About all

What is hep c caused by: Hepatitis C – What Is Hep C? Symptoms, Causes, Diagnosis, Treatment

Содержание

Hepatitis C | Boston Children’s Hospital

What is hepatitis C?

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). For a small number of people, hepatitis C, sometimes referred to as hep C, is a mild illness that clears on its own in a matter of weeks. In most cases, hepatitis C becomes a chronic condition that may progress to chronic liver failure or liver cancer.

According to the Centers for Disease Control, an estimated 3.5 million people in the U.S. are living with hepatitis C and there are more than 40,000 new cases of hepatitis C in the country each year. Because most children and adults with hepatitis C do not have specific symptoms, many do not realize they are infected.

HCV spreads through the blood. The most common way children become infected with hepatitis C is during the birth process if they are born to a mother with the virus. Researchers do not believe a mother can pass the virus to a fetus in the womb. Older children can become infected through injection drug use or other unsafe needle practices.

There are two phases of hepatitis C: acute and chronic.

  • Acute hepatitis C is a mild illness that children and adults experience within the first six months of infection. As many as a quarter of children infected with HCV clear the virus on their own without any treatment during the acute phase.
  • Chronic hepatitis C is a serious, long-term infection that develops when the virus remains in the blood. Over the course of decades, chronic hepatitis C can damage the liver to the point that a liver transplant becomes necessary.

What are the symptoms of hepatitis C?

The majority of children with acute or chronic hepatitis C have no symptoms. As they age, the virus can cause ever-greater damage to the liver. In later stages, symptoms of hepatitis C may include:

  • tiredness
  • itchy skin
  • dark urine
  • muscle soreness
  • nausea
  • loss of appetite
  • stomach pain
  • jaundice

What causes hepatitis C?

Hepatitis C is caused by infection with the hepatitis C virus (HCV). The virus is passed from person to person through contact with blood infected with HCV. Mothers infected with HCV can pass the virus on to their children at birth. While this is the most common way for a child in the United States to become infected with HCV, it is unusual. A mother infected with HCV has about a 5 percent (1 in 20) chance of passing the virus to her child. About a quarter of infants infected with the virus clear it without treatment by the time they reach age 3.

Older children, especially teenagers, can contract HCV through injection drug use. The virus can spread through other forms of contact with potentially infected blood (e.g., needle stick in a health care setting). Tattoos and body piercings appear to be safe as long as they are done with sterile instruments.

What is the liver, and what does it do?

The liver is the second largest organ in the body and it helps the body in many ways:

  • the liver produces proteins that allow blood to clot normally, transport oxygen and support the immune system
  • it produces bile, a substance that helps digest food
  • it stores extra nutrients
  • it helps clean the bloodstream of harmful substances
  • it helps control blood sugar and cholesterol levels

How does hepatitis C affect the liver?

When infected, the liver becomes inflamed, which may cause the healthy, soft tissues in the liver to harden and scar. If not stopped, inflammation and scarring can lead to serious liver diseases such as cirrhosis of the liver or liver tumors. If the damage is severe enough, the liver may not perform all of its functions normally.

How we care for hepatitis C

The Center for Childhood Liver Disease at Boston Children’s Hospital is one of the leading centers in the world for the care of children with hepatitis C. The center’s director, Maureen Jonas, MD is a national leader in the care, diagnosis and treatment for children with viral hepatitis. Dr. Jonas, along with her team, wrote the clinical guidelines that shape the way pediatric GI specialists and pediatricians around the country treat hepatitis C.

In addition to the standard treatments, our team of certified pediatric hepatologists is also at the forefront of treatment research, treating adolescents with newly approved treatments for adults and conducting clinical trials to help make them available to children as young as 3 years of age.

Our areas of innovation for hepatitis

Liver biopsies provide a great deal of information about the extent of damage in a child’s liver, but the procedure is invasive and can be both painful and risky. Researchers at Boston Children’s use an ultrasound-based imaging technology called FibroScan that may be able to help doctors assess liver scarring without a liver biopsy.

What Is Hepatitis C? Symptoms, Causes, Diagnosis, Treatment, and Prevention

Favorite Orgs for Essential Hep C Info

Hepatitis C Association

This organization is dedicated to educating the public about all aspects of the hepatitis C virus. The site presents the latest hep C news and events, as well as resources for those without insurance. The association is the managing partner for the Help4Hep toll-free support and resource line at 877-435-7443.

Hepatitis Foundation International

We like the foundation’s dedication to promoting healthy living habits for people with hep C, especially those that can benefit the liver. The group produced the DVD Live-R-Die to educate young adults about binge drinking, drug abuse, and other liver-damaging behaviors.

American Liver Foundation

The viral infection hep C can take its toll on the liver. This foundation supports education, advocacy, and research for the prevention of liver disease. It has a nationwide network of offices ready to help individuals with any related questions.

United Network for Organ Sharing

One of the most common reasons for liver transplantation in the United States is organ failure due to hep C. This network serves as a comprehensive resource for those exploring liver transplant options, organ donation, and medical advances. Profiles of people who have had transplants and connections to support groups are available.

Favorite Hep C Financial Resources

NeedyMeds

This nonprofit devotes its energies to help people afford healthcare and medication. It offers a free drug discount card that extends a discount of up to 80 percent at more than 65,000 pharmacies nationwide. Anyone (and their family and friends) can use the card regardless of income level or insurance status.

RxAssist

RxAssist guides people to free or low-cost medicine programs. Visitors to the website can type a drug’s name into the search tool to find patient assistance programs that can help with costs. The group also gives a wealth of information on various drug discount cards.

Partnership for Prescription Assistance

Plug the name of a drug into this free service and it searches for patient assistance programs that will help pay for the medication. It also has a great tool to help find free or low-cost clinics near you.

Patient Advocate Foundation Co-Pay Relief

Those who qualify can get awards of up to $15,000 a year to pay for hep C treatment. Eligibility requirements include an income below 400 percent of the federal poverty guidelines. In addition, the foundation presents links to other financial resources and pharmaceutical assistance programs.

Favorite Hep C Alternative Medicine Resource

National Center for Complementary and Integrative Health (NCCIH)

Although hep C can be successfully treated with modern medicine, many people turn to dietary supplements with the goal of curing their illness. The most commonly used is silymarin (milk thistle). Although the NCCIH says that no supplement is effective for hep C, the center provides the latest scientific data on a range of products, including probiotics, zinc, licorice root, and colloidal silver.

Favorite Hep C Support Networks

Hepatitis Central

This site gives a very detailed listing of live hep C support groups in cities across the country. Meetings are often for those undergoing treatment or people who have questions about treatment. A database that searches by ZIP code makes it simple to find a support group near you.

+supportgroups

This online support network has about 34,000 members at latest count. People can anonymously post about all concerns related to the disease, including issues about stigma, depression, and care.

Favorite Hep C Online Magazine and Blogs

Hep Mag

Hep Mag publishes current articles about people living with hep C, plus it offers a forum for people to ask questions and share stories and information with other readers. The online magazine also features a blog on funding, cures, liver disease, and related matters.

Feedspot

Feedspot, a feed compiling news from online sources, lists 20 top blogs and websites to explore concerning hepatitis C. Readers can connect with one another and find out about the latest drug research developments.

Favorite Hep C App

HepCure

This web-based app for people infected with the hepatitis C virus offers health management, decision support, and regular educational webinars. Developed in part by the Icahn School of Medicine at Mount Sinai in New York City, the app also gives providers a way to track their hep C patients.

Favorite Sites for Hep C Products

Hep C can now be cured with an 8- to 12-week course of medication. The pharmaceutical companies that produce these drugs all present useful information and, in some cases, details on how to get the medication at a lower cost. Here are the latest hep C drugs approved by the FDA:

Additional reporting by Laura McArdle.

How hepatitis C damages the liver

Hepatitis C causes damage to the liver mainly in the form of inflammation, which then leads to scarring or fibrosis.

Hepatitis C results in the death of liver cells. It is uncertain whether the virus kills the cells or if it is the immune system’s response to invasion by the virus. At present it is thought that it is probably a combination of the two, but that the immune system’s response is what causes the most damage. The death of liver cells triggers the dispatching of inflammatory cells to the affected area. Inflammation leads to the enlargement of the liver (hepatomegaly) in over 60% of people infected with hepatitis C and can cause the fibroelastic sheath (Glisson’s capsule) surrounding the liver to stretch, which may be the cause of pain in the liver area.

Inflammation begins the processes that lead to fibrosis. Fibrosis is not a disease but is a condition caused by the body’s response to liver damage. Inflammation triggers a reaction by a group of cells in the liver called stellate (literally star-shaped) or fat cells. When the liver is functioning normally stellate cells store fat and vitamin A in the liver. They also help regulate the flow of blood through the liver. But when the liver is inflamed by the presence of hepatitis C, a reaction occurs amongst different liver cells. This leads stellate cells to dispense with vitamin A, altering their function.

Infected and inflamed liver cells release chemical signals called ‘cytokines’. These activate leukocytes (white blood cells) from outside the liver which travel to the area of infection. On arrival they team up with Kupffer cells (specialised white blood cells that neutralise and remove bacteria, viruses, parasites and tumour cells from the liver) and produce further chemical signals. These signals cause stellate cells to begin producing and laying down collagen fibres in the extra cellular matrix, which is the area between the cells.

Collagen is a fibrous protein which is fundamental to the formation of scar tissue. The body’s use of collagen in an area of injury is an attempt to limit the spread of infection to other cells. As an infection or injury resolves, the collagen matrix enclosing the injury is normally dissolved. The activated stellate cells then die off, allowing the tissue to return to normal.

In a chronic illness such as hepatitis C the collagen matrix grows too fast and cannot be properly dissolved. This results in a build up of scar tissue around cells. Liver cells lose vital access to the blood carrying nutrients and oxygen and so die. A vicious circle results in which inflammation and fibrogenic cells stimulate each other leading to increased fibrosis.

Free Radicals and Fibrosis

A further possible cause of fibrosis is due to damage by free radicals. Free radicals are highly reactive chemical substances. They are the by-product of a cell’s normal reactions such as energy generation and the breakdown of fats. During these reactions oxygen is transformed into the free radical superoxide. Normally cells have mechanisms for protecting themselves from the dangers of free radicals. When too many are generated, or if they are not controlled properly, there is a danger that they will cause cell and tissue damage.

Free radicals are of concern for people with hepatitis C for a number of reasons:

  • Chronic liver inflammation may lead to over-production of free radicals within the liver.
  • There is evidence that free radicals play a role in liver fibrosis. Free radicals can chemically alter fat in the body. This is called lipid peroxidation. The free radicals attack the cell membrane and can injure and eventually kill cells. If this happens to liver cells, this will lead to fibrosis.

If the liver function is already impaired and this has led to an overload of iron, the free radicals may interact with the iron causing further damage.

The liver is famed for its ability to regenerate, so why doesn’t liver regeneration prevent liver damage in hepatitis?

Hepatitis C is usually characterised by a degeneration of the liver through slow but progressive scarring. The liver has two responses to harmful agents which are capable of damaging its cell structure. Either there is regeneration with complete restoration of the liver structure and function or there is sustained scarring of liver tissue leading to damage. When the liver is damaged by a single strong injury, regeneration is highly likely even if a large area is affected. But if the injury is repetitive as is the case with hepatitis C infection – the liver cannot effectively cope. It does not have the time and space to heal and regenerate.

Hepatitis C | UC San Diego Health

Hepatitis C is a liver infection caused by the hepatitis C virus (HCV). Hepatitis C is spread through contact with blood from an infected person. It is often caused by sharing needles or other items used to prepare and inject drugs.

For some people, hepatitis C is a short-term illness, but for many it becomes a long-term, chronic infection that can lead to serious conditions such as
cirrhosis and
liver cancer.

More about hepatitis C

For the most experienced and customized care, turn to our team of liver experts (hepatologists),
infectious disease experts, and
specialty pharmacists. Our collaborative efforts improve quality of life for many patients with difficult cases, including those co-infected with HIV.

UC San Diego Health also is a leader in the development of new, more effective treatments with cure rates of over 90 percent.

Learn About Hepatitis C Clinical Trials

Diagnosis for Hepatitis C

Once you’ve been infected with hepatitis C, the virus stays in your body for life. Diagnosing an existing hepatitis C infection requires several blood tests.

Blood tests used in hepatitis C diagnosis:

  1. Hepatitis C antibody test – A blood test that shows whether you’ve
    ever had hepatitis C. If this test comes back positive, your doctor will follow up with a viral load test.
  2. Viral load test – A test that measures ribonucleic acid (RNA) in the blood. Viral RNA signals there is virus in your blood.
  3. Genotype – If the viral load test is positive, you’ll be given a blood test to determine which hepatitis strain (genotype) you have. There are currently six known genotypes. Knowing the genotype is essential as it determines which treatment you’ll receive.

It’s important that you get tested for hepatitis C often if you’re at higher risk of contracting the disease.
See if you should get tested and learn more about
hepatitis C diagnosis.

Liver Damage

Once HCV infection is confirmed, the next step is determining the extent of damage. Non-invasive tests such as a CT scan, MRI or ultrasound can provide detailed images of the liver. A liver biopsy may be necessary to determine the degree of liver damage.

Phases of Hepatitis C

Acute Phase

The six month period of time after hepatitis C first enters your body is called the acute phase. Approximately 30 percent of people are able to clear the disease from their body naturally during this time.

During the acute phase, most people experience no symptoms at all, or they develop non-specific symptoms such as appetite loss or fatigue. Only about 20 percent of people who first get the virus develop jaundice.

Since symptoms are usually vague, most people do not know to seek medical help.

Reinfection

It’s important to note that if you are infected with hepatitis C and successfully clear the virus, you are not protected against reinfection.

Chronic Phase

The 70 percent of people whose bodies are unable to fight off the hepatitis C virus during the first six months of infection enter the chronic phase (long-term infection).

The chronic phase is diagnosed after the infection is identified on at least two different hepatitis C virus (HCV) RNA tests. The chance of your body naturally clearing the virus during the chronic phase is highly unlikely.

Nearly 25 to 30 percent of people who reach the chronic phase of hepatitis C will get cirrhosis.

Treatment for Hepatitis C

New treatments can clear hepatitis C at every stage. Of course, the disease causes damage over time, so it’s best treat it as early as possible.

At UC San Diego Health, we treat hepatitis C with antiviral medications. The type of medications you receive is based on the strain (genotype) of hepatitis C you have. Treatment length depends on severity of condition and treatment response, and can range anywhere from 8 to 24 weeks.

Antiviral medications stop the enzymes produced by hepatitis C. This helps to:

  • Prevent and slow the development of scarring in the liver.
  • Reduce the chances of developing liver cancer and cirrhosis.
  • Clear the virus from the bloodstream.

Antiviral Medications

In the past, the only treatment for hepatitis C was a combination of interferon alfa (self-injected) and ribavirin (pill). This regimen was often poorly tolerated and had suboptimal cure rates.

Depending on your genotype, new interferon-free treatments are available with cure rates over 90 percent.

Antiviral drugs used to treat hepatitis C:

Hepatitis C Genotype

One of the factors that affects the type of treatment you receive for your hepatitis C is your genotype.

There are 6 different genotypes:

Genotype 1: This type of hepatitis C is found worldwide. It accounts for roughly 70% of all hepatitis C cases in U.S.

Genotypes 2, 3: This type of hepatitis C is found worldwide. It accounts for roughly 30% of all hepatitis C cases in U.S.

Genotype 4: This type of hepatitis C is most common in Africa and the Middle East.

Genotype 5: This type of hepatitis C is most common in South Africa.

Genotype 6: This type of hepatitis C is most common in Southeast Asia.

Hepatitis C genotypes 1, 2 and 3 are the most common genotypes found in the U.S.

In the past, treatment with interferon and ribavirin was most effective in patients with genotype 2 and 3. But thanks to the development of new direct antiviral drugs or DAAs, treatment success has increased dramatically for all genotypes.

Factors That Affect Treatment

In addition to genotype, several factors impact the success of treatment and should be considered.

Treatment success is more likely if you:

  • Are young
  • Have a low amount of virus in your blood (known as hepatitis C viral load)
  • Have moderate liver scarring
  • Have a shorter length of time with infection (before fibrosis has occurred)

Lifestyle factors also play a role. Make sure to:

  • Avoid alcohol
  • Maintain a healthy weight
  • Exercise regularly
  • Eat healthfully

Monitoring Progress

Your level of hepatitis C virus will be periodically checked through the course of treatment. Expect to see your provider regularly for evaluation while on antiviral medications to monitor for side effects and response to treatment. 

Liver Transplant

Untreated hepatitis C can eventually develop into end-stage liver disease (decompensated cirrhosis), in which case liver transplantation is necessary.

Liver transplantation
does not cure hepatitis C. If your infection is still present at the time of transplant, the new liver will become infected. However, treatment can be started after you recover from surgery.
More about our Liver Transplant Program

Related Services

Hepatitis C | Cedars-Sinai

Not what you’re looking for?

What is hepatitis C?

Hepatitis C is a liver disease that
is caused by the hepatitis C virus. There are several types of hepatitis C viruses.
Hepatitis C is one type of hepatitis.

Hepatitis is a redness and swelling
(inflammation) of the liver that sometimes causes lasting damage. The liver isn’t
able
to work the way it should.

Hepatitis C can be short-term
(acute) or long-term (chronic):

  • Acute hepatitis C. When people first get hepatitis C, this
    a brief infection that lasts 6 months or less. Some people are able to fight the
    infection at this stage and become cured. But most people go on to develop a chronic
    infection where the virus remains in their body.
  • Chronic hepatitis C. This is a long-lasting infection that
    happens when your body can’t get rid of the virus. It causes long-term liver
    damage.

It is rare to recover from
hepatitis C infection, but some people are able to clear the virus from their body.
Most
people with hepatitis C have the virus for the rest of their life. Most people with
hepatitis C have no or only mild symptoms, so they don’t always know they are
infected.

Talk with your healthcare provider
about getting tested for hepatitis C. Experts recommend all people over age 18 get
tested at least once in a lifetime. Testing more often is advised for people with
risk
factors.

What causes hepatitis C?

Hepatitis C is caused by infection
from the hepatitis C virus. Like other viruses, hepatitis C is passed from person
to
person. This happens when you have contact with an infected person’s blood.

You may get the virus if you:

  • Share needles used for illegal
    drugs
  • Share drug-snorting equipment
  • Have unprotected sex with someone who
    has hepatitis C
  • Get a tattoo with infected
    equipment

 Babies may also get the disease if
their mother has the hepatitis C virus.

Who is at risk for hepatitis C?

Anyone can get hepatitis C by
having contact with the blood of someone who is infected with the virus.

But some people are at higher risk
for the disease. They include:

  • Children born to mothers who are
    infected with hepatitis C
  • People who have jobs that involve
    contact with human blood, body fluids, or needles
  • People who have a blood-clotting
    disorder, such as hemophilia, and received clotting factors before 1987
  • People who need dialysis treatment for
    kidney failure
  • People who had blood transfusions,
    blood products, or organ transplants before the early 1990s
  • People who take IV (intravenous)
    drugs
  • People who have unprotected
    heterosexual or homosexual sex
  • People with HIV
  • People in prison

What are the symptoms of hepatitis C?

Many people with hepatitis C don’t
know they have it. In most cases, people who are infected with hepatitis C may not
show
any symptoms for several years.

It is still possible to pass the
virus to someone else if you have hepatitis C but do not have any symptoms.

Each person’s symptoms may vary.
Some of the most common symptoms include:

  • Loss of appetite
  • Extreme tiredness (fatigue)
  • Nausea and vomiting
  • Stomach pain
  • Yellowing of the skin and eyes
    (jaundice)
  • Fever
  • Diarrhea
  • Dark yellow urine
  • Light-colored stools
  • Muscle and joint pain

Hepatitis C symptoms may look like
other health problems. Always see your healthcare provider to be sure.

How is hepatitis C diagnosed?

Your healthcare provider will give
you a physical exam and ask about your past health. They will also do a blood test
to
see if you have hepatitis C.

If your provider thinks you have long-term (chronic) hepatitis C,
they may do other tests to see how well your liver is working. These tests may include:

  • More blood tests
  • Special ultrasound or other imaging
    test
  • Liver biopsy. For this, the doctor
    takes a small tissue sample from your liver. The sample is checked under a microscope
    to see what type of liver disease you have and how severe it is.

How is hepatitis C treated?

Your healthcare provider will
monitor you closely and discuss treatments with you. Hepatitis C is usually treated
because it often becomes a long-term or chronic infection. Hepatitis C can be cured.
Your treatment may include taking one or more medicines for several months. Your
symptoms will be closely watched and managed as needed.

If severe liver damage takes place,
you may need a liver transplant.

What are possible complications of hepatitis C?

Many people with hepatitis C
develop chronic liver disease. You could need a liver transplant. Hepatitis C is the
most common cause of liver transplants in the U.S.

Liver failure can lead to
death.

The risk for liver cancer is higher
in some people with hepatitis C.

What can I do to prevent hepatitis C?

There is no vaccine to prevent
hepatitis C. But you can protect yourself and others from getting infected by:

  • Making sure any tattoos or body
    piercings are done with sterile tools
  • Not sharing needles and other drug
    materials
  • Not sharing toothbrushes or
    razors
  • Not touching another person’s blood
    unless you wear gloves
  • Using condoms during sex

Key points about hepatitis C

  • Hepatitis C is a liver disease caused
    by infection from the hepatitis C virus.
  • The virus spreads when you have
    contact with an infected person’s blood or body fluid.
  • Anyone can get hepatitis C, but some
    people are at higher risk. Ask your healthcare provider about your level of risk and
    getting tested.
  • You may not have any symptoms for
    years.
  • The risk for liver cancer is higher in
    people with hepatitis C.
  • Treatment may include taking one or
    more medicines for several months.

Next steps

Tips to help you get the most from
a visit to your healthcare provider:

  • Know the reason for your visit and
    what you want to happen.
  • Before your visit, write down
    questions you want answered.
  • Bring someone with you to help you ask
    questions and remember what your provider tells you.
  • At the visit, write down the name of a
    new diagnosis and any new medicines, treatments, or tests. Also write down any new
    instructions your provider gives you.
  • Know why a new medicine or treatment
    is prescribed and how it will help you. Also know what the side effects are.
  • Ask if your condition can be treated
    in other ways.
  • Know why a test or procedure is
    recommended and what the results could mean.
  • Know what to expect if you do not take
    the medicine or have the test or procedure.
  • If you have a follow-up appointment,
    write down the date, time, and purpose for that visit.
  • Know how you can contact your provider
    if you have questions.

Medical Reviewer: Jen Lehrer MD

Medical Reviewer: Marianne Fraser MSN RN

Medical Reviewer: L Renee Watson MSN RN

© 2000-2021 The StayWell Company, LLC. All rights reserved. This information is not intended as a substitute for professional medical care. Always follow your healthcare professional’s instructions.

Not what you’re looking for?

Hepatitis C

Diagnosing Hepatitis C

While the hepatitis C virus (HCV) can be detected in blood between one to three weeks after the initial exposure, 80 percent of people with hepatitis C have no symptoms and go undiagnosed. Within approximately 50 days, most will begin to develop liver cell injury, although they will be asymptomatic (symptom-free).

About 15 percent of those exposed to HCV will clear their system of the virus within six months.

The remaining 85 percent will develop some level of chronic hepatitis C. Over time, this can cause serious liver damage, although the rate of progression can vary significantly from individual to individual.

Symptoms of hepatitis C

Symptoms may include:

  • Fatigue
  • Loss of appetite
  • Jaundice (yellowing of the eyes and skin)
  • Abdominal pain
  • Aches and pains
  • Itching
  • Hives
  • Joint pain
  • Darker colored urine
  • Loose, light-colored stool
  • Nausea
  • Vomiting

And, cigarette smokers may suddenly dislike the taste of cigarettes.

In addition to some of the above symptoms, chronic hepatitis C infection may also cause:

  • Weakness
  • Severe fatigue
  • Loss of appetite

Testing for hepatitis C

To diagnose hepatitis C, your doctor will ask about your symptoms and medical history, and perform a physical exam.

Your doctor will also want to discuss your risk factors for hepatitis C.

Tests may include:

  • Blood tests — to look for hepatitis C antibodies (proteins that your body has made to fight the hepatitis C virus) or genetic material from the virus
  • Liver biopsy — removal of a sample of liver tissue to be examined

Complications of hepatitis C

Serious complications of hepatitis C infection include:

  • The possibility that the infection will become chronic, leading to progressive liver failure
  • Increased risk of liver cancer
  • Cirrhosis

Within about 20 years of exposure, approximately 20 percent of individuals develop cirrhosis, which leads to end-stage liver disease. Alcohol use can dramatically speed the onset of cirrhosis.

Hepatitis C – Symptoms, Diagnosis and Treatment