Hep C Discussion Forum

Tig · Admin

RE: Healio/HCV Updates

Tig · Admin

HCV treatment with Epclusa safe in patients undergoing dialysis for ESRD

Borgia SM, et al. J Hepatol. 2019;doi:10.1016/j.jhep.2019.05.028.

June 14, 2019

Although not currently licensed for patients undergoing dialysis for severe renal impairment, researchers found that treatment with Epclusa for hepatitis C was safe and effective in patients with end-stage renal disease.

“Chronic HCV infection has a significant negative impact on morbidity and mortality in patients undergoing dialysis,” Sergio M. Borgia, MD, FRCPC, from Brampton Civic Hospital in Ontario, Canada, and colleagues wrote. “HCV-infected patients with [chronic kidney disease (CKD)] have an accelerated rate of loss of kidney function, risk of progression to end-stage renal disease (ESRD), and increased risk of all-cause mortality when undergoing dialysis.”

Borgia and colleagues enrolled 59 patients with HCV and ESRD to undergo 12 weeks of treatment with Epclusa (sofosbuvir/velpatasvir, Gilead Sciences). Most were treatment-naive (78%), 92% were undergoing hemodialysis for a mean duration of 7 years (range, 0-40 years), and 8% were undergoing peritoneal dialysis.

Fifty-six patients achieved SVR (95% CI, 86-99), of whom 53 had study drug adherence rates of 90% or higher. Two patients experienced virologic relapse posttreatment and one patient was discontinued from the study after 11 weeks due to nonadherence.

Most patients experienced a mild to moderate adverse event (80%) such as fatigue, headache, nausea, vomiting and insomnia. The researchers noted no adverse events associated with renal dysfunction among the patients and that the incidence of grade 3 and grade 4 laboratory abnormalities was consistent with patients undergoing dialysis for ESRD.

“Over the last few years, several HCV treatments have been approved for use in patients with HCV infection and CKD, and each regimen has limitations,” the researchers wrote. “The data collected in this study provide information to support the use of sofosbuvir/velpatasvir in HCV-infected patients with ESRD.” – by Talitha Bennett

Disclosure: Borgia and his institution have received honoraria from AbbVie, Gilead Sciences and Merck. Please see the full study for all other authors’ relevant financial disclosures.

Canuck · Guru

This IS an interesting update. Maybe why us 3's were seen to be harder to treat. Good reading here and i had also stuffed it over here ... ( GT3's - (and more so, maybe "certain" GT3 sub-types) - perhaps why we have most often been considered "hard to treat" ) - where the other post (another study/some similarities) also presented some differing resistance info and additionally why us 3's could have been harder to treat. Thank goodness for the things we learn. : )

Tig · Admin

Common polymorphism responsible for HCV genotype 3 resistance to Sovaldi

Wing PAC, et al. Gastroenterol. 2019;doi:10.1016/j.gastro.2019.05.007.

May 28, 2019 Researchers identified a common polymorphism and a rare variant combination in hepatitis C genotype 3 that are responsible for a reduced response to Sovaldi, according to a study published in Gastroenterology.

“Studies on [Sovaldi] ‘resistance’ have been hampered by the extraordinary efficacy of the drug, which has led to very few treatment failures,” Peter A.C. Wing, PhD, from the Queen Mary University of London in the United Kingdom, and colleagues wrote. “Our analysis shows that reduced response to [Sovaldi] may occur if multiple viral polymorphisms are combined.”

To evaluate resistance to Sovaldi (sofosbuvir, Gilead Sciences) as well as ribavirin, Wing and colleagues used capture-fusion assays to assess 14 samples of HCV genotype 3. Ten of the samples were from treatment-naive patients with advanced liver disease, while the other four were from patients who had shown response in early access programs or in vitro testing.

They found that alanine at position 150 was particularly common (40.55%) along with the valine variant (36.66%). At position 206, lysine demonstrated a frequency of 76.31% and glutamic acid presented at a frequency of 12.74%. However, an analysis of the combination of polymorphisms (A150V and K206E) showed both were present in less than 4% of the population.

Using transient replicon assay, the researchers found that each common polymorphism correlated with an eightfold reduction in sensitivity to sofosbuvir and the combination correlated with a reduced sensitivity of more than 35-fold.

The effect of these polymorphisms on ribavirin sensitivity ranged from 10-fold for K206E to more than 40-fold for A150V, but in combination, the effect was enhanced to approximately 70-fold.

“For treatment naive patients, responses to [sofosbuvir] based treatments are so effective that any impact of these viral variants is likely to be minimal and we would not recommend that such patients undergo pre-treatment ‘resistance’ testing,” Wing and colleagues concluded. “For patients who have been exposed to multiple drug regimens (including interferon and NS5a inhibitors that can lead to resistance associated polymorphisms) we speculate that the polymorphisms identified here might be of significance and we suggest that pre-treatment viral sequencing may be useful in selecting the optimal regimen for such patients.” – by Talitha Bennett

Disclosure: Wing reports no relevant financial disclosures. Please see the full study for all other author’s relevant financial disclosures.

Genotype 3 & Polymorphisms

Cheddy · Moderator

Wow! Such progress!

Tig · Admin

A new update on a promising HCV vaccine! Appears there is much work to be done, but they are making some advances.

HCV Vaccine Progress

Annie · Member

Thankfully, my Hepatologist has been working with and training family doctors to treat HCV. It actually is a pretty simple process for most of us. Where I live, we also have trained teams who will come to the local hospital to get you treated. It should be that easy everywhere.

Tig · Admin

Here’s a good article on the need for Generalists/GPs to get together with Specialists and bridge the gap in HCV diagnosis and treatment. There are too many people falling through that gap, for whatever reason. IMO, there’s no reason a GP couldn’t provide care. It’s not like it used to be, it’s far more effective and relatively side effect free. Well within their ability. It’s all about eradicating the virus and saving lives!

Bridge the Gap

Tig · Admin

I’d like to see Medicare be part of this, as well as Medicaid and the incarcerated. People on Medicare should be given the same consideration. Most aren’t rolling in the dough, either... We can do better! It’s good to see the attention being given to this. I hope to see other states get on board with more programs like this.

Canuck · Guru

Lucky the 10,000 people in Louisiana (patients who are on medicare or are incarcerated), they will be the recipients (over the next 1 1/2 years) to get treated with Epclusa.

Helio - HCV Next

Louisiana picks Gilead subsidiary for Netflix style HCV subscription plan

April 2, 2019

The Louisiana Department of Health selected Asegua Therapeutics, a subsidiary of Gilead Sciences, as their pharmaceutical partner in a subscription style payment plan designed to provide state residents with access to hepatitis C treatment, according to a press release from the department.

The State will pay a fee to the manufacturer for unrestricted access to its direct-acting antiviral Epclusa (sofosbuvir/velpatasvir) for 5 years. Access will be available for patients enrolled in Medicaid and incarcerated patients.

The next step is to complete the contract between Asegua and our agency, Rebekah E. Gee, MD,secretary of the Louisiana Department of Health, said in the release. We were extremely pleased that three manufacturers offered proposals, with the plan submitted by Asegua offering us a clear path forward to offer a hepatitis C cure to our most vulnerable patients.

According to the press release, the department expects to have a contract in place by June 1 and to launch the subscription model on July 1. The States elimination goal is to treat more than 10,000 Medicaid-enrolled and incarcerated individuals by the end of 2020.

We are excited that Asegua has been selected to partner with the Department of Health and look forward to working on an agreement for this groundbreaking subscription model to increase access to a cure for people living with hepatitis C in Louisiana, Gregg Alton, a representative for Asegua, stated in the release. This is an important step forward on the path to eliminating the virus in Louisiana.

Click here to read an interview with the departments chief of staff, Pete Croughan, MD, regarding the plan.

Reference: www.ldh.la.gov

Tig · Admin

This is great news and a very positive step toward eradicating this disease in our Veterans!

The US Veterans Administration is on course to eliminate HCV in Veterans in the next 2 months! That’s a great (lofty) goal and I hope they’re successful! They have some work to do. Best of luck to all!

Veterans Hope

Cheddy · Moderator

Lots of positive articles and news in these updates. Wow.

Canuck · Guru

There's an article around here (somewhere) about how we are doing in the likelihood of eradicating HCV ... and this link (a trial) has to do with that. This trial experiment ( https://clinicaltrials.gov/ct2/show/NCT01436357 ) was mentioned in the article - and scientists/infection control people are all awaiting the outcomes, to see the results, the data on this very long trial - 5 years all in all?? Wouldn't we all like to know whether these "vaccinations" will provide significant protection to high exposure risk groups to prevent them from getting chronic hep C (being that they say eradication will be difficult to achieve without vaccines).

I wonder ... if the "actual" trial start was in 2011?, that seems SO long ago, and if that means the trial data is now being finalized for publication soon?? With only 500-600 participants recruited in 2011?, over all these years I bet they lost more than few to dropping out of the trial for one reason or another!

I hope they publish trial outcomes soon, and, that we get to hear about it! C.

Tig · Admin

HBV related HCC risks reduced by Aspirin therapy? Yep...

HBV/HCC Aspirin Therapy

Tig · Admin

There are some informative and yes, interesting articles this month. The testosterone piece is worth a read for the men. We have had discussions on this in the past. Good to see them figure it out. It might explain the fatigue and slow metabolism...

Healio/HCV Next Updates

Canuck · Guru

Helio - News

Dicerna completes first dosing in phase 1 trial of RNA-based HBV therapy

January 29, 2019

Dicerna Pharmaceuticals announced the dosing of the first volunteer in a phase 2 clinical trial of DCR-HBVS, the company's investigational GalXCTM-based therapy for the treatment of chronic hepatitis B, according to a press release.

"The dosing of the first human in the DCR-HBVS-101 trial brings us a step closer to the potential availability of an innovative therapy for patients with chronic hepatitis B," Ralf Rosskamp, MD, chief medical officer at Dicerna, said in the release. "We are hopeful that this three-part phase 1 trial will validate RNA interference as a viable clinical strategy against chronic hepatitis B infection, based upon our encouraging preclinical data on DCR-HBVS."

DCR-HBVS comprises a single GalXC molecule that targets HBV messenger RNAs within the hepatitis B surface antigen gene sequence region.

The current randomized control trial was designed to evaluate the safety and tolerability of DCR-HBVS in healthy volunteers and patients with chronic HBV without cirrhosis.

"RNAi-based therapy has the potential to change the treatment paradigm for patients with chronic HBV infection," Edward Gane, MBCHB, MD, from the New Zealand Liver Transplant Unit at Auckland City Hospital and principal investigator, said in the release. "By silencing not only the S antigen but also other viral genes, through a powerful and long-acting mechanism, RNAi-based therapy could tip the balance toward allowing the patient's own immune system to mount an effective immune response. This approach could help eradicate HBV and remove the need for life-long therapy."

Dicerna anticipates proof-of-concept data from the phase 1 trial in the second half of 2019.

Reference: www.dicerna.com

Canuck · Guru

This is not a "Helio" article (it's a Medscape" one) but it does have the very same concern/topic as the prior Helio article in this thread - just thought i would drop this second similar article here so they could both be read side by side.

Screen All New Cancer Patients for Hepatitis?

Kristin Jenkins, January 23, 2019

A new study has found "a large reservoir of patients with cancer and undiagnosed hepatitis virus infections" and has reignited the question of whether all newly diagnosed cancer patients should be screened for hepatitis.

The Viral Screening in Newly Diagnosed Cancer Patients (S1204) study involved 3051 patients and found that 6.5% had previously been infected with hepatitis B virus (HBV), 0.6% had chronic HBV infection, 2.4% had hepatitis C(HCV) infection, and 1.1% were infected with HIV.

The study was published online on January 17 in JAMA Oncology.

At enrollment, 87.3% of patients did not know that they had previously been infected with HBV. Similarly, 42.1% of the cases of chronic HBV infection, 31.0% of the cases of HCV infection, and 5.9% of the cases of HIV infection were undiagnosed.

Cancer patients with HBV or HCV infection are at risk for viral reactivation and potentially life-threatening clinical outcomes, say the authors, led by Scott D. Ramsay, MD, PhD, director of the Hutchinson Institute for Cancer Outcomes Research at the Fred Hutchinson Cancer Research Center, in Seattle, Washington.

"Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient," they add.

Universal screening for HBV and HCV prior to cancer therapy "may be warranted," they write.

The investigators conclude, however, that "[t]he low rate of undiagnosed HIV infection may not support universal screening of newly diagnosed cancer patients [for HIV]."

Screening Could Prevent Complications

Universal screening for HBV, HCV, and HIV infection is not routinely performed in patients diagnosed with cancer. What's more, the use of such screening remains controversial among oncologists, the researchers point out.

These results "provide new evidence to inform a discussion in the oncology community about whether we should require hepatitis screenings," said Ramsay in a statement.

Universal screening could prevent complications from hepatitis, such as liver failure and kidney disease, the investigators say. Immunosuppressive cancer drugs such as rituximab (Rituxan, Genentech, Biogen Idec) - used to treat CD20-positive T-cell lymphomas and leukemias - can cause some viruses to reactivate and multiply.

"Because the true risk of severe adverse events associated with most cancer treatments in persons with latent infections is unknown, the putative benefits of delaying or modifying cancer treatment remain speculative...," the authors say.

However, they add, "...the risk that these changes pose to outcomes for patients with newly diagnosed cancer are real."

Study Details

For the study, data were collected from patients enrolled at nine academic and nine community oncology centers affiliated with the SWOG (formerly the Southwest Oncology Group) Cancer Research Network, a National Cancer Institutesponsored cancer clinical trials cooperative group.

Data were collected between August 29, 2013, and February 15, 2017. The median age of the patients was 60.6 years, 60.4% of the patients were women, 18.1% were African Americans, and 18.3% were of Hispanic ethnicity.

Breast cancer was diagnosed in 34.7% of patients, blood/marrow malignancy in 12.1%, colorectal cancer in 11.9%, and lung cancer in 11.7%.

Of those patients who did not know that they had previously been infected with HBV, 27.4% had no known risk factors. Similarly, 21.1% of patients with chronic HBV, 32.4% of those with HCV, and 20.6% with undiagnosed HIV had no identifiable risk factors. This suggests that current risk-based models for screening may be insufficient, the researchers say.

Universal Screening for All New Cancer Patients

When approached for comment, Harrys A. Torres, MD, associate professor in the Department of Infectious Diseases at the MD Anderson Cancer Center, Houston, Texas, said this 18-center evaluation study was "extremely important."

Torres, who is also associate adjunct professor in the Department of Gastroenterology, Hepatology and Nutrition, is founding director of the HCV clinic - the first in the United States to manage HCV infection in all cancer patients.

"We agree with the authors that all cancer patients should be screened for HBV and HCV," said Torres.

All cancer patients should be screened for HBV and HCV.Dr Harrys Torres

"Now the push for universal screening is coming from a great many academic and community cancer centers, not just one," he told Medscape Medical News.

At MD Anderson, universal screening for HBV, HCV, and HIV has been standard practice in hematologic services since 2007. "This started after rituximab was found to be associated with hepatitis B reactivation," Torres said.

In 2016, screening for HCV infection at MD Anderson was expanded to include all patients with cancer, including those with solid tumors. The vast majority of cases are newly diagnosed, said Torres. The next step is to screen most patients for HBV and HIV as part of a stepwise plan.

Torres partially agreed with the study authors on the matter of universal HIV screening. However, he emphasized that more data are needed before it can be said that universal HIV screening is not warranted, particularly if screening is recommended for HBV and HCV.

Results from a 2014 MD Anderson study supported HIV testing in cancer patients before they started cancer therapy, he noted.

"These three infections can be acquired in the same way, have common risk factors, and can induce other cancers that can present as second primary cancers in patients coming with different underlying malignancies. I see this from an infection perspective, and transmission is going to be an issue. Now that we have the data for HBV and HCV, we have to get the data for HIV."

Torres pointed out that in the current analysis, Ramsay and colleagues found an increased risk for liver cancer as well as cancer of the prostate, lung, and breast.

In a 2018 study, Torres and colleagues reported that 15% of HCV-infected patients who had different primary cancers developed HCV-associated hepatocellular carcinoma as a second primary malignancy. This is an often overlooked presentation of liver cancer, they say.

The current study findings validate those from a 2018 MD Anderson study led by Jessica Hwang, MD, MPH, said Torres. That study demonstrated that universal HBV testing was more efficient than risk-based screening.

The results from the current study also parallel findings from 2017 study and a 2018 study, both of which showed that selective screening practices for HCV were not optimal for identifying all infected cancer patients, he said.

"With the availability of nucleos(t)ide analogues to treat HBV and direct-acting antivirals to treat HCV, infected cancer patients can be treated to prevent viral reactivation, progression of liver disease, and allow access to cancer treatment, including clinical trials," said Torres.

As previously reported by Medscape Medical News, there is evidence of the impact of reactivation of HBV and HCV infection in patients undergoing immunosuppressive chemotherapy. In two separate studies, researchers at MD Anderson concluded that greater surveillance for HBV and safer hematologic-sparing treatments for HCV are required.

In 2015, the American Gastroenterological Association issued a guideline for the prevention and treatment of HBV reactivation during immunosuppressive drug therapy.

Subsequently, a review and meta-analysis of prophylaxis management for HBV reactivation in patients with breast cancer undergoing chemotherapy was published, as reported by Medscape Medical News.

Until more data are available, the US Centers for Disease Control and Prevention and the US Preventive Services Task Force (USPSTF) recommend that universal one-time HIV screening be conducted in patients aged 13 to 65 years and in women who are pregnant, Torres pointed out.

One-time screening for HCV is also recommended for individuals born between 1945 and 1965, Ramsay and colleagues note.

"This is particularly relevant if we want to reduce transmission to uninfected persons and reduce the risk of AIDS-related events, such as development of AIDS-defining cancers," said Torres. The USPSTF is currently reviewing its screening guidelines and is expected to issue new recommendations, he pointed out.

The National Comprehensive Cancer Network recommends HIV screening for persons with newly diagnosed lymphomas, the researchers say. However, the American Society of Clinical Oncology and the National Comprehensive Cancer Network do not have recommendations for universal HCV and HIV screening.

In their article, Ramsay and colleagues acknowledge that universal screening would increase the cost of cancer care. Ramsay is currently conducting an analysis of results from another SWOG study to determine the cost-effectiveness of universal hepatitis and HIV screening. The results are expected later this year.

Torres said that three recently published articles that present cost analyses in the United States and Europe show that universal HCV screening in the community is cost-effective. Similar results are expected in cancer patients, given the significant morbidity and mortality of HCV in this patient population, he added.

The study was funded by the National Cancer Institute of the National Institutes of Health. Ramsey has disclosed no relevant financial relationships. A number of coauthors have disclosed relationships with industry. Torres has relationships with Gilead Sciences, Inc, and Merck & Company Inc, with all funds paid to the University of Texas MD Anderson Cancer Center. He also has financial relationships with Gilead Sciences, Inc, Merck & Company Inc, and Dynavax Technologies.

JAMA Oncol. Published online January 17, 2019. Full text

Canuck · Guru

Helio - HCV Next

IN THE JOURNALS

Undiagnosed HBV, HCV, HIV prevalent in newly diagnosed cancer cases

Ramsey SD, et al. JAMA Oncol. 2019;doi:10.1001/jamaoncol.2018.6437.

January 17, 2019

Researchers discovered a substantial proportion of patients with newly diagnosed cancer and concurrent hepatitis C or hepatitis B were unaware of their viral infection and many had no identifiable risk factors, according to a recently published study.

Although the rate was low, some patients also presented with undiagnosed HIV.

"Screening may be especially important now that we've entered the age of immunotherapies for cancer - treatments that may affect cancer patients' immune systems and alter the course of their viral infections," Scott D. Ramsey, MD, PhD, lead study author from the Fred Hutchinson Cancer Research Center in Washington said in a press release. "While we don't know much about the impact of immunotherapies on patients with cancer and hepatitis and other viral infections, oncologists should know as much as possible about the overall health of the people they treat."

The study comprised 3,051 patients with cancer who underwent testing for HBV, HCV or HIV.

The overall rate of previous HBV infection was 6.5% (95% CI, 5.6-7.4) with 172 patients who were newly diagnosed. The rate of unknown HBV cases was 87.3% (95% CI, 81.8-91.6) and the rate of unknown chronic HBV cases was 42.1% (95% CI, 20.3-66.5).

Previous HBV infection was most common in patients with prostate cancer (12%; 95% CI, 6.4-20) and gastrointestinal cancers other than liver or colorectal (9.4; 95% CI, 6.-13.8). The rates of previous HBV and chronic HBV were similar among patients after excluding those with liver cancer.

The rate of HCV infection was 2.4% (95% CI, 1.9-3) with 22 patients who were newly diagnosed. The rate of unknown HCV was 31% (95% CI, 20.5-43.1). HCV was most common in patients with liver cancer (17.3%; 95% CI, 8.2-30.3).

Thirty-four patients had HIV for an overall rate of 1.1% (95% CI, 0.8-1.6). Two patients were newly diagnosed (5.9% unknown cases; 95% CI, 0.7-19.7).

Many patients had no known infection risk factors, including 54 patients with previous HBV (27.4%; 95% CI, 21.3-34.2), four with chronic HBV (21.1%; 95% CI, 6.1-45.6), 23 with HCV (32.4%; 95% CI, 21.8-44.5), and seven with HIV (20.6%; 95% CI, 8.7-37.9).

"Our results were consistent with [previous] studies, suggesting that substantial portions of HBV and HCV infections prevalent at the time of cancer diagnosis were unknown to patients," Ramsey and colleagues concluded. "We believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost-effective." - by Talitha Bennett

Disclosure: Ramsey has received grants from the National Cancer Institute. Please see the full study for the other authors' relevant financial disclosures.

Canuck · Guru

Re: references to "Polaris 1" = Vosevi, and references to "C-Swift" = Zepatier.

BTW, Dr. Lawitz is named on C-Swift trials.

_____________________________________________________________

Helio - HCV Next - COVER STORY

Looking Back on an Unprecedented Revolution in Medicine

HCV Next, January/February - Eric Lawitz, MD

As we conclude another year now past the peak of hepatitis C research, HCV Next asked me to consider where we came from, where we are now, and where we're headed. They wanted me to address potential new mechanisms of action for DAA therapies, shorter durations of treatment, and how to deal with the small population of treatment failures, among others. But perhaps it is best to start with the biggest and most important question: Are we done? Have we succeeded in hepatitis C?

A historical transformation of therapy in hepatitis C occurred, considering the rapid evolution of therapy from the days of PEG-interferon and ribavirin. As a reference point we should think back to the IDEAL study published in the New England Journal of Medicine in 2009 demonstrating sustained virologic response rates of 40% to 41%, with the associated toxicity well described of interferon. Now, less than 15 years later, we have multiple direct-acting, all-oral combination antiviral therapies with SVR12 rates of 95% to 100% and adverse event profiles similar to placebo. We witnessed a historic pace of development of new agents that now approach universal success. I think we all would agree these developments are remarkable and an unprecedented occurrence in medicine.

It would be hard to believe we're not done, at least in terms of the therapies themselves. With the antivirals we have and combinations thereof, we can cure 96% to 99% of patients with HCV. We can treat patients who historically have been difficult to treat in the past - this includes end-stage renal disease, decompensated liver disease and DAA failures.

Once difficult-to-treat

We historically worried about patients who failed DAA therapy because treatment-emergent resistance gave us few retreatment options. The POLARIS-1 trial demonstrated the once difficult-to-treat DAA failure now has therapeutic options. Even patients who have previously failed two classes of antivirals (NS5A and NS3) can now achieve an SVR12 of 96%, independent of frequency or class of resistance associated substitutions.

Looking at the current mathematics of therapy, we have therapies with virologic failure rates of 2% to 4% and, now based on the POLARIS 1 trial, we can successfully retreat 96% of those DAA failures, bringing us down to about one in 1,000 patients who are left behind and will not respond to even the latest combination antiviral regimen. We have addressed every population in need of therapy and demonstrated SVR12 rates above 95% in most of these populations.

The good news is that these non-responders or recurring relapsers comprise a miniscule population. The bad news is that we don't currently have an answer for these few patients left behind. In evaluating these few patients, I would encourage clinicians to look at these patients' resistance profiles and closely consider all the options in our armamentarium. The likelihood of developing new salvage therapies for these patients seems remote. Development of new salvage therapies have two significant barriers: first, novel antivirals are likely to be required, and secondly, the ability to find enough patients to enroll in a clinical trial would be problematic given the very high efficacy of today's regimens.

Duration, Mechanism of Action

What about the concept of shorter duration therapy? Despite the advances this is a topic that is still frequently discussed. As we consider the concept of shorter therapy, it is essential to remember that we currently have almost universally successful therapy with a side effect profile that is essentially similar to placebo. Shorter durations would be useful from a compliance and simplicity standpoint, however there is no enthusiasm to accept lower SVR12 rates or increased adverse event profiles to accomplish this goal.

Thinking about it practically, I would define two possible ways to shorten duration of therapy. First, would be to develop more potent antivirals that, in combination, could achieve a 95% to 100% SVR12 with 4 weeks of therapy or less. The second would be a directly-observed, single-dose parenteral therapy. Let's consider each of these two scenarios separately.

First, a 4-week or shorter duration of therapy would require combinations of antivirals more potent than the agents of today. In C-SWIFT, we demonstrated 4 weeks of therapy produced a suboptimal SVR12 with today's antivirals. Importantly, it taught us that a 4-week duration is plausible; however, current antivirals require a specific phenotype of patient to achieve high rates of SVR12 with a short 4-week duration. Given the biologic plausibility demonstrated by C-SWIFT one can hypothesize that it is possible to achieve high rates of SVR12 with 4-week duration therapy if we had significantly more potent antivirals.

In the second case, a single-dose parenteral therapy would be a paradigm shift for the hepatitis C field. It would involve technology that is not currently available with HCV antivirals, but has been demonstrated with HIV antivirals.

Despite the astounding success of therapies today, if we were able to achieve either of these scenarios - one, a 4-week or less treatment duration or, two, single-dose parenteral therapy - the current universally successful therapy could be displaced.

In terms of new mechanisms of action or new delivery techniques, the enthusiasm of drug developers appears to be decreasing based on the universal success of today's therapies and the decreasing cost of HCV therapies (see Feature on page 16). The scientist in me would like to see a new mechanism of action and novel delivery technology, but the realities of the current market place appear to make these possibilities unlikely.

Competition, Eradication

The good news for patients is that same competition that makes it unlikely we will develop new technology has driven down the cost of therapy. The recent additions to the market have significantly decreased the cost of therapy. This is great for all of our patients and those of us who treat these patients. The pricing environment also now increases the likelihood of further opening up access to therapy to the broad population of patients with hepatitis C.

Thinking more broadly about the current landscape in the U.S., there is obviously a lot of debate about health care right now. Giving HCV patients more and better access to curable therapies is most important to society. The big drivers toward HCV eradication start with screening and linkage to care. We are driven by the opportunity to provide our patients with the best chance to get diagnosed and linked to care.

Eradication of HCV has many challenges including effective delivery of these therapies to all parts of the world. However; with the right motivations and the correct distribution methods, eradication is a tangible possibility in the future. There are obviously many obstacles to achieve this goal. We will have to treat people in some hard-to-reach places, and we will have to think about the populations prone to reinfection, among many other challenges.

Certainly, eradication would be given a boost with an effective vaccine. With the need for treatment research dwindling, perhaps we should double up our efforts in vaccine research or consider treatment as prevention being touted by patient advocacy groups.

Eradication may be a dream but I hope it can occur in the future. We shouldn't give up on this goal. Nothing is impossible, and I look forward to future progress toward this lofty goal.

We have seen a remarkable change in the state of HCV therapy and the medical community should be proud of the successes that have been achieved.

Tig · Admin

More good news on Mavyret!

Mavyret achieves 97% SVR in real-world cohort of patients with HCV

Estevez J, et al. Am J Gastroenterol. 2018;doi:10.1038/s41395-018-0261.

December 3, 2018

Mavyret demonstrated 97% sustained virologic response in a large, real-world cohort of patients with hepatitis C over an 8-week course and extended 12-week to 16-week courses, according to recently published data.

“In clinical trials, restricted inclusion and exclusion criteria for the targeted patients may influence outcomes,” Roberta D'Ambrosio, MD, from the University of Milan in Italy, and colleagues wrote. “We demonstrated for the first time the excellent effectiveness and safety of [Mavyret] in a large cohort of HCV patients treated in an Italian real-life setting.”

The real-world cohort comprised 723 patients with hepatitis C who underwent treatment with Mavyret (glecaprevir/pibrentasvir, AbbVie) for 8 weeks (88%), 12 weeks (11%) or 16 weeks (1%). Fifty-seven participants had compensated cirrhosis and 116 were interferon-experienced. Genotypes included 1, 2, 3 and 4.

Thirty-five patients were lost to follow-up and three patients died during the study due to reasons unrelated to treatment.

At end of treatment, 97% of patients in all treatment duration groups achieved SVR. Specifically, the rate of SVR by intention-to-treat was 94% (95% CI, 92-96) and by per-protocol analysis was 99.3% (95% CI, 98.6-99.9).

The researchers noted that therapy compliance was excellent across all centers. Of the 10 patients who were undertreated, nine achieved SVR and one was lost to follow-up.

Four patients discontinued treatment early due to adverse events. However, all four achieved SVR.

Referring to patients with genotypes 1a and 3, advanced fibrosis, high HCV RNA, and high BMI, D’Ambrosio and colleagues wrote that “even in the relatively limited subgroup of patients carrying clinical features usually associated with lower chances of achieving an SVR, [glecaprevir/pibrentasvir] treatment resulted in optimal effectiveness.” – by Talitha Bennett

Disclosure: D’Ambrosio reports financial connections with AbbVie, Gilead and Merck Sharp & Dohme. Please see the full study for the other authors’ relevant financial disclosures.

Tig · Admin

I knew this, but this is the kind of information we need to share with those thinking they have time to wait. Never forget, the Dragon never sleeps...

DAAs reduce HCC, decompensation risk compared with no treatment

November 12, 2018

SAN FRANCISCO — Individuals with hepatitis C who underwent DAA therapy experienced significant reductions in both hepatocellular carcinoma and decompensation risk compared with untreated patients, according to data presented at The Liver Meeting 2018.

Haesuk Park, MD, assistant professor in the College of Pharmacy at the University of Florida, aimed to determine the impact of all-oral DAA treatment on the incidence rate of HCC and decompensated cirrhosis, along with the economic outcomes of DAA treatment. “We looked at liver-related costs, and all-cause costs,” Park said.

She noted that access to HCV therapy has been frequently restricted due to high drug costs, among other reasons, leading to treatment delays. “This delay may have costly consequences,” she said.

The cohort for clinical outcomes included 26,105 patients. Of that group, 7,928 received DAA’s and 18,177 were untreated. For the economic outcomes, there were 8,064 patients, with 4,032 patients each in the treated and untreated groups.

Treatment outcomes showed that DAA therapy yielded a significant reduction in risk for developing HCC compared with no treatment (HR = 0.28; 95% CI, 0.15-0.52) among patients with compensated cirrhosis. This trend persisted among those without cirrhosis, with DAA therapy also reducing HCC risk compared with no treatment (HR = 0.43; 95% CI, 0.26-0.71). “The crude incidence for HCC risk was four times higher in the untreated patients compared with treated patients,” Park said.

Sensitivity and subgroup analyses shows that this trend of reduced HCC risk for treatment vs. no treatment persisted, regardless of cirrhosis status, among patients with no cancer history; among those diagnosed with HCC 3 or more months after baseline; and among those who received minimum effective treatment. “The results were consistent,” Park said.

She added that factors associated with HCC included male sex, older age, diabetes, cirrhosis, and cancer history.

Among participants with compensated cirrhosis, DAA treatment reduced decompensation risk compared with no treatment (HR = 0.38; 95% CI, 0.26-0.56). Similarly, treatment also decreased decompensation risk among those without cirrhosis (HR = 0.42; 95% CI, 0.3-0.58). “We found that DAA therapy was associated with a 62% decrease in [decompensated cirrhosis] risk in patients with compensated cirrhosis and a 58% decrease in patients without cirrhosis,” Park said.

Cost analysis findings showed that compared with no treatment, DAA treatment reduced liver-related costs among patients with compensated cirrhosis by $2,826 (P <. 001). For all-cause costs, this reduction was $13,739 (P < .001).

“In the short term, all-oral DAA treatment for HCV infection was associated with a decreased risk of developing HCC and [decompensated cirrhosis],” Park said. “DAA treatment was associated with a decline in health expenditures for both liver-related and all-cause related costs in patients with compensated cirrhosis.”

Park noted that a longitudinal study is necessary to confirm these findings. “Despite these positive findings, and the availability of these highly effective, all-oral DAA therapies, the majority of HCV patients within our study were not treated,” Park said. – by Rob Volansky

Reference:

Park H, et al. Abstract 146. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.

Canuck · Guru

Lam and Tig - I have never been one for any "budget" when it comes to MY health, and I have always defaulted to .... when in doubt, more should be better, in this article below, the part that was most appealing to me was the increased frequency of the VL and lab testing, the "concept" of "individualized" care versus cookie cutter care, I do not like to see blind molds that do not fit everyone, and the shoving of squares through round holes is not the ideal in many treatment models. I am still having trouble with VL's being taken at week 4 (on a 12 week course) and then nothing until SVR12!

I am not condoning the shortening of treatments, I am merely presenting the data that has come out, as interesting fodder to think about, here, and in the other posting I made (on the same study material).

Yes, a very small study and numbers, but still, it IS published, (and we have already seen course lengths drop,people have already been getting 8 week harvey therapy!). Shortened courses is still a hot and current topic in Mav articles too, not just the other drugs mentioned here. This small data was heaviest for VEL, ZEP, Harvey in that order and very few Mavs. Also too bad, was that even though this was a re-treatment for some, of these 19 people, Vosevi was not a drug used here.

I keep "re"-reading that skinny-looking 83%, but then I also keep RE-READing the whole of the info and paragraphs and suss the "original" number of participants - they originally started out (technically) with 22 people total, but in the end, they only used 16 people to see who was SVR12? ... out of the 16, only one person failed. What is the success rate of 15 SVR12's out of 16 people? ... that might be another way to read this data! ... 15 people with SVR12, plus one failed GT3 = 16 total, 3 further people seem to drop off their measuring at EOT and at EOT+4weeks (which would have totaled 19 people), and no mention of the last (just now missing?) 3 people (who would have been included in the original 22 people)!

Was never no good with math - you guys enlighten me please with your counting of heads? How I am "countings" heads, and interpreting their study "semantics" (endpoints), of who had what, when and how many of them did so, may be skewing how bad or good this 83% is. How do you decipher all their data to equate to 83%? - basically, I see 15 out of 16 people with SVR12 (and that works out to about 93.75%)!

Another oddity to keep in mind, as far as measuring/counting, is that there were only 11 people total (out of this so-called original 22 people) who even ended up having their course length reduced to be less than 12 weeks, the rest of the folk (who at least started treatment, if not finishing it) were determined to need the whole 12 weeks.

I prefer big studies too, like some of Gileads. Mind you, there were not that many of us 3's in their trials, nor too many of us in their 8 week Vosevi arms.

Studies can always start off small, but may grow as they garner merit to improve on the data gathering.

I wish they HAD spoken more about the math "formula" they used ... how much of a dropped VL (or whatever) at "day 2, week 1, and perhaps even more importantly, at week 2 and week 4" was used as their ruler. THAT would have been interesting to know as well!

Lots of labs and liberal drugs I say, until I stand corrected (hm, heehee, I do stand here as a cured 3 though, and only on 8 weeks duration of Vosevi!) but, then again, ... Vosevi IS in a league all of it's own (i care to believe), I would still err on the side of overkill, over-treatment. Gilead, once they made their triplet available as a rescue treatment, has made no peep to decrease their 12 week scripts to 8 weeks. Fine by me. I am still for individualized/personalized courses of whatever in medicine (IF we want to talk about frequent following and assessments), for safe but efficient "response-guided" therapies. C.

-- Edited by Canuck on Monday 26th of November 2018 12:06:28 AM

Tig · Admin

Agreed.... There’s too much attention being made to cost savings by shortening courses of care. If they want to actually win this battle, profits need to be secondary. If manufacturers can make sweetheart deals with other countries utilizing generic substitutes, that cost 1/10th the price, they should do it for everyone. We have to make our thoughts known and advocate for affordable access to these life saving drugs, in sufficient quantities and courses of care.

jmho... ¯\_(ツ)_/¯

lamassu · Senior Member

Only 83% reaching SVR12 is not acceptable IMO ... but the study is too small to be statistically significant at this time. I trust the large studies like ASTRAL 1 - 3. Saving 20% is not a fair trade off if you do not reach SVR12 and then have to also pay for a course of Vosevi.

-- Edited by lamassu on Sunday 25th of November 2018 09:20:52 AM

Canuck · Guru

See also, a previous (earlier) article (posted here - Shortening HCV Treatment Courses ) -the same topic/same meeting/same info as below, but this article does contains more (further) specific info on which drugs were used though:

Helio article on the Liver Meeting

Response-guided therapy may shorten HCV treatment time by 50%

November 21, 2018

The use of response-guided therapy, or RGT, reduces effective treatment times by up to 50% in patients with hepatitis C virus infection and could significantly cut costs for expensive direct-acting antiviral therapy, according to research presented at the Liver Meeting 2018 in San Francisco.

"Treatment currently is standardized to be given for a set period of time, usually 12 weeks, rather than being tailored to individual patients," Scott Cotler, MD, head of Loyola Medicine's division of hepatology and a professor at Loyola University Chicago Stritch School of Medicine, said in a news release.

In a proof-of-concept pilot study, Cotler and colleagues enrolled patients with HCV and compensated liver disease, genotypes 1 to 6, who were either treatment naive or interferon experienced. Participants were treated with one of four all-oral DAA regimens, and their viral loads were measured at baseline, day 2 and weeks 1, 2 and 4 after beginning treatment.

Cotler and colleagues used mathematical modeling-based RGT when possible at treatment weeks 2 and 4 to project a time to cure. Treatment duration was then individualized based on the projections. The primary endpoint was proportion of patients with undetectable HCV RNA at 12 weeks after treatment.

The ongoing study includes 22 patients so far (mean age, 49.8 years, 50% female). The patients' most common genotype was G1b (59%), followed by G3 (27%). Forty-one percent received Epclusa (sofosbuvir/velpatasvir, Gilead), 31% received Zepatier (elbasvir/grazoprevir, Merck), 23% received Harvoni (sofosbuvir/ledipasvir, Gilead) and 5% received Mavyret (glecaprevir/pibrentasvir, AbbVie).

According to the findings, modeling predicted that treatment duration could be shortened to 10 weeks in one patient, 8 weeks in eight patients and 6 weeks in two patients. At the time of study presentation, 19 patients had completed therapy, with 100% experiencing an undetectable viral load when their treatment ended. Eighteen of the 19 patients (95%) were still HCV undetectable 4 weeks after treatment, Cotler and colleagues reported. Sixteen patients were assessed 12 weeks after treatment, with 83% attaining primary endpoint of undetectable HCV RNA. The only patient to relapse was a treatment-naive man with genotype 3 HCV who had been treated with sofosbuvir/velpatasvir for 6 weeks, the researchers reported.

Cotler and colleagues said the shortened treatment duration using real-time RGT did not compromise efficacy or patient safety. They noted that a larger, multicenter study was being conducted to validate the results.

In the accompanying news release, it was noted that HCV drugs have a high cure rate but can cost more than $50,000 per patient.

"There's a potential to save up to 20% of the costs of hepatitis C drugs," study author Harel Dahari, PhD, co-director of the Program for Experimental and Theoretical Modeling in the hepatology division of Loyola Medicine and Loyola University Chicago Stritch School of Medicine, said in the release. - by Bruce Thiel

Reference:

Etzion O, et al. Abstract LB-34. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.

Tig · Admin

EXPEDITION-8: Mavyret nearly perfect in 8-week regimen. (Link)

November 13, 2018

SAN FRANCISCO — Mavyret yielded nearly perfect SVR rates after 8 weeks of therapy in compensated cirrhosis with HCV, according to data presented at The Liver Meeting 2018.

“Excellent real-world data confirms the high SVR data,” Robert S. Brown Jr., MD, of the Center for Liver Disease and Transplantation at New York Presbyterian Hospital and Cornell Medical College Department of Medicine, said. “The idea came to us to investigate an 8-week duration in treatment-naive patients with compensated cirrhosis, so we were looking at exactly that question.”

Brown presented data for the ongoing phase 3, non-randomized, single arm, open-label, multicenter study in 280 treatment-naive patients dosed with Mavyret (glecaprevir/pibrentasvir, AbbVie). The presentation included data from patients with all HCV genotypes except genotype 3.

The study included both per-protocol and intention-to-treat (ITT) analyses. The per-protocol analysis had a non-inferiority margin of 94% SVR, while the boundary for the ITT analysis was 99%. Virologic failures, relapses, adverse events, and resistance variants comprised secondary endpoints.

Results indicated an SVR rate of 100% in the per protocol analysis and 98% in the ITT population. “There were no virologic failures,” Brown said.

Safety data showed six serious adverse events. “None were determined to be drug-related,” Brown said. No events led to discontinuation of therapies, and no events were seen in more than 10% of the population. “This was consistent with what we’ve seen in prior [glecaprevir/pibrentasvir] trials.”

Brown added that there were no alanine aminotransferase elevations above twice or three times the upper limit of normal. “There were no liver related toxicities,” he added.

Baseline data showed that patients had a mean FibroScan (Echosens) score of 23.7, according to Brown. “Bilirubin was normal,” he said. “About 20% had platelets under 100,000.”

“These results support an 8-week duration of [glecaprevir/pibrentasvir] for treatment-naive patients with HCV,” Brown said. “We eagerly await the genotype 3 data. This adds to our treatment regimen.” – by Rob Volansky

lamassu · Senior Member

Great thread Tig thanks. I spoke with my GE last week and he said he and his colleagues have been writing more scripts for Mavyret than Epclusa or Harvoni due to the cost difference. Gilead has been losing market share and had no choice but to come out with generic Epclusa and Harvoni in the US. Then the generic Epclusa or Harvoni will be less costly than Mavvret. When I was treated earlier this year Epclusa was my only choice as my Medicare advantage plan did not cover Mavyret yet. Starting in 2019 they will and also Vosevi. Competition is good for consumers. Since Vosevi is the DAA of last resort I don't expect a generic any time soon.

Tig · Admin

Genetic study and FDA approval into the use of 23 and Me to determine advances in medication metabolism. This used to be helpful in determining RAS impact on rates of success and treatment length. Nice to see it is expanding.

Medication Metabolism

Tig · Admin

Here’s some information on HCV vaccine research.

HCV vaccine critical for global virus control

Bailey JR, et al. Gastroenterol. 2018;doi:10.1053/j.gastro.2018.08.060.

October 5, 2018 Experts in a recent review stated that an effective hepatitis C vaccine is critical for significant global control of the infection in combination with increased screening and treatment.

However, there are several barriers to HCV vaccine development, including virus diversity, limited models for testing vaccines, and incomplete understanding of protective immune responses.

“Although pharmaceutical companies invest in drug development, vaccine development requires investment from sources beyond government and charitable foundations,” Justin R. Bailey, MD, PhD, from the Johns Hopkins University School of Medicine in Maryland, and colleagues wrote. “A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge.”

HCV genetic diversity presents one of the principal challenges for vaccine development, considering there are seven known genotypes — and a possible eighth recently discovered — with more than 80 subtypes. Additionally, immune selection and error-prone polymerase of the virus generate “a diverse quasispecies of related but genetically distinct viral variants” in individuals, according to Bailey and colleagues.

Another barrier to HCV vaccine development is the lack of in vitro or animal models available to determine whether a vaccine induces protective immunity.

“Direct infusion of HCV-infected human plasma might be considered, but would require careful screening for other pathogens and, even with thoughtful selection of inoculum levels and HCV genotypes, might fail to completely recapitulate natural exposure,” the researchers wrote. “Although our incomplete understanding of protective immunity against HCV is a barrier to vaccine development, studies have provided substantial evidence that protective immunity does exist.”

Regarding spontaneous clearance of HCV, both chimpanzees and humans have demonstrated recurrent HCV viremia following additional HCV exposure after initial control. This, according to the researchers, shows that spontaneous clearance of primary HCV does not generate sterilizing immunity.

However, previous studies have reported clearance of multiple infections with homologous and heterologous viruses in chimpanzees and humans. Rapid and effective control of viral replication with subsequent exposures indicates that adaptive immunity is induced and protects against chronic infection.

“Additional research on effective immune control of HCV is needed to develop a vaccine, including studies of people with repeated spontaneous control of diverse HCV infections over time,” Bailey and colleagues wrote. “Vaccine strategies meant to overcome the enormous diversity of HCV must generate a broad immune response, capable of responding to abundant variations. Selecting antigens to maximize the induction of T-cell and antibody responses that elicit successful responses remains an active area of research.” – by Talitha Bennett

Tig · Admin

You beat me to this notice. My email must be slower than yours. Mine just arrived!

This is great news, but I’m thinking Gilead can beat that price by $20K, considering it’s available overseas for less than $2K. Oh well, every step forward that makes these great new treatments more available, to all that need it, the better. Hopefully we’ll see insurance carriers more willing to treat on demand, when requested by healthcare providers. Fingers crossed for that day!

Canuck · Guru

Interesting! A price "reduction" (sometime in 2019) for long-time existing Harvoni, and, for the relatively (comparatively) new-comer Epclusa as well! Hm - food for thought there.

Helio - HCVnext

Gilead announces launch of Epclusa, Harvoni generics for HCV

October 1, 2018

Gilead Sciences announced plans to launch authorized generic versions of Epclusa and Harvoni, according to a company press release.

The generics will launch at a list price of $24,000 for the most common course of hepatitis C therapy in January 2019 through a newly created subsidiary, Aseguea Therapeutics LLC.

Launching these authorized generics is the best solution available to us today to quickly introduce a lower-priced alternative to our HCV medications without significant disruption to the healthcare system and our business, John F. Milligan, PhD, president and CEO of Gilead Sciences, said in the lease. This launch also will hopefully help increase transparency by more closely aligning our medications list prices with their cost.

The authorized generics of Epclusa (sofosbuvir/velpatasvir) and Harvoni (sofosbuvir/ledipasvir) will be priced to reflect the discounts that health insurers and government payers currently receive, according to the release. Additionally, Gilead stated that the generics should provide substantial savings for patients with Medicare or Medicaid.

Our ultimate goal is to lower the list price of Epclusa ... and Harvoni, Milligan said in the release. We are committed to working with all of our partners in the healthcare system to help enable list price reductions of our HCV medications and find better solutions to reduce patients out-of-pocket costs.

Reference: www.gilead.com

Canuck · Guru

The Louisiana-access thing article is a very good one! - i used it already, over in "Access to drugs " ... as it also fits in there, along the "access to drugs/treatment and barrier removal" theme. smile

Don't we appreciate these good topics! Oh we live in curious times. wink C.

Tig · Admin

Hmmm... Does this mean we have to tune in for further developments? wink

FEATURE

Louisiana developing ‘Netflix’ style subscription plan for HCV treatment

September 18, 2018

The Louisiana Department of Health is currently developing a “subscription style” payment plan with pharmaceutical manufacturers to provide state residents with access to hepatitis C treatment.

Pete Croughan

HCV Next spoke with the department’s chief of staff, Pete Croughan, MD, about the landscape of HCV in the state and the novel payment model designed to expand treatment despite the expensive cost of direct-acting antivirals.

“Hepatitis C is definitely an epidemic here, like it is in many places, and equally tied to the opioid epidemic due primarily to transmission through reuse of needles,” Croughan told HCV Next. “National data has shown that rates of acute infections tripled in the last 5 years. This corresponds with our own internal data on increased rates of infection.”

While the state has adequate data on the number of individuals infected with HCV through Medicaid, Croughan explained that the health department is focused on improving surveillance in correctional facilities, which is significantly lacking. National data, he said, place HCV prevalence in correctional facilities between 15% and 40%. Until screening is expanded in Louisiana, “we’re not going to know how many people are infected with HCV in our justice system,” he said.

Prior authorization criteria had also presented a barrier to treatment for state residents. Like many states, prior authorization initially restricted treatment based on at least 1 year of sobriety, prescriber specialty and the patient’s fibrosis score. However, cost-effective data that followed the introduction of new DAAs led the health department to evaluate what criteria was the most restrictive and least evidence-based with the help of the physician community and health advocates in New Orleans.

“We wound up changing our sobriety restriction to only needing a provider access statement that the patient is able to complete treatment, we removed the provider specialty restriction, and we eliminated fibrosis scores for HCV and HIV-coinfected individuals,” Croughan said. “Our hope is to eliminate this disease — that’s been our goal from the beginning — but the challenge has been how to pay for it. We’re among the poorer states and we’re trying to find space to treat large numbers of people. That’s where we think the subscription model in a win-win-win, for patients, the state and potentially pharmaceutical partners.”

Working with Rebekeh Gee, MD, Secretary of the Louisiana Department of Health, Croughan and colleagues developed the concept of a subscription payment model that has been described by some as the “Netflix model.

Tig · Admin

Seems they are developing a new test that is referred to as a “Liquid Biopsy”. Sounds very promising and combines with other fibrosis testing models, should help to identify problems well ahead of some conventional means.

Healio Updates Credit

Liquid biopsy identifies chronic liver disease, liver cancer vs. healthy blood

Bhan I, et al. Gastroenterol. 2018;doi:10.1053/j.gastro.2018.09.020.

September 13, 2018 A recently developed liquid biopsy cell-sorting device was able to detect circulating epithelial cells of hepatocyte origin in blood from healthy individuals, patients with chronic liver disease without hepatocellular cancer, and those with HCC, according to a recently published study.

Canuck · Guru

Eww!

Read one on "bio-film" and what's left after hundreds of ineffectual wipes/swipes/scrubs/cleanings of high risk objects in high risk places when cleaning is not done right, places the public can end up being in - like ... in hospitals - more ew! Splashing or spraying around a potent broad spectrum solution does not necessarily make up for bad cleaning technique. Ya jes kint be too careful alright. wink C.

Tig · Admin

While on treatment or not, it’s very important to protect yourself from all beasties, great and small. This article regarding airport security trays (TSA), is sure to make you sit up and take notice. Always, always, wash your hands thoroughly after handling them or any public surface. They are ALL contaminated and you never know what you are being exposed to. Consider the recent discussion we had on the possibility of exposure to Hepatitis A. This is exactly how some can be exposed to a virus, regardless of how cautious we are.

Airport Beasties

Canuck · Guru

So, the Eugene Melnyk (owner of the Ottawa Senators hockey team here in Ontario, Canada) that I had mentioned in my prior post below? ... here is the link to the old, old post I first made about him and his transplant, and how since then he has been active and fundraising to improve liver transplantation conditions. It was in his first interviews that he and his docs were speaking of the want to improve the "keeping of livers" (among other things).

Eugene Melnyk - transplant recipient

Here is another article regarding work at Ontario's "Toronto General Hospital" transplant facility (dated summer of 2015) - we can see they have been working on this kind of "keeping" equipment for some time now (and, all over the world as well it seems).

Device keeps donor liver healthy outside body until transplant

https://www.uhn.ca/.../device_keeps_donor_liver_healthy_outside_body_until_transpl...

Jul 22, 2015 - Device keeps donor liver healthy outside body until transplant ... Dr. Selzner, who is also a clinician-scientist at the Toronto General Research ... The technique of warm organ perfusion outside the body was pioneered in the ...

Eugene keeps having these annual fund and awareness raising campaign galas for "The Organ Project", good for him. He had "Bare Naked Ladies" there this year, and he gets very interesting and talented people there! Good people doing good things. smile

Canuck · Guru

Helio - Transplants

I posted elsewhere on the site about the owner of the hockey team the "Senators?" here in Canada land - he had hisef a shocking and successful transplant, and learned a lot through the process and in short order, he did some fund raising to try to support and assist his transplant hospital docs drum up better means of dealing with the donor livers whilst they are being kept for placement. I wonder how similar (or not) the Canadian docs methods were to these US docs system?

UT Southwestern demonstrates efficacy of portable donor liver system

August 28, 2018

UT Southwestern announced its participation in the Liver PROJECT trial of a portable system designed to keep livers warm and blood circulating prior to liver transplantation, according to a press release.

Its like a virtual transplant, Malcolm MacConmara, MD, from UT Southwesterns department of surgery and lead researcher of the Liver PROTECT study, said in the release. By putting the liver on the machine, we can truly approximate the conditions of the body. We provide oxygen, blood and nutrition to the liver and watch how it functions before the patient receives the organ.

According to the release, the portable Organ Care System (TransMedics) is approximately the size of a shopping cart. The interior design connects the donor liver to tubes that infuse the organ with blood.

In a recent transplant case, a 59-year-old patient with liver failure related to cirrhosis and liver cancer underwent transplant at UT Southwestern with a liver transported from a local donor hospital. The patient tolerated the surgery, was removed from the ventilator at the end of the procedure and continued to demonstrate rapid recoverywith discharge 3 days posttransplant.

The longer a liver sits on ice, the more likely it is to have problems after transplant. The liver will become unusable if it has been stored for too long, Parsia Vagefi, MD, from UT Southwestern and lead surgeon of the recent cases surgery team, said in the release. With many patients waiting for organs, this new way of treating organs may expand the number of donated livers that can be used for transplant.

Reference: www.utsouthwestern.edu

-- Edited by Canuck on Friday 31st of August 2018 01:18:31 AM

Hoodietree · Senior Member

Cool pic, Tig!

Tig · Admin

The graininess keeps the facial recognition software confused... wink

Canuck · Guru

Yes, it is a beautiful thing this Vosevi! I was just about to post this very same article (that you just did), and voila, you have done the good news service, and here the article sits and shines in all it's glory! Seems people can't keep good news quiet too long! We have to thank (credit) Gilead for bringing us all these new "good news" drugs! biggrin C.

Hey, who's that guy in your avatar, looks kinda familiar, i think? Um, kinda grainy that photo tho ain't it? Could ya meebe play with the contrast tools?

Tig · Admin

It’s simply an excellent treatment...

Resistance did not affect SVR rates in trials of Vosevi for HCV

Sarrazin C, et al. J Hepatol. 2018;doi:10.1016/j.jhep.2018.07.023.

August 13, 2018Baseline resistance associated substitutions did not impact sustained virologic response among direct-acting antiviral-experienced patients who underwent hepatitis C therapy with Vosevi for 12 weeks, according to a recently published study.

“In contrast to the prior studies of regimens targeting two distinct HCV proteins, the presence of NS3, NS5A and/or NS5B NI RASs did not affect treatment outcome in DAA-experienced patients including those who were previously treated with NS5A inhibitors upon treatment with [Vosevi] for 12 weeks in phase 3 trials,” Christoph Sarrazin, MD, from the Goethe University Hospital in Frankfurt, Germany, and colleagues wrote.

Sarrazin and colleagues’ review included data from the POLARIS-1 and POLARIS-4 studies of Vosevi (sofosbuvir/velpatasvir/voxilaprevirfor, Gilead Sciences), which included patients with HCV genotype 1 through 6.

SVR rates were 96.8% or higher for patients with either or both NS3 and NS5A RASs and 97.7% or higher for patients without RASs, which was not significantly different.

In a subanalysis of patients who had experience with earlier generation pegylated interferon therapy, the researchers found SVR rates of 95.1% or higher among patients with NS3 RASs.

Additionally, despite RAS position among patients with NS5A RASs, patients achieved SVR rates of 97% or higher.

“NS5A inhibitors are a common component of DAA regimens and more recently developed agents have demonstrated pangenotypic activity,” Sarrazin and colleagues wrote. “These results show that daily treatment with the single-tablet regimen of [Vosevi] for 12 weeks is highly effective for a broad range of DAA-experienced patients infected with HCV of any genotype regardless the presence of RASs.” – by Talitha Benenett

Disclosure: Sarrazin reports he has received research or grant support from Abbott, Achillion, Astra, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, Qiagen, Roche and Siemens. Please see the full study for the other authors’ relevant financial disclosures

Canuck · Guru

Helio - HCV Next

FDA NEWS

FDA updates Mavyret label for new safety, efficacy data - August 8, 2018

The FDA recently approved safety and efficacy revisions to the Mavyret label based on data from a hepatitis C/HIV-1 collection study and a liver and renal transplant study.

Ongoing studies from the past year have shown Mavyret (glecaprevir/pibrentasvir, AbbVie) to be a pangenotypic treatment that is highly effective over an 8-week course for most patients.

According to the released revisions, the FDA recommends a 12-week course of glecaprevir/pibrentasvir for liver or kidney transplant recipients. The FDA also recommends a 16-week course for patients with genotype 1 and NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor, and for patients with genotype 3 who are treatment-experienced with Sovaldi (sofosbuvir, Gilead Sciences) and ribavirin.

Regarding adverse reactions, results of two studies of patients with HCV/HIV-1 coinfection and genotypes 1, 2, 3, 4 or 6 showed a similar safety profile compared with HCV mono-infected patients. The FDA announced similar results from a study of patients treated post- liver and kidney transplant with genotypes 1, 2, 3, 4 or 6.

Among patients without cirrhosis or with compensated cirrhosis, both patients from the HCV/HIV-1 collection study and patients from the liver and renal transplant study demonstrated an overall sustained virologic response rate of 98%.

Reference: www.fda.gov

Tig · Admin

Good news for US Veterans!

The American Legion joins AbbVie to provide free HCV testing for veterans

August 1, 2018

The American Legion, in partnership with AbbVie, announced the launch of its “Take on Hep C” nationwide initiative designed to provide free hepatitis C antibody testing to veterans and their communities, according to a press release.

Tig · Admin

This is great news!

Heart transplant with HCV-positive organs successful, virus cleared

Schlendorf KH, et al. J Heart Lung Transplant. 2018;doi:10.1016/j.healun.2018.01.1293.

August 2, 2018

Patients without hepatitis C who underwent heart transplantation with an HCV-positive organ were likely to develop HCV viremia posttransplant, but had high rates of sustained virologic response following direct-acting antiviral therapy, according to published results of a recent prospective study.

“Given the shortage of donor hearts available for transplantation, and the favorable safety and efficacy of DAAs used to treat HCV, our institution piloted transplantation of selected patients using HCV-positive donors,” Kelly H.Schlendorf, MD, from the Vanderbilt University Medical Center in Tennessee, and colleagues wrote.

Beginning in September 2016, Schlendorf and colleagues enrolled 12 HCV-naive patients and one patient with a history of HCV that was cured before listing in the study. Patients elected to undergo heart transplantation with organs from HCV-positive donors.

Waitlist time varied based on recipient consent to receive an HCV-positive heart, with a median time of 256 days (range, 1-202 days).

Nine patients developed HCV viremia posttransplant and underwent subsequent treatment with DAAs. All nine patients received organs from donors with detectable HCV antibody and positive nucleic acid amplification test results. Median time from transplant to detection of viremia was 4 days (range, 2-13 days).

As of October 2017, eight patients completed 12 weeks of DAA therapy and demonstrated sustained virologic response. One patient died due to pulmonary embolism during week 7 of treatment.

“Ongoing follow-up will allow us to better assess the safety and efficacy of transplanting hearts from HCV-positive donors into HCV-negative patients,” Schlendorf and colleagues wrote. “There are ongoing questions as to the effect, if any, HCV infection or DAA therapy have on graft function, endothelial function, incidence of rejection, CAV, renal and hepatic function, and survival. If utilization of HCV-positive donors proves to be safe and efficacious in the long term, there is a potential for this strategy to have a major impact on reducing morbidity and mortality of waitlisted patients.” – by Talitha Bennett

Tig · Admin

Improvements following SVR. Positive reports!

Hepatic manifestations and SVR

Vasculitic Manifestations

Canuck · Guru

Insight on the Social Science of HCV

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Real world study proves efficacy of Mavyret.

Thomas Berg, MD, Paris, France

Canuck · Guru

Article about kratom use in U.S.

The good, the bad, and the maybe, about kratom

Canuck · Guru

Lots of info/news/reports starting to come out of Paris, France right now, from the big "International Liver Meeting" being held there Apr 11 - 17:

Helio - Meeting News

Early-stage HCV treatment saves money, improves QOL

April 12, 2018

PARIS - Treating hepatitis C virus in the early stage of disease saves money in drug and medical costs while lowering risk for decompensated cirrhosis, hepatocellular carcinoma, liver transplant and liver-related death, according to a presentation at the International Liver Congress 2018.

"For all these outcomes, the best outcome is experienced by those who started at [fibrosis stage 0 and 1] and the worst by those who have advanced disease," Scott Johnson, PhD, MHA, an economist with Medicus Economics LLC, said during a press conference. "The advanced patients have ten-sixteenths of the lifespan and quality of life of those who were treated when they were mild."

Johnson explained that this modeling study was based upon Scotland's estimated 46,657 people with HCV. Scotland restricts access to HCV treatment to those people with late-stage disease, he said. As this model is based upon Mavyret (glecaprevir/pibrentasvir, AbbVie), Johnson explained that this policy to restrict often requires longer treatment of 12 weeks vs. 8 weeks if treating early-stage disease.

Lifetime risk for decompensated cirrhosis when treated at F0/F1 was 4%, as compared to 11.6% when treated at F4 or compensated cirrhosis. Lifetime risk for HCC when treated at F0/F1 was 1.8% vs. 35.2% when treated at F4 or compensated cirrhosis. Lifetime risk for liver transplant was 0.4% at F0/F1 vs. 2.6% at F4/compensated cirrhosis. Lastly, lifetime risk for liver-related death was 3.8% at F0/F1 vs. 41.1% at F4/compensated cirrhosis.

Johnson showed that although overall sustained virologic response rates were very similar, lifetime quality-associated life-years decreased as initial disease level increased. Patients treated for HCV when still at F0/F1 gained 16.2 lifetime QALYs. If patients reached F2/F3 before treatment, they gained 13.9 QALYs. If patients did not receive HCV treatment until F4 or compensated cirrhosis, they gained 10 QALYs.

"The cost of treating the F4/CC patient ... is much higher. It's almost twice what it is to treat the mild patient. The payer is actually paying more to treat these advanced patients," Johnson said. "That's because there's a greater disease burden ... but also because you're treating them with a longer regimen."

Direct medical costs also nearly doubled when treatment is withheld until late-stage disease, Johnson showed. If treated at F0/F1, costs are estimated to be £32,996; at F4 or compensated cirrhosis, costs are estimated to be £60,963. Johnson said £40,000 of the advanced treatment costs are drug costs.

"Even just based on drug treatment cost alone, it makes more sense to treat the earlier stage patient," Johnson said.

"This study shows the impact that delayed treatment can have on a patient's life, including consequences such as liver morbidity and mortality, as well as extrahepatic complications," Sammy Saab, MD, professor of medicine and surgery at the University of California, Los Angeles, said in a press release. "Beyond benefits to the patients, early treatment can generate significant savings by reducing clinical risks and allowing for a shorter, 8-week duration of treatment across all genotypes." - by Katrina Altersitz

For more information:

Pinsky B, et al. PS-058. Presented at: International Liver Congress; Apr. 11-15, 2018; Paris, France.

Disclosure: This study was supported by AbbVie. Medicus Economics, LLC received consulting fees for research from AbbVie. Saab reports being a consultant to and serves on speaker bureaus for AbbVie Inc., Bristol-Myers Squibb, Gilead, Janssen and Merck.

Hep C Discussion Forum

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Early-stage HCV treatment saves money, improves QOL

April 12, 2018

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