Category Archives: 2017

Direct-acting Antiviral Combo Effective Against Treatment-resistant Hepatitis C | Kenneth Bender

A triple drug regimen effectively cured patients with hepatitis C virus (HCV) after they had failed to respond to a combination of 2 oral direct-acting antivirals (DAA), according to a report of 2 international trials.

Lead author David L Wyles (pictured), MD, Chief of Infectious Diseases Denver Health, Medical Center, University of Colorado, and colleagues set out to treat HCV patients he characterized as “one of the most difficult-to-treat populations studied thus far with new DAA regimens.”

The patients had previously failed treatment with an oral DAA combination that included an NS5A inhibitor. The 2 trials feature patient groups with genotype 1 (GT1) in one, and GT1, 2, or 3 in the other, respectively.

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Drug Approval

July and August are very important months in hepatitis C treatment for patients.  On July 18, 2017, the Food and Drug Administration (FDA) approved  Gilead’s sofosbuvir/velpatasvir/voxilaprevir—brand name Vosevi–to re-treat adults with hepatitis C. In August 2017 the FDA is expected to approve  AbbVie’s glecaprevir/pibrentasvir—brand name Maviret.  The July and August approvals will push hepatitis C cure rates up to nearly 100%!

Vosevi

Gilead’s three drug combination is a pan-genotypic HCV medication co-formulated into one pill, taken once-a-day.  The FDA stipulates that Vosevi is approved to treat people who have previously been treated with a DAA but who did not achieve a cure.  The treatment period is 12 weeks is considered a salvage therapy—a term used for people who have failed another DAA therapy.

For the people who were treated prior with DAAs but who did not achieve a cure, 12 weeks of treatment cured up to 100% of patients.

The most common side effects were a headache, fatigue, diarrhea, and nausea.

This is very good news for the 5% to 10% of people who have failed prior DAA therapy who had few treatment options until now.

Be sure to check out our Hep C Medications Blog for more detailed information about Vosevi and the other HCV medications approved to treat hepatitis C.

http://hepatitiscmedications.hcvadvocate.org/

Maviret

Update:  Since the newsletter was published Mavyret has been approved by the FDA.

AbbVie’s two drug combination is also a pan-genotypic (genotypes 1 through 6) co-formulated into one pill, once-a-day treatment for people with hepatitis C and compensated cirrhosis.  The treatment period is 8 weeks and cure rates in the clinical trials were 95% to 99%.

The most common side effects were fatigue and headache.

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Favourable virological and clinical outcomes at 1 year after liver transplantation in hepatitis C virus-positive patients who received direct-acting antivirals on the waiting list

Source: Abstract #THU-457 Favourable virological and clinical outcomes at 1 year after liver transplantation in hepatitis C virus-positive patients who received direct-acting antivirals on the waiting list-S. Martini, et al.

Study Aims and Results: The return of hepatitis C is very common for people who are viremic when receiving a liver transplant. Significant liver stiffness was highly linked with the transplantation failure one year post treatment. This study looked at what effects treatment of hepatitis C with direct acting antivirals (DAAs) pre-transplant had on health outcomes 1 year after transplantation. From July 2014 and October 2016 there were 64 hepatitis C positive people treated with direct acting antivirals + ribavirin while on the wait list who underwent a transplantation. Of those, 16 participants made the transition from pre-to post-transplant and remained hepatitis C negative. The median age of recipients was 57 years old; 84% were male. The median donor was 66 years old. The amount of time participants who were hepatitis C negative prior to liver transplant was 94 days. Of the 55 participants who reached SVR12 post-transplant, 54 of them were hepatitis C negative. The median number of days for follow up post-transplant was 377.

Conclusion: This study was able to show that using DAAs pre-, and close to, transplantation resulted in 98% of the participants being hepatitis C negative. Treating before transplant also led to fewer post-transplantation liver complications and rejections. Even though many of the transplantation donors were elderly, 75% of the participants showed absent/mild liver scarring 1 year after transplantation.

Editorial Comments: Liver transplantation is expensive, scary and comes with a risk of failure. This study showed that curing someone of hepatitis C before they receive a transplant can significantly reduce the poor outcomes that have been shown among those who don’t receive similar treatment. Being able to reduce liver scarring and the risk of transplant being rejected is encouraging. This gives hope to those seeking a transplant and confidence for all involved that it will work and they can remain cured.

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Interferon-free therapy is effective and safe for hepatitis C recurrence in liver transplant hepatitis C virus/human immunodeficiency virus coinfected recipients: a case-control study

Source:  Abstract #THU-439 interferon-free therapy is effective and safe for hepatitis C recurrence in liver transplant hepatitis C virus/human immunodeficiency virus coinfected recipients: a case-control study- M.-C. Londoño, et al.

Study Aims and Results: Current studies show interferon-free treatments are successful and safe for monoinfected liver transplant recipients with hepatitis C. There are fewer examples looking at how successful direct acting antivirals are in HCV/HIV co-infected liver transplant recipients. This study focused on looking at the success and side effects of interferon-free treatment in a national cohort of HCV/HIV coinfected participants who had HCV return after transplantation. There were 38 HCV/HIV-coinfected and 133 HCV monoinfected liver transplant participants enrolled in the study. The two groups were fairly similar in gender, age, genotype, viral load, fibrosis stage and the amount of time from transplantation to treatment at 38 and 47 months. All coinfected participants were on HIV treatment; 84% had a RNA viral load of less than 50 copies/ml (undetectable) and a median white blood cell count of 367 cells/uL. For comparison, 1100-1400 white blood cells/ul is the range of someone who is not immunocompromised. The top three direct acting antiviral treatments that were used are as follows: ledipasvir + sofosbuvir ± ribavirin (RBV) (33%), simeprevir+ sofosbuvir ± RBV (31%), daclatasvir + sofosbuvir ± RBV (28%), simeprevir+daclatasvir ± RBV (5%), and AbbVie’s 3D (3%).  More than half of each cohort received RBV. The treatment success was also close among the cohorts, with 92% of the coinfected group having a sustained virologic response 12 weeks post treatment (cure), and 96% of the monoinfected group. There were no serious side effects of treatment or differences in success related to genotype and advanced fibrosis.

Conclusion: This study was able to show interferon-free treatments for HIV-positive people who have had hepatitis C return are successful with few side effects. As important, this study showed that the success rates of interferon-free treatment were similar to hepatitis C monoinfected participants.

Editorial Comments: Tackling the issue of treatment for people who receive a liver transplant and have hepatitis C return is crucial to any elimination plan. This is important not only among monoinfected people but those who are coinfected with compromised immune systems. The closer we can get to a treatment that is effective on both cohorts and has fewer side effects, the more likely we are to eliminate hepatitis C and save lives. Most importantly, this study shows that even after liver transplants people can be treated.

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Treatment with direct-acting antiviral agents is associated with improvement of renal function in a cohort of hepatitis C virus infected patients with chronic kidney disease

Source:  Abstract # THU-244 Treatment with direct-acting antiviral agents is associated with improvement of renal function in a cohort of hepatitis C virus infected patients with chronic kidney disease—C Masetti et.al.

Study Aims and Results: The hepatitis virus causes kidney disease through a complex process of an interaction with the immune system, the liver and the kidney.

The goal of the study was to understand the improvement in kidney function after being cured of hepatitis C.

The study included 42 HCV patients with kidney disease (38 pts stage III; 2 pts stage IV; 2 pts stage V). Note:  Kidney disease is staged from Stage 1 to Stage 5 with Stage 1 mild kidney disease through Stage 5 kidney failure.

The results reported are end-of-treatment results.  All patients were HCV RNA (viral load) negative.  The cure rates are pending.  Seventy-four percent had an improvement in kidney function.  The increase in kidney function was more pronounced in people with cirrhosis.  Seven patients (17%) had a slight worsening of kidney functioning.

Conclusion: The majority of patients with impaired kidney function who had an undetectable end-of-treatment response had improvements in kidney functions.  Some patients (17%) had a slight worsening of kidney functions.

Editorial Comments: This is good news for people with hepatitis C and kidney disease. I want to see more information about the slight worsening of kidney functioning. I also want to understand if the results are different once the cure rates are known and if the kidney function has recovered once significant time has elapsed.

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Improvement of glycemic state among responders to sofosbuvir-based DAA

Source: Abstract # THU 271: Improvement of glycemic state among responders to sofosbuvir-based DAAs—S. A Alem et. al.

Study Aims and Results: Egypt has the highest percentage of hepatitis C worldwide as HCV genotype 4 is the most common one in Egypt.  The aim of the study was to understand the effect of sofosbuvir-based therapy on blood sugar levels.

Sixty patients—mostly male (70%); mean age 55yo; 48% cirrhotic; treatment naïve (70%) were treated with a variety of sofosbuvir-based therapies including simeprevir, ledipasvir or daclatasvir with and without ribavirin. The treatment period was 12 weeks. Thirty-six patients were on oral diabetic medications; 7 patients were on oral and insulin diabetic medications and one patient was on no diabetic medication. The fasting blood sugar levels (FBS) and hemoglobin A1C (HbA1c) were assessed at week 0 (baseline) and at 12-week post follow-up (SVR12-cure).

All of the patients in the study were cured of hepatitis C.  There was a significant decline in the FBS and HbA1c between baseline and at the time of cure regardless of which drug was combined with sofosbuvir. The decline in FBS and HbA1c was more significant in the cirrhotic patients.

Conclusions: Treatment of hepatitis C in people with diabetes resulted in a significant decline in fasting FBS and HbA1c levels.

Editorial Comments: The link between diabetes and hepatitis C is a controversial issue.  This study shows that there is an improvement in the levels of blood sugar numbers.  Before drawing final conclusion I will need to read the journal article to support this study.  As someone who is living with diabetes, I hope that this and other studies support the conclusion that being cured of hepatitis C improves the outlook of people with hepatitis C and diabetes.

*Fasting blood sugar levels (FBS) is a blood test —usually done in the morning before someone has eaten.  The normal levels of fasting blood sugar levels are 70 to 100 mg/dl.

*Hemoglobin A1C (HbA1c) – sugar (glucose) substances becomes ‘stuck’ to hemoglobin—molecules in the blood.  The test can measure how much of the sugar has become ‘stuck’ to hemoglobin over the previous three months. It is a test that is used to understand how well type 1 and type 2 diabetes is being controlled.

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Efficacy and safety of Epclusa (sofosbuvir plus velpatasvir) in people with chronic hepatitis C virus infection and recent injecting drug use: The SIMPLIFY study

Abstract #FRI-234: Efficacy and safety of Epclusa (sofosbuvir plus velpatasvir) in people with chronic hepatitis C virus infection and recent injecting drug use: The SIMPLIFY study—J. Grebely et. al.

Study Aims and Results: The study was an international study to evaluate the safety and effectiveness of sofosbuvir and velpatasvir in people infected with hepatitis C.

The people in the study included HCV Genotypes 1 (35%); 2 (5%); 3 (58%); 4 (2%), age <40yo 24%, female sex 28%, no opioid substitution therapy, but were injecting drugs 32%; opioid substitution and injecting drugs 42%, minimal/early fibrosis (F0-F1) 62% or early/severe fibrosis (F2-F3) 26%, cirrhosis (F-4) 9%.

The study recruited patients from 19 international sites.  There were 114 people recruited for the study; 103 who started treatment.  Three patients discontinued treatment who were lost to follow-up and there was one death.  There was one case of relapse due to reinfection of hepatitis C. The cure rate was 94% (96 of 102 people).

Conclusion

There were very high cure rates and only one reinfection. The people in this trial will be followed for a period of three years.

Editorial Comments

The clinical trial validates that people who inject drugs who are on or off opioid substitution therapy can be successfully treated with direct-acting antiviral therapy.  We need to treat people everyone with hepatitis C including injection drug users.

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Gender differences on long-term outcomes in patients with dual chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection

Source: Abstract #SAT-201 Gender differences on long-term outcomes in patients with dual chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection—S. Shah, et al.

Study Aims and Results: Male gender is a proven risk factor among those with chronic mono HCV infection to develop end-stage liver disease and liver cancer (hepatocellular carcinoma or HCC). What is unclear is if any gender differences persistently exist among patients with dual HBV/HCV infection. This study investigated the occurrence of cirrhosis, hepatic decompensation and HCC in HBV/HCV dual infected individuals. 239 men and 120 women with HBV/HCV infection that were seen from 1999 through 2015 at U.S. tertiary care centers were evaluated for this study. Subject’s medical records yielded laboratory values, imaging results and necessary treatment information.  The main outcomes were the 10-year occurrence of cirrhosis, hepatic decompensation and HCC. The demographic breakdown is as follows: 41% White, 31% Asian, 15% Hispanic and 13% identified as Other. The mean age was 55.2 with a plus or minus of 10.9 years among men and 56.8 with a plus or minus of 13.1 among women. There was no baseline gender difference in HCV viral load or level of liver scarring, however, men did have higher rates of alcohol and tobacco use, as well as diabetes, lower number of blood clotting agents and were more likely to present with HCC than women. The 10-year occurrence of cirrhosis in individuals without baseline cirrhosis was high yet similar across genders. Despite this, men were significantly more likely to develop HCC. The occurrence of HCC in men and women was 101.6 (men) and 57.8 (women) per 1,000 person years. This means that 101.6 and 57.8 cases would be expected in a given year among HBV/HCV dual infected people. The 10-year total HCC occurrence was 37% among men and 17% among women. Men also showed a higher total trend of a 10-year occurrence in hepatic decompensation than women.

Conclusion: The occurrence of cirrhosis and HCC was high in both men and women with HBV/HCV dual infection. Still, men showed a significantly higher risk for HCC. There also were no gender differences in the occurrence of cirrhosis development.

Editorial Comments: This study showed the importance of early antiviral therapy among HBV/HCV dual infected individuals. An approach of early treatment intervention among this group will help prevent long-term complications. A focus on those who are at a higher risk is especially important. Testing for HBV upon HCV diagnosis is key to this approach as well. This study shows the potentially negative outcomes of failing to address HBV/HCV dual infection among both men and women while underscoring the significant risk posed to men who go untreated.

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Field evaluation of Xpert® HCV Viral Load point-of-care test for detection of hepatitis C virus infection by venipuncture-collected and finger-stick capillary whole-blood samples

Source:  Abstract #SAT-206 Field evaluation of Xpert® HCV Viral Load point-of-care test for detection of hepatitis C virus infection by venipuncture-collected and finger-stick capillary whole-blood samples—J. Grebely, et al.

 Study Aims and Results: Improving HCV testing, diagnosis and linkage to care is a continuing challenge. Current point-of-care testing allows for easy and quick delivery of HCV antibody results. Developing a similar HCV RNA point-of-care test will allow for the diagnosis of active infection at the same time. This study evaluates the Xpert® HCV Viral Load assay using samples collected by venipuncture and finger stick capillary whole-blood. The needed samples were collected from people in a study where they were observed receiving services in Australia. Xpert® HCV Viral Load assay’s reliability and accuracy was compared to the current “gold standard”, Abbott Real Time HCV Viral Load assay. There were 150 participants in the study. The median age was 44 years, 87% were male and 65% reported a history of injection drug use. There were 45 HCV RNA positive people. The reliability and accuracy of the Xpert® HCV Viral Load assay for HCV RNA detection in blood draw samples was 100% and 99.1%. In the one instance where the Abbott Real Time HCV RNA was undetectable and the Xpert® HCV RNA was detectable HCV RNA was confirmed with a RT-PCR HCV RNA assay. This confirmation determined the Xpert® was false positive. The reliability and accuracy of the Xpert assay for HCV RNA detection in finger stick samples was 95.5% and 98.1%.

Conclusion: The study showed that the Xpert® HCV Viral Load assay had comparatively reliable results to the Abbott Real Time HCV RNA Viral Load assay in terms of reliability and accuracy

Editorial Comments: The reliability of the Xpert® HCV Viral Load assay when compared to the Abbott Real Time HCV RNA Viral Load assay is promising. The inability to provide on-site HCV RNA confirmation for the existing OraQuick HCV Antibody point-of-care test has shown to be unable to improve the HCV Treatment Cascade issues of client confirmation. Providing an HCV antibody result is important but if we are unable to confirm active infection providing a positive antibody assay runs the potential of increasing anxiety without providing concrete answers. The Xpert® HCV Viral Load assay looks to be a promising step towards improving that.

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Abstract #THU-184 An assessment of physical activity levels and cardiorespiratory fitness in individuals living with hepatitis C—A.M. Monaghan, et al.

Source: Abstract #THU-184 An assessment of physical activity levels and cardiorespiratory fitness in individuals living with hepatitis C—A.M. Monaghan, et al.

Study Aims & Results: Chronic hepatitis C is associated with increased risk of developing cardiovascular disease. Physical inactivity and poor aerobic fitness are also well-known predictors of heart disease. This study assessed physical activity and cardiorespiratory fitness in 94 individuals living with chronic hepatitis C. Most of the participants had poor aerobic capacity and were not adequately physically active.

Conclusion:  These results suggest that low levels of physical activity and aerobic capacity are factors that may need to be addressed when profiling the cardiovascular risk associated with chronic hepatitis C.

Editorial Comments: This is a proverbial chicken/egg problem. Hepatitis C causes fatigue, inflammation and body aches, making it difficult to be physically active.  On the other hand, being physically active helps to reduce fatigue, inflammation and body aches. Studies show us that successful hepatitis C treatment leads to improved quality of life. (See May Healthwise: Abstract # 215 Risk of cardiovascular and cerebrovascular events in hepatitis C patients following completion of direct-acting antiviral therapy—A.W. Singer, et al. and PS-032 HCV eradication reduces the occurrence of major adverse cardiovascular events in hepatitis C cirrhotic patients—P. Cacoub, et al)

Hepatitis C is a monumental health threat, and we need to eliminate it. Universal access to hepatitis C treatment is a right; it’s time to make this a reality.

To read the entire June HCV Advocate newsletter, click here

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Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6–11 years old

Source: Abstract #PS-101 Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6–11 years old with chronic hepatitis C infection—K.F. Murray, et al.

Study Aims and Results: The U.S. Food and Drug Administration (FDA recently expanded the use of Sovaldi (sofosbuvir) and Harvoni (sofosbuvir/ledipasvir) to adolescents 12 years and older who have hepatitis C virus (HCV). However, the only FDA-approved hep C treatment for children under age 12 is peginterferon plus ribavirin, a combination that has many side effects and poor response rates when compared to the new DAAs. This ledipasvir/sofosbuvir +/- ribavirin study enrolled 90 HCV+ children, ages 6–11 years old. The SVR4 rate among the 88 patients who completed the posttreatment Week 4 visit was 99%; one GT1a patient relapsed after 12 weeks.

Conclusion: This all-oral, interferon-free regimen was well tolerated, suggesting its potential as an important treatment option for children 6–11 years old. The study is continuing in children aged 3–5 years old.

Editorial Comments: This study is small and missing the final week 12 data. However, with few options for children, these results seem robust and point towards a hopeful future for children with hepatitis C. It also increases hope for parents; what parent would want to put their child through 24 to 48 weeks of peginterferon rather than 12 weeks of a DAA?

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Ledipasvir/sofosbuvir for 12 weeks is safe and effective in patients with chronic hepatitis C and hepatitis B coinfection: A phase 3 study in Taiwan C—J. Liu, et al.     

Source: Abstract #PS-098 Ledipasvir/sofosbuvir for 12 weeks is safe and effective in patients with chronic hepatitis C and hepatitis B coinfection: A phase 3 study in Taiwan C—J. Liu, et al.

Study Aims and Results: Compared to people who have either hepatitis B or C, patients who are coinfected with both have more rapid liver disease. This study evaluated the safety and efficacy of treatment using ledipasvir (LDV)/sofosbuvir (SOF) for 12 weeks in patients with chronic HCV and HBV coinfection in Taiwan, which has a high prevalence of HCV/HBV coinfection. The main goal was to measure SVR12 while monitoring HBV DNA during treatment and for 2 years post-treatment. At the time of this presentation, SVR4 rate was 100% based on 111 patients. Although most patients experienced an increase in HBV DNA during treatment, this was not associated with ALT elevations ≥2 × baseline, and no patients started HBV therapy to date.

Conclusions: LDV/SOF was well tolerated, and is a potential treatment option for HCV/HBV coinfected patients.

Editorial Comments: Hepatitis C direct-acting antivirals (DAAs) carry a black box warning, stating that there is a risk of hepatitis B virus reactivation in patients coinfected with hepatitis C and B virus. The FDA reported at least 24 cases of hepatitis B reactivation from 2013-2016. Of these, two patients died; one required a liver transplant. The FDA believes that there may be additional unreported cases of hepatitis B reactivation that occurred with DAA treatment for hepatitis C.

This study is entirely too small and too preliminary to draw conclusions about the safety of HCV treatment using DAAs in coinfected patients, albeit it is a good study. If you are coinfected, be sure your medical provider tests for current or prior hep B infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), prior to starting hepatitis C treatment with the commonly used DAAs, Click here to read the entire FDA Hepatitis Update.

To read the entire June HCV Advocate newsletter, click here

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