Written By: Teri Gottlieb
Treating Hepatitis C
Treatment for HCV is NOT always necessary. Just because you have received a diagnosis of Hepatitis C does not mean that you need to rush into treatment. You may not need to treat at all. In all actuality, only about 20% of the people who have HCV will go on to develop any serious liver problems. If you do not have any liver abnormalities or if they are very slight, you might not need treatment because your risk of future liver problems may be very low. Your doctor may decide that all that is needed is for you to have yearly follow-up blood tests to monitor your situation. Every case is different. Please discuss this with your physician. Having an open and honest conversation with your doctor will help you feel comfortable with any treatment decision that you have to make.
Can Hepatitis C Be Cured?
YES! The word cured has been used in conjunction with Hepatitis C since 2010. Until that time, there wasn't enough data to support that when the virus was cleared, it stayed cleared. Because of that, the word "remission" was used. In 2010, there were ten years worth of data to prove that the virus did, in fact, stay gone once it was eliminated. The success of Hepatitis C treatment is defined as an undetectable HCV viral load test six months after completing HCV treatment. This milestone is called a sustained virological response or SVR. Once you achieve SVR you are considered to be cured.
There are three other terms that are used throughout the course of some forms of treatment that are important in predicting whether or not a person is likely to achieve an SVR status and in one instance, whether treatment needs to end after the first 12 weeks. These are the terms.
RVR or Rapid Virological Response - This is an undetectable HCV level at the completion of the first four weeks of treatment.
EVR or Early Virological Response - This is an undetectable HCV level at the completion of 12 weeks of treatment.
ETR or End of Treatment Response - This is an undetectable HCV level at the completion of treatment.
With the exception of ETR, these terms are used in conjunction with a treatment that is just using Peg-Interferon and Ribavirin. The EVR test at 12 weeks is important in that it decides the direction of treatment. If the patient has not achieved EVR after 12 weeks, all indications are that this form of treatment will not work at all. At this time, with a detectable viral load, treatment is most always terminated.
Antiviral Medications - Current Medication Protocols and Standards of Care
Currently, several pharmaceutical companies are in the midst of creating new drugs for the treatment of Hepatitis C. Two of these drugs are already on the market but are not yet approved for all genotypes. Within the next year, we will see major advances in treatment that will render some of the current treatments obsolete. The new drugs are designed to deliver fewer side-effects, shorten the length of treatment and increase the number of people who will respond. The goal of HCV treatment is to clear the virus. Currently, this is done with a combination of drugs. The standard of care and length of treatment for Hepatitis C depends on the genotype of the patient along with the patient's response during the initial stages of therapy. As this is a quickly changing landscape, the protocols listed here are current as of August 1, 2014. Updates will be posted as new drugs and protocols are approved by the FDA.
Hepatitis C Genotype 1 - is treated with a combination of 3 drugs: Pegylated Interferon, Ribavirin and either a Protease Inhibitor (Incivek, Victrelis or Olysio) or Sovaldi. Treatment can range anywhere from 12 to 48 weeks and SVR rates fluctuate depending on treatment history and drug used. Genotype 1 has always been the hardest strain of this virus to treat which is why Peg-Interferon is still a necessity. Please check with your physician to find out what your chances of achieving SVR are when using these treatments as all medications have different SVR rates depending on circumstances.
Hepatitis C Genotype 2 - is treated with either Sovaldi and Ribavirin for 12 weeks or with Peg-Interferon and Ribavirin for 24 weeks. SVR Rates among treatment naive patients can be over 90%.
Hepatitis C Genotype 3 - is treated with either Sovaldi and Ribavirin for 24 weeks or with Peg-Interferon and Ribavirin for anywhere from 24 to 48 weeks depending on response.
Hepatitis C Genotype 4 - is treated with Peg-Interferon and Ribavirin with Sovaldi for 12 weeks or without Sovaldi for 48 weeks.
Sovaldi: Sovaldi is a brand new drug that is manufactured by Gilead. Currently, not all insurance companies are approving the use of this medication due to its exorbitant cost. One round of treatment with this drug is eighty thousand dollars and no, that is not a typo. Eighty thousand dollars $80,000 and that is just for the Sovaldi. Sovaldi is a Hepatitis C virus polymerase inhibitor that is used as a component of a combination antiviral treatment regimen. Sovaldi is a pill that is taken once daily.
Pegylated interferon: Interferon is a protein made by the immune system, named because it interferes with viral reproduction. In addition, interferon signals the immune system to recognize and respond to microorganisms, including viral and bacterial infections. Infected cells release interferon to trigger the immune response. There are three types of interferon: alfa, beta and gamma. Interferon alfa is used to treat viral hepatitis and some types of cancer.
In the 1980s, researchers were able to create interferon alfa in a laboratory. Hepatitis C is treated with man-made interferon alfa that has a molecule attached to keep it in the body longer and make it more effective, called pegylated interferon. There are two brands of pegylated interferon, Merck’s PegIntron, which is dosed according to weight, and Genentech’s Pegasys, which is given at a fixed dose (i.e., the same dose for everybody).
During HCV treatment, pegylated interferon is given by weekly injections, for up to 12 months, at a much higher dose than what the body produces, causing many side effects. These include flu-like symptoms, laboratory abnormalities such as anemia (abnormally low red blood cell count), neutropenia (a decrease in neutrophils, a type of white blood cells that fight bacterial infections) and thrombocytopenia (low platelets), as well as psychiatric problems (e.g., depression, irritability, insomnia, moodiness). The good news is that clinicians have had years of experience with side effects management.
Ribavirin: Ribavirin is a nucleoside inhibitor. It comes as a pill, capsule or liquid. Ribavirin is taken twice daily, and dosing is based on weight. Although it is not effective against hepatitis C when used alone, ribavirin plays an important role in HCV combination treatment. Although scientists have not discovered exactly how it works, it is clear that adding ribavirin boosts cure rates and reduces the risk of relapse.
The major side effect of ribavirin is anemia, which is dose-dependent and can be managed with red blood cell growth factors, or by lowering the dose of ribavirin. Additional side effects include heart problems, depression, dry skin, itching, rash, headache, cough and sinus problems, fatigue, diarrhea, dizziness, appetite loss, nausea and vomiting.Ribavirin causes birth defects in animals, so it cannot be used by pregnant or breastfeeding women and their male partners. Men and women who are having intercourse must use birth control during HCV treatment, and for the next six months afterwards, since ribavirin can remain in the bloodstream for many months after treatment has ceased.
Protease Inhibitors: Three Hepatitis C protease inhibitors, Merck's Victrelis (boceprevir), Vertex's Incivek (telaprevir) and Jannsen's Olysio (simeprevir) have been approved to treat Hepatitis C Genotype 1, in combination with Peg-Interferon and Ribavirin. These oral antiviral drugs are used twice a day for 12 to 24 weeks.
Protease inhibitors block an important step in HCV replication. The Hepatitis C virus uses its protease enzyme to cut, or cleave, long strands of virus into shorter pieces, so that they can be rearranged and reassembled to form new viruses. Protease inhibitors stop viral cleavage by binding to the protease enzyme so it cannot be cut, similar to covering scissor blades with glue.
Side effects of HCV protease inhibitors vary according to the particular drug. Incivek and Victrelis can cause anemia, Victrelis can cause a metallic taste in the mouth, dry mouth, vomiting and diarrhea. Incivek and Olysio can cause a rash and nausea. Check each drug individually for more information on side effects.
When Should Treatment Be Started?
Determining when and if treatment for Hepatitis C should start is a complicated issue. Many factors come into play here. HCV treatment can cause some pretty uncomfortable side effects. It doesn't happen for everyone but it does for some. For these people working while on HCV treatment is not a possibility and financial arrangements need to be made. This is a time when if you've had the foresight to opt into long term disability benefits at your place of employment, some fears can be calmed. Knowing that you will have at least 60% of your salary coming in if you cannot work can be a Godsend. Because of the side effects of treatment and the fact that there is absolutely no guarantee that the treatment will work, people with HCV must weight the risks of therapy against the benefits in deciding if and when to start treatment.
The American Academy for the Study of Liver Diseases (AASLD) recommends that treatment be started before cirrhosis occurs but only for those who are considered to be at "high risk" for developing cirrhosis in the future. Typically, this is only about 20% of the folks with HCV. This list includes the following people, all of whom are 18 years of age or older and willing to be treated and adhere to the strict treatment requirements with the following:
- HCV that is detectable by PCR. and...
- A liver biopsy showing severe signs of fibrosis. and...
- Compensated liver disease (laboratory signs and symptoms that suggest the liver is still functioning normally) and...
- Blood tests indicating that certain blood cell counts and organ enzymes are still within healthy ranges.
If these criteria are met, a patient should be offered treatment, regardless of the presence or absence of symptoms, the route of HCV infection, the Genotype of HCV or the HCV viral load.
Treatment should NOT be offered in certain situations. These include:
- Major uncontrolled depression as this can be exacerbated further by HCV treatment.
- Solid organ transplant (e.g., kidney, heart or lung)
- Autoimmune hepatitis or other autoimmune condition which can be exacerbated further by HCV treatment.
- Untreated thyroid disease.
- Pregnant or unwilling to practice effective birth control.
- Severe accompanying diseases such as very high blood pressure, heart failure, significant coronary disease, poorly controlled diabetes and chronic obstructive disease/emphysema.
- A parent of children younger than 2 years old.
- Known allergies to the drugs used to treat HCV.
AASLD also notes that treatment should be individualized, timed and tailored based on the risks and benefits of therapy in each patient in the following circumstances:
- Failed earlier treatment. It is now being suggested that the maximum use of Peg-Interferon is 48 weeks. This rules out second rounds of treatment with an Interferon based regimen.
- Current users of alcohol and illicit drugs but willing to participate in a substance abuse program.
- Liver biopsy evidence of either no or mild fibrosis
- Acute Hepatitis C
- Younger than 18 years old.
- Chronic kidney disease,
- Decompensated cirrhosis or severe liver disease
- Liver transplant recipients
.Above all else, deciding when and if to start treatment is an individualized thing. Meaning, no matter what the "official" guidelines say, it is up to you and your doctor to create the best plan for you based on your own thoughts, concerns and capabilities.
Treating patients with cirrhosis.
Patients with Hepatitis C can be cured when they have compensated cirrhosis. Meaning the liver is still able to function despite scarring. Treatment is less effective for people who have severe liver damage and the presence of cirrhosis can make the side effects worse. This is a conversation to have with a physician who is skilled in the area of Hepatitis C and liver damage.
For people with Genotype 1 HCV, adding one of the protease inhibitors will increase the cure rate, even if they have already treated unsuccessfully in the past.
Liver Transplant Patients -- Pre and Post Transplant
People with end stage liver disease (ESLD - also known as decompensated cirrhosis) are in need of a liver transplant. At this stage, treating is usually not recommended because of abnormally severe side effects -- including life-threatening bacterial infections, anemia and low platelets. Plus there is also the possibility that liver function may actually worsen during Hepatitis C treatment. Some doctors will start treatment with very low doses of Peg-Interferon and Ribavirin, gradually increasing the dosages as tolerated. If the treatment works and the HCV viral load becomes undetectable and stays undetectable until transplantation, the HCV is cured and re-infection of the new liver is avoided.
Receiving a new liver will not cure you of Hepatitis C unless you have treated and cleared prior to the transplant, otherwise the HCV will always come back. The virus is not contained to your liver and is circulating in your bloodstream so the new liver will become infected. Some of the anti-rejection drugs that are used tend to aggravate the HCV virus and it comes back quickly. Hepatitis C can be treated after liver transplantation.