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.
What are the goals of therapy for hepatitis C
infection?
The ultimate goals of antiviral therapy are to eliminate HCV, prevent
transmission, improve or
normalize the liver tests and histology (microscopic
appearance), prevent
progression to cirrhosis and liver cancer, prolong survival, and improve the
quality of life.
As already stated, only a sustained virologic response provides the
possibility of achieving all of these goals since most patients who have a
sustained response will remain in remission indefinitely. The rest of the patients
(non-responders, partial responders and relapsers) may show improvement in blood
tests with or without relief of symptoms.
What are the therapy options for previously untreated patients with chronic hepatitis C
infection?
For previously untreated patients who are candidates for therapy, the optimal
approach is combined treatment with
pegylated interferon
and ribavirin (Rebetol, Copegus). Patients who have reasons not to receive ribavirin may be treated
solely with pegylated interferon. Older preparations (nonpegylated forms)of interferon are less
effective and less commonly used.
Pegylated interferon: Interferons are a family of naturally occurring proteins that are produced by
the body to fight viral infections. To produce
pegylated interferon, the
interferon is processed by attaching ethylene glycol to it. This process is
called pegylation and it slows the elimination of interferon from the body so
that its effects are more prolonged. There are currently two types of pegylated
interferon: pegylated interferon alpha 2b (Peg-Intron A) and pegylated
interferon alpha 2a (Pegasys). Both pegylated interferon alpha 2b and 2a; are
given as a subcutaneous injection once a week.
Optimally, pegylated interferon therapy should be combined with ribavirin. In
persons who cannot take ribavirin, monotherapy with pegylated interferon may be
used. Monotherapy has been shown to achieve sustained virologic response rates
of 23% to 25% in patients.
Ribavirin: The antiviral agent,
ribavirin (Rebetol, Copegus), is a nucleoside analogue that is taken by mouth.
Nucleoside analogues are man-made molecules that closely resemble the
biochemical units that make up genetic material (RNA and DNA). Ribavirin works
by fooling the virus into using it instead of the normal building blocks,
thereby slowing viral reproduction. Ribavirin has not worked
well when used alone for hepatitis C.
Combined pegylated interferon and ribavirin: Combined therapy with both pegylated interferon and ribavirin produces a
sustained virologic response in 28% to 50% of patients with genotype 1. Genotype
1 is the most common genotype in the U.S., but also the most resistant to
treatment. For unknown reasons, response rates are lower in African American
persons and higher in Caucasians. In patients with genotype 2, sustained
response rates are higher (76% to 82%).
The duration of therapy depends on the genotype of the HCV.
Hence
the recommended duration of treatment for HCV genotype 2 and 3 is 24 weeks and
for genotype 1 is 48 weeks.
Sustained virologic response usually is accompanied
by a return to normal serum ALT levels and improvement in inflammation within
the liver.
Combination therapy is associated with more side effects than therapy with
single drugs
(see below). In research studies, up to 20% of patients receiving combination
therapy required a reduction in the doses or discontinuation of therapy because
of the side effects. Nevertheless, combination therapy represents significant
progress in the treatment of chronic HCV and is the current standard of care.
Some patients treated successfully with combination therapy still have
detectable virus after 12 weeks of treatment but go on to have a sustained
response. Therefore, patients on combination therapy should have hepatitis C
virus RNA measured at 24 weeks of therapy. In those who are still positive for
the virus at that time, consideration is given to stopping treatment, since the
chance of sustained response is small.
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.
Diabetes mellitus is a chronic condition characterized by high levels of sugar (glucose) in the blood. The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent). Symptoms of diabetes include increased urine output, thirst, hunger, and fatigue. Treatment of diabetes depends on the type.
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.
Non-Hodgkin's lymphoma is cancer of the lymphatic system, a vital part of the body's immune system. Symptoms include swollen lymph nodes, fever, night sweats, coughing, weakness, chest pain, unexplained weight loss, and abdominal pain. Treatment depends on which type of non-Hodgkin's lymphoma you have, the stage of the cancer, your age, how fast the cancer is growing, and whether you have other health problems.
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).
Raynaud's phenomenon is characterized by a pale-blue-red sequence of color changes of the digits, most commonly after exposure to cold. Occurring as a result of spasm of blood vessels, the cause is unknown. Symptoms of Raynaud's phenomenon depend on the severity, frequency, and duration of the blood vessel spasm. Treatments include protection of the digits, medications, and avoiding emotional stresses, smoking, cold temperature, and tools that vibrate the hands.
Alcoholism is a disease that includes alcohol craving and continued drinking despite repeated alcohol-related problems, such as losing a job or getting into trouble with the law.
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.
The hepatitis B virus is a unique, coated DNA virus belonging to the Hepadnaviridae family of viruses. The course of the virus is determined primarily by the age at which the infection is acquired and the interaction between the virus and the body's immune system. Successful treatment is associated with a reduction in liver injury and fibrosis (scarring), a decreased likelihood of developing cirrhosis and its complications, including liver cancer, and a prolonged survival.
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.
Lichen planus is a common skin disease that features small, itchy pink or purple spots on the arms or legs. the abnormal areas on the skin in lichen planus are typically flat-topped (hence the term planus), itchy, and frequently have a polygonal or angular shape.
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.
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.
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.
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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