Interferons, for example, Roferon-A and Infergen, and pegylated interferons such as Peg-IntronT, Pegasys, were mainstays of treatment for years. Interferons produced sustained viral response (SVR, or cure) of up to 15%. Later, peglatedll forms produced SVR of 50%-80%. These drugs were injected, had many adverse effects, required frequent monitoring, and were often combined with oral ribavirin, which caused anemia. Treatment durations ranged up to 48 weeks.
Direct-acting agents (DAA) are antiviral drugs that act directly on hepatitis C multiplication.
- They are taken by mouth, are well-tolerated, and cure over 90% of patients.
- Treatment time is much shorter, often 12 weeks, depending on drug and genotype.
- Similar to treatments for HIV, treatment of HCV is most effective if the drugs are given in combination.
- The earliest options were sofosbuvir (Sovaldi) and simeprevir (Olysio). These were approved by the Food and Drug Administration (FDA) in 2013.
- Ledipasvir and sofosbuvir (Harvoni) followed as a once-a-day combination pill, in 2014.
- With this combination of DAAs, about 94%-99% of people achieve an SVR (cure) in 12 weeks with few side effects.
- Ombitasvir, paritaprevir and ritonavir co-packaged with dasabuvir tablets (Viekira Pak), is a combination approved in 2014. SVR with this combination is 91%-100%. The combination of elbasvir and grazoprevir (Zepatier) was approved in 2016. SVR with this combination depends on the HCV genotype and whether individual patient factors require the addition of ribavirin. Genotype 1 has a 94%-97% SVR, and SVR is 97%-100% in genotype 4.
- In August 2017, FDA approved an 8-week regimen of glecaprevir and pibrentasvir (Mavryet) for all HCV genotypes. Unlike some of the earlier regimens, this combination is effective whether or not the patient has cirrhosis. It also can be given to people on kidney dialysis, whose kidney function limits treatment options. Moreover, this regimen is effective in people with genotype 1 who have failed treatment with some of the other regimens.
What are the treatment guidelines for hepatitis C?
The treatment of hepatitis C is best discussed with a doctor or specialist familiar with current and developing options as this field is changing, and even major guidelines may become outdated quickly.
The latest treatment guidelines by the American Association for the Study of Liver Disease (AASLD) and Infectious Disease Society of America (IDSA) recommends use of DAAs as first-line treatment for hepatitis C infection. The choice of DAA varies by specific virus genotype, and the presence or absence of cirrhosis. In the U.S., specific insurance providers also might influence the choice due to the high cost of DAAs. Although the individual, public health, and cost benefits of treating all patients with hepatitis C is clear, the most difficult barrier to treating all people with HCV is the very high cost of the drug regimens.Patients are encouraged to discuss options with their health-care professional. Treatment is recommended in all patients with chronic hepatitis C unless they have a short life expectancy that is not related to liver disease. Severe life-threatening liver disease may require liver transplantation. Newer therapies with DAAs have allowed more and more patients to be treated.
What are the goals of therapy for hepatitis C infection?
The ultimate goals of antiviral therapy are to
- prevent transmission of hepatitis C,
- normalize liver tests,
- reduce inflammation and scarring,
- prevent progression to cirrhosis and liver cancer, and
- improve survival and quality of life.
A side goal is preventing co-infections with other hepatitis viruses, such as A and B, which can cause more liver disease than HCV alone. These can be prevented by vaccines and treatment.
What is the treatment for people with acute hepatitis C infection?
When people first get hepatitis C, the infection is said to be acute. Most people with acute hepatitis C do not have symptoms so they are not recognized as being infected. However, some have low-grade fever, fatigue or other symptoms that lead to an early diagnosis. Others who become infected and have a known exposure to an infected source, such as a needle-stick injury, are monitored closely. Treatment decisions should be made on a case-by-case basis. Response to treatment is higher in acute hepatitis infection than chronic infection. However, many experts prefer to hold off treatment for 8-12 weeks to see whether the patient naturally eliminates the virus without treatment. Approaches to treatment is evolving. Patients with acute hepatitis C infection should discuss treatment options with a health-care professional who is experienced in treating the disease. There is no established treatment regimen at this time.
How effective is hepatitis C treatment?
If the hepatitis C RNA remains undetectable at the end of the treatment and follow-up period, this is called a sustained virologic response (SVR) and is considered a cure. Over 90% of people treated with DAAs are cured. These people have significantly reduced liver inflammation, and liver scarring may even be reversed. About 5% of people who are treated for HCV infection are not cured by some of the older regimens. These people may still have options for cure with the newer regimens.
Who should not receive treatment with antiviral therapy?
Few people with hepatitis C are at risk for problems if they are treated, however there are some factors that affect treatment regimens, such as concurrent HIV medications and kidney dysfunction. Some drugs are not safe for people with cirrhosis. Individuals who are unable to comply with the treatment schedule for psychological reasons or ongoing drug or alcohol abuse may not be good candidates for treatment because the drugs are very costly and require adherence to the pill regimen and regular follow-up visits. There are some important drug interactions with some of the medications that should be considered by the health-care professional.
People with past hepatitis B or who have chronic active hepatitis B should not be treated for HCV without treating for HBV as well. As highly effective treatment for HCV has emerged, reports of serious hepatitis B have come to light. Similar to HCV, hepatitis B usually does not clear from the liver after acute infection, even though it is far less likely to cause chronic active hepatitis than hepatitis C infection. It remains dormant in most people, but it can reactivate with changes in the immune system. It is not clear why eliminating the HCV can allow the HBV infection to flare up. Hepatitis B screening is an important part of the hepatitis C evaluation.
What are the side effects of treatments for hepatitis C infection?
Side effects of interferon or pegylated interferon
- The most common side effects of interferon or pegylated interferon include fever, flu-like symptoms, and depression. Patients must be monitored closely for depression. Risk of suicide is a reason to avoid interferons.
- Interferons also reduce white blood cell and/or red blood cell counts (leucopenia and anemia, respectively). This may cause increased susceptibility to infection. Interferons also increase the risk of certain cancers. Death rarely occurs as a result of therapy, but may occur from progression of liver failure in patients with advanced cirrhosis.
Side effects of ribavirin
- Ribavirin most commonly causes anemia due to destruction of red blood cells (hemolysis). This can be severe enough that people with heart disease may suffer a heart attack from insufficient blood flow, so people with heart disease should not receive this drug. Anemia improves with a reduction in the dose of ribavirin. Injected growth factor (erythropoietin) that stimulates the production of red blood cells often is used to improve the anemia associated with ribavirin. Ribavirin also accumulates in the testicles and ovaries and causes birth defects in animals. Although no birth defects have been reported in humans, both men and women should use contraceptive measures to avoid pregnancy during and for at least six months after ribavirin treatment.
Side effects of DAAs
Compared to these drugs, the side effects of DAAs are far fewer and more tolerable. These side effects usually do not require discontinuation of therapy and are self-limiting after completion of therapy.
The most common and significant side effects of boceprevir (Victrelis), sofosbuvir (Sovaldi), and ledipasvir/sofosbuvir (Harvoni) include
- fatigue (feeling tired),
- headache, and
- trouble sleeping (insomnia).
The most common side effects of simeprevir (Olysio) include
- skin rash, and
- photosensitivity (tendency to get sunburns).
Simeprevir has significant drug interactions with other medications. Certain medications can affect levels of simeprevir in the body and make simeprevir less effective or more toxic.
The combination of ombitasvir, paritaprevir, and ritonavir tablets with dasabuvir tablets (Viekira Pak) is very well tolerated, and the most commonly reported side effects are
- trouble sleeping, and
The combination of elbasvir and grazoprevir (Zepatier) is well-tolerated. Most common side effects include
- headache, and
- It may be used with ribavirin, which adds the side effect of anemia.
- About 1% of people in studies may develop elevated liver enzyme blood tests last into treatment or afterward, so these tests are closely monitored.
Use of milk thistle should be discussed with the treating doctor, because it interacts with several DAAs.Patients with hepatitis B co-infection should be monitored for symptoms of reactivation of hepatitis, which are the same as the symptoms of acute hepatitis. The treating doctor may perform blood screening for this as well.
Is liver transplantation an option for a person with hepatitis C?
Hepatitis C is the leading reason for 40% to 45% of liver transplants in the U.S. Hepatitis C usually recurs after transplantation and infects the new liver. Approximately 25% of these patients with recurrent hepatitis will develop cirrhosis within five years of transplantation. Despite this, the five-year survival rate for patients with hepatitis C is similar to that of patients who are transplanted for other types of liver disease. Most transplant centers delay therapy until recurrent hepatitis C in the transplanted liver is confirmed. Oral, highly effective, direct-acting antivirals have shown encouraging results in patients who have undergone liver transplantation for hepatitis C infection and have recurrent hepatitis C. The choice of therapy needs to be individualized and is rapidly evolving.
How is monitoring done after treatment for hepatitis C?
Once patients successfully complete treatment, the viral load after treatment determines if there is an SVR or cure. If cure is achieved (undetectable viral load after treatment), no further additional testing is recommended unless the patient has cirrhosis. Those who are not cured will need continued monitoring for progression of liver disease and its complications. While cure eliminates worsening of fibrosis by hepatitis C, complications may still affect those with cirrhosis. These individuals still need regular screening for liver cancer as well as monitoring for esophageal varices that may bleed. Because hepatitis B co-infection may reactivate or worsen even after treatment for HCV, monitoring for hepatitis symptoms may be needed after the end of therapy.
What home remedies are available for hepatitis C?
At this time there are no effective home or over-the-counter treatments for hepatitis C.