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INFORMATION PROVIDED BY http://www.uptodate.com/patients HEPATITIS C INTRODUCTION — The term "hepatitis" is used to describe a common form of liver injury. Hepatitis simply means "inflammation of the liver" (the suffix "itis" means inflammation, and "hepa" means liver). Hepatitis can be caused by a number of factors, including alcohol abuse, large doses of certain medications, poisonous mushrooms, and viruses. Hepatitis C is caused by a virus that is spread from one person to another in blood and body fluids, such as by sharing IV drug needles or "works" or during pregnancy and delivery. Chronic hepatitis C is the most common chronic liver disease and accounts for 8,000 to 13,000 deaths each year. The majority of liver transplants performed in the United States are done for people with chronic hepatitis C. This topic review discusses the symptoms, causes, and long term management of hepatitis C virus (HCV). Topic reviews that discuss hepatitis A and B are available separately. (See "Patient information: Hepatitis A" and see "Patient information: Hepatitis B"). HEPATITIS C SYMPTOMS — When a person is first exposed to the hepatitis C virus and becomes infected, they are said to have "acute hepatitis C". Most people have no symptoms of infection during this time. In 70 to 80 percent of people, the infection becomes chronic. The word "chronic" implies that the infection will be prolonged, or even lifelong, unless treatment is given and results in a cure. Chronic infection with hepatitis C has the potential to cause liver damage, ranging in severity from mild to severe. This is in contrast to other types of viral hepatitis (such as hepatitis A), which causes symptoms after the person is infected and then resolve as the virus is cleared from the body. (See "Patient information: Hepatitis A"). Many people with chronic hepatitis C have no symptoms, even if there is significant liver damage. Of those who do develop symptoms, the most common symptom is fatigue; other less common symptoms include nausea, lack of appetite, muscle or joint aches, weakness, and weight loss. The cause of these symptoms is not entirely clear. Not having symptoms does not necessarily mean that the infection is under control. HOW DID I BECOME INFECTED WITH HEPATITIS C ? — The hepatitis C virus is spread by contact with blood. Thus, patients with hepatitis should avoid activities that could expose other people to their blood. Examples include sharing a toothbrush, nail clippers, razors, and needles (show table 1). Blood and blood products — Hepatitis C was commonly spread by contaminated blood transfusions until the early 1990s, when a blood test was developed that could accurately screen blood donors for hepatitis C infection. As a result, the current risk of becoming infected with hepatitis C from a blood transfusion is quite small, estimated at one in 1.9 million. (See "Patient information: Blood donation and transfusion"). Sexual transmission — The virus can be spread sexually, although the risk is much smaller than with other types of viruses. The risk of transmission between stable monogamous sexual partners (ie, between sexual partners who have no other sexual contacts) is estimated to be approximately one in a thousand per year. Use of a condom is not routinely recommended due to the very low risk. People who do not have a stable monogamous sexual partner should use condoms. This is to protect the person with hepatitis C from new infections (such as HIV or other sexually transmitted diseases) as well as to protect the partner from acquiring hepatitis C. The risk of transmitting the virus is higher in people who are infected with both hepatitis C and HIV. Furthermore, care of patients who are coinfected with HIV and hepatitis C often differs from those with hepatitis C alone. Other transmission — There is no evidence that kissing, hugging, sneezing, coughing, casual contact, sharing food, water, eating utensils or drinking glasses, or having other contact without blood exposure can spread the hepatitis C virus. However, sharing toothbrushes, razors, and other objects that might be contaminated with blood is NOT recommended. This also applies to implements (such as straws) used to inhale cocaine and needles and syringes used to inject drugs. Daily use of marijuana has been associated with worsening liver disease and is not recommended, particularly for people with hepatitis C. Transmission during pregnancy — The risk of transmitting hepatitis C during pregnancy may depend upon the level of virus in the blood stream. In general, the risk is about 5 to 6 percent (about 1 in 20) but is increased in people who are also infected with HIV, in whom the risk increases to 12 percent or 1 in 8. Women with hepatitis C who are pregnant or contemplating pregnancy should speak to their healthcare provider about these risks. HEPATITIS C DIAGNOSIS Blood tests — Hepatitis C is diagnosed with a blood test. In most cases, a screening blood test (hepatitis C virus antibody) is done because a person has risk factors for the infection, including the following [4]: Recent exposure to blood infected with HCV (eg, an accidental needle stick) Being HIV positive Past or current sexual partner of a person with HCV Previous or current use of IV drugs Previous or current use of hemodialysis for kidney failure Anyone who was given donated blood or organs before July 1992 or blood clotting factors before 1987 Less commonly, a screening test is done because a person has symptoms of recent infection, such as a lack of appetite, nausea, flu-like symptoms, or pain under the ribs on the right side (where the liver is located). If the screening test is positive for hepatitis C, further testing is performed to confirm that the virus is present. Results of these tests are used to guide treatment: Hepatitis C virus (HCV) RNA is a measure of the amount of virus circulating in the blood. HCV RNA is detectable in the blood within days to eight weeks following exposure. Hepatitis C genotype testing determines the specific type of HCV; most people in the United States have type I. Liver biopsy — A liver biopsy is not required to diagnose hepatitis C. However, a biopsy is often performed if hepatitis C treatment is being considered. Results of the biopsy can help to determine the stage of the disease and the long-term prognosis. Liver biopsy is done as a day surgery procedure, and involves taking a tiny sample of the liver tissue and looking at it under a microscope. The procedure is described in detail in a separate topic review. (See "Patient information: Liver biopsy"). HEPATITIS C COMPLICATIONS — The hepatitis C virus causes a variable amount of damage to the liver, although the liver is able to repair itself to some degree. This damage occurs over many years (show histology 1). In some people, scar tissue (called fibrosis) accumulates in the liver, which can eventually become extensive, leading to cirrhosis, in which the liver is severely scarred (show histology 2). People with cirrhosis are at increased risk for developing complications because the scarred liver is less able to function normally. (See "Patient information: Cirrhosis"). One of the most feared complications of cirrhosis is the development of liver cancer (called hepatocellular carcinoma), which occurs almost exclusively in people with cirrhosis. About 2 percent of people with cirrhosis (1 in 50) develop hepatocellular carcinoma each year. Therefore, the majority of people with cirrhosis due to hepatitis C will not get hepatocellular carcinoma. Risk factors for complications — Researchers have studied large groups of people with hepatitis C to find out what happens to them over time. Only about 20 percent (or one in five) will develop cirrhosis within 20 years of acquiring the infection. Most others will have some degree of inflammation in the liver, but without a significant amount of scarring. Researchers have tried to identify factors that increase the risk of developing cirrhosis after patients have become infected with hepatitis C. The most important include: Consuming alcohol — People with hepatitis C who drink alcohol are at much greater risk for developing cirrhosis. The amount of alcohol that is safe to consume is not well established for people with hepatitis C. Even small amounts (social drinking) have been linked to an increased risk of cirrhosis in people with hepatitis C. Until more is known, we recommend completely avoiding alcohol. Amount of liver damage — Increasing amounts of inflammation make it more likely that the liver will become scarred. There are many tools for determining how much damage hepatitis C has caused, including blood tests, an ultrasound examination of the liver, and liver biopsy. Liver biopsy is the "gold standard" test, although it is not recommended in everyone (see "Liver biopsy" above). HEPATITIS C TREATMENT OPTIONS — The goal of treating hepatitis C is to prevent progression of liver disease. As mentioned above, about 20 percent of people will develop cirrhosis 20 years after becoming infected. Therefore, people with hepatitis C who are young have a greater chance of developing cirrhosis and complications of cirrhosis during their lifetime. Unfortunately, it is not always possible to accurately predict who will develop progressive disease. Pegylated interferon and ribavirin — The most common treatment for hepatitis C is a combination of two medications, pegylated interferon and ribavirin. The recommended duration of treatment with this combination is 48 weeks for genotype 1, and usually 24 weeks for genotype 2 and 3. During therapy, the level of the virus in the blood (called the viral load) will be monitored, with the goal of completely eliminating the virus. Therapy may be stopped early if the virus does not respond or if there are intolerable treatmentrelated side effects. Side effects occur in almost 80 percent of patients who are given pegylated interferon and ribavirin. The most common side effects include flu-like symptoms, low red and white blood cell counts, and fatigue. Treatments to minimize these symptoms are available. Should I be treated? — The decision to undergo treatment for chronic hepatitis C infection is based upon a number of factors, some of which are discussed below. Treatment for hepatitis C is not recommended for everyone; the patient and healthcare provider should carefully discuss the potential risks and benefits of treatment before making a plan to proceed. Treatment with interferon is not recommended for people whose depression is not well controlled because this group is at risk for committing suicide during treatment. Interferon may be used in people with well-controlled depression. Ribavirin is not recommended in women who are pregnant, contemplating pregnancy or unable to use a reliable form of birth control. People with underlying autoimmune disorders (eg, lupus, rheumatoid arthritis) may be at increased risk of treatment-related complications related to interferon. People with normal liver function tests (ALT) who acquired hepatitis C under the age of 35 years, are women, do not drink alcohol, and have no or minimal fibrosis on liver biopsy may develop hepatic fibrosis at a slow rate. In such patients, it is reasonable to delay treatment until fibrosis progresses, liver function testing becomes abnormal, or clinical trials prove that earlier treatment is of benefit. Cure — The chance of being cured depends in part upon the specific type of hepatitis C virus (ie, the genotype). Overall, the chance is approximately 40 to 50 percent for genotype 1 and 80 percent or more with genotypes 2 and 3. To determine if the treatment has cured the infection, the person must wait six months after therapy is completed since the virus can recur after therapy has been discontinued. Recurrence happens in about 25 to 30 percent of cases. Cure is defined as absence of the virus for more than six months after stopping therapy. Follow-up studies of these patients show no trace of the virus in the blood or liver for over 10 years. Treatment of non-responders or recurrences — There are several options for people who do not respond or whose infection recurs after the first round of treatment. The best option depends upon what medications and doses were used initially, how well the person tolerated the previous treatment, the current liver function, and other factors. Options may include observation, retreatment with a different regimen, or enrollment in a clinical trial (see "Clinical trials" below). These issues should be discussed with a physician who specializes in liver diseases (a hepatologist) or infectious diseases. LONG-TERM MANAGEMENT OF HEPATITIS C Screening tests — People with hepatitis C who have cirrhosis should have regular screening tests for hepatocellular carcinoma, which usually includes an ultrasound examination of the liver plus a blood test (alpha fetoprotein level) every year or every other year. In addition, a procedure called an upper gastrointestinal endoscopy may be done to evaluate for esophageal varices (enlarged veins in the esophagus). Varices develop in roughly 50 percent of people with cirrhosis. Upper endoscopy uses a thin, flexible fiberoptic instrument to inspect the esophagus (food pipe) and stomach. (See "Patient information: Upper endoscopy"). Diet — No specific diet improves signs or symptoms of hepatitis C. The best advice is to eat a normal, healthy, and balanced diet. It is reasonable to take a multivitamin without iron. It is safe to drink coffee; in fact some studies suggest that coffee is good for the liver. Drinking alcohol is strongly discouraged to protect the liver from further damage. Vaccines — Anyone who is infected with hepatitis C should be vaccinated against hepatitis A and B, unless they are already known to be immune. Pneumococcal vaccine should be given every five years while influenza vaccination should be given yearly in addition to other routine vaccinations. Routine vaccinations included diphtheria and tetanus booster immunizations every ten years. Read more about adult immunizations here. (See "Patient information: Adult immunizations"). Exercise — Exercise is good for overall health and is encouraged, but it has no effect on the virus. Prescription and nonprescription drugs — Many drugs are broken down by the liver. Thus, it is always best to check with a clinician or pharmacist before starting a new prescription. Most drugs are safe for people with hepatitis C unless the liver is scarred. One important exception is acetaminophen (Tylenol); the maximum recommended dose is no more than 2000 milligrams or 2 grams per 24 hours or 500 mg every 6 hours (four times per day). Herbal medications — Many herbal products claim to "cure" or improve hepatitis C; none of these claims has been proven true. In addition, some herbal medications can seriously injure the liver. Support — Patients with hepatitis C should not underestimate the value of sharing their concerns with others who have the same diagnosis. The American Liver Foundation has helpful advice and list of support groups (www.liverfoundation.org). If you have recently discovered that you or someone you care about has hepatitis C, there are many reasons to be optimistic: Hepatitis C progresses slowly, and many people who harbor the virus will never get sick. You are not alone; about 2.7 million people in the United States have hepatitis C. Treatment is available and researchers are constantly working to develop new and better therapies. CLINICAL TRIALS — Even though combination therapy with interferon plus ribavirin cures about 50 percent of people with hepatitis C (up to 80 percent with genotype 2 and 3), many are not cured. Thus, new treatments for hepatitis C are actively being developed. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials or read about clinical trials at http://clinicaltrials.gov/.