Patient information: Hepatitis C

HEPATITIS C OVERVIEW

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 article 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 "Patient information: Hepatitis B".)

HEPATITIS C SYMPTOMS

When you are first exposed to the hepatitis C virus and become infected, you 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 you are 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 your infection is under control.

HOW DID I BECOME INFECTED WITH HEPATITIS C?

The hepatitis C virus is spread by contact with blood. Thus, if you have hepatitis C, you should avoid activities that could expose other people to your blood. Examples include sharing a toothbrush, nail clippers, razors, and needles (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 hepatitis C 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. 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 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.

Transmission during pregnancy — The risk of transmitting hepatitis C to your baby during pregnancy may depend upon the level of virus in your 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. (See "Perinatal transmission of hepatitis C virus" and "Pregnancy in women with underlying 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 [1]:

• 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
• 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, 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 liver 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 article. (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 (picture 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 (picture 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). 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 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 becoming infected with hepatitis C. The most important include:

Consuming 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.

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 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 hepatitis C treatment is to prevent worsening of liver disease. As mentioned above, about 20 percent of people will develop cirrhosis 20 years after becoming infected. Therefore, people who develop hepatitis C while 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. (See "Treatment of chronic hepatitis C virus infection: Recommendations for adults".)

Pegylated interferon and ribavirin — The most common treatment for hepatitis C is a combination of two medications, pegylated interferon and ribavirin. The treatment is taken as a pill. 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 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, 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; you and your 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 before the age of 35 years, are female, do not drink alcohol, and have no or minimal fibrosis on liver biopsy may develop hepatic fibrosis at a slow rate. In these peoplle, 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 of hepatitis C 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, you 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 people have shown 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 you tolerated the previous treatment, your current liver function, and other factors.

Options may include watching and waiting, 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: Screening for esophageal varices".)

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 you are already immune. Pneumococcal vaccine is recommended every five years. Influenza (flu) vaccination should be given yearly, usually in the fall. Routine vaccinations are also recommended, including diphtheria and tetanus booster immunizations every ten years. Read more about adult immunizations separately. (See "Patient information: Adult immunizations" 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 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).

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

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 — 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 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 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/.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Hepatitis A
Patient information: Hepatitis B
Patient information: Blood donation and transfusion
Patient information: Liver biopsy
Patient information: Cirrhosis
Patient information: Screening for esophageal varices
Patient information: Adult immunizations

Professional Level Information:
Characteristics of the hepatitis C virus
Clinical features and natural history of hepatitis C virus infection
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
Hepatitis C virus infection in patients with normal serum aminotransferases
Investigational therapies for hepatitis C virus infection
Liver transplantation for hepatitis C virus infection
Management of treatment induced side effects for chronic hepatitis C
Pegylated interferon in the treatment of chronic hepatitis C virus infection
Perinatal transmission of hepatitis C virus
Pregnancy in women with underlying chronic liver disease
Ribavirin in the treatment of hepatitis C virus infection
Screening for and diagnostic approach to hepatitis C virus infection
Standard interferon in the treatment of chronic hepatitis C virus infection
Treatment of chronic hepatitis C virus infection: Recommendations for adults
Treatment of hepatitis C virus infection in the HIV-infected patient
Immunizations for patients with chronic liver disease

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

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

• Centers for Disease Control

      (www.cdc.gov)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (www.niddk.nih.gov)

• American Gastroenterological Association

      (www.gastro.org)

• American Liver Foundation

      (www.liverfoundation.org)

[1-4]