Medicine For Hepatitis C Virus

Daa Treatment And Hepatocellular Carcinoma

The impact of DAA treatment on hepatocellular carcinoma incidence, recurrence and tumor aggressiveness in patients with chronic HCV infection has been intensively discussed over the last 2 years. Shortly after DAA approval, an observed increase in early occurrence or recurrence of HCC after HCV eradication with DAA has been reported .

However, the higher incidence of de novo HCC compared to historical data was most likely related to a significantly higher proportion of older patients as well as those with end-stage liver disease certainly ineligible for IFN-based regimens. Later on, further data analysis revealed that HCV eradication due to DAA treatment reduces the risk of HCC development to a comparable level as with IFN-based therapies . These findings were supported by results from prospective studies showing a reduction of HCC incidence in patients with HCV-related liver cirrhosis . Nevertheless, the absolute risk of HCC development remains high in patients with established cirrhosis. Ongoing HCC surveillance is mandatory despite HCV clearance .

Patients With Coexisting Hepatitis B Infection

Patients who are coinfected with chronic hepatitis B and C virus are at increased risk for liver disease, and the presence of each virus may suppress the replication of the other pathogen . Some coinfected patients are at risk for HBV reactivation with or without HBV flare during or after curative HCV therapy . The risk of HBV reactivation varies by HBV serological status. In a recent meta-analysis of 17 studies, including 1621 patients , the incidence was 24% among patients with chronic untreated HBV and 1.4% among patients with resolved HBV . Among patients with chronic HBV 9% had evidence of hepatitis with reactivation. None of the patients with resolved hepatitis B had hepatitis with HBV reactivation. Overall, there were significant clinical events related to HBV reactivation in 3 patients with chronic HBV, 1 hepatic decompensation, and 2 liver failure events, 1 of whom required liver transplantation. Patients with active HBV infection, defined as positive HBsAg, should have HBV DNA testing and consideration of HBV treatment before starting HCV therapy. If HBV treatment is not initiated before HCV treatment, patients should be monitored with liver function tests or HBV DNA at 4-week intervals until 12 weeks after HCV treatment completion. If the HBV DNA level increases > 10-fold or to > 1000 IU/mL from a previously undetectable HBV DNA, HBV treatment should be initiated.

Getting Tested Is The Only Way To Know If You Have Hepatitis C

A blood test called a hepatitis C antibody test can tell if you have been infected with the hepatitis C viruseither recently or in the past. If you have a positive antibody test, another blood test is needed to tell if you are still infected or if you were infected in the past and cleared the virus on your own.

• Are 18 years of age and older
• Are pregnant
• Currently inject drugs
• Have ever injected drugs, even if it was just once or many years ago
• Have HIV
• Have abnormal liver tests or liver disease
• Are on hemodialysis

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Path From The Discovery To The Elimination Of Hepatitis C Virus: Honoring The Winners Of The Nobel Prize In Physiology Or Medicine 2020

• orcid.org/0000-0001-8145-1900

Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan

Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan

Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence

• orcid.org/0000-0001-8145-1900

Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan

Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

Correspondence

• Wechat

Patients Who Did Not Achieve Hcv Cure With Prior Second

Among patients who do not achieve cure with an NS5A-containing oral DAA regimen including sofosbuvir-based regimens, sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is recommended for retreatment and does not require RAS testing before retreatment . This is supported by data from the POLARIS-1 and POLARIS-4 studies among patients who had previously received an NS5A inhibitorcontaining DAA regimen. The rate of SVR was 96% in POLARIS-1 and 98% in POLARIS-4 . Among genotype 1infected patients, SVR rates were similar among those with baseline RAS and those without RAS . Attention should be given to factors that may have played into nonresponse to the prior NS5A-containing regimen, including drug-drug interactions and nonadherence, and any issues identified should be addressed before retreatment.

Among genotype 1 patients who fail a sofosbuvir-based regimen not inclusive of an NS3/4 protease inhibitor, glecaprevir/pibrentasvir for 16 weeks is an alternative regimen .

Among patients who fail glecaprevir/pibrentasvir, sofosbuvir/velpatasvir/voxilaprevir is an option for retreatment . Due to historically lower SVR rates in patients with cirrhosis, addition of RBV should be considered in patients with cirrhosis. In a study of patients without cirrhosis who failed treatment with glecaprevir/pibrentasvir, retreatment with sofosbuvir plus glecaprevir/pibrentasvir plus RBV for 16 weeks led to SVR in 22 of 23 patients .

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Who Is At Risk For Hepatitis C

You are more likely to get hepatitis C if you

• Have injected drugs

• Pain in your abdomen
• Jaundice

If you have chronic hepatitis C, you probably will not have symptoms until it causes complications. This can happen decades after you were infected. For this reason, hepatitis C screening is important, even if you have no symptoms.

How Will My Provider Monitor Me During The Treatment

Your provider will meet with you during treatment to review how well you are tolerating treatment and review laboratory results. Laboratory tests help keep tabs on your health, track the viral load, and determine your response to treatment. You will be given specific dates to go get your blood tested at the lab during and after the treatment.

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Ifn Monotherapy In Acute Hepatitis C

Although the short courses of standard IFN monotherapy introduced in the 1980s by Hoofnagle et al, Davis et al, and Di Bisceglie et al led to sustained improvement in liver disease and loss of virus in less than 10% of patients, these therapies were the first to cure chronic viral hepatitis.

Jaeckel et al reported that treatment with IFN alfa-2b prevented chronic infection in 98% of a group of 44 German patients with acute hepatitis C. In this study, patients received 5 million U/day of IFN alfa-2b subcutaneously for 4 weeks and then three times per week for another 20 weeks the IFN alfa-2b was well tolerated in all patients but one.

Because it has the poorest safety profile of all the HCV antiviral agents, with few exceptions PEG-IFN is no longer recommended in combination regimens. Spontaneous resolution of acute HCV infection may occur in 15% to 50% of patients. Monitoring for spontaneous clearance for a minimum of 6 months before initiating any treatment is therefore recommended.

References

Enormous Impacts Of The Hcv Discovery

The breakthrough in HCV discovery has had enormous impacts from two main perspectives: elimination of post-transfusion HCV infection and advent of antivirals against HCV.

In addition to Houghton’s magnificent works, a highly sensitive assay for the detection of HCV in blood transfusion has been developed. This led to a dramatic decline in the risk of post-transfusion HCV infection in the 90s. Since then, transfusion-transmitted HCV infection has been effectively prevented in most countries, ensuring the safety of blood transfuison on a global scale.

”A cure is possible,” Rice said. With this belief, he was continuously dedicated to his work in exploring the structure and function of HCV NS5A protein, now an important target against HCV. Since the first introduction of direct-acting antivirals in 2011, the standard of care for HCV treatment has grown from DAA plus peginterferon/ribavirin therapy to interferon-free DAA therapy. Eventually, the advent of DAA boosted the sustained virologic response rates to 95%â99%, which was a huge advancement as compared to interferon-based therapies .- Following the implementation of DAA treatment, the incidence of HCV-related hepatocellular carcinoma in the Veterans Health Administration reduced by 29.6% from 2015 to 2018.

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Evolution Of Hepatitis C Treatment

Discovered in 1989, HCV is an enveloped 9.6 kb positive-sense single-stranded RNA virus classified in the Hepacivirus genus within the Flaviviridae family . Based on virus genetic differences, HCV is classified into 7 genotypes, of which 16 are considered clinically relevant. HCV infects and replicates in human hepatocytes, does not integrate into the human host, and, as such, does not have a latent phase. Advances in the understanding of the HCV life cycle have led to tremendous progress in HCV treatments, leading to curative therapy.

Because HCV does not integrate into the human host, viral clearance of HCV is possible . Sustained virologic response is equivalent to HCV cure, which leads to reduced risk of cirrhosis, hepatic decompensation, hepatocellular cancer, liver-related mortality, and all-cause mortality . HCV treatment and cure are also associated with improvement of extrahepatic manifestations and quality of life . Hepatitis C cure is classically assessed by evaluating HCV RNA in blood at least 12 weeks after the completion of therapy the absence of detectable HCV RNA at this time is defined as SVR12. Data demonstrating that the majority of patients who achieve SVR12 will have no evidence of active HCV infection for years following therapy led to the acceptance of SVR12 as a surrogate for HCV cure .

Hepatitis C And Health

How can health-care personnel avoid exposure to HCV?

Avoiding occupational exposure to blood is the primary way to prevent transmission of bloodborne illnesses among health-care personnel. To promote blood safety in the workplace, health-care personnel should consult infectious-disease control guidance from the National Institute for Occupational Safety and Health and from CDC. Depending on the medical procedure involved, Standard Precautions may include the appropriate use of personal protective equipment .

What is the risk of acquiring hepatitis C after being accidentally exposed to HCV-contaminated blood or body fluids in the workplace?

Although sharps injuries have decreased in recent decades due to improved prevention measures, they continue to occur, placing health-care personnel at risk for several bloodborne pathogens like hepatitis C. A recent analysis of several studies revealed an overall 0.2% risk for infection among those exposed to HCV-antibody-positive blood through needlestick or sharps injuries . Updated guidelines for management and treatment of hepatitis Cexternal icon are available to provide guidance for health-care personnel who become infected via exposure to contaminated blood at the workplace.

Other than needlesticks, do other exposures place health-care personnel at risk for hepatitis C?

Should HCV-infected health-care personnel be restricted in their work?

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Safety Across Astral Studies

Rate of adverse events and treatment discontinuation because of AEs was the secondary end point of the ASTRAL-1 study . Treatment was interrupted by 1 patient in the SOF/VEL group and by 2 patients in the placebo group. Serious AEs occurred in 15 patients treated with SOF/VEL and in none of the patients who received a placebo. Overall, AEs were recorded in 78% of subjects who underwent SOF/VEL therapy, and in 77% of those in the placebo group, without any significant difference .

In the ASTRAL-2 and ASTRAL-3 studies, a patient included in the ASTRAL-2 study interrupted treatment after the first pill due to anxiety and a headache . In ASTRAL-3, RBV was only discontinued by 9 patients as a result of AEs. In the ASTRAL-2 study, the percentage of serious AEs was the same in those who received and those who did not receive RBV in the ASTRAL-3 study, 2% of subjects who did not receive RBV experienced serious AEs compared to 15% of those who received RBV. Considering both studies, AEs were generally frequent in patients who underwent RBV-including regimens and the types of AEs were typical of RBV . Two ASTRAL-2 patients died during the post-treatment follow-up and 3 ASTRAL-3 patients died during treatment. All the deaths seemed to be due to causes unrelated to therapy or were categorized as unknown .

Pruritus was not observed in any patient of the ASTRAL studies among the AEs .

Antiviral Treatment For Hepatitis C Virus Reduces Risk Of Post

In a new cohort study of patients with hepatitis C virus -related hepatocellular carcinoma , a disease with a high recurrence rate, researchers at the Osaka City University Graduate School of Medicine reported that after receiving cancer treatment, the oral administration of direct-acting antivirals reduces the risk of tumor progression following recurrence of the liver disease. The findings were published in the Journal of Viral Hepatitis.

Led by Norifumi Kawada, professor of the Department of Hepatology, the study investigated the effect eliminating HCV had on tumor progression of early-stage HCC. “DAA therapy is effective at eradicating the hepatitis C virus, a major risk factor for HCC” says Professor Kawada. “While it is deemed low or inconclusive whether DAA therapy helps prevent HCC recurrence, little is known about how the antiviral therapy affects progression of the liver disease after cancer treatment.”

“Usually, cancer cells grow over long periods of time before they can be detected as a tumor,” states first author Hiroko Ikenaga. “Our study showed that eliminating the hepatitis C virus with DAA suppresses tumor progression, which we suggest contributes to overall patient survival.”

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Persons With No Prior Hcv Treatment And No Evidence Of Cirrhosis

The approach to persons who are HCV treatment naive is relatively simple, with 4 safe, well-tolerated recommended DAA regimens that deliver HCV cure in > 95% of patients treated for 812 weeks . In clinical trials of modern oral DAAs, < 1% of patients discontinued oral DAAs due to an adverse event . Adverse events reported were similar among participants who received oral DAA and placebo with the most common side effects being fatigue, headache, nausea, and diarrhea . The safety and tolerability of these drug regimens allow for the delivery of HCV treatment by both specialists and generalists, including those in nontraditional medical practices such as addiction treatment centers.

What Does It Mean To Have A Successful Treatment What Is A Sustained Virologic Response

In an untreated state, the hepatitis C virus infects the cells of the liver and then continuously lives there, making copies of itself that circulate in the bloodstream. Antiviral medications can destroy the ability of the virus to reproduce, so the amount of virus in the bloodstream then decreases. The amount of virus in the blood is measured by aviral load.

Treatment is successful when the viral load drops toundetectablelevels, which means the virus cannot be detected in the bloodstream at all. The viral load becomes undetectable during treatment and remains undetected after treatment has ended. If there is still no detectable virus in the blood 12 weeks after the end of the treatment, the treatment was successful. This is called a Sustained Virologic Response .

A patient who has achieved an SVR is considered to be cured of the hepatitis C virus.

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What Drugs Cure Hepatitis C Infection

Most hepatitis C is currently treated with all-oral medical regimens of “direct-acting antivirals” or DAAs. DAAs is a term used to distinguish these hepatitis C drugs from an older generation of injected medicines that act indirectly on the immune response to the hepatitis C virus. DAAs act directly on the virus to block different steps in its life cycle. There are several DAAs that are used in combinations that have been scientifically proven to cure hepatitis C. They are not interchangeable, and some are only available combined in one pill or dose pack as a specific combination. DAAs are not used as single-drug therapy because of the high risk of the virus developing resistance and because they work best in combinations. The choice of which regimen to use depends upon the genotype of the virus, the level of liver fibrosis , and any drug resistance that may be present .

Examples of combination DAAs with cure rates between 91%-100% include:

• Harvoni
• Zepatier
• Mavyret

Genotype 1a and 1b are the commonest genotypes in the United States. Of all the genotypes, genotype 3 has been the most difficult to treat with DAAs alone and required the use of ribavirin, which has significant side effects. All genotypes can now be treated with oral DAAs without ribavirin. Some genotypes may still require the use of injected pegylated interferon and/or ribavirin if there is no response to DAAs.

What Can People Do To Help The Medications Work Best

• Take the medications every day
• Stay in touch with pharmacy to be sure that all refills are ready on time
• Take the medications exactly as prescribed
• Do not skip doses
• Get all blood tests done on time
• Go to all visits with providers as recommended
• Tell the provider about all other medications that are being taken – including over-the-counter medicines, vitamins, herbs, and supplements
• Complete the entire course of medication

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