Showing posts with label children treating HCV. Show all posts
Showing posts with label children treating HCV. Show all posts

Thursday, April 26, 2018

A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6‐ to 12‐ year old children

A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6‐ to 12‐ year old children
M. H. F. El‐Shabrawi N. M. Kamal H. R. El‐Khayat E. M. Kamal M. M. A. H. AbdElgawad M. Yakoot

First published: 25 April 2018 https://doi.org/10.1111/apt.14677

Full-Text
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Summary
Background
No available data on the use of sofosbuvir/ledipasvir combination in treatment of hepatitis C virus (HCV) infection in children 6‐ to 12‐ year old.

Aim
To assess the safety and efficacy of sofosbuvir plus ledipasvir in children 6‐ to 12‐ year old with chronic HCV genotype 4 infection.

Methods
This is a pilot prospective single arm observational open‐label multicentre study. A total of 20 consecutive eligible chronic HCV infected children, aged from 6‐ to 12‐ years were included in this study and treated with a fixed sofosbuvir/ledipasvir combination in half the adult dose (200/45 mg) once daily for 12 weeks. Laboratory tests including virological markers were measured at baseline, 2, 4, 8 and 12 weeks (end of treatment [EOT]), and 12 weeks after end of treatment for sustained virological response 12 (SVR12).

Results
The intention‐to‐treat (ITT) SVR12 rate was 19/20 (95%; 95% CI: 76.4%‐99.1%). SVR12 was not assessed in one patient who was lost to follow‐up after showing viral negativity at the EOT12. All the remaining 19 patients (100%, 95% CI: 83.18%‐100%) who completed the full protocol and follow‐up visits achieved SVR12 with normal liver, haematological, and renal function tests and no side effects or fatalities.

Conclusions
This pilot study demonstrated that the fixed dose sofosbuvir/ledipasvir combination could be safe and effective treatment in children 6‐ to 12‐ years with chronic hepatitis C genotype 4 infection. Our pilot results might encourage larger and multicentre studies in this age group.

Friday, March 23, 2018

A serious liver ailment is stalking Kentucky's children. But they aren't getting care

A serious liver ailment is stalking Kentucky's children. But they aren't getting care
The Courier-Journal
A Courier Journal investigation found hepatitis C has skyrocketed among Kentucky births amid the state's raging drug epidemic, but attempts to prevent, track and control the infectious, curable disease have fallen short. That means many kids don't get the care they need, risking cirrhosis and liver cancer ...

Continue reading: https://www.courier-journal.com/story/news/2018/03/22/kentucky-children-hepatitis-c-disease-control/1021704001/

Of Interest
http://www.croiwebcasts.org/console/player/37030?mediaType=slideVideo&&crd_fl=0&ssmsrq=1521820659195&ctms=5000&csmsrq=5182
Webcast lecture presented at Conference on Retroviruses and Opportunistic Infections (CROI)
March 4 to March 7, 2018
Boston MA

Link - HCV Prevention and Treatment In Children
INTERACTIVE CASE-BASED WORKSHOP ON HEPATITIS C.
QUESTIONS AND ANSWERS.
View all...

Monday, February 26, 2018

Podcast: What happens when a pregnant woman has hepatitis C

Host: Amber Smith

What happens when a pregnant woman has hepatitis C
Rates of hepatitis C infections are on the rise among adults in the United States, and some of those adults are pregnant women. Helene Bernstein, MD, PhD, explains how the disease can easily be diagnosed through a blood test and treated with medication. (Click here for a paper she published on this topic.) She’s an associate professor of obstetrics and gynecology and of microbiology and immunology at Upstate.

Listen here:
Podcast: Play in new window | Download
Thursday, February 22nd, 2018
Upstate University Hospital

Sunday, December 31, 2017

Treatment of HCV in Children - Position Paper by the Hepatology Committee of European Society of Paediatric Gastroenterology, Hepatology and Nutrition

Treatment of Chronic Hepatitis C Virus Infection in Children. A Position Paper by the Hepatology Committee of European Society of Paediatric Gastroenterology, Hepatology and Nutrition
Indolfi Giuseppe; Hierro, Loreto; Dezsofi, Antal; Jahnel, Jörg; Debray, Dominique; Hadzic, Nedim; Czubowski, Piotr; Gupte, Girish; Mozer-Glassberg, Yael; van der Woerd, Wendy; Smets, Françoise; Verkade, Henkjan J; Fischler, Bjorn

Journal of Pediatric Gastroenterology and Nutrition: Post Acceptance: December 28, 2017
doi: 10.1097/MPG.0000000000001872 

What is known 
Direct-acting antiviral drugs active against hepatitis C virus (HCV) infection are highly effective and safe for treatment of adults with chronic HCV infection.

Pegylated interferon (PEG IFN) and ribavirin are no more recommended for treatment of adults.

What is new 
The fixed-dose combination of sofosbuvir/ledipasvir and the combination of sofosbuvir and ribavirin have been recently approved for treatment of children ≥12 years or weighing >35 Kg with chronic HCV genotype 1, 4, 5 and 6 and 2 and 3 infection, respectively.

PEG IFN and ribavirin are no more recommended for treatment of children older than 12 years of age.

ABSTRACT
Objectives:
In 2017, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12–17 years, weighing more than 35 kg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5 and 6 and genotype 2 and 3 infections, respectively. Although trials with direct acting antivirals (DAAs) are ongoing for younger children, the only available treatment in US and Europe for those < 12 years is still the dual therapy of pegylated interferon (PEG IFN) and ribavirin. There is currently a lack of a systematic approach to the care of these patients. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed an evidence-based position paper for the management of chronic HCV infection in children.Methods:A systematic literature search and meta-analysis were performed using MEDLINE and Embase from June 1, 2007 to June 1, 2017. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcomes. ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.Results:The efficacy of the different DAAs combinations tested was higher, the relapse and the treatment discontinuation rates lower when compared to PEG IFN and ribavirin.Conclusions:This position paper addresses therapeutic management issues including goals, endpoints, indications, contra-indications and the optimal treatment regimen in children with chronic HCV infection.

Objectives:
In 2017, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12–17 years, weighing more than 35 kg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5 and 6 and genotype 2 and 3 infections, respectively. Although trials with direct acting antivirals (DAAs) are ongoing for younger children, the only available treatment in US and Europe for those < 12 years is still the dual therapy of pegylated interferon (PEG IFN) and ribavirin. There is currently a lack of a systematic approach to the care of these patients. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed an evidence-based position paper for the management of chronic HCV infection in children.

Methods:
A systematic literature search and meta-analysis were performed using MEDLINE and Embase from June 1, 2007 to June 1, 2017. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcomes. ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.

Results:
The efficacy of the different DAAs combinations tested was higher, the relapse and the treatment discontinuation rates lower when compared to PEG IFN and ribavirin.

Conclusions:
This position paper addresses therapeutic management issues including goals, endpoints, indications, contra-indications and the optimal treatment regimen in children with chronic HCV infection.

Article - Download PDF

Friday, November 3, 2017

Viral Hepatitis Hit 52 Million Children Worldwide – NGO

Viral Hepatitis Hit 52 Million Children Worldwide – NGO
World Hepatitis Alliance, in a report on Friday, children are suffering a huge burden of viral hepatitis worldwide, and the public health implications of this are enormous.

The analysis in the report was conducted by Manal El-Sayed, professor of pediatrics at Ain Shams University, Cairo, Egypt, and the Polaris Observatory, led by Dr. Homie Razavi with the Center for Disease Analysis Foundation in Colorado, the U.S. Raquel Peck, CEO of the World Hepatitis Alliance.

“Most infected infants and children are not diagnosed, prioritized or treated effectively,’’ Peck said.
Read more: https://www.frontiersnews.com/viral-hepatitis-hit-52-million-children-worldwide-ngo/

Focus on children with viral hepatitis imperative for elimination goals
November 3, 2017
Recent data revealed that, worldwide, 52 million children are living with viral hepatitis, compared with 2.1 million children with HIV or AIDS, according to data presented at the World Hepatitis Summit 2017 in São Paulo, Brazil.

“We must act and treat as many children as possible. The economic and social benefit of early hepatitis C treatment in children is substantial,” Manal El-Sayed, MD, professor of pediatrics at Ain Shams University, Cairo, Egypt, said in a related press release. “This includes avoiding disease progression, removing social stigma and improving activity and school performance, and reducing fatigue. However, the fundamental principle is to avoid transmission by adopting ‘cure as prevention’ at an early age and before high risk behaviors emerge that enable transmission.”
Read more: https://www.healio.com/hepatology/hepatitis-c/news/online/%7B8a1cc8fe-43db-4e18-9140-bbc9ccac0c58%7D/focus-on-children-with-viral-hepatitis-imperative-for-elimination-goals

Thursday, August 24, 2017

Harvoni in adolescents 12-17 years old with HCV genotype 1

In Case You Missed It

In the Journals
Balistreri WF, et al. Hepatol. 2017;doi:10.1002/hep.28995
All adolescent patients available for follow-up after treatment with Harvoni for chronic hepatitis C genotype 1 achieved sustained virologic response at 12 weeks with no serious adverse events, further supporting its approval in this population.
“Treatment of pediatric patients has been controversial as the current standard of care, pegylated interferon and weight-based ribavirin, is associated with significant side effects, including growth impairment, and poor tolerability,” William F. Balistreri, MD, from the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “Similar to what has been observed in adults, treatment with ledipasvir-sofosbuvir was well tolerated in adolescents.”
Continue reading @ Healio

Full Text 
Research Article
No all-oral, direct-acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a Phase 2, multi-center, open-label study to evaluate the efficacy and safety of ledipasvir–sofosbuvir in adolescents with chronic HCV genotype 1 infection.

Abstract
The safety and effectiveness of ledipasvir−sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection

Recommended Reading

HCV Advocate
Hepatitis C in Children
In this article, I will discuss the various aspects of hepatitis C (HCV) in children including what we know and what we don’t know!  The topics I will cover are mother-to-child transmission, hepatitis C transmission among children, HCV disease progression in children, which tests to monitor children with hepatitis C, and the newly approved medications to treat children.  The outlook for children with hepatitis C is looking better now that we have direct-acting antiviral medications to treat children with hepatitis C but we first have to identify, manage and treat them.
Read more...

Wednesday, July 26, 2017

Hepatitis C Virus in Children: The Global Picture Archives of Disease in Childhood, July 26, 2017

Hepatitis C Virus in Children: The Global Picture

Friday, June 30, 2017

Hepatitis C is a pediatric disease now

Related
Hepatitis C and women of childbearing age
July 03, 2017
A pregnant woman with evidence of HCV antibodies but no detectable active virus in her body is very unlikely to transmit HCV to her baby. On the other hand, pregnant women with very high viral loads are believed to be at increased risk for vertical transmission of HCV.

Commentary
Hepatitis C is a pediatric disease now
Publish date: June 27, 2017
By: Kristina K. Bryant, MD
It is estimated that there are 23,000 to 46,000 U.S. children living with HCV. The wait for pediatricians is over. HCV is a pediatric disease now, and we need to educate ourselves about diagnosis and management. A first step might be to begin asking expectant mothers and the mothers of newborns if they know their HCV status.
Continue reading....
Follow @IDPractitioner  

Recommended Reading
Hepatitis C increasing among pregnant women
Published:



FDA approves two hepatitis C drugs for pediatric patients
Published: April 7, 2017
The U.S. Food and Drug Administration today approved supplemental applications for Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) to treat hepatitis C virus (HCV) in children ages 12 to 17. Harvoni and Sovaldi were previously approved to treat HCV in adults.
Read the announcement @ FDA Newsroom

FDA Approval Of Hepatitis C Drugs For Kids Is Likely To Speed Treatment









I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C. 

Wednesday, May 17, 2017

Hepatitis C: 16 May 2017 - 2017 Post-EASL Report

In Case You Missed It
Review Published May 2, 2017
Oral Direct-Acting Agents for the Treatment of HCV Annals of Internal Medicine
Purpose: To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection.

Post-LT biopsies show histologic features of HCV following SVR
May 17, 2017
Results of a retrospective analysis showed histologic changes associated with active hepatitis C in patients who had achieved sustained virologic response following liver transplantation for chronic HCV.

Review article - Journal of Clinical and Translational Hepatology 2017 vol. 5 | 59–66
The role of direct-acting antivirals in the treatment of children with chronic hepatitis C

2017 Post-EASL Report                                  
16 May 2017 

by Michael Haydock
In this report we summarize several notable highlights from this year’s EASL conference. Also included are key abstracts featuring commentary from Biomedtracker and Datamonitor Healthcare analysts including any changes in Likelihood of Approval (LOA), if applicable.

Summary  
As chronic hepatitis C virus (HCV) drug development approaches the end-game following the launch of the first pan-genotypic regimen, Epclusa (sofosbuvir/velpatasvir; Gilead), recent and upcoming advances in chronic hepatitis B virus (HBV) treatment emerged as an important focus of The International Liver Conference (ILC) 2017, the annual meeting of the European Association for the Study of the Liver (EASL), which took place in Amsterdam, the Netherlands, on 19–23 April 2017. Particular interest was paid to 96week safety data from pivotal studies of Vemlidy (tenofovir alafenamide [TAF]; Gilead), which Gilead hopes will drive its uptake in the face of imminent competition from generic versions of Viread (tenofovir disoproxil fumarate [TDF]; Gilead). Updated EASL guidelines for the management and treatment of chronic HBV were also released, which included a novel recommendation for the use of Vemlidy as a firstline agent in select patients, as well as a revised nomenclature for classifying the stages of chronic HBV infection. 

There was also considerable optimism regarding the potential of new modes of action in early-phase development for the treatment of HBV to improve upon the disappointingly low rates of hepatitis B surface antigen (HBsAg) loss observed after treatment with currently available therapies. While there are very limited efficacy data available for early-phase approaches, there was consensus during panel discussions of available data that combining currently approved nucleos(t)ide analogs (NAs) with novel agents, such as RNA interference, capsid assembly inhibitors, nucleic acid polymers, and immunostimulatory agents, represents a promising approach towards achieving “functional cure”.

Multiple abstracts for HCV therapies were also presented as AbbVie, Merck & Co, and Johnson & Johnson attempted to demonstrate differentiation in a highly-competitive market with few unmet needs remaining. AbbVie presented data from multiple Phase III studies which highlighted glecaprevir/pibrentasvir’s pan-genotypic efficacy in non-cirrhotic genotype 3 (GT-3) patients (ENDURANCE-3) and cirrhotic GT-1/2/4/5/6 patients (EXPEDITION-1), as well as its maintenance of competitive cure rates in direct-acting antiviral-experienced GT-1/4 patients (MAGELLAN-1) and posttransplant patients (MAGELLAN-2). Merck & Co presented data from the Phase II C-SURGE study in DAAexperienced patients which demonstrated that its triple combination of uprifosbuvir/grazoprevir/ruzasvir was an effective salvage regimen in DAA-experienced patients with resistance-associated substitutions, and future studies will investigate the regimen in both DAA-naïve and DAA-experienced patients. Finally, Johnson & Johnson suffered a setback as its triple combination of AL-335/odalasvir/simeprevir failed to demonstrate competitive efficacy in GT-3 patients, prompting the company to discontinue development for this subgroup and putting an end to the company’s hopes of marketing a pan-genotypic regimen. While AL-335/odalasvir/simeprevir is still being developed for the remaining GTs and could shorten treatment duration to just six weeks in non-cirrhotic GT-1 patients, it is likely that Johnson & Johnson will be forced to offer significant discounts to compensate for its late entry to the market.

2017 Post-EASL Report
Source

Wednesday, April 26, 2017

Factors that predict HCV vertical transmission - Mother to Child Transmission

Factors that predict HCV vertical transmission
The latest issue of  Liver International investigates what factors should be optimized using data mining computational analysis to predict HCV vertical transmission. Neonates born to hepatitis C virus (HCV)-positive mothers are usually not screened for HCV. 

Unscreened children may act as active sources for social HCV transmission, and factors contributing for vertical HCV transmitting still remained controversial and needed optimization. 

Dr Abd Elrazek and colleagues from Egypt investigated the factors contributing for vertical HCV transmission in Egypt, which has the highest HCV prevalence worldwide.

The researchers prospectively followed the neonates born to HCV-positive mother in the child-bearing period, to identify mother-to-child transmission factors from 2015 to 2016. 

HCV vertical transmission was identified in 18% of neonates Liver International Data mining computational analysis was used to quantify the findings. The team found that among 3000 randomized pregnant women, prevalence of HCV was 2%.  HCV vertical transmission was identified in 18% of neonates. 

The researchers identfied that only high viral load at 975.000 IU was the predictor risk for mother-to-child transmission.

Dr Elrazek's team concluded, "Hepatitis C virus in pregnancy has substantial risk for vertical HCV transmission." "High viral load in HCV-positive women increases the risk of HCV transmission to neonates."

"Screening pregnant women during early stage of pregnancy, and optimizing the HCV viral load in HCV-positive women might prevent vertical HCV transmission to neonates.
GastroHep

"Liver International
Volume 37, Issue 4
April 2017
Pages 529–533
Prediction of HCV vertical transmission: what factors should be optimized using data mining computational analysis
Authors Abd Elrazek, Mohamed Amer, Bahaa El-Hawary, Altaher Salah, Akshaya S. Bhagavathula, M. Alboraie, Samy Saab First published: 16 June 2016Full publication history DOI: 10.1111/liv.13146

Abstract
Background & Aims
Neonates born to hepatitis C virus (HCV)-positive mothers are usually not screened for HCV. Unscreened children may act as active sources for social HCV transmission, and factors contributing for vertical HCV transmitting still remained controversial and needed optimization. We aimed to investigate the factors contributing for vertical HCV transmission in Egypt; the highest HCV prevalence worldwide.

Methods
We prospectively followed the neonates born to HCV-positive mother in the child-bearing period, to identify mother-to-child transmission (MTCT) factors from January 2015 to March 2016. Data mining computational analysis was used to quantify the findings.

Results
Among 3000 randomized pregnant women, prevalence of HCV was 46/3000 (1.53%). HCV vertical transmission was identified in eight neonates (17.39%). Only high viral load identified at 975.000 IU was the predictor risk for MTCT.

Conclusions
Hepatitis C virus in pregnancy has substantial risk for vertical HCV transmission: High viral load in HCV-positive women increases the risk of HCV transmission to neonates. Screening pregnant women during early stage of pregnancy and optimizing the HCV viral load in HCV-positive women might prevent vertical HCV transmission to neonates.

Friday, April 21, 2017

ILC 2017: An investigational dosage of an oral interferon-free treatment regimen can cure chronic Hepatitis C virus in children 

ILC 2017: An investigational dosage of an oral interferon-free treatment regimen can cure chronic Hepatitis C virus in children 

The study evaluated the use of a direct-acting antiviral treatment in children aged six to 11, for whom the standard of care has been pegylated interferon plus ribavirin
 

April 21, 2017, Amsterdam, The Netherlands: A study presented today that evaluated an investigational dosage of once-daily ledipasvir 45 mg/sofosbuvir 200 mg (LDV/SOF) in children aged six to 11 years infected with the Hepatitis C virus (HCV), found that 99% of children (n=89/90) had undetectable levels of HCV-RNA 12 weeks after treatment. The study, presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, also showed that the fixed-dose combination of LDV/SOF was well-tolerated, and no patients experienced a serious adverse event considered related to the study drug. 

Around 180 million people globally have chronic HCV infection,1 including approximately 15 million people in the EU.2 The prevalence of HCV infection in children varies from 0.05%0.36% in the United States and Europe and up to 1.8%-5.8% in some developing countries.3 While direct-acting antivirals have been used to treat and cure adult patients with HCV,4–7 until now children have been mainly treated for 24 to 48 weeks with pegylated interferon plus ribavirin (RBV), an older treatment which causes severe side effects.8 

“Direct-acting antivirals have transformed the treatment of adults with chronic HCV, however, studies of these new therapies in children are required,” said Dr Karen Murray, University of Washington School of Medicine and Seattle Children’s, Seattle, United States, and lead author of the study. “These data establish the use of the oral direct-acting antivirals as an important treatment option in HCV-infected children aged six to 11 years old.”

This ongoing, open-label study enrolled 90 children aged between six and 11 years with chronic HCV, mostly genotype 1 (n=86). Children with HCV genotype 1 infection received 12 weeks of treatment (n=85) or 24 weeks of treatment if they had cirrhosis and failed prior treatment with pegylated interferon plus RBV (n=1); genotype 3 patients received LDV/SOF plus RBV for 24 weeks (n=2); genotype 4 patients received LDV/SOF for 12 weeks (n=2). Most children were male (59%), white (79%), treatment naïve (80%), and vertically infected (97%). Of the study population, 89/90 achieved a sustained virologic response 12 weeks after treatment (SVR12); one treatment-naïve genotype 1 patient with cirrhosis relapsed. No children discontinued the study due to side effects or had a severe or life-threatening adverse event related to the study drug. The most common side effects reported in 10% or more of patients were headache, fever, abdominal pain, diarrhoea, vomiting, cough, fatigue, sore throat and nausea. 

“This study is a breakthrough for the management of children aged six to 11 years old with Hepatitis C, demonstrating that the new DAA regimen is highly efficacious and, more importantly, safe in this group of HCV-infected children”, said Prof Frank Tacke, University Hospital Aachen, Germany, and EASL Governing Board Member.

References 1 EASL Recommendation on Treatment of Hepatitis C 2016. Available from: http://www.easl.eu/medias/cpg/HCV2016/English-report.pdf. Last accessed: April 2017. 2 World Health Organization. Global Alert and Response – Hepatitis C. Available from: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index3.html. Last accessed: April 2017. 3 Pawlowska M, Malgorzata et al. What’s new in hepatitis C virus infections in children?  WJG. 2015;21(38):10783-10789.  4 Afdhal N, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98.  5 Afdhal N, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93.  6 Kowdley KV, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. 

Thursday, April 20, 2017

ILC 2017: Serious liver disease develops in over one-third of young people in the UK with childhood acquired Hepatitis C virus

ILC 2017: Serious liver disease develops in over one-third of young people in the UK with childhood acquired Hepatitis C virus

In the UK, the main route of Hepatitis C virus infection in young people is intravenous drug abuse

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April 20, 2017, Amsterdam, The Netherlands: Results from a retrospective review of a UK national Hepatitis C virus (HCV) database found that over one-third of young people (<18 years old) with childhood acquired HCV develop serious long-term liver disease, 5% develop liver cancer and more than 4% undergo a liver transplant. The cohort study, presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, revealed intravenous drug abuse as the main route of HCV infection in young people in the UK (53%, n=535/1,014).

HCV is one of the most widespread transmissible diseases globally.1 It is estimated to infect over 185 million people worldwide, of whom 350,000 die each year, with 84,000 of those being in Europe.2 HCV is considered a silent pandemic as most people do not know that they have it.1 HCV causes both acute and chronic infection, with about 55–85% of HCVinfected individuals developing chronic infection.2 HCV is a leading cause of chronic liver disease, end-stage cirrhosis and liver cancer.3 In the United States, 23,000 to 46,000 children are estimated as having chronic HCV infection.4 In developed countries, transmission of HCV in children is mainly through the mother at birth (perinatal transmission).5 HCV increases the risk of liver-related death by 26 times when acquired during childhood.

“Our study showed that more than one-third of young people infected with HCV in childhood have serious long-term liver disease,” said Dr Line Modin, Birmingham Children’s Hospital, United Kingdom, and first author of the study. “Detection of HCV should be aimed at relevant risk groups, particularly young intravenous drug abusers.” 

Data on patients with an estimated age at first HCV infection between 0 and 18 years old were analysed from a national clinical database (HCV Research UK) that covered 51 adult and seven paediatric centres. Data were collected between July 2012 and October 2016. The study included 1,014 patients, 731 (72%) of whom were males. 

The most prevalent route for infection with HCV was intravenous drug abuse (535 individuals). Other means of infection included blood products (244 people) and acquiring HCV around the time of birth (116). Other risk factors accounted for HCV infection in 119 individuals. The most common HCV genotype in the study was genotype 1 (57%). Over onethird (35%) had genotype 3, which is the most difficult subgroup of patients to cure and for which treatment options remain suboptimal.6 Liver disease was found in 354 patients (33%), with cirrhosis in 269 (27%), liver cancer (hepatocellular carcinoma) in 55 (5%) and 47 (5%) had undergone a liver transplant. Patients with perinatal exposure to HCV developed cirrhosis at an earlier age than the intravenous drug group (median of 36 years versus 48 years). 

“Our study highlights how important it is that clinical trials of antiviral therapy are performed in children, to develop clear treatment guidelines to prevent long-term liver disease,” said Professor Deirdre Kelly, Birmingham Children’s Hospital, United Kingdom, and study lead. 

“This study from the UK suggests that many children infected perinatally may develop cirrhosis at a young age, if left untreated. Safe and efficacious direct-acting antiviral treatment should be made available to children, to prevent liver disease progression and viral spread at a later age,” said Prof Francesco Negro, Divisions of Gastroenterology and Hepatology of Clinical Pathology, University Hospital of Geneva, Switzerland and EASL Governing Board Member.

About The International Liver Congress™ This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hematology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2017 will take place from April 19 – 23, at the RAI Amsterdam, Amsterdam, The Netherlands.

About The European Association for the Study of the Liver (EASL) (www.easl.eu) Since its foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European Association with international influence, with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Onsite location reference Session title: Late breaker poster session Time, date and location of session: 08:00 – 18:00, Thursday 20 April to Saturday 22 April, Hall 1 Presenter: Line Modin, United Kingdom Abstract: Epidemiology of hepatitis C infection in children and young people in the UK (LBP-525)

Author disclosures
None. 

References 1 World Health Organization. Access to new medicines in Europe: technical review of policy initiatives and opportunities for collaboration and research. March 2015. Available from: http://apps.who.int/medicinedocs/documents/s21793en/s21793en.pdf. Last accessed: April 2017.  2 World Health Organization. Hepatitis C in the WHO European Region Fact Sheet. July 2015. Available from: http://www.euro.who.int/__data/assets/pdf_file/0010/283357/factsheet-en-hep-c.pdf?ua=1. Last accessed: April 2017.  3 Mühlberger N, et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health. 2009;9:34. 4 Khaderi S, et al. Hepatitis C in the pediatric population: Transmission, natural history, treatment and liver transplantation. World J Gastroenterol. 2014;20(32):11281–6. 5 El-Guindi M. Hepatitis C viral infection in children: Updated review. Pediatr Gastroenterol Hepatol Nutr. 2016;19(2):83–95. 6 Tapper EB, Afdhal N. Is 3 the new 1: perspectives on virology, natural history and treatment for hepatitis C genotype 3. J Viral Hepat. 2013 Oct;20(10):669-77.

International Liver Congress
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Wednesday, April 19, 2017

FDA Approval Of Hepatitis C Drugs For Kids Is Likely To Speed Treatment

FDA Approval Of Hepatitis C Drugs For Kids Is Likely To Speed Treatment
Michelle Andrews
The two drugs approved for pediatric use by the Food and Drug Administration, Harvoni and Sovaldi, have both been highly effective in treating adults with the disease, though Medicaid programs and private insurers often have balked at paying for the pricey drugs for adults.

"The short answer is that [Medicaid] will likely require coverage for all kids, regardless of whatever the coverage policies for adults may be," said Matt Salo, executive director of the National Association of Medicaid Directors.
Continue reading.....

Friday, April 7, 2017

FDA Approves HCV Sovaldi and Harvoni For Children Ages 12 to 17

Gilead Press Release
(FDA) has approved supplemental indications for Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) tablets and Sovaldi® (sofosbuvir 400 mg) tablets for the treatment of chronic hepatitis C virus (HCV) infection in adolescents without cirrhosis or with compensated cirrhosis, 12 years of age and older, or weighing at least 35kg. Harvoni was approved for pediatric patients with genotype 1, 4, 5 or 6 chronic HCV infection. Sovaldi was approved for pediatric patients with genotype 2 or 3 chronic HCV infection, in combination with ribavirin. There are an estimated 23,000-46,000 pediatric HCV patients in the United States, most of whom were infected with the virus at birth.
http://www.businesswire.com/news/home/20170407005379/en/

FDA Update

FDA approves two Hepatitis C drugs for pediatric patients

Today, April 7, 2017 the FDA approved supplemental applications for Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) to treat hepatitis C virus (HCV) in children ages 12 to 17 or weighing at least 35 kilograms.

These approvals provide pediatric treatment options for six major genotypes, or strains, of the HCV virus. Harvoni is indicated for the treatment of pediatric patients 12 years of age and older or weighing at least 35 kilograms with HCV genotype 1, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis. Sovaldi in combination with ribavirin is indicated for the treatment of pediatric patients 12 years of age and older or weighing at least 35 kilograms with genotype 2 or 3 HCV infection without cirrhosis or with compensated cirrhosis.

The specific changes for each label are summarized below

Sovaldi
Section 1: INDICATIONS AND USAGE
Pediatric Patients:
SOVALDI is indicated for the treatment of chronic HCV genotype 2 or 3 infection in pediatric patients 12 years of age and older or weighing at least 35 kg without cirrhosis or with compensated cirrhosis for use in combination with ribavirin


Section 2: DOSAGE AND ADMINISTRATION
2.3        Recommended Dosage in Pediatric Patients 12 Years of Age and Older or Weighing at Least 35 kg
The recommended dosage of SOVALDI in pediatric patients 12 years of age and older or weighing at least 35 kg is one 400 mg tablet taken orally once daily with or without food in combination with ribavirin [see Clinical Pharmacology (12.3) and Clinical Studies (14.5)].
The recommended treatment regimen and duration for SOVALDI combination therapy is provided in Table 2.  provides the weight-based dosage of ribavirin when used in combination with SOVALDI for pediatric patients. For patients with HCV/HIV-1 coinfection, follow the dosage recommendations in Table 2 and Table 3. Refer to Drug Interactions (7) for dosage recommendations for concomitant HIV-1 antiviral drugs.

Table 2  Recommended Treatment Regimen and Duration in Pediatric Patients 12 Years of Age and Older or Weighing at Least 35 kg

Patient Population
Treatment Regimen And Duration
Genotype 2
Treatment-naïve and treatment-experienceda without cirrhosis or with compensated cirrhosis (Child-Pugh A)
SOVALDI + ribavirinb 12 weeks
Genotype 3
Treatment-naïve and treatment-experienceda without cirrhosis or with compensated cirrhosis (Child-Pugh A)
SOVALDI + ribavirinb 24 weeks
a. Treatment-experienced patients have failed an interferon based regimen with or without ribavirin.
b. See Table 3 for weight-based ribavirin dosing recommendations.

             
Table 3 Recommended Dosing for Ribavirin in Combination Therapy with SOVALDI for
Pediatric Patients 12 Years of Age and Older or Weighing at Least 35 kg
Body Weight kg
Ribavirin Daily Dosagea
less than 47
15 mg/kg/day
47–49
600 mg/day
50–65 
800 mg/day
66–80
1000 mg/day
greater than 80
1200 mg/day
a. The daily dosage of ribavirin is weight-based and is administered orally in two divided doses with food

Section 6: ADVERSE REACTIONS
Adverse Reactions in Pediatric Subjects 12 Years of Age and Older
The safety assessment of SOVALDI in pediatric subjects 12 years of age and older is based on data from 50 subjects who were treated with SOVALDI plus ribavirin for 12 weeks (genotype 2 subjects) or 24 weeks (genotype 3 subjects) in a Phase 2, open-label clinical trial. The adverse reactions observed were consistent with those observed in clinical studies of SOVALDI plus ribavirin in adults.
8.4        Pediatric Use
The safety, pharmacokinetics, and efficacy of SOVALDI in pediatric patients 12 years of age and older or weighing at least 35 kg with genotype 2 and 3 infection have been established.  SOVALDI was evaluated in an open-label clinical trial (Study 1112), which included 50 subjects (13 genotype 2; 37 genotype 3) 12 years of age and older. The safety, pharmacokinetics, and efficacy were comparable to that observed in adults.
The safety and efficacy of SOVALDI in pediatric patients 12 years of age and older or weighing at least 35 kg with compensated cirrhosis is supported by comparable sofosbuvir and GS-331007 exposures between: 1) adults and adolescents without cirrhosis and 2) adults without cirrhosis and adults with compensated cirrhosis. Thus, similar efficacy would be expected for adolescent patients with compensated cirrhosis as adults with compensated cirrhosis.
The safety and efficacy of SOVALDI have not been established in pediatric patients less than 12 years of age and weighing less than 35 kg with HCV genotype 2 or 3.  The safety and efficacy of SOVALDI have not been established in pediatric patients with HCV genotype 1 or 4.
Section 12: CLINICAL PHARMACOLOGY
Pediatric Patients
The pharmacokinetics of sofosbuvir and GS-331007 were determined in 50 pediatric subjects 12 years of age and older, infected with HCV genotype 2 or 3, receiving a daily dose of SOVALDI (400 mg sofosbuvir). The pharmacokinetic properties of sofosbuvir and GS‑331007 in pediatric subjects 12 years of age and older are provided in table 4. Exposures in pediatric subjects were similar to those observed in adults.             

Table 4   Pharmacokinetic Properties of SOVALDI in HCV-infected
Pediatric Subjects 12 Years of Age and Older
a
Geometric Mean
Sofosbuvirb
GS-331007b
AUCtau (ng•hr/mL)
1060
7570
Cmax (ng/mL)
472
572
a. Population PK derived parameters
b. Sofosbuvir N=28; GS-331007 N=50

The pharmacokinetics of sofosbuvir have not been established in pediatric subjects less than 12 years of age.

Section 14: CLINICAL STUDIES
Clinical Trial in Pediatrics
The efficacy of SOVALDI in HCV-infected pediatric subjects 12 years of age and older was evaluated in 50 subjects with HCV genotype 2 (N = 13) or genotype 3 (N = 37) in a Phase 2, open label clinical trial. Subjects with HCV genotype 2 or 3 infection in the trial were treated with SOVALDI and weight-based ribavirin for 12 or 24 weeks, respectively [see Dosage and Administration (2.3)].
Of the 50 treated subjects, the median age was 15 years (range: 12 to 17); 42% of the subjects were female; 90% were White, 4% were Black, and 2% were Asian; 4% were Hispanic/Latino; mean weight was 61 kg (range: 30 to 101 kg); 18% were treatment experienced; 66% had baseline HCV RNA levels greater than or equal to 800,000 IU/mL; 74% of subjects had non-CC IL28B alleles (CT or TT); and no subjects had known cirrhosis. The majority of subjects (69%) had been infected through vertical transmission.
The SVR12 rate was 100% (13/13) in genotype 2 subjects and 97% (36/37) in genotype 3 subjects. No subject experienced on-treatment virologic failure or relapse.
Harvoni
S
ection 1: INDICATIONS AND USAGE
Pediatric Patients:
HARVONI is indicated for the treatment of pediatric patients 12 years of age and older or weighing at least 35 kg with HCV genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis
Section 2: DOSAGE AND ADMINISTRATION

2.3        Recommended Dosage in Pediatric Patients 12 Years of Age and Older or Weighing at Least 35 kg
The recommended dosage of HARVONI in pediatric patients 12 years of age and older or weighing at least 35 kg is one tablet (90 mg ledipasvir and 400 mg sofosbuvir) taken orally once daily with or without food for 12 weeks.
Table 2 shows the recommended HARVONI duration based on pediatric patient population.
For patients with HCV/HIV-1 coinfection, follow the dosage recommendations in Table 2 [.

Table 2 Recommended Regimen and Duration for HARVONI in Pediatric Patients 12 Years of Age or Older or Weighing at Least 35 kg with Genotype 1, 4, 5, or 6 HCV without Cirrhosis or with Compensated Cirrhosis
Patient PopulationTreatment Regimen and Duration
Genotype
1
Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A)HARVONI 12 weeks
Treatment-experienceda without cirrhosisHARVONI 12 weeks
Treatment-experienceda with
compensated cirrhosis (Child-Pugh A)
HARVONI 24 weeks
Genotype
4, 5, or 6
Treatment-naïve and treatment-experienceda
without cirrhosis or with compensated
cirrhosis (Child-Pugh A)
HARVONI 12 weeks
a. Treatment-experienced patients have failed an interferon based regimen with or without ribavirin.

Section 6: ADVERSE REACTIONS
Adverse Reactions in Pediatric Subjects 12 Years of Age and Older
The safety assessment of HARVONI in pediatric subjects 12 years of age and older is based on data from a Phase 2, open-label clinical trial (Study 1116) that enrolled 100 subjects without cirrhosis or with compensated cirrhosis who were treated with HARVONI for 12 weeks. The adverse reactions observed were consistent with those observed in clinical studies of HARVONI in adults. Limited safety data are available in pediatric subjects receiving HARVONI for 24 weeks. No Grade 3 or 4 adverse reactions or discontinuation due to an adverse reaction was observed in those pediatric subjects receiving HARVONI for 24 weeks.

6.2        Postmarketing Experience
Skin and Subcutaneous Tissue Disorders
AngioeAngioedema
8.4        Pediatric Use
The safety, pharmacokinetics, and efficacy of HARVONI for treatment of HCV genotype 1 infection in treatment-naïve and treatment-experienced pediatric patients 12 years of age and older without cirrhosis or with compensated cirrhosis have been established in an open-label, multicenter clinical trial (Study 1116, N=100; 80 treatment-naïve, 20 treatment-experienced) and are comparable to that observed in adults.
The safety and efficacy of HARVONI for treatment of HCV genotypes 4, 5, or 6 infection in pediatric patients 12 years of age and older or weighing at least 35 kg without cirrhosis or with compensated cirrhosis is supported by comparable ledipasvir, sofosbuvir, and GS-331007 exposures between adults and adolescents with HCV genotype 1 and similar efficacy and exposures across HCV genotypes 1, 4, 5, and 6 in adults.
The safety and efficacy of HARVONI have not been established in pediatric patients less than 12 years of age and weighing less than 35 kg, in pediatric patients with decompensated cirrhosis, or in pediatric liver transplant recipients

Section 12: CLINICAL PHARMACOLOGY

Pediatric Patients:  The pharmacokinetics of ledipasvir, sofosbuvir, and GS-331007 were determined in 100 pediatric subjects 12 years of age and older infected with HCV genotype 1 receiving a daily dose of HARVONI (90 mg ledipasvir and 400 mg sofosbuvir). The pharmacokinetic properties of ledipasvir, sofosbuvir, and GS-331007 in pediatric subjects 12 years of age and older are provided in Table 6. Exposures in pediatric subjects were similar to those observed in adults.



The pharmacokinetics of ledipasvir or sofosbuvir have not been established in pediatric patients less than 12 years of age

Section 14: CLINICAL STUDIES
14.6      Clinical Trial in Pediatric Subjects
The efficacy of HARVONI was evaluated in an open-label trial (Study 1116) that evaluated 12 weeks of treatment with HARVONI once daily in genotype 1 HCV treatment-naïve (N=80) and treatment-experienced (N=20) pediatric subjects 12 years of age and older without cirrhosis or with compensated cirrhosis.
Demographics and baseline characteristics were balanced across treatment-naïve and treatment-experienced subjects (patients had failed an interferon based regimen with or without ribavirin). Of the 100 treated subjects, the median age was 15 years (range: 12 to 17); 63% of the subjects were female; 90% were White, 7% were Black, and 2% were Asian; 13% were Hispanic/Latino; mean body mass index was 23 kg/m2 (range: 13.1 to 36.6 kg/m2); mean weight was 61 kg (range 33 to 126 kg); 55% had baseline HCV RNA levels greater than or equal to 800,000 IU/mL; 81% had genotype 1a HCV infection; 76% had non-CC IL28B alleles (CT or TT).  One subject had known compensated cirrhosis. The majority of subjects (84%) had been infected through vertical transmission.

The SVR12 rate was 98% overall (98% [78/80] in treatment-naïve subjects and 100% [20/20] in treatment-experienced subjects). No subject experienced on-treatment virologic failure or relapse. Two subjects were lost to follow-up.
You will be able to view the updated labels at drugs@fda or dailymed.
Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
For more information about the Hepatitis Liaison Program visit the FDA Patient Network

Tuesday, March 14, 2017

HCV infection in children

Gastroenterology & Hepatology
March 3, 2017, Volume 13, Issue 3
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Karen F. Murray, MD
Professor and Vice Chair of Clinical Affairs
Chief, Division of Gastroenterology and Hepatology
Department of Pediatrics
Seattle Children’s and University of Washington
Seattle, Washington

ADVANCES IN HEPATOLOGY
Section Editor: Eugene R. Schiff, MD
Current Developments in the Treatment of Hepatitis and Hepatobiliary Disease

G&H What is the prevalence of hepatitis C virus infection in children?

KM In comparison to adults, the prevalence of this disease is relatively low in children. The overall prevalence of hepatitis C virus (HCV) antibody positivity is approximately 1% to 1.5% in North American children. Looking at specific age groups, approximately 0.2% of children age 6 to 11 years and approximately 0.4% of children age 12 to 19 years are HCV antibody–positive, which equates to approximately 31,000 and 100,000 children, respectively. The prevalence of HCV infection in North America is approximately 0.1% to 2% of all children, with approximately 1.3% of children over the age of 6 years infected; between 23,000 and 46,000 children are infected in the United States and approximately 6,600 in Canada.

G&H What are the most common causes of HCV infection in children?

KM Although vertical transmission of HCV (ie, transmission from an infected mother to an infant) only occurs in approximately 5% of pregnancies in which the mother is HCV RNA–positive, most children with HCV have acquired the infection this way (approximately 60%). The remainder of infections are caused by contaminated blood products, horizontal transmission, and, depending upon the age, transmission via contaminated drug paraphernalia.

G&H Can mother-to-child transmission be prevented or reduced?

KM At this point, universal screening of pregnant women for HCV infection is not recommended unless the subject is identified as having a high-risk history for the infection (eg, intravenous drug use). However, if the subject is found to be infected, treatment is not recommended during pregnancy. Current guidelines for HCV management do not discriminate between methods of delivery, and the decision to deliver by Caesarean section vs vaginal delivery does not depend upon the patient’s infected status.

G&H How does the HCV disease course compare between children and adults?

KM Although it is difficult to directly compare due to differing confounding variables, it is generally thought that children fare better than adults for the same duration of infection. The rate of cirrhosis in published pediatric populations with HCV infection is around 2%, but ranges from no cirrhosis to 8%. Bridging (ie, significant) fibrosis, on the other hand, ranges from 4% to as high as 44% in some series of HCV-infected children. The hepatic inflammation observed with pediatric HCV, in comparison to that observed in adults, is less and generally mild.

G&H When is the appropriate time to initiate treatment in HCV-infected children?

KM Currently, the most effective approved treatment for children is pegylated interferon, a2a or a2b, plus ribavirin. Pegylated interferon a2b plus ribavirin was approved in 2008, while pegylated interferon a2a plus ribavirin was approved in 2011 for children over 3 and 5 years, respectively. Because these treatment regimens have toxicities, it is important to consider the safety and tolerance of the drugs, as well as the likelihood of adherence to therapy and the required monitoring. The pediatric community feels very strongly that treatment should not be held until a child develops advanced liver disease; any opportunity should be taken to intervene earlier and potentially clear the infection and halt the progression of disease before there is significant impact on the patient’s health and quality of life.

With the new direct-acting antiviral agents for HCV now approved for adult use (and in clinical trials for pediatric use), the efficacy and tolerance are so excellent, and treatment duration so short, that there may be no medical reason not to treat children with HCV infection if and when these agents are found safe and approved for use in children.

G&H According to the long-term data currently available, how effective is pegylated interferon plus ribavirin for the treatment of HCV infection in children?

KM A number of series have looked at the efficacy of pegylated interferon a2a or a2b plus ribavirin. In
children infected with HCV genotype 1 or 4, which tend to be the hardest genotypes to treat with these medications, sustained virologic response (the rate of undetectable virus by polymerase chain reaction 6 months after the end of treatment) is approximately 50% (ranging from 44% to 57% in reported trials). In children infected with HCV genotype 2 or 3, sustained virologic response is typically between 80% and 90%, with several studies showing 100% sustained virologic response.

G&H Are there any significant adverse events or tolerance issues associated with this treatment in HCV-infected children?

KM Much like adults, the most common adverse events
are flulike symptoms, and these affect most treated child­ren. Approximately 27% of children who are treated dev­elop neutropenia to the point of requiring a dose adjustment, with a small percentage developing thrombocytopenia or anemia. The adverse events unique to children treated with pegylated interferon are the drug’s effects on growth. Most children treated with pegylated interferon and ribavirin will experience decrements in their height, weight, and body mass index (BMI) during treatment that correlate with the duration of treatment. Weight and BMI tend to return to baseline by approximately 48 weeks posttreatment; however, 33% of children experience a significant decrement in height (≥-0.5 z score), and for most, this had not returned to baseline 96 weeks posttreatment. The impact on linear growth and its subsequent return to baseline after the end of treatment are most prominent in children younger than age 12 years.

G&H How are patients who do not respond to pegylated interferon therapy currently being managed?

KM For the most part, these patients are being managed just by following them, as there are no other approved treatment options for children with HCV infection. If patients are eligible (depending upon the unique criteria of each trial), they may be enrolled into clinical trials with direct-acting antiviral agents. Clinical trial investigators are generally open to taking referrals of patients from other centers who would like to participate, as long as the participants are able to comply with the requirements of the trial.

G&H According to the data released to date from these clinical trials, how effective do direct-acting antiviral agents appear to be in HCV-infected children?

KM Thus far, data published on 12 weeks of sofosbuvir and ledipasvir (Harvoni, Gilead) in HCV genotype 1 subjects ages 12 to 17 years demonstrate a sustained virologic response of 98% at 12 weeks; 2 of 100 subjects were lost to follow-up and were counted as nonresponders. At 4 weeks, prior to the 2 subjects being lost to follow-up, sustained virologic response was 100%. Treatment of younger age groups with HCV genotype 1 is currently underway using this treatment regimen.

In addition, in HCV genotype 2 (12 weeks) and 3 (24 weeks) subjects ages 12 to 17 years, treatment with sofosbuvir (Sovaldi, Gilead) and ribavirin led to sustained virologic response of 100% at 4 weeks. Sustained virologic response was also 100% at 12 weeks for HCV genotype 2 subjects, but it was 97% for HCV genotype 3 subjects
(1 of 37 subjects was lost to follow-up).

G&H Have there been any adverse events or safety concerns in these pediatric clinical trials thus far?

KM There have not been any serious adverse events to date. Adverse events occurring in 10% or more of treated teen subjects have included abdominal pain, headache, nausea, vomiting, diarrhea, fatigue, cough, and oropharyngeal pain.

When conducting clinical trials in children, there are almost always some safety data already known from adult trials with the given medications. In general, children tolerate medications better than, or at least similarly to, adults. Despite these reassurances, it is important to remember that the metabolism of children may be different from that of adults, and drug effects may be further influenced by weight, area of distribution, or surface area differences. Thus, pharmacokinetics and pharmacodynamics in different age groups are important to study with new medications, and doses for children should be determined physiologically and not simply based on what they were for adults.

G&H Is a pediatric indication expected soon for these agents?

KM Yes. For example, Gilead has already submitted an application to the US Food and Drug Administration for approval of sofosbuvir and ledipasvir for the treatment of HCV infection in children ages 12 to 17 years.

G&H How is quality of life affected in children with HCV infection?

KM Quality of life is an important issue in these patients. We know that HCV infection in adults is associated with decrements in quality of life, cognitive performance (especially attention and higher executive functioning), and psychological functioning (such as anxiety and depression). There have been several studies looking at similar indicators in children. A study of 19 children infected with HCV found that there was a decrease in global health and parental emotion in comparison to healthy, noninfected children. In addition, the infected children reported reduced physical functioning, although they did not complain of any specific symptoms, and parents were concerned about the future health of their children.

A larger study, conducted by Rodrigue and colleagues, used a number of psychological inventory tools in 114 HCV-infected children (mean age of 10 years) and compared the results to those of a normative pediatric population, as well as a population of children with other chronic conditions, specifically children with attention deficit hyperactivity disorder (ADHD) and children with chronic liver disease who were undergoing evaluation for liver transplantation. The researchers found that the children with HCV did not have global impairment in quality of life or cognitive, behavioral, or emotional functioning. Similarly, symptoms of stress, depression, and anxiety were not pervasive in children and adolescents with HCV infection, unlike in adults. However, approximately 20% of HCV-infected children had executive function impairments, which exhibited in their ability to plan, organize, and inhibit their own behaviors. In addition, children with HCV infection had worse cognitive functioning than the normal com­parative group, although not as bad as children with ADHD. Another noteworthy finding is that the primary caregivers did not experience any decrements in quality of life generally; however, HCV-infected mothers had compromised quality of life compared to noninfected caregivers. This is important to point out because 60% of infected children contract HCV from their infected mother. All caregivers of HCV-infected children reported higher stress and concern over their child’s health, believing that it would deteriorate, and reported that HCV infection had a negative impact on the overall functioning of the family.

G&H Are there any restrictions or precautions that are recommended for HCV-infected children?

KM All children infected with HCV should be vac­cinated for hepatitis A virus as well as hepatitis B virus, which are vaccines universally recommended for children anyway. Additionally, HCV-infected children should not share with others anything that is likely to transmit blood, such as toothbrushes or razors, which is a good recommendation for all people.

G&H Do you anticipate that most medical insurance companies will pay for treatment with the direct-acting antiviral medications for children infected with HCV?

KM The financial impact of HCV infection in a person’s lifetime vs the cost of treatment is very important. Right now, insurance companies are commonly not approving HCV medications without evidence of advanced fibrosis and/or an extenuating circumstance. Because of these limitations, most children with HCV infection do not qualify, and even patients over the age of 18 years, in whom the direct-acting antiviral medications are currently approved, are being denied. Doctors and families do not want to wait for treatment until the liver is fibrotic. Thus, it is important to understand the impact and cost of living with the infection, dealing with disease progression and the possibility of developing advanced liver disease vs treating children when they are young, before the negative impacts of HCV infection develop.

G&H What are the next steps in research in terms of the management of HCV-infected children?

KM Most active ongoing research involves examining the efficacy and tolerability of the new HCV drugs in the pediatric population. It is important that this research continue so that these drugs can become available and ultimately approved for children as appropriate. Another important area of research involves better understanding of the immunologic response in viral hepatitis as well as further understanding of the mechanisms that lead to viral clearance vs chronic infection.

Dr Murray receives research funding from Gilead and owns Merck stock. 

Suggested Reading
Balistreri WF, Murray KF, Rosenthal P, et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12 to 17 years old with hepatitis C virus genotype 1 infection [published online December 20, 2016]. Hepatology. doi:10.1002/hep.28995.
Jonas MM, Balistreri W, Gonzalez-Peralta RP, et al. Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial. Hepatology. 2012;56(2):523-531.
Jonas MM, Schwarz KB, Gonzalez-Peralta R, et al. Long-term growth outcomes in children treated for chronic hepatitis C. J Pediatr. 2014;165(6):1252-1254.
Rodrigue JR, Balistreri W, Haber B, et al. Peginterferon with or without ribavirin has minimal effect on quality of life, behavioral/emotional, and cognitive outcomes in children. Hepatology. 2011;53(5):1468-1475.
Schwarz KB, Molleston JP, Jonas MM, et al. Durability of response in children treated with pegylated interferon alfa 2a ± ribavirin for chronic hepatitis C. J Pediatr Gastroenterol Nutr. 2016;62(1):93-96.

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