Diseases that travelers may pick up from contaminated water or food, insect or animal bites, or from other people include malaria, meningococcal meningitis, yellow fever, hepatitis A, typhoid fever, polio, and cholera.
Septic arthritis, or infectious arthritis, is infection of one or more joints by bacteria, viruses, or fungi. Symptoms and signs of septic arthritis include fever, joint pain, chills, swelling, redness, warmth, and stiffness. Treatment involves antibiotics and the drainage of the infected joint.
Anabolic steroids are synthetic substances that are related to testosterone and promote skeletal muscle growth and the development of male sexual characteristics in both men and women. In the 1930s, it was discovered that anabolic steroids could promote skeletal muscle growth in lab animals, which lead to anabolic steroid abuse by bodybuilders and weight lifters.
Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
Hemophilia is one of a group of inherited bleeding disorders. Hemophilia A and B are inherited in an X-linked recessive genetic pattern and is more common in males. Symptoms of hemophilia include bleeding into the joints, muscles, GI or urinary tract, or brain or skull. Treatments for hemophilia is generally replacement of blood clotting factors.
Hepatitis means inflammation of the liver. Hepatitis A is one type of liver disease caused by a virus. Since hepatitis A is a virus, it can pass from person to person from eating or drinking contaminated food or coming into contact with contaminated materials containing the virus. Symptoms of hepatitis A include stomach pain, diarrhea, dark yellow urine, jaundice, and more. There is a vaccine to prevent contracting hepatitis A.
Polyarteritis nodosa is a rare autoimmune disease characterized by spontaneous inflammation of the arteries of the body. The most common areas of involvement include the muscles, joints, intestines (bowels), nerves, kidneys, and skin. Poor function or pain in any of these organs can be a symptom. Polyarteritis nodosa is most common in middle age persons. Polyarteritis is a serious illness that can be fatal. Treatment is focused on decreasing the inflammation of the arteries by suppressing the immune system.
Hepatitis A and hepatitis B are the two most commnon viruses that infect the liver. Hepatitis A and Hepatitis B can be prevented and treated with immunizations (vaccinations) such as Havrix, Vaqta, Twinrix, Comvax, Pediarix, and hepatitis b immune globulin (HBIG).
When you are pregnant, many sexually transmitted diseases (STDs) can be especially harmful to you and your baby. These STDs include herpes, HIV/AIDS, genital warts (HPV), hepatitis B, chlamydia, syphilis, gonorrhea, and trichomoniasis. Symptoms include bumps, sores, warts, swelling, itching, or redness in the genital region. Treatment of STDs while pregnant depends on how far along you are in the pregnancy and the progression of the infection.
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