Update On Hepatitis C: Direct
Correspondence to: Aijaz Ahmed, MD, Associate Professor of Medicine, Medical Director Liver Transplant Program, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite 210, Stanford, CA 94305, United States.
Telephone: +1-650-4986091 Fax: +1-650-4985692
Causes Of Hepatitis C
You can become infected with hepatitis C if you come into contact with the blood of an infected person.
Other bodily fluids can also contain the virus, but blood contains the highest level of it. Just a small trace of blood can cause an infection. At room temperature, it’s thought the virus may be able survive outside the body in patches of dried blood on surfaces for up to several weeks.
The main ways you can become infected with the hepatitis C virus are described below.
Challenges And Future Direction Of Daa
Though DAA has provided much needed, safe and effective therapeutic option for chronic HCV patient, some challenges need further effort. Such challenges include the presence of resistant variance, low efficacy in cirrhotic patients, presence of drug-drug interactions, and the cost. The future direction should go through multiple directions, for example, continuous monitoring and developing DAA, use of combined groups of DAA with different mechanisms of action to minimize resistance, searching for other antiviral groups with different mechanisms of action, and finding a solution for improving cirrhosis by developing antifibrotic drugs. A recent study showed promising results in the possible incorporation of a new cyclophilin inhibitor, STG-175 in DAA-regimen.
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Ethics Approval And Consent To Participate
All procedures performed in this study were in accordance with the ethical standards of Ain Shams University Research Committee and with the 1964 Helsinki declaration and its later amendments.
Ethics committees reference number: 000017585.
Address: Faculty of Medicine, Ain Shams University, Cairo 11211, Egypt.
Informed written consent was obtained from each participant before enrolment in the study.
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Recommended Monitoring For Pregnancy
RECOMMENDED RATING Women of childbearing potential and their partners should not receive ribavirin during or for at least 6 months prior to pregnancy. I, C Women of childbearing potential should be counseled not to become pregnant while receiving a ribavirin-containing antiviral regimen, and for at least 6 months after stopping the regimen. I, C Male partners of women of childbearing potential should be cautioned to prevent pregnancy while they are receiving a ribavirin-containing antiviral regimen, and for up to 6 months after stopping the regimen. I, C Serum pregnancy testing is recommended for women of childbearing potential prior to beginning treatment with a regimen that includes ribavirin. I, C Assessment of contraceptive use and of possible pregnancy is recommended at appropriate intervals during ribavirin treatment for women of childbearing potential, and for female partners of men who receive ribavirin treatment. I, C
Ribavirin causes hemolysis. Patients receiving ribavirin should have hemoglobin levels checked during treatment, often after 2 weeks, and the ribavirin dose reduced if the patient develops significant anemia, often defined as hemoglobin < 10 g/dL.
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Cirrhosis And Metabolic Measures
Participants with cirrhosis had higher baseline insulin and HOMA-IR than non-cirrhotic patients in the RBV-sparing group . These measures remained unchanged from baseline while on treatment and 12 weeks following dosing in the overall study population as well as in cirrhotic and non-cirrhotic participants. Twenty-four weeks post-treatment, an increase in insulin and HOMA-IR was noted in cirrhotic participants, which was not observed in non-cirrhotic participants. When the results of a single outlier were removed, this finding was no longer present . Participants with cirrhosis had similar trajectories of HbA1c and lipid measures compared to those in the non-cirrhotic ribavirin-containing treatment group .
apoA1, apoA2, and apoE were lower at baseline in the cirrhotic participants compared with non-cirrhotic participants . There were no observed changes from baseline in mean glucose and apolipoprotein measures among cirrhotic patients over the study period.
Data Collection And Analysis
We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis Crelated morbidity, serious adverse events, and quality of life. Our secondary outcomes were allcause mortality, ascites, variceal bleeding, hepatorenal syndrome, hepatic encephalopathy, hepatocellular carcinoma, nonserious adverse events , and sustained virological response. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eightstep procedure to assess thresholds for statistical and clinical significance. The overall quality of the evidence was evaluated using GRADE.
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Reasons To Delay Treatment
Pregnancy
Hepatitis C treatment is generally not recommended during pregnancy. There is not a lot of information on the effects of DAAs during pregnancy. Research is being done on taking DAAs during pregnancy so this may change in the future.
Treatment that includes ribavirin can cause severe birth defects and must not be taken during pregnancy. When a couple wants to have a baby, both partners should avoid using ribavirin for at least six months before trying to get pregnant.
A healthcare provider can help determine a treatment plan and timeline for a person who has hepatitis C and wants to have a baby.
Children and adolescents
Hepatitis C treatment for children over the age of 12 is available in Canada. It is recommended that children who require treatment for hepatitis C be connected to a specialist with experience treating the pediatric population.
Resources for service providers
The Following Monitoring Is Not Recommended During Or After Therapy
NOT RECOMMENDED RATING Monitoring for HCV drug resistance-associated substitutions during or after therapy is not recommended unless retreatment will be performed. RAS testing is recommended in advance of retreatment therapy. See the Retreatment section for recommendations regarding RAS testing prior to retreatment. Additional information about RAS testing can be found in the HCV Resistance Primer. IIb, C
Patients who do not achieve SVR retain the possibility of continued liver injury, progression of hepatic fibrosis, and the potential to transmit HCV infection to others. Such patients should be considered for retreatment per the Retreatment of Persons in Whom Prior Therapy Has Failed section.
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Evolution Of Hcv Therapy
The ultimate goal of hepatitis C treatment is to reduce the occurrence of end-stage liver disease and its complications, including decompensated cirrhosis, liver transplantation, and HCC. Treatment success is assessed by sustained virologic response , defined by the presence of undetectable HCV RNA in blood several months after completing a course of treatment .
Figure 6.1. Evolution of chronic HCV therapies. DAA, direct-acting antiviral agent HCV, hepatitis C virus IFN, interferon PEG, pegylated RBV, ribavirin SVR, sustained virologic response.
Graham A.W. Rook, Christopher A. Lowry, in, 2018
How Effective Is Treatment
Direct-acting antivirals cure 9 out of 10 patients with hepatitis C.
Successful treatment does not give you any protection against another hepatitis C infection. You can still catch it again.
There’s no vaccine for hepatitis C.
If treatment does not work, it may be repeated, extended, or a different combination of medicines may be tried.
Your doctor or nurse will be able to advise you.
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What Happens When Initial Treatment Fails
In a small number of patients, antiviral drugs might fail to cure hepatitis C.
People with hepatitis C that is difficult to cure may have better results with multiple antiviral drug regimens or longer treatment courses.
The authors of a 2020 paper estimate that DAA therapy cures HCV in more than 95% of people who undergo retreatment. However, they emphasize that there is no clinical trial-proven treatment regimen for people with difficult-to-cure HCV.
In a study, the researchers had success treating a patient with difficult-to-cure HCV for 24 weeks with three antiviral drugs: sofosbuvir, glecaprevir/pibrentasvir, and ribavirin.
are not part of the standard treatment regimen for hepatitis C.
However, a healthy lifestyle may improve liver health and reduce the risk of cardiovascular complications. For example, a 2021 study found improved cardiometabolic health and improved quality of life among people with hepatitis C who exercise.
Some lifestyle changes to consider include:
- avoiding alcohol, since it can damage the liver
- talking with a doctor about a liver-healthy diet
- seeking care to manage any chronic medical conditions
- taking DAA drugs exactly as a doctor prescribes them
- avoiding using illegal or unnecessary drugs or medications
- not sharing needles with other people
Tips And Remedies To Help With Side Effects
There are things you can do to ease many of the side effects from hepatitis C treatment.
Remember that these side effects will typically go away once you’re cured, so stick with your treatment. Work with your doctor on your treatment plan so that you can manage any problems and try to get the virus out of your body as soon as possible
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Treatment Regimens And Efficacy
We simulated two strategies: no treatment and treatment with available DAAs. The DAA treatment regimens used were determined by individual patients HCV genotype and METAVIR fibrosis stage. The treatment efficacy in various scenarios was based on the SVR rate reported in clinical trials of DAAs, and uncertainty in SVR rates was incorporated in sensitivity analysis. Regimen-specific treatment discontinuation rates were also incorporated in the model. Data about the treatment regimens were obtained from recent clinical trials of DAAs in treatment-naïve patients,,, and are provided in Supplementary Table .
Access To Hepatitis C Care In Prisons
Direct-acting antivirals were listed on Australias Pharmaceutical Benefits Schedule in 2016. These subsidised medicines were made available to all Australians, including people in prison. Prisoners are usually excluded from the federal governments PBS subsidies, with medication costs falling to states and territories.
While overall hepatitis C treatment rates stagnated in Australia, the prison sector accounted for a rising percentage of all people treated. Between March 2016 and February 2017, around 6% of all hepatitis C treatments occurred in Australian prisons. In 2020, this rose to 37% .
For some people, prison is one of few places they can receive hepatitis C treatment.
A pilot evaluation of a nurse outreach program in Victorian prisons found of the 416 people who started direct-acting antiviral treatment, most had never had hepatitis C care before.
An additional 75 people were released from prison before they could start treatment. After referral to their preferred physician, only 19 were prescribed direct-acting antivirals within six months of release. Seven of those people were treated only after they were re-incarcerated.
Many people leaving prison face multiple challenges, including housing instability, poverty, obtaining meaningful and reliable employment, and social connectedness. These are all potential barriers to accessing health care, including hepatitis C treatment.
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Viral Kinetics In Response To Ribavirin
When used as monotherapy, ribavirin results in either a transient initial decline or no decrease in HCV RNA level., The addition of RBV to IFN-ñ, however, has dramatically improved the long-term outcome of therapy.,, In some patients, RBV induced an increase in the slope of the second phase decline, whereas in other patients, it did not significantly affect the second phase, although it decreased the frequency of viral rebound observed when only pegylated IFN was administered. In patients with a triphasic decline after treatment with IFN or pegylated IFN, administration of RBV seemed not to affect the first phase decline, but enhanced the third phase decline.,
The antiviral mechanisms of RBVâs action against HCV have not been fully elucidated. A number of mechanisms have been proposed , and mathematical models have been developed to test possible mechanisms. In one study, RBV was assumed to serve as an immune modulator. A model was developed based on this mechanism and used to study the effect of RBV on HCV kinetics. The model included an inflation factor that represents the increase in the death rate of infected cells after an initial delay . Model results suggested that RBV did not have a noticeable effect on the first phase decline and the second shoulder phase. However, it significantly increased the slope of the third phase decline.
Ombitasvir Paritaprevir And Ritonavir
Doctors may prescribe this combination of drugs to treat hepatitis C genotype 4. They may also prescribe ribavirin.
- Facts about Technivie include:
- Treatment time is 12 weeks.
- Dosage is a fixed-dose combination of 12.5 mg ombitasvir, 75 mg paritaprevir, and 50 mg ritonavir taken once daily.
- Common side effects include weakness, tiredness, nausea, and sleep problems.
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Recommended Monitoring For Patients In Whom Treatment Failed To Achieve A Sustained Virologic Response
RECOMMENDED For patients with cirrhosis, endoscopic surveillance for varices should be performed in accordance with the AASLD guidance on portal hypertension bleeding in cirrhosis. Guidanceb a For, please refer to the appropriate section.b Unlike the AASLD/IDSA HCV guidance, the AASLD guidelines use the GRADE system to rate recommendations please see that document for further information about this rating system.
Substance Use Disorder Treatment
If you have a substance use disorder , treatment and support is available. Treating SUD involves addressing both the physical and mental health effects of addiction, and helping you develop a strategy for long-term recovery.
Individual therapy and support groups, such as Narcotics Anonymous, can help support you in stopping IV drug use. Inpatient and outpatient treatment programs created specifically to treat SUD can also be a part of your treatment plan.
Medication can help reduce your bodys chemical reaction to IV drugs. Methadone or buprenorphine may be prescribed during the initial withdrawal stage to help you cope as you stop using IV drugs. For some people, these medications may be advised more long term.
Visit the Substance Abuse and Mental Health Administration treatment portal to find a support group, rehab facility, or counselor near you, as well as recommendations for hotlines and online resources.
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New Hep C Treatments Usually Cure People In One Cycle
In the past, some people needed to be treated as many as four times something that put them through hell, says Laryea.
Hepatitis C was complicated to treat, she says. Every patient required different combinations of medications for different lengths of time. Factors including age and the amount of scarring of the liver impacted treatment. Today, she continues, Weve taken hepatitis C from something very complicated to something that is treated like a typical infection.
Other Side Effects Of Ribavirin
Other side effects of ribavirin may include:
- nausea and vomiting
All DAAs are oral drugs that you swallow. Follow your doctors or pharmacists instructions on how to take these medications. They can also tell you what side effects are possible and symptoms of any serious side effects to look out for.
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Political Commitment And Increased Government Expenditure
The countries in this study earmarked only 3.7%7.7% of their GDP to health, and OOPE in these countries is as high as 71%. Committed and strong leadership, which is willing to improve health financing, able to negotiate for price reduction, and keep to strengthen partnership for advocacy and resource mobilization, is needed to reduce the burden of DAAs on patients and countries.
In Egypt, the price of sofosbuvir for all patients with HCV is equivalent to 48% of the THE and 150% of the government budget for health. In spite of this, Egypt is expanding access to DAAs due to high level of political commitment, effective price negotiations, and local production . Almost 88% of treated patients were sponsored by the government whereas only 12% of patients paid OOP .
This is a demonstration that it is feasible to increase access to DAAs if governments are committed to the health of their citizens providing resources are available and can be mobilized to that end. It is important that governments increase their health budget to at least 15% of their GDPs as per the Abuja declaration . Governments should also be committed to establish or strengthen their social health insurance system as it is very weak or non-existent in these countries .
New Drugs Cure Hepatitis C
Hepatitis C is a that can cause serious and permanent liver damage. The goal of treatment is to clear the virus from the body and stop, slow and prevent liver problems. Until recently, doing that involved inconvenient and painful injections of interferon and a pill called ribavirin. That therapy is known for its toxic side effects and has been compared to low-grade chemo. Worse, it doesnt always work that well. These traditional drugs offer a 50% cure rate at best.
But today, were witnessing a revolution in hepatitis C treatment, as more and more medications that directly target the virus gain approval. These medications offer a cure, instead of a partial clearing of the virus. And, as a bonus, most come in the form of a pill. They have fewer side effects and work much fasterwhich means you dont have to stay on treatment as long as compared to interferon and other drugs.
The rapidly-evolving hep C medication list is giving new hope for the 3.2 million Americans living with the chronic form of the disease. Antiviral therapy for hep C continues to rapidly evolve with the introduction of new drugs and treatment regimens that vary based on hep C genotype, previous treatments, and the presence of cirrhosis. Heres a closer look at some of the currently prescribed interferon-free medicines for hepatitis C.
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