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 has a number of causes, including alcohol abuse, large doses of certain medicines, 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 causes 8000 to 13,000 deaths each year among people who have developed advanced cirrhosis and complications related to cirrhosis. The majority of liver transplants performed in the United States are done for people with chronic hepatitis C.

This article discusses the symptoms, causes, and long-term management of hepatitis C virus (HCV). Articles about hepatitis A and B are available separately. (See "Patient information: Hepatitis A (Beyond the Basics)" and "Patient information: Hepatitis B (Beyond the Basics)".)

HEPATITIS C SYMPTOMS

When you are first exposed to the hepatitis C virus and become infected, you 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 you get treatment that cures the infection.

Many people with chronic hepatitis C have no symptoms, even if there is serious 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.

HOW DID I BECOME INFECTED WITH HEPATITIS C?

The hepatitis C virus is spread by contact with blood.

Blood and blood products — Hepatitis C was commonly spread by contaminated blood transfusions until the early 1990s, when a blood test was developed to screen blood donors for hepatitis C. As a result, the current risk of becoming infected with hepatitis C from a blood transfusion is quite small, estimated at 1 in 1.9 million. (See "Patient information: Blood donation and transfusion (Beyond the Basics)".)

Sex — The hepatitis C virus can be spread through sex, 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 1 in 1000 per year. Because of this small risk, most experts do not feel that use of condoms is necessary to prevent transmission of hepatitis C in monogamous couples.

However, if you do NOT have a stable monogamous sexual partner, you SHOULD use condoms. This is to protect you from new infections (such as HIV or other sexually transmitted diseases), as well as to protect your partner from acquiring hepatitis C.

The risk of transmitting the virus is higher in people who are infected with both hepatitis C and HIV. Condoms are recommended during sex for all people who have HIV.

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.

Pregnancy — The risk of transmitting hepatitis C to your baby during pregnancy probably depends on the level of virus in your bloodstream. 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 one in eight.

Women with hepatitis C who are pregnant or thinking about getting pregnant should speak to their doctor about these risks. (See "Vertical transmission of hepatitis C virus" and "Pregnancy in women with pre-existing chronic liver disease".)

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 you have one or more risk factors for the infection, including the following:

• 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 (a treatment for kidney failure)
• Recipient of donated blood or organs before July 1992 or blood clotting factors before 1987

Less commonly, a screening test will be done because you have symptoms of recent hepatitis infection, such as a lack of appetite, nausea, flu-like symptoms, yellow discoloration of the skin (jaundice), or pain under the ribs on the right side (where the liver is located) (figure 1).

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 1, but types 2 and 3 are also common. Type 4 is sometimes seen but is uncommon.

Liver biopsy — Liver biopsy is done as an outpatient procedure and involves taking a tiny sample of the liver tissue and looking at it under a microscope. This procedure is described in detail in a separate article. (See "Patient information: Liver biopsy (Beyond the Basics)".)

A liver biopsy is not required to diagnose hepatitis C. However, a liver biopsy is often performed if your doctor is planning to start hepatitis C treatment. Results of the biopsy can help to determine how much the disease has advanced and the long-term prognosis.

HEPATITIS C COMPLICATIONS

The hepatitis C virus causes damage to the liver, although the liver is able to repair itself to some degree. This damage occurs over many years.

In some people, scar tissue (called fibrosis) accumulates in the liver and can eventually become extensive, leading to cirrhosis. People with cirrhosis have a severely scarred liver and are at increased risk for serious complications. (See "Patient information: Cirrhosis (Beyond the Basics)".)

One of the most feared complications of cirrhosis is the development of liver cancer (called hepatocellular carcinoma). 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 develop 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 becoming infected with hepatitis C. Most others will have some inflammation in the liver but will not have significant scarring.

Researchers have tried to identify factors that increase the risk of developing cirrhosis after infection with hepatitis C. The most important include:

Drinking alcohol — People with hepatitis C who drink alcohol are at a 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.

Marijuana use — Using marijuana can lead to faster scarring of the liver in some people, and people with hepatitis C should not use marijuana.

Obesity — Obesity can lead to the deposition of fat in the liver (steatosis), which increases the risk of developing cirrhosis. Fat in the liver may also make some treatments for hepatitis C less effective.

Amount of liver damage — Increasing amounts of inflammation in the liver 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 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 hepatitis C treatment is to prevent worsening of liver disease and to get rid of the virus. (See "Overview of the management of chronic hepatitis C virus infection".)

Pegylated interferon (peginterferon) and ribavirin — The most common treatment for hepatitis C is a combination of two medicines, pegylated interferon (also called peginterferon) and ribavirin. The ribavirin treatment is taken as a pill, and the pegylated interferon is taken as a weekly shot. The recommended duration of treatment with this combination is usually 24 weeks for genotypes 2 and 3. In the past, patients with genotype 1 were all treated for 48 weeks. However, treatment for patients with genotype 1 now includes an additional medication that improves cure rates, and the length of treatment depends upon whether a person has been treated in the past and upon changes in the level of the virus in the blood during treatment. (See 'Protease inhibitors' below.)

During treatment, you will have tests to monitor the level of the virus in your blood (called the viral load). The goal of treatment is to completely get rid of the virus. Treatment may be stopped early if the virus does not respond or if you have intolerable treatment-related 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 levels of red and white blood cells, depression, and fatigue. Treatments to minimize these symptoms are available.

Protease inhibitors — Patients with genotype 1 are also treated with a protease inhibitor in addition to pegylated interferon and ribavirin. Protease inhibitors became available in May 2011, so patients treated before to this time did not receive them.

Protease inhibitors do not work if taken by themselves because the virus quickly becomes resistant. By taking the protease inhibitors with peginterferon and ribavirin, resistance is much less likely. Protease inhibitors are pills and include boceprevir (brand name: Victrelis^TM) and telaprevir (brand name: Incivek^TM). These medications are used only for patients with genotype 1 and significantly increase cure rates in patients with genotype 1.

Common side effects of protease inhibitors include low blood counts (anemia) and rashes.

Should I be treated? — The decision to have 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; you and your doctor should discuss the potential risks and benefits of treatment before you begin.

• Treatment with peginterferon is not recommended for people whose depression is not well controlled. People with uncontrolled depression are at risk for committing suicide during treatment. Interferon can be used in people with well-controlled depression.
• Ribavirin should not be used by women who are pregnant, thinking about getting pregnant, or unable to use a reliable form of birth control, because it can cause severe birth defects. In addition, protease inhibitors (boceprevir and telaprevir) decrease how well birth control pills work, so women who are also taking a protease inhibitor need to use a second reliable form of birth control. Likewise, ribavirin should not be used by men whose partners are trying to become pregnant or men who are not using a reliable form of birth control. Ribavirin can damage the sperm of men who use the drug and can lead to birth defects, even if the father is the only parent taking the drug. Also, women and men should continue to use a reliable form of birth control for six months after stopping ribavirin.
• People with underlying autoimmune disorders (eg, lupus, rheumatoid arthritis) might have an increased risk of treatment-related complications related to peginterferon.
• Certain groups of people develop liver scarring at a slow rate. In this group, it is reasonable to delay treatment until fibrosis progresses, liver function test results become abnormal, or clinical trials prove that earlier treatment is beneficial. This group includes people who:

• Have normal liver function test results (ALT)
• Were infected with hepatitis C before age 35 years
• Are female
• Do not drink alcohol
• Have no or minimal scarring on liver biopsy

Cure — The chance of being cured of hepatitis C depends in part on the type of hepatitis C virus (ie, the genotype). Overall, the chance is approximately 70 to 80 percent for people with genotype 1 who take all three drugs (peginterferon, ribavirin, and a protease inhibitor), and 80 percent or more with genotypes 2 and 3. The chance of cure is 50 to 70 percent for genotype 4.

To determine if you are cured, you must wait six months after finishing treatment. Cure is defined as having no detectable levels of the virus for more than six months after stopping treatment. Follow-up studies of these people have shown no trace of the virus in the blood or liver for over 10 years.

If hepatitis C does not respond or comes back — There are several options for people whose viral levels do not drop or whose infection comes back after the first round of treatment. The best option depends upon what medicines you took before, how well you tolerated the previous treatment, your current liver function, and other factors.

Options include watching and waiting, trying a different treatment regimen, or enrolling in a clinical trial. (See 'Clinical trials' below.) Discuss your options with a doctor who specializes in liver diseases (a hepatologist) or infectious diseases.

LONG-TERM MANAGEMENT OF HEPATITIS C

Screening tests — If you have hepatitis C and cirrhosis, you should have screening tests for liver cancer. These tests usually include an ultrasound of the liver twice a year. Some doctors also check a blood test (to measure a protein called alpha fetoprotein level).

In addition, a procedure called an upper endoscopy might be done to look 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: Screening for esophageal varices (Beyond the Basics)".)

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 he or she is already immune. A blood test can tell if you are immune.
• A vaccine that helps to prevent pneumonia is recommended. (See "Patient information: Pneumonia prevention (Beyond the Basics)".)
• Influenza (flu) vaccination is recommended every year, usually in the fall. (See "Patient information: Influenza prevention (Beyond the Basics)".)
• Routine vaccines are also recommended, including diphtheria and tetanus booster every 10 years. Read more about adult vaccines separately. (See "Patient information: Adult vaccines (Beyond the Basics)" and "Immunizations for patients with chronic liver disease".)

Exercise — Exercise is good for overall health and is encouraged, but it has no effect on hepatitis C virus.

Prescription and nonprescription medicines — The liver breaks down many medicines, including prescription and nonprescription medicines, supplements, and herbs. Thus, it is always best to check with your doctor or pharmacist before starting a new medicine. Most medicines are safe for people with hepatitis C, unless the liver is scarred.

One important exception is acetaminophen (Tylenol®); the maximum recommended dose is 500 milligrams every six hours. Some medicines, such as cold medicines, may contain acetaminophen, so it is important to always check ingredient labels.

You should completely avoid ibuprofen (sold as Advil®, Motrin®, and store brands), naproxen (sold as Aleve® and store brands), and aspirin (sold as Bufferin®, Excedrin®, and store brands).

Daily use of marijuana has been associated with worsening liver disease and is not recommended, particularly for people with hepatitis C.

Herbal medicines — Many herbal products claim to "cure" or improve hepatitis C; none of these claims has been proven true. In addition, some herbal medicines can seriously injure the liver.

Support — Sharing your concerns with others who have the same diagnosis can help you learn to live with hepatitis C. The American Liver Foundation has helpful advice and a 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 are infected 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 peginterferon plus ribavirin (and protease inhibitors in people with genotype 1) cures up to 80 percent of people with hepatitis C, some are not cured. Thus, new treatments for hepatitis C are actively being developed.

A clinical trial is a carefully controlled way to study how well new treatments or new combinations of known therapies work. Ask for more information about clinical trials or read about clinical trials at http://clinicaltrials.gov/.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient information: Hepatitis C (The Basics)
Patient information: Latest medicines for hepatitis C (The Basics)
Patient information: Vaccines when you have hepatitis C (The Basics)
Patient information: Cirrhosis (The Basics)
Patient information: Blood or body fluid exposure (The Basics)
Patient information: Treatment for hepatitis C (The Basics)
Patient information: Liver transplant (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient information: Hepatitis A (Beyond the Basics)
Patient information: Hepatitis B (Beyond the Basics)
Patient information: Blood donation and transfusion (Beyond the Basics)
Patient information: Liver biopsy (Beyond the Basics)
Patient information: Cirrhosis (Beyond the Basics)
Patient information: Screening for esophageal varices (Beyond the Basics)
Patient information: Pneumonia prevention (Beyond the Basics)
Patient information: Influenza prevention (Beyond the Basics)
Patient information: Adult vaccines (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Characteristics of the hepatitis C virus
Clinical manifestations and natural history of chronic hepatitis C virus infection
Clinical manifestations, diagnosis, and treatment of acute hepatitis C in adults
Diagnosis of hepatitis C virus infection in patients on dialysis
Epidemiology and etiologic associations of hepatocellular carcinoma
Epidemiology and transmission of hepatitis C virus infection
Epidemiology, natural history, and diagnosis of hepatitis C in the HIV-infected patient
Extrahepatic manifestations of hepatitis C virus infection
Hepatitis C and alcohol
Hepatitis C and transfusion: A 'lookback' primer
Hepatitis C virus infection and renal transplantation
Hepatitis C virus infection in patients on maintenance dialysis
Approach to patients with chronic hepatitis C virus infection and normal serum aminotransferases
Investigational therapies for hepatitis C virus infection
Liver transplantation for hepatitis C virus infection
Management of the side effects of peginterferon and ribavirin being used for treatment of chronic hepatitis C virus infection
Mechanism of action and efficacy of peginterferon for the treatment of chronic hepatitis C virus infection
Vertical transmission of hepatitis C virus
Pregnancy in women with pre-existing chronic liver disease
Mechanism of action and efficacy of ribavirin for the treatment of chronic hepatitis C virus infection
Screening for and diagnosis of chronic hepatitis C virus infection
Mechanism of action and efficacy of standard interferon alfa for the treatment of chronic hepatitis C virus infection
Overview of the management of chronic hepatitis C virus infection
Treatment of hepatitis C virus infection in the HIV-infected patient
Immunizations for patients with chronic liver disease
Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4
Predictors of a sustained virologic response following treatment with peginterferon and ribavirin for chronic hepatitis C virus infection

The following organizations also provide reliable health information:

• National Library of Medicine

     (www.nlm.nih.gov/medlineplus/hepatitisc.html)

• National Institute of Diabetes and Digestive and Kidney Diseases

     (http://digestive.niddk.nih.gov/ddiseases/pubs/hepc_ez/)

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