“Remaining current on screening for hepatocellular carcinoma correlated with a “survival benefit” in older adults with hepatitis C virus-related cirrhosis who achieved viral cure but later developed HCC, according to researchers”
I find this discovery to be a real head scratcher. Alcohol fuels the damage HCV causes, so this kind of information fuels uncertainty. I guess it’s above my pay grade ¯\_(ツ)_/¯
Sadly the scourge of these diseases is back on the rise. Young women are at elevated risk of infection if they use injectable drugs. Like Nancy Reagan said, “Just Say No”…
This is a good article. It describes the current approach to care as well as some shortcomings reaching the goal of eradication by 2030. Check it out and expand your knowledge!
I find it sad when I hear these kind of things. With treatment so effective, why aren’t people lining up to rid themselves of this disease? It shouldn’t be a matter of funding when our governments throw money at everything, much of it wasted. These DAAs are tested and true. Let’s get these treatment opportunities made [easily] available, free, or at affordable costs to those wanting the cure. Rant over… for now.
We’re finally starting to see new action and studies into HCV. The last two years have been primarily Covid coverage. I’m glad science has continued to work on the Hep C virus. Here is some current news on recent advances.
Healio spoke with experts in HCV about treatment, the importance of screening, transplantation of HCV-positive organs, how the COVID-19 pandemic has affected hepatitis C elimination goals and challenges in the field.
Peer support greatly increases the success of others. Of course, we as a group of Dragon Warriors already knew that. This just provides additional proof of that!
Healio spoke with experts in HCV about treatment, the importance of screening, transplantation of HCV-positive organs, how the COVID-19 pandemic has affected hepatitis C elimination goals and challenges in the field.
How the COVID-19 pandemic has impacted the hepatitis C elimination goals – “we’re going to have to put our foot back on the gas and really accelerate our screening efforts and treatment efforts;”
It sounds like you’re dealing with the same Covid circus that we are. I don’t agree with the lockdown strategy at all, but they didn’t ask me and likely don’t care. The states here with the most restrictions are also the areas with the highest rates of infection. Our small businesses are being ruined by this and with that, the middle class citizens. Schools are shut down and video education has taken its place. It’s taking a grim toll on everyone.
Let‘s hope that this is behind us soon. Until 70% of the population is vaccinated, they say this will continue to be a problem. I don’t think they’ll get that many people to take it. At least not the first generation vaccine. There are too many questions surrounding the contents in it. They rushed it through, so I’m going to be watching for short and long term reactions before I take it. I hate to think they might try and make it mandatory by threatening your freedom to travel and work. Let’s hope it doesn’t come to that.
Stay safe, Brother! I’m glad you got that air conditioning. Sounds like you’ll need it soon!
Cheers!
Harry said
Dec 26, 2020
G'day Tig,no mate I don't think I will ever be ready for the heat of summer ,weather over here is getting more extreme, it's been a very quite Xmas ,all the borders are closed at the moment so makes it bit hard catching up with family,just hope the vaccine works out for U.S best wishes from Oz.
Cheddy said
Dec 20, 2020
Thanks, Harry! What a planet. We're just going in the dark, cold, short and rainy days of winter.
I hope your summer is not so blazing hot this year. Are you ready?
Harry said
Dec 19, 2020
Just sending prayers and best wishes to Tig,cheddy,815 everyone, from Harry in Australia,starting to get hot here now, please try stay safe.
Higher fibroscan liver stiffness after hepatitis C antiviral treatment was associated with the development of decompensated cirrhosis, according to study results.
“There are many routinely available clinical and laboratory predictors of the development of liver-related complications after anti-viral treatment, including age, a clinical diagnosis of cirrhosis, fibrosis-4 score, model for end-stage liver disease score and viral clearance by sustained virological response,” George N. Iaonnou, MD, MS, of Veterans Affairs Puget Sound Healthcare System, and colleagues wrote. “It is unclear if liver stiffness before or after treatment is independently associated with adverse liver outcomes even after adjustment for these predictors.”
Researchers analyzed data collected from United States veterans who initiated HCV treatment and had at least one liver stiffness before (n = 492) or after (n = 877) therapy. They assessed whether that liver stiffness impacted development of decompensated cirrhosis, hepatocellular carcinoma or death after adjusting for several factors, including history of cirrhosis, BMI and MELD score.
In the group that experienced post-treatment liver stiffness, 21 patients developed decompensated cirrhosis (2.4%), 26 developed HCC (3%) and 57 died or underwent liver transplantation (6.5%). Patients with post-treatment liver stiffness greater than 20 kilopascals had higher rates of developing decompensated cirrhosis (adjusted HR = 3.85; 95% CI, 1.29-11.5) compared with patients with liver stiffness no greater than 12.5 kPa. They also had higher rates of composite outcome of death, liver transplantation, decompensated cirrhosis or HCC (aHR = 1.95; 95% CI, 1.07-3.56).
Researchers found no associations between pre-treatment liver stiffness and any adverse outcome.
“In patients with HCV treated with anti-viral therapies, obtaining a post-treatment liver stiffness measurement may be beneficial in identifying patients at risk for long-term adverse outcomes,” Iaonnou and colleagues wrote.
Times are definitely a strange-o world! We're in the midst of some cataclysmic outbreak one day and then today they are saying many of the tests being done by small labs have been wrought with errors and false positives. I'm starting to waver in my belief that we're being told the truth, or at the least being able to trust the data. There are some genuine issues that must be dealt with, no question about that, but we need a consensus on the real impact and real solutions, not hyperbole from all directions. We've been promised that for too many decades with our own little problem! We have all learned to accept success with a large dose of skepticism!
I do believe we'll see a lessening of problems related to Covid, but think a lot of that will be allowing it to run it's course. In the meantime, I'm doing my part, by staying away from people and avoiding the argument. That works just fine for me. I wish I had a cabin in the Yukon, and no bills! Not much to ask is it?
Observer said
Jul 14, 2020
interesting.... I sure hope a universal cure is found and fast
please stay safe Tig ...the news makes it sound pretty frightening there right now
Tig said
Jul 13, 2020
This is interesting!
July 09, 2020
HCV DRUGS SOFOSBUVIR, DACLATASVIR SHOW PROMISE AS POTENTIAL COVID-19 TREATMENT
According to Hill, there is already enough generic mass produced to treat millions of people, if the treatment proves to be effective in larger trials.
To assess the effectiveness of the drug combination for moderate or severe COVID-19, Hill and colleagues gathered data on patients with COVID-19 at four Iranian University hospitals who were given the treatment during the first wave of the epidemic. Patients were randomly assigned to standard care (hydroxychloroquine ± lopinavir/ritonavir) with or without sofosbuvir and daclatasvir.
Of 66 patients assessed in the study, 33 received sofosbuvir and daclatasvir; the rest received the standard of care. Baseline characteristics were similar between the treatment groups.
Results showed that after 14 days, 29 patients (88%) in the sofosbuvir and daclatasvir group reached clinical recovery compared with 22 (67%) in the control group (P =.076). Patients in the sofosbuvir and daclatasvir group experienced a shorter duration of hospital stay and median time to discharge compared with the control group (6 vs. 8 days and 6 vs. 11 days, respectively).
Three patients in the sofosbuvir and daclatasvir group died compared with five in the control group. No serious adverse events were reported.
[Despite] these encouraging results, we believe it’s too early to reach a verdict on this treatment, Hill said. We need larger, well-designed studies to confirm our results. According to Hill, researchers have already set up a network of randomized trials to test the combination of sofosbuvir and daclatasvir in more than 2,000 patients with COVID-19 in Brazil. Egypt, South Africa and Iran. There are also more than 2,000 set to be enrolled in prevention trials testing the same drug combination.
National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, who spoke during the session, said the results from Hill and colleagues are really interesting and provocative.
The preliminary information is really interesting, because we desperately need an antiviral that can be given early on in the course of the disease to prevent individuals from going on to require hospitalization, Fauci said. I would encourage, as Dr. Hill did himself very clearly, further studies on this to nail this down in a randomized control trial.
Tig said
Apr 17, 2020
This is disturbing. Testing needs to be a front and center discussion!
More than 80% of people with chronic HBV in US are undiagnosed
In the United States, more than 80% of privately insured people with chronic hepatitis B infection remain undiagnosed, according to a recent study.
“As of 2015, WHO estimated that despite an effective vaccine that provides 98% to 100% protection against the hepatitis B virus (HBV), an estimated 292 million people were still living with chronic hepatitis B infection (CHB) worldwide. Left untreated, CHB can progress to cirrhosis and hepatocellular carcinoma,” EiichiOgawa,MD,PhD, of the division of gastroenterology and hepatology at Stanford University Medical Center, and colleagues wrote. “However, the number of people aware of having CHB is strikingly low. In 2016, the WHO suggested that only 10.5% (27 million) of those with CHB were aware of their illness; and of those, only 16.5% (4.5 million) were receiving treatment.”
To provide an accurate accounting of the number of patients with CHB aged 6 years or older in the U.S. who have not yet been diagnosed, Ogawa and colleagues performed a cross-sectional study using the commercial U.S. Truven Health Market Scan Database to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB.
According to the study, the researchers calculated the total population with CHB and the proportion of those who remained undiagnosed among 198,073,302 privately insured individuals and identified diagnosed CHB patients who received one or more prescription for CHB medications to calculate the treatment rate for those with severe disease.
Results showed that only 18.6% (95% CI, 13.5%-29.92%) of the 511,029 (95% CI, 317,733-704,325) individuals with CHB had been diagnosed, meaning that 81.4% (95% CI, 70.08%-86.5%) were undiagnosed. Additionally, treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma.
“This study found low rates of hepatitis B diagnosis among privately insured individuals, suggesting that barriers to diagnosis may be both financial and nonfinancial,” the authors concluded. “Additional research is needed to characterize these barriers and to develop interventions to improve diagnosis rates.” – by Caitlyn Stulpin
Disclosures: Ogawa reports no relevant financial disclosures. Please see the study for all other author’s relevant financial disclosures.
Cheddy said
Mar 25, 2020
Wow! Now, that's progress.
Tig said
Mar 25, 2020
FDA approves Epclusa for pediatric HCV
March 20, 2020
Epclusa is now available for the treatment of children with any of the six genotypes ofhepatitis C virusafter obtaining approval from the FDA, according to a press release.
Previously approved to treat HCV in adults, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) is indicated in pediatric patients aged 6 years and older or weighing at least 37 pounds.
“This approval will provide additional treatment options for children and adolescents with HCV,” Debra Birnkrant, MD, director of the division of antivirals in the FDA’s Center for Drug Evaluation and Research, said in the release. “This approval will also be important in settings where there is limited ability for health care professionals to conduct HCV genotype testing.”
Epclusa was evaluated in an open-label study of 173 pediatric patients with and without mild cirrhosis. Investigators found no difference between the pharmacokinetics seen in children and those found in adults. Additionally, among 102 patients between ages 12 and 17 years, 93% of patients with genotype 1 and 100% of patients with genotypes 2, 3, 4 and 6 had no detectable virus in the blood 12 weeks after finishing treatment.
For 71 patients between ages 6 and 11 years with HCV genotypes 1, 2, 3 and 4, 93% with genotype 1, 91% with genotype 3 and 100% with genotypes 2 and genotype 4 had no virus detected in the blood 12 weeks after finishing treatment.
“Gilead’s continued commitment to HCV elimination includes bringing our medicines to the most difficult-to-cure populations and today’s decision by the FDA represents an important step toward that goal,” MerdadParsey, MD, PhD, chief medical officer at Gilead Sciences, said in a company press release. “With consistently high cure rates in clinical trials and in the real world, Epclusa has the potential to help many of the children living with HCV in the United States.”
Combination therapy prevents HCV infection in non-viremic organ recipients
November 10, 2019
Jordan J. Feld
BOSTON — Hepatitis C infection was prevented or rapidly cured in transplant recipients who received organs from donors infected with the virus following combined treatment with ezetimibe and direct-acting antiviral therapy, according to study results presented at The Liver Meeting 2019.
“Unfortunately, most of you know that the opioid epidemic continues and, with that, an overdose crisis,” Jordan J. Feld, MD, MPH, FAASLD, from the University of Toronto University Health Network, said during a press conference. “What has been observed is that among potential organ donors, particularly those who died of overdose, the prevalence of hepatitis C has increased dramatically.”
During the study period, transplant specialists considered donors infected with HCV for lung, heart, kidney or kidney-pancreas recipients.
To test the possibility of preventing HCV infection, recipients received Mavyret (glecaprevir/pibrentasvir, AbbVie) with ezetimibe 6 hours to 12 hours before transplantation and then daily for 1-week posttransplant.
“Ezetimibe is a cholesterol-lowering drug that is approved and quite safe, but also happens to be a ligand ... for one of the entry factors that hepatitis C uses to enter hepatocytes,” Feld explained.
Of the 13 recipients without HCV who received HCV-infected organs, four developed quantifiable viremia posttransplant with a maximum HCV RNA of 2.96 log 10 IU/mL. HCV RNA declined rapidly and was unquantifiable by day 4 after transplant in all patients.
Six other patients had detectable but unquantifiable HCV RNA at day 1 posttransplant which was undetectable by day 2 in five patients and by day 4 in one patient.
All four patients with quantifiable HCV RNA received kidney or kidney-pancreas transplants, but no other factors correlated with posttransplant viremia. Additionally, Feld reported no relapses to date with a median follow-up of 10.2 weeks (range, 1-12.1 weeks).
Medication was well-tolerated with no serious adverse events related to treatment.
“Despite the horrible tragedy of the opioid epidemic, there is some good to come from the epidemic by using these organs for others,” Feld said. “But we must also focus on what we can do about this epidemic.” – by Talitha Bennett
Disclosure: Feld reports receiving grant or research support, and serving as a consultant for Abbott, AbbVie, Enanta, Gilead, Janssen, Merck and Roche.
PERSPECTIVE
Carlos Romero-Marrero
The proportion of hepatitis C-positive transplant donors has risen significantly with the opioid epidemic and several large series have shown that direct acting antiviral therapy is very effective among HCV-positive transplant recipients, with cure rates near 100%. In the past 2 years, emerging evidence has proven that the use of HCV-positive organs on transplant candidates who do not have HCV infection offers excellent patient and allograft outcomes.
The current posttransplant DAA treatment protocol in our center is to treat these patients for 12 weeks. This adds additional cost to the already high expense of organ transplantation. In this study, Feld and colleagues showed that a short-course therapy with Mavyret (glecaprevir/pibrentasvir, AbbVie) and ezetimibe (acting as an HCV cell entry blocker), given for one dose before transplant and 7 days after transplant, effectively and safely prevented HCV transmission in uninfected organ recipients receiving HCV infected donors.
Importantly, no liver transplant recipients were included in this study and therefore this is applicable for heart, lung, and kidney recipients. If these results are validated in other centers, this preemptive treatment should become the new standard of care to prevent HCV transmission in this patient population. The implementation of this strategy would lower the cost of treating these patients by more than 90% and allow for potential completion of HCV therapy before posttransplant hospital discharge.
Carlos Romero-Marrero, MD
Section Head of Hepatology Cleveland Clinic
Tig said
Dec 17, 2019
HCV-positive transplants into aviremic patients safe for multiple organs
Data from a large, real-world study contributed to the growing safety and efficacy evidence of transplanting hepatitis C-infected organs into aviremic patients in the direct-acting antiviral era.
“The introduction of direct-acting antiviral agents (DAAs) has led to a paradigm shift in the way HCV is approached. Several studies have now demonstrated their efficacy and safety in the posttransplant population,” Nikhil Kapila, MD, from the Cleveland Clinic in Florida and colleagues wrote. “More recently, HCV viremic allografts have been utilized successfully in viremic recipients, however their use in aviremic recipients is an area of intense interest.”
Between January 2018 and December 2018, 297 patients without HCV underwent solid organ transplants with viremic organs at the Cleveland Clinic. These included 64 cases of kidney transplantation, seven cases of heart transplantation, four cases of liver transplantation, two patients who underwent combined liver-kidney transplant, and one who underwent combined heart-kidney transplant.
“The optimal timing for initiation of DAA therapypost-transplant remains controversial,” the researchers wrote. “Initially, our center’s approach was to initiate DAA therapy within one month of transplant, however 10 patients were observed to have detectable HCV after 4 weeks of treatment. The persistence of HCV, despite DAA treatment, led to a modification in our protocol whereby we aimed to begin DAA therapy 12 weeks after transplant.”
As of April 20, 2019, 58 patients who received HCV-infected kidneys have either started or completed DAA treatment. Forty-one patients achieved SVR, 10 patients achieved undetectable viral loads posttreatment without clinical SVR, and seven patients remain on treatment. One patient did not respond to DAA therapy due to NS5A resistance and remains on treatment.
All patients who received liver transplants started treatment with Mavyret (glecaprevir/pibrentasvir, AbbVie) without ribavirin posttransplant. Three achieved SVR, one completed therapy and is awaiting SVR readout, and two remain on treatment.
Patients who received heart transplants also started DAA therapy posttransplant, of whom four received glecaprevir/pibrentasvir and the other half received Harvoni (ledipasvir/sofosbuvir, Gilead Sciences). Six achieved SVR and the others remain on treatment.
“Based on our center’s real-world experience, we believe that DAA therapy should be ordered and initiated once a patient is confirmed to be viremic, clinical parameters have stabilized, and insurance approval is obtained,” Kapila and colleagues wrote. “As transplant centers expand their donor pool and increase utilization of HCV viremic organs, the early initiation of anti-viral therapy should become the standard of care.” – by Talitha Bennett
Disclosures: The authors report no relevant financial disclosures.
Tig said
Dec 15, 2019
Retreatment for HCV May Require Switching DAA inhibitor Classes
Dietz J, et al. Clin Gastroenterol Hepatol. 2019;doi:10.1016/j.cgh.2019.10.051. December 10, 2019
Patients who failed to achieve sustained virologic response after initial treatment for hepatitis C achieved high cure rates during retreatment after switching from an NS5A inhibitor direct-acting antiviral to a protease inhibitor.
“The management of DAA failure patients remains a challenge,” Julia Dietz, MD, from the Goethe University Hospital in Frankfurt, Germany, and colleagues wrote. They highlighted the fact that many patients develop resistance associated substitutions (RASs), particularly NS5A RASs, and there remains limited data on retreatment success.
To analyze the efficacy of retreatment with first generation DAAs, Dietz and colleagues reviewed data from 631 patients, 262 of whom completed retreatment.
Patients with genotype 1 initially received a combination of Sovaldi (sofosbuvir, Gilead Sciences) and an NS5A inhibitor, and those with genotype 3 underwent treatment with combination Daklinza (daclatasvir, Bristol-Myers Squibb) and sofosbuvir.
The SVR rates at follow-up were overall 84% among patients with genotype 1, 91% for those who received a regimen with sofosbuvir and a protease inhibitor, and 90% among those with RASs. Retreatment with a protease inhibitor without sofosbuvir was less effective with an SVR rate of 82%.
Repetition of treatment with sofosbuvir and an NS5A inhibitor without a protease inhibitor was comparatively ineffective with an SVR of 68%.
All patients with genotype 3 underwent retreatment with an NS5A inhibitor and sofosbuvir and 60% achieved SVR. Most of these patients had developed NS5A RASs (93%) and the SVR rates were higher in the absence of cirrhosis and Y93H.
“Interestingly, in a recent study with inclusion of a [protease inhibitor] ... the majority of treatment failures had [genotype 3],” Dietz and colleagues wrote, referring to Vosevi (sofosbuvir/velpatasvir/voxilaprevir, Gilead Sciences). “Thus, retreatment of [genotype 3] remains a challenge.” – by Talitha Bennett
Disclosures: Dietz reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
Tig said
Nov 23, 2019
Here’s a good article. It’s nice to know these DAA’s are very safe and effective in patients with severe renal disease.
Gilead DAAs safe, effective for adults with HCV, severe renal impairment
November 21, 2019
The FDA approved changes to the product labels for direct-acting antivirals Harvoni, Epclusa, and Vosevi to include new efficacy and safety data for adults with hepatitis C and severe renal impairment, including those who require dialysis.
“The product labeling updates for Epclusa, Harvoni and Vosevi recognize the high unmet need for effective HCV treatments for patients with severe renal impairment, including those with end stage renal disease (ESRD) who are on dialysis,” Gilead said in a statement sent to Healio Gastroenterology and Liver Disease. “People with chronic HCV who are on dialysis as a result of ESRD have an increased risk of morbidity and mortality. Prior HCV treatment options for this population have been associated with clinical barriers resulting in continued unmet medical need, and these approvals provide important new options for these patients.”
Harvoni (sofosbuvir/ledipasvir, Gilead Sciences) required no dosage adjustment for patients with mild, moderate or severe renal impairment including end-stage renal disease. The most common adverse events among patients with ESRD were insomnia and headache.
In a trial of adults with chronic HCV and ESRD requiring dialysis, the sustained virologic response was 93% in 45 treatment-naive patients who received 8 weeks of sofosbuvir/ledipasvir, 100% in 12 patients who received 12 weeks of treatment, and 83% in six treatment-experienced patients with cirrhosis who received 24 weeks of treatment.
Similarly, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) required no dosage adjustment for any degree of renal impairment and the most common adverse event among patients with ESRD was nausea.
Results from a trial of 59 patients with HCV and ESRD requiring dialysis showed an overall SVR rate of 95% after 12 weeks of treatment with sofosbuvir/velpatasvir, including patients with cirrhosis (29%) and those who were treatment-experienced (22%).
Vosevi (sofosbuvir/velpatasvir/voxilaprevir or SOF/VEL/VOX, Gilead Sciences) also required no dosage adjustment for any degree of renal impairment.
Pharmacokinetics of sofosbuvir and velpatasvir among patients with HCV and ESRD requiring dialysis for 12 weeks were consistent with patients with ESRD without HCV. The pharmacokinetics of voxilaprevir have not been studied in patients with ESRD; however, the FDA noted that voxilaprevir exposure following treatment with SOF/VEL/VOX combination is not expected to be meaningfully altered in patients with HCV and ESRD requiring dialysis compared with patients with normal renal function.
Reference: www.fda.gov
Tig said
Oct 30, 2019
HCV vaccine regimen fails to prevent chronic infections
October 5, 2019
Andrea L. Cox, MD, PhD
WASHINGTON — An investigational vaccine regimen failed to prevent chronic hepatitis C virus infection in a cohort of at-risk adults, according to results of a clinical trial presented at IDWeek.
Recently, study findings published in The Lancet suggested the WHO goal to eliminate HCV globally by 2030 will be “narrowly missed.” A vaccine, researchers said, will be crucial to elimination efforts.
Andrea L. Cox, MD, PhD, a professor of medicine at Johns Hopkins University, and colleagues conducted the first prophylactic HCV vaccine efficacy trial — a randomized, multicenter, double-blind, placebo-controlled study called Vaccine is Prevention. The vaccine regimen is based on viral vectors, consisting of a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara virus boost. In the study, 455 participants aged 18 to 45 years who injected drugs received either the vaccine regimen or placebo at days 0 and 56.
The study took place at three sites in the United States — the University of California, San Francisco, Johns Hopkins and the University of New Mexico, Cox said.
According to the researchers, the overall incidence of HCV infection at 6 months was 13 infections per 100 person-years. This is substantially lower than the incidence in the background populations of the study sites, Cox said, probably because of “aggressive counseling and referral to drug treatment and needle exchange programs” during the trial.
Cox and colleagues found no difference in the development of chronic infection between the vaccine and placebo arms, with 14 cases in each. The regimen’s efficacy in preventing chronic infection was –0.53 (95% CI, –2.5 to 0.34).
However, the vaccine regimen blunted the peak HCV RNA level in recipients 1 month after vaccination compared with placebo — a statistically significant finding, Cox noted. In terms of immunogenicity, the vaccine regimen induced an immune response in 78% of recipients, which is a less robust response that what was observed in an earlier study of healthy volunteers, she said.
According to the researchers, there were no safety signals in the study, and the regimen was well-tolerated, with no serious vaccine-related adverse events.
“There remains a significant need for vaccine to interrupt transmission, and it will be critical for achieving WHO elimination goals,” Cox said. “Testing vaccines in [people who inject drugs] is possible, but additional strategies will need to be considered — ideally, with information gained from this vaccine, informing future vaccine design.” – by John Schoen
Heffernan A, et al. Lancet 2019;doi:10.1016/S0140-6736(18)32277-3.
Tig said
Oct 5, 2019
Here’s some good news!
FDA NEWS
FDA expands Mavyret approval for adults, children with any HCV genotype
September 27, 2019
The FDA has expanded the approval of Mavyret for a treatment duration of 8 weeks to include treatment-naive adults and children aged 12 years and older with chronic hepatitis C genotype 1 through 6 and compensated cirrhosis.
The label expansion of Mavyret (glecaprevir/pibrentasvir, AbbVie) was based on data from the phase 3b EXPEDITION-8 study that included patients with any of the six HCV genotypes. Twelve weeks after treatment, 98% of the 343 enrolled patients achieved sustained virologic response.
“This approval provides a treatment duration of 8 weeks for both pediatric and adult patients with compensated cirrhosis regardless of HCV genotype,” Jeffrey Murray, MD, deputy director of the division of antiviral products in the FDA’s Center for Drug Evaluation and Research, said in the FDA brief. “[Glecaprevir/pibrentasvir] is a combination of direct-acting antiviral drugs that reduce the amount of HCV in the body to undetectable levels by preventing the virus from multiplying, and in most cases, curing HCV infection.”
Additional data from the EXPEDITION-8 study showed that the most common adverse events were fatigue (8%), pruritus (7%) and headache (6%).
“While over 100,000 patients have been prescribed [glecaprevir/pibrentasvir] for chronic HCV in the U.S., there are still a significant number of patients that need options,” Janet Hammond, MD, PhD, vice president of the general medicine and virology therapeutic area at AbbVie, said in a press release. “This approval provides more HCV patients an option to treat their disease in as little as 8 weeks.”
Resistance-guided direct-acting antiviral retreatment resulted in nearly 90% sustained virologic response rates among patients with hepatitis C who developed resistance-associated substitutions after failing treatment with NS5A inhibitors.
In their study, Ana Belén Pérez, from the University Hospital Reina Sofía in Córdoba, Spain, and colleagues provided indications on how to use resistance information in settings where Vosevi (sofosbuvir/velpatasvir/voxilaprevir, Gilead Sciences) may not be available.
“We believe that our data may be of special relevance for those countries where new drug combinations are still not available, and may allow treating patients at a lower cost, avoiding drug-drug interaction and preserving the three-drug combination regimen,” they wrote. “We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians.”
The study comprised 185 patients who did not respond to Harvoni (sofosbuvir/ledipasvir, Gilead Sciences), 79 who did not respond to combination Sovaldi (sofosbuvir, Gilead Sciences) and Daklinza (daclatasvir, Bristol-Myers Squibb), and 68 who did not respond to Viekira Pak (paritaprevir/ritonavir/ombitasvir/dasabuvir), all of whom also received ribavirin.
All patients received retreatment with sofosbuvir with an NS5A inhibitor and ribavirin for 12 or 24 weeks.
“When available, velpatasvir should be the NS5A component of the new retreatment regimen; if not available, the previously used NS5A inhibitor may be recycled adding ribavirin and extending the duration for 24 weeks,” the researchers wrote.”
Results from modified intention-to-treat analysis — excluding all patients unavailable for follow-up at 12 weeks — the SVR rates were 88.1% for those previously treated with sofosbuvir/ledispasvir, 83.3% for those treated with sofosbuvir and daclatasvir and 93.7% for those treated with ombitasvir-containing regimens.
“When possible, simeprevir-based regimens should be avoided, especially for patients with cirrhosis,” Pérez and colleagues explained. They continued to explain that most of the patients infected with genotype 3 were retreated and cured with a combination of sofosbuvir, an NS5A inhibitor and ribavirin after 24 weeks or a regimen of sofosbuvir with an additional two or three drugs and ribavirin, especially if Y93H is present. – by Talitha Bennett
Disclosures: Pérez reports that the study was supported in part by grants from Fondo de Investigación Sanitaria, Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER, Fundación Progreso y Salud, Junta de Andalucia, and GEHEP-SEIMC.
Tig said
Sep 10, 2019
The benefits of treatment and SVR continue to soar!
Patient-reported outcomes greatly altered by HCV treatment results
In a follow-up analysis of participants in clinical trials, researchers found that patient-reported outcome scores increased in patients who achieved sustained virologic response after treatment for hepatitis C, whereas scores decreased in those who did not.
“Although historical treatment regimens with interferon were plagued by low efficacy and significant side effects impairing patients’ well-being and, thus, PROs, the trajectory of HCV treatment changed about 5 years ago with the development of direct-acting antiviral (DAA) agents,” Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Hospital in Virginia, and colleagues wrote. “The PRO evidence generated by these two prospective registry studies support the unquestionable benefit of SVR for patients’ experience as opposed to the clear deleterious impact of HCV viremia.”
Younossi and colleagues assessed the health-related quality of life of 4,234 patients who achieved SVR and 242 patients who did not using the SF-36 instrument. Before treatment, PRO scores of both groups were similar to or higher than the general U.S. population and similar to each other.
At baseline for this study, patients who achieved SVR experienced improvements in all eight domains of the SF-36 (range increase, 3.6-8.1; P < .0001), while the scores of those without SVR remained the same with the exception of the General Health domain, which decreased by 2.8 points (P = .008).
Patients without SVR experienced further PRO decrements at 12-week follow-up: up to –7 points from before treatment in the Role Physical, General Health, Social Functioning and Role Emotional domains and both summary scores; up to –9.2 points in all PRO domains at week 24; up to –8.3 points in five domains at week 48; and up to –9 points in four domains at week 96 (P < .05).
In contrast, patients with SVR experienced sustained improvement of PRO scores with up to 7 points at week 24, up to 6.9 points at week 48, and up to 6.1 points at week 96 (P < .001). Multivariate analysis confirmed that SVR correlated independently with superior scores in all PRO domains with an increased range of 4.8 points to 15.9 points (P < .01).
“In order to fully understand the comprehensive benefit of HCV cure, these PRO gains should always accompany the clinical consequences of SVR, such as lower rates of cirrhosis and hepatocellular carcinoma,” Younossi and colleagues concluded. “These data must be considered by providers, payers, and policy makers to fully appreciate the comprehensive benefit of HCV cure and to assure that all HCV patients are identified and treated with the most effective antiviral regimens.” – by Talitha Bennett
Disclosures: Younossi reports that the study was partially supported by Gilead Sciences and that he has received research funds or served as consultant to AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept, Novo Nordisk, Terns and Viking. Please see the full study for all other authors’ relevant financial disclosures.
Tig said
Aug 28, 2019
Some recent updates regarding initial testing recommendations. No longer are Boomers the only age group being targeted for testing. With the illegal opioid problem, the exposure from IVDU and other forms of blood exposure, we are seeing a resurgence in HCV diagnosis.
The U.S. Preventive Services Task Force has issued a draft recommendation that encourages clinicians to screen all adults aged 18 to 79 years for hepatitis C virus infection.
The task force also suggests that physicians consider screening patients for HCV who are aged younger than 18 years and older than 79 years if they are at high risk for infection.
The USPSTF reported that in 2016, there were an estimated 41,200 new HCV infections in the United States and that the number of cases of acute HCV infection have increased approximately 3.5-fold over the last 10 years. The increase is largely attributable to young, white people who inject drugs, particularly those who live in rural areas, and a hike in number of women aged 15 to 44 years infected with HCV, according to the task force. obe
“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening,” Douglas K. Owens, MD, MS, task force chair and general internist at the Veterans Affairs Palo Alto Health Care System, said in a press release.
The USPSTF’s draft statement and evidence review has been posted for public comment on the USPSTF website: www.uspreventiveservicestaskforce.org. Input will be accepted through Sept. 23, 2019, at www.uspreventiveservicestaskforce.org/tfcomment.htm.
The new “B” recommendation replaces the USPSTF’s 2013 recommendation that clinicians screen patients at high risk for HCV and offer one-time testing to adults born between 1945 and 1965. The CDC currently recommends HCV testing for baby boomers, injection drug users, and recipients of organ transplants or blood transfusions prior to July 1992. – by Janel Miller
Disclosures: Owens reports no relevant financial disclosures. Please see the USPSTF website for all other task force members’ relevant financial disclosures.
Cheddy said
Aug 18, 2019
Really good news. We're definitely closing in on this virus.
Having been cured with Sovaldi and Ribavirin, I have to be thankful for it, but it was not pretty. I wonder if there is a reason to use this combo specifically when more recent treatments have become so much kinder?
Bridging the data gap is essential to eliminating Hep C. Sadly we are far behind in our goal to eliminate HCV by 2030. Much work is needed with PWID.
Data Gap and HCV
Advances in Robotic Liver Transplantation
This is an incredible advancement in care!
Fully Robotic Transplant
Very informative, and worth reviewing. We have a lot more to accomplish!
World Hepatitis Day July 28th
It remains important!
“Remaining current on screening for hepatocellular carcinoma correlated with a “survival benefit” in older adults with hepatitis C virus-related cirrhosis who achieved viral cure but later developed HCC, according to researchers”
HCC Screening after HCV
Key takeaways:
DAA treatment ‘longitudinally continues to improve’ liver-related survival in HCV
This is an interesting finding. Aspirin for the win!
Low dose Aspirin and fatty liver reduction
It’s time for Gastro’s to step up!
Chronic Liver Disease
Triple Testing: HIV, HBV, HCV
Liver Fibrosis Screening: ALD and MASLD
I find this discovery to be a real head scratcher. Alcohol fuels the damage HCV causes, so this kind of information fuels uncertainty. I guess it’s above my pay grade ¯\_(ツ)_/¯
Alcohol doesn’t impact SVR?
Thanks Tig. That was really great.
This is worth a read.
‘We’re not waiting’: World Hepatitis Day
Well, this isn’t going in the right direction
HCV Cure Rates Jarringly Low
Sadly the scourge of these diseases is back on the rise. Young women are at elevated risk of infection if they use injectable drugs. Like Nancy Reagan said, “Just Say No”…
Young Women IVDU at Higher Risk for HCV & HIV
This is a good article. It describes the current approach to care as well as some shortcomings reaching the goal of eradication by 2030. Check it out and expand your knowledge!
HCV Elimination 2030
Controlling HCV
I find it sad when I hear these kind of things. With treatment so effective, why aren’t people lining up to rid themselves of this disease? It shouldn’t be a matter of funding when our governments throw money at everything, much of it wasted. These DAAs are tested and true. Let’s get these treatment opportunities made [easily] available, free, or at affordable costs to those wanting the cure. Rant over… for now.
Although cure rates with DAAs top 97%, less than two-thirds of patients receive treatment
This is a good article on the use of Vosevi as a rescue treatment in the rare instance of initial (DAA) treatment failure. Check it out.
Vosevi Rescue
I believe this will be in the future for HCV care. If we’re going to beat it we have to widen our approach. Safely, of course.
HCV care must ‘move away from the ivory tower’ to achieve elimination
Ramping up HCV elimination tactics could save 90,000 lives, $60 billion by 2050
This is a substantial increase over previous beliefs. Increasing testing across the board will be a valuable step.
Vertical Transmission
We’re finally starting to see new action and studies into HCV. The last two years have been primarily Covid coverage. I’m glad science has continued to work on the Hep C virus. Here is some current news on recent advances.
HCV Updates
Healio spoke with experts in HCV about treatment, the importance of screening, transplantation of HCV-positive organs, how the COVID-19 pandemic has affected hepatitis C elimination goals and challenges in the field.
HCV Video Perspectives
Peer support greatly increases the success of others. Of course, we as a group of Dragon Warriors already knew that. This just provides additional proof of that!
Peer Support Works
HCC algorithm to assess risk.
Liver Cancer Testing
More European countries suspend AstraZeneca's Covid19 vaccine rollout.
Healio Update
Healio spoke with experts in HCV about treatment, the importance of screening, transplantation of HCV-positive organs, how the COVID-19 pandemic has affected hepatitis C elimination goals and challenges in the field.
How the COVID-19 pandemic has impacted the hepatitis C elimination goals – “we’re going to have to put our foot back on the gas and really accelerate our screening efforts and treatment efforts;”
HCV Video Perspectives
Seven recent reports in Hepatology.
Healio/HCV Updates
I'm going with Fauci.
Q&A: What do we know so far about the SARS-CoV-2 variant in the UK?
Healio Update UK
Hello Harry,
It sounds like you’re dealing with the same Covid circus that we are. I don’t agree with the lockdown strategy at all, but they didn’t ask me and likely don’t care. The states here with the most restrictions are also the areas with the highest rates of infection. Our small businesses are being ruined by this and with that, the middle class citizens. Schools are shut down and video education has taken its place. It’s taking a grim toll on everyone.
Let‘s hope that this is behind us soon. Until 70% of the population is vaccinated, they say this will continue to be a problem. I don’t think they’ll get that many people to take it. At least not the first generation vaccine. There are too many questions surrounding the contents in it. They rushed it through, so I’m going to be watching for short and long term reactions before I take it. I hate to think they might try and make it mandatory by threatening your freedom to travel and work. Let’s hope it doesn’t come to that.
Stay safe, Brother! I’m glad you got that air conditioning. Sounds like you’ll need it soon!
Cheers!
Thanks, Harry! What a planet. We're just going in the dark, cold, short and rainy days of winter.
I hope your summer is not so blazing hot this year. Are you ready?
Just sending prayers and best wishes to Tig,cheddy,815 everyone, from Harry in Australia,starting to get hot here now, please try stay safe.
Updates in Hepatology - HCV
Holy Smokes! An actual HCV Video Update, woohoo
HCV Video Perspectives
Post-HCV treatment liver stiffness linked with adverse outcomes
Higher fibroscan liver stiffness after hepatitis C antiviral treatment was associated with the development of decompensated cirrhosis, according to study results.
“There are many routinely available clinical and laboratory predictors of the development of liver-related complications after anti-viral treatment, including age, a clinical diagnosis of cirrhosis, fibrosis-4 score, model for end-stage liver disease score and viral clearance by sustained virological response,” George N. Iaonnou, MD, MS, of Veterans Affairs Puget Sound Healthcare System, and colleagues wrote. “It is unclear if liver stiffness before or after treatment is independently associated with adverse liver outcomes even after adjustment for these predictors.”
Researchers analyzed data collected from United States veterans who initiated HCV treatment and had at least one liver stiffness before (n = 492) or after (n = 877) therapy. They assessed whether that liver stiffness impacted development of decompensated cirrhosis, hepatocellular carcinoma or death after adjusting for several factors, including history of cirrhosis, BMI and MELD score.
In the group that experienced post-treatment liver stiffness, 21 patients developed decompensated cirrhosis (2.4%), 26 developed HCC (3%) and 57 died or underwent liver transplantation (6.5%). Patients with post-treatment liver stiffness greater than 20 kilopascals had higher rates of developing decompensated cirrhosis (adjusted HR = 3.85; 95% CI, 1.29-11.5) compared with patients with liver stiffness no greater than 12.5 kPa. They also had higher rates of composite outcome of death, liver transplantation, decompensated cirrhosis or HCC (aHR = 1.95; 95% CI, 1.07-3.56).
Researchers found no associations between pre-treatment liver stiffness and any adverse outcome.
“In patients with HCV treated with anti-viral therapies, obtaining a post-treatment liver stiffness measurement may be beneficial in identifying patients at risk for long-term adverse outcomes,” Iaonnou and colleagues wrote.
Healio Link
Hi Obs,
Times are definitely a strange-o world! We're in the midst of some cataclysmic outbreak one day and then today they are saying many of the tests being done by small labs have been wrought with errors and false positives. I'm starting to waver in my belief that we're being told the truth, or at the least being able to trust the data. There are some genuine issues that must be dealt with, no question about that, but we need a consensus on the real impact and real solutions, not hyperbole from all directions. We've been promised that for too many decades with our own little problem! We have all learned to accept success with a large dose of skepticism!
I do believe we'll see a lessening of problems related to Covid, but think a lot of that will be allowing it to run it's course. In the meantime, I'm doing my part, by staying away from people and avoiding the argument. That works just fine for me. I wish I had a cabin in the Yukon, and no bills! Not much to ask is it?
interesting.... I sure hope a universal cure is found and fast
please stay safe Tig ...the news makes it sound pretty frightening there right now
This is interesting!
According to Hill, there is already enough generic mass produced to treat millions of people, if the treatment proves to be effective in larger trials.
To assess the effectiveness of the drug combination for moderate or severe COVID-19, Hill and colleagues gathered data on patients with COVID-19 at four Iranian University hospitals who were given the treatment during the first wave of the epidemic. Patients were randomly assigned to standard care (hydroxychloroquine ± lopinavir/ritonavir) with or without sofosbuvir and daclatasvir.
Of 66 patients assessed in the study, 33 received sofosbuvir and daclatasvir; the rest received the standard of care. Baseline characteristics were similar between the treatment groups.
Three patients in the sofosbuvir and daclatasvir group died compared with five in the control group. No serious adverse events were reported.
[Despite] these encouraging results, we believe it’s too early to reach a verdict on this treatment, Hill said. We need larger, well-designed studies to confirm our results.
According to Hill, researchers have already set up a network of randomized trials to test the combination of sofosbuvir and daclatasvir in more than 2,000 patients with COVID-19 in Brazil. Egypt, South Africa and Iran. There are also more than 2,000 set to be enrolled in prevention trials testing the same drug combination.
National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, who spoke during the session, said the results from Hill and colleagues are really interesting and provocative.
The preliminary information is really interesting, because we desperately need an antiviral that can be given early on in the course of the disease to prevent individuals from going on to require hospitalization, Fauci said. I would encourage, as Dr. Hill did himself very clearly, further studies on this to nail this down in a randomized control trial.
This is disturbing. Testing needs to be a front and center discussion!
More than 80% of people with chronic HBV in US are undiagnosed
Ogawa E, et al. JAMA Netw Open. 2020;doi:10.1001/jamanetworkopen.2020.1844.
April 13, 2020
In the United States, more than 80% of privately insured people with chronic hepatitis B infection remain undiagnosed, according to a recent study.
“As of 2015, WHO estimated that despite an effective vaccine that provides 98% to 100% protection against the hepatitis B virus (HBV), an estimated 292 million people were still living with chronic hepatitis B infection (CHB) worldwide. Left untreated, CHB can progress to cirrhosis and hepatocellular carcinoma,” EiichiOgawa, MD, PhD, of the division of gastroenterology and hepatology at Stanford University Medical Center, and colleagues wrote. “However, the number of people aware of having CHB is strikingly low. In 2016, the WHO suggested that only 10.5% (27 million) of those with CHB were aware of their illness; and of those, only 16.5% (4.5 million) were receiving treatment.”
To provide an accurate accounting of the number of patients with CHB aged 6 years or older in the U.S. who have not yet been diagnosed, Ogawa and colleagues performed a cross-sectional study using the commercial U.S. Truven Health Market Scan Database to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB.
According to the study, the researchers calculated the total population with CHB and the proportion of those who remained undiagnosed among 198,073,302 privately insured individuals and identified diagnosed CHB patients who received one or more prescription for CHB medications to calculate the treatment rate for those with severe disease.
Results showed that only 18.6% (95% CI, 13.5%-29.92%) of the 511,029 (95% CI, 317,733-704,325) individuals with CHB had been diagnosed, meaning that 81.4% (95% CI, 70.08%-86.5%) were undiagnosed. Additionally, treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma.
“This study found low rates of hepatitis B diagnosis among privately insured individuals, suggesting that barriers to diagnosis may be both financial and nonfinancial,” the authors concluded. “Additional research is needed to characterize these barriers and to develop interventions to improve diagnosis rates.” – by Caitlyn Stulpin
Disclosures: Ogawa reports no relevant financial disclosures. Please see the study for all other author’s relevant financial disclosures.
Wow! Now, that's progress.
FDA approves Epclusa for pediatric HCV
March 20, 2020
Epclusa is now available for the treatment of children with any of the six genotypes of hepatitis C virus after obtaining approval from the FDA, according to a press release.
Previously approved to treat HCV in adults, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) is indicated in pediatric patients aged 6 years and older or weighing at least 37 pounds.
“This approval will provide additional treatment options for children and adolescents with HCV,” Debra Birnkrant, MD, director of the division of antivirals in the FDA’s Center for Drug Evaluation and Research, said in the release. “This approval will also be important in settings where there is limited ability for health care professionals to conduct HCV genotype testing.”
Epclusa was evaluated in an open-label study of 173 pediatric patients with and without mild cirrhosis. Investigators found no difference between the pharmacokinetics seen in children and those found in adults. Additionally, among 102 patients between ages 12 and 17 years, 93% of patients with genotype 1 and 100% of patients with genotypes 2, 3, 4 and 6 had no detectable virus in the blood 12 weeks after finishing treatment.
For 71 patients between ages 6 and 11 years with HCV genotypes 1, 2, 3 and 4, 93% with genotype 1, 91% with genotype 3 and 100% with genotypes 2 and genotype 4 had no virus detected in the blood 12 weeks after finishing treatment.
“Gilead’s continued commitment to HCV elimination includes bringing our medicines to the most difficult-to-cure populations and today’s decision by the FDA represents an important step toward that goal,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in a company press release. “With consistently high cure rates in clinical trials and in the real world, Epclusa has the potential to help many of the children living with HCV in the United States.”
Reference:
FDA.gov
Gilead.com
Good article
Combination therapy prevents HCV infection in non-viremic organ recipients
November 10, 2019
BOSTON — Hepatitis C infection was prevented or rapidly cured in transplant recipients who received organs from donors infected with the virus following combined treatment with ezetimibe and direct-acting antiviral therapy, according to study results presented at The Liver Meeting 2019.
“Unfortunately, most of you know that the opioid epidemic continues and, with that, an overdose crisis,” Jordan J. Feld, MD, MPH, FAASLD, from the University of Toronto University Health Network, said during a press conference. “What has been observed is that among potential organ donors, particularly those who died of overdose, the prevalence of hepatitis C has increased dramatically.”
During the study period, transplant specialists considered donors infected with HCV for lung, heart, kidney or kidney-pancreas recipients.
To test the possibility of preventing HCV infection, recipients received Mavyret (glecaprevir/pibrentasvir, AbbVie) with ezetimibe 6 hours to 12 hours before transplantation and then daily for 1-week posttransplant.
“Ezetimibe is a cholesterol-lowering drug that is approved and quite safe, but also happens to be a ligand ... for one of the entry factors that hepatitis C uses to enter hepatocytes,” Feld explained.
Of the 13 recipients without HCV who received HCV-infected organs, four developed quantifiable viremia posttransplant with a maximum HCV RNA of 2.96 log 10 IU/mL. HCV RNA declined rapidly and was unquantifiable by day 4 after transplant in all patients.
Six other patients had detectable but unquantifiable HCV RNA at day 1 posttransplant which was undetectable by day 2 in five patients and by day 4 in one patient.
All four patients with quantifiable HCV RNA received kidney or kidney-pancreas transplants, but no other factors correlated with posttransplant viremia. Additionally, Feld reported no relapses to date with a median follow-up of 10.2 weeks (range, 1-12.1 weeks).
Medication was well-tolerated with no serious adverse events related to treatment.
“Despite the horrible tragedy of the opioid epidemic, there is some good to come from the epidemic by using these organs for others,” Feld said. “But we must also focus on what we can do about this epidemic.” – by Talitha Bennett
Reference: Feld JJ. Abstract 0038. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Disclosure: Feld reports receiving grant or research support, and serving as a consultant for Abbott, AbbVie, Enanta, Gilead, Janssen, Merck and Roche.
Carlos Romero-Marrero
The proportion of hepatitis C-positive transplant donors has risen significantly with the opioid epidemic and several large series have shown that direct acting antiviral therapy is very effective among HCV-positive transplant recipients, with cure rates near 100%. In the past 2 years, emerging evidence has proven that the use of HCV-positive organs on transplant candidates who do not have HCV infection offers excellent patient and allograft outcomes.
The current posttransplant DAA treatment protocol in our center is to treat these patients for 12 weeks. This adds additional cost to the already high expense of organ transplantation. In this study, Feld and colleagues showed that a short-course therapy with Mavyret (glecaprevir/pibrentasvir, AbbVie) and ezetimibe (acting as an HCV cell entry blocker), given for one dose before transplant and 7 days after transplant, effectively and safely prevented HCV transmission in uninfected organ recipients receiving HCV infected donors.
Importantly, no liver transplant recipients were included in this study and therefore this is applicable for heart, lung, and kidney recipients. If these results are validated in other centers, this preemptive treatment should become the new standard of care to prevent HCV transmission in this patient population. The implementation of this strategy would lower the cost of treating these patients by more than 90% and allow for potential completion of HCV therapy before posttransplant hospital discharge.
Cleveland Clinic
HCV-positive transplants into aviremic patients safe for multiple organs
Kapila N, et al. Hepatol. 2019;doi:10.1002/hep.31011.
December 16, 2019
Data from a large, real-world study contributed to the growing safety and efficacy evidence of transplanting hepatitis C-infected organs into aviremic patients in the direct-acting antiviral era.
“The introduction of direct-acting antiviral agents (DAAs) has led to a paradigm shift in the way HCV is approached. Several studies have now demonstrated their efficacy and safety in the posttransplant population,” Nikhil Kapila, MD, from the Cleveland Clinic in Florida and colleagues wrote. “More recently, HCV viremic allografts have been utilized successfully in viremic recipients, however their use in aviremic recipients is an area of intense interest.”
Between January 2018 and December 2018, 297 patients without HCV underwent solid organ transplants with viremic organs at the Cleveland Clinic. These included 64 cases of kidney transplantation, seven cases of heart transplantation, four cases of liver transplantation, two patients who underwent combined liver-kidney transplant, and one who underwent combined heart-kidney transplant.
“The optimal timing for initiation of DAA therapypost-transplant remains controversial,” the researchers wrote. “Initially, our center’s approach was to initiate DAA therapy within one month of transplant, however 10 patients were observed to have detectable HCV after 4 weeks of treatment. The persistence of HCV, despite DAA treatment, led to a modification in our protocol whereby we aimed to begin DAA therapy 12 weeks after transplant.”
As of April 20, 2019, 58 patients who received HCV-infected kidneys have either started or completed DAA treatment. Forty-one patients achieved SVR, 10 patients achieved undetectable viral loads posttreatment without clinical SVR, and seven patients remain on treatment. One patient did not respond to DAA therapy due to NS5A resistance and remains on treatment.
All patients who received liver transplants started treatment with Mavyret (glecaprevir/pibrentasvir, AbbVie) without ribavirin posttransplant. Three achieved SVR, one completed therapy and is awaiting SVR readout, and two remain on treatment.
Patients who received heart transplants also started DAA therapy posttransplant, of whom four received glecaprevir/pibrentasvir and the other half received Harvoni (ledipasvir/sofosbuvir, Gilead Sciences). Six achieved SVR and the others remain on treatment.
“Based on our center’s real-world experience, we believe that DAA therapy should be ordered and initiated once a patient is confirmed to be viremic, clinical parameters have stabilized, and insurance approval is obtained,” Kapila and colleagues wrote. “As transplant centers expand their donor pool and increase utilization of HCV viremic organs, the early initiation of anti-viral therapy should become the standard of care.” – by Talitha Bennett
Disclosures: The authors report no relevant financial disclosures.
Retreatment for HCV May Require Switching DAA inhibitor Classes
Dietz J, et al. Clin Gastroenterol Hepatol. 2019;doi:10.1016/j.cgh.2019.10.051.
December 10, 2019
Patients who failed to achieve sustained virologic response after initial treatment for hepatitis C achieved high cure rates during retreatment after switching from an NS5A inhibitor direct-acting antiviral to a protease inhibitor.
“The management of DAA failure patients remains a challenge,” Julia Dietz, MD, from the Goethe University Hospital in Frankfurt, Germany, and colleagues wrote. They highlighted the fact that many patients develop resistance associated substitutions (RASs), particularly NS5A RASs, and there remains limited data on retreatment success.
To analyze the efficacy of retreatment with first generation DAAs, Dietz and colleagues reviewed data from 631 patients, 262 of whom completed retreatment.
Patients with genotype 1 initially received a combination of Sovaldi (sofosbuvir, Gilead Sciences) and an NS5A inhibitor, and those with genotype 3 underwent treatment with combination Daklinza (daclatasvir, Bristol-Myers Squibb) and sofosbuvir.
The SVR rates at follow-up were overall 84% among patients with genotype 1, 91% for those who received a regimen with sofosbuvir and a protease inhibitor, and 90% among those with RASs. Retreatment with a protease inhibitor without sofosbuvir was less effective with an SVR rate of 82%.
Repetition of treatment with sofosbuvir and an NS5A inhibitor without a protease inhibitor was comparatively ineffective with an SVR of 68%.
All patients with genotype 3 underwent retreatment with an NS5A inhibitor and sofosbuvir and 60% achieved SVR. Most of these patients had developed NS5A RASs (93%) and the SVR rates were higher in the absence of cirrhosis and Y93H.
“Interestingly, in a recent study with inclusion of a [protease inhibitor] ... the majority of treatment failures had [genotype 3],” Dietz and colleagues wrote, referring to Vosevi (sofosbuvir/velpatasvir/voxilaprevir, Gilead Sciences). “Thus, retreatment of [genotype 3] remains a challenge.” – by Talitha Bennett
Disclosures: Dietz reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
Here’s a good article. It’s nice to know these DAA’s are very safe and effective in patients with severe renal disease.
Gilead DAAs safe, effective for adults with HCV, severe renal impairment
November 21, 2019
The FDA approved changes to the product labels for direct-acting antivirals Harvoni, Epclusa, and Vosevi to include new efficacy and safety data for adults with hepatitis C and severe renal impairment, including those who require dialysis.
“The product labeling updates for Epclusa, Harvoni and Vosevi recognize the high unmet need for effective HCV treatments for patients with severe renal impairment, including those with end stage renal disease (ESRD) who are on dialysis,” Gilead said in a statement sent to Healio Gastroenterology and Liver Disease. “People with chronic HCV who are on dialysis as a result of ESRD have an increased risk of morbidity and mortality. Prior HCV treatment options for this population have been associated with clinical barriers resulting in continued unmet medical need, and these approvals provide important new options for these patients.”
Harvoni (sofosbuvir/ledipasvir, Gilead Sciences) required no dosage adjustment for patients with mild, moderate or severe renal impairment including end-stage renal disease. The most common adverse events among patients with ESRD were insomnia and headache.
In a trial of adults with chronic HCV and ESRD requiring dialysis, the sustained virologic response was 93% in 45 treatment-naive patients who received 8 weeks of sofosbuvir/ledipasvir, 100% in 12 patients who received 12 weeks of treatment, and 83% in six treatment-experienced patients with cirrhosis who received 24 weeks of treatment.
Similarly, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) required no dosage adjustment for any degree of renal impairment and the most common adverse event among patients with ESRD was nausea.
Results from a trial of 59 patients with HCV and ESRD requiring dialysis showed an overall SVR rate of 95% after 12 weeks of treatment with sofosbuvir/velpatasvir, including patients with cirrhosis (29%) and those who were treatment-experienced (22%).
Vosevi (sofosbuvir/velpatasvir/voxilaprevir or SOF/VEL/VOX, Gilead Sciences) also required no dosage adjustment for any degree of renal impairment.
Pharmacokinetics of sofosbuvir and velpatasvir among patients with HCV and ESRD requiring dialysis for 12 weeks were consistent with patients with ESRD without HCV. The pharmacokinetics of voxilaprevir have not been studied in patients with ESRD; however, the FDA noted that voxilaprevir exposure following treatment with SOF/VEL/VOX combination is not expected to be meaningfully altered in patients with HCV and ESRD requiring dialysis compared with patients with normal renal function.
Reference: www.fda.gov
October 5, 2019
Andrea L. Cox, MD, PhD
WASHINGTON — An investigational vaccine regimen failed to prevent chronic hepatitis C virus infection in a cohort of at-risk adults, according to results of a clinical trial presented at IDWeek.
Recently, study findings published in The Lancet suggested the WHO goal to eliminate HCV globally by 2030 will be “narrowly missed.” A vaccine, researchers said, will be crucial to elimination efforts.
Andrea L. Cox, MD, PhD, a professor of medicine at Johns Hopkins University, and colleagues conducted the first prophylactic HCV vaccine efficacy trial — a randomized, multicenter, double-blind, placebo-controlled study called Vaccine is Prevention. The vaccine regimen is based on viral vectors, consisting of a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara virus boost. In the study, 455 participants aged 18 to 45 years who injected drugs received either the vaccine regimen or placebo at days 0 and 56.
The study took place at three sites in the United States — the University of California, San Francisco, Johns Hopkins and the University of New Mexico, Cox said.
According to the researchers, the overall incidence of HCV infection at 6 months was 13 infections per 100 person-years. This is substantially lower than the incidence in the background populations of the study sites, Cox said, probably because of “aggressive counseling and referral to drug treatment and needle exchange programs” during the trial.
Cox and colleagues found no difference in the development of chronic infection between the vaccine and placebo arms, with 14 cases in each. The regimen’s efficacy in preventing chronic infection was –0.53 (95% CI, –2.5 to 0.34).
However, the vaccine regimen blunted the peak HCV RNA level in recipients 1 month after vaccination compared with placebo — a statistically significant finding, Cox noted. In terms of immunogenicity, the vaccine regimen induced an immune response in 78% of recipients, which is a less robust response that what was observed in an earlier study of healthy volunteers, she said.
According to the researchers, there were no safety signals in the study, and the regimen was well-tolerated, with no serious vaccine-related adverse events.
“There remains a significant need for vaccine to interrupt transmission, and it will be critical for achieving WHO elimination goals,” Cox said. “Testing vaccines in [people who inject drugs] is possible, but additional strategies will need to be considered — ideally, with information gained from this vaccine, informing future vaccine design.” – by John Schoen
References:
Cox AL, et al. Abstract LB10. Presented at: IDWeek; Oct. 2-6, 2019; Washington.
Heffernan A, et al. Lancet 2019;doi:10.1016/S0140-6736(18)32277-3.
Here’s some good news!
FDA expands Mavyret approval for adults, children with any HCV genotype
September 27, 2019
The FDA has expanded the approval of Mavyret for a treatment duration of 8 weeks to include treatment-naive adults and children aged 12 years and older with chronic hepatitis C genotype 1 through 6 and compensated cirrhosis.
The label expansion of Mavyret (glecaprevir/pibrentasvir, AbbVie) was based on data from the phase 3b EXPEDITION-8 study that included patients with any of the six HCV genotypes. Twelve weeks after treatment, 98% of the 343 enrolled patients achieved sustained virologic response.
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“This approval provides a treatment duration of 8 weeks for both pediatric and adult patients with compensated cirrhosis regardless of HCV genotype,” Jeffrey Murray, MD, deputy director of the division of antiviral products in the FDA’s Center for Drug Evaluation and Research, said in the FDA brief. “[Glecaprevir/pibrentasvir] is a combination of direct-acting antiviral drugs that reduce the amount of HCV in the body to undetectable levels by preventing the virus from multiplying, and in most cases, curing HCV infection.”
Additional data from the EXPEDITION-8 study showed that the most common adverse events were fatigue (8%), pruritus (7%) and headache (6%).
“While over 100,000 patients have been prescribed [glecaprevir/pibrentasvir] for chronic HCV in the U.S., there are still a significant number of patients that need options,” Janet Hammond, MD, PhD, vice president of the general medicine and virology therapeutic area at AbbVie, said in a press release. “This approval provides more HCV patients an option to treat their disease in as little as 8 weeks.”
Reference: www.fda.gov; www.abbvie.com
Resistance (RAV/RAS) and retreatment success.
Resistance-guided HCV retreatment achieves nearly 90% SVR
Pérez AB, et al. J Hepatol. 2019;doi:10.1016/j.jhep.2019.06.022.
September 7, 2019
Resistance-guided direct-acting antiviral retreatment resulted in nearly 90% sustained virologic response rates among patients with hepatitis C who developed resistance-associated substitutions after failing treatment with NS5A inhibitors.
In their study, Ana Belén Pérez, from the University Hospital Reina Sofía in Córdoba, Spain, and colleagues provided indications on how to use resistance information in settings where Vosevi (sofosbuvir/velpatasvir/voxilaprevir, Gilead Sciences) may not be available.
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“We believe that our data may be of special relevance for those countries where new drug combinations are still not available, and may allow treating patients at a lower cost, avoiding drug-drug interaction and preserving the three-drug combination regimen,” they wrote. “We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians.”
The study comprised 185 patients who did not respond to Harvoni (sofosbuvir/ledipasvir, Gilead Sciences), 79 who did not respond to combination Sovaldi (sofosbuvir, Gilead Sciences) and Daklinza (daclatasvir, Bristol-Myers Squibb), and 68 who did not respond to Viekira Pak (paritaprevir/ritonavir/ombitasvir/dasabuvir), all of whom also received ribavirin.
All patients received retreatment with sofosbuvir with an NS5A inhibitor and ribavirin for 12 or 24 weeks.
“When available, velpatasvir should be the NS5A component of the new retreatment regimen; if not available, the previously used NS5A inhibitor may be recycled adding ribavirin and extending the duration for 24 weeks,” the researchers wrote.”
Results from modified intention-to-treat analysis — excluding all patients unavailable for follow-up at 12 weeks — the SVR rates were 88.1% for those previously treated with sofosbuvir/ledispasvir, 83.3% for those treated with sofosbuvir and daclatasvir and 93.7% for those treated with ombitasvir-containing regimens.
“When possible, simeprevir-based regimens should be avoided, especially for patients with cirrhosis,” Pérez and colleagues explained. They continued to explain that most of the patients infected with genotype 3 were retreated and cured with a combination of sofosbuvir, an NS5A inhibitor and ribavirin after 24 weeks or a regimen of sofosbuvir with an additional two or three drugs and ribavirin, especially if Y93H is present. – by Talitha Bennett
Disclosures: Pérez reports that the study was supported in part by grants from Fondo de Investigación Sanitaria, Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER, Fundación Progreso y Salud, Junta de Andalucia, and GEHEP-SEIMC.
The benefits of treatment and SVR continue to soar!
Patient-reported outcomes greatly altered by HCV treatment results
Younossi ZM, et al. Clin Gastroenterol Hepatol. 2019;doi:10.1016/j.cgh.2019.07.047.
August 20, 2019
In a follow-up analysis of participants in clinical trials, researchers found that patient-reported outcome scores increased in patients who achieved sustained virologic response after treatment for hepatitis C, whereas scores decreased in those who did not.
“Although historical treatment regimens with interferon were plagued by low efficacy and significant side effects impairing patients’ well-being and, thus, PROs, the trajectory of HCV treatment changed about 5 years ago with the development of direct-acting antiviral (DAA) agents,” Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Hospital in Virginia, and colleagues wrote. “The PRO evidence generated by these two prospective registry studies support the unquestionable benefit of SVR for patients’ experience as opposed to the clear deleterious impact of HCV viremia.”
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Younossi and colleagues assessed the health-related quality of life of 4,234 patients who achieved SVR and 242 patients who did not using the SF-36 instrument. Before treatment, PRO scores of both groups were similar to or higher than the general U.S. population and similar to each other.
At baseline for this study, patients who achieved SVR experienced improvements in all eight domains of the SF-36 (range increase, 3.6-8.1; P < .0001), while the scores of those without SVR remained the same with the exception of the General Health domain, which decreased by 2.8 points (P = .008).
Patients without SVR experienced further PRO decrements at 12-week follow-up: up to –7 points from before treatment in the Role Physical, General Health, Social Functioning and Role Emotional domains and both summary scores; up to –9.2 points in all PRO domains at week 24; up to –8.3 points in five domains at week 48; and up to –9 points in four domains at week 96 (P < .05).
In contrast, patients with SVR experienced sustained improvement of PRO scores with up to 7 points at week 24, up to 6.9 points at week 48, and up to 6.1 points at week 96 (P < .001). Multivariate analysis confirmed that SVR correlated independently with superior scores in all PRO domains with an increased range of 4.8 points to 15.9 points (P < .01).
“In order to fully understand the comprehensive benefit of HCV cure, these PRO gains should always accompany the clinical consequences of SVR, such as lower rates of cirrhosis and hepatocellular carcinoma,” Younossi and colleagues concluded. “These data must be considered by providers, payers, and policy makers to fully appreciate the comprehensive benefit of HCV cure and to assure that all HCV patients are identified and treated with the most effective antiviral regimens.” – by Talitha Bennett
Disclosures: Younossi reports that the study was partially supported by Gilead Sciences and that he has received research funds or served as consultant to AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept, Novo Nordisk, Terns and Viking. Please see the full study for all other authors’ relevant financial disclosures.
Some recent updates regarding initial testing recommendations. No longer are Boomers the only age group being targeted for testing. With the illegal opioid problem, the exposure from IVDU and other forms of blood exposure, we are seeing a resurgence in HCV diagnosis.
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USPSTF recommends screening all adults for HCV
August 27, 2019
The U.S. Preventive Services Task Force has issued a draft recommendation that encourages clinicians to screen all adults aged 18 to 79 years for hepatitis C virus infection.
The task force also suggests that physicians consider screening patients for HCV who are aged younger than 18 years and older than 79 years if they are at high risk for infection.
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The USPSTF reported that in 2016, there were an estimated 41,200 new HCV infections in the United States and that the number of cases of acute HCV infection have increased approximately 3.5-fold over the last 10 years. The increase is largely attributable to young, white people who inject drugs, particularly those who live in rural areas, and a hike in number of women aged 15 to 44 years infected with HCV, according to the task force. obe
“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening,” Douglas K. Owens, MD, MS, task force chair and general internist at the Veterans Affairs Palo Alto Health Care System, said in a press release.
The USPSTF’s draft statement and evidence review has been posted for public comment on the USPSTF website: www.uspreventiveservicestaskforce.org. Input will be accepted through Sept. 23, 2019, at www.uspreventiveservicestaskforce.org/tfcomment.htm.
The new “B” recommendation replaces the USPSTF’s 2013 recommendation that clinicians screen patients at high risk for HCV and offer one-time testing to adults born between 1945 and 1965. The CDC currently recommends HCV testing for baby boomers, injection drug users, and recipients of organ transplants or blood transfusions prior to July 1992. – by Janel Miller
Disclosures : Owens reports no relevant financial disclosures. Please see the USPSTF website for all other task force members’ relevant financial disclosures.
Really good news. We're definitely closing in on this virus.
Having been cured with Sovaldi and Ribavirin, I have to be thankful for it, but it was not pretty. I wonder if there is a reason to use this combo specifically when more recent treatments have become so much kinder?