Snapshots Alan Franciscus, Editor-in-Chief

Article: Hepatitis C in children in times of change—RD Baker et al.
  Source:  Curr Opin Pediatr. 2015 Jul 18. [Epub ahead of print]

Results and Conclusions
The main focus of the abstract was when to initiate treatment and when it is safe to wait for approval of the new highly effective direct-acting antiviral therapies to treat hepatitis C (HCV).

Pegylated interferon and ribavirin is the current standard of care to treat children with hepatitis C.  There are pediatric clinical trials of sofosbuvir/ledipasvir, ribavirin, and Vieikira Pak, with and without ribavirin. Approval of these drugs is expected in the near future.    

The authors make a good case for their recommendations:

• Wait: Children generally have a slow disease progression so in most cases it is safe to wait for the interferon- and ribavirin-free medications to be approved.
  
  
• Treat: In the case of children who do have serious disease progression treatment now is warranted.  Genotype information should be factored into the treatment decision process since genotype 2 and 3 cure rates are higher and treatment durations are shorter with pegylated interferon and ribavirin combination therapy.   

The Bottom Line
All children with HCV should be monitored on a regular basis.  Any treatment decisions for children should be evaluated on a case-by-case basis.

Editorial Comment
The general consensus is to wait (if possible) until the interferon- and ribavirin- free therapies are available. However, there is a small percentage of children with HCV who progress on to serious liver disease very quickly—this is why it is so important to identify and monitor children on a regular basis. 

It will be very interesting once the new therapies are approved to treat children with HCV.  Will insurance companies be as restrictive as they are with adults?  Hopefully not!  But if they are it just might be enough to raise the level of public ire to demand that they cover the medications for everyone.  It might also be enough that the public finally demand that the prices come down so that everyone affected by hepatitis C can afford the medications. 

Coming soon:  An Overview of HCV in Children

Article:  Prevalence of Cirrhosis in Hepatitis C Patients in the Chronic Hepatitis Cohort Study (CHeCS): A Retrospective and Prospective Observational Study—S C Gordon et. al
  Source:  Am J Gastroenterol. 2015 Jul 28. doi: 10.1038/ajg.2015.203. [Epub ahead of print]

Results and Conclusions
In the Chronic Hepatitis Cohort Study (CHeCS) there were 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%).  Other parameters, such as the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) were not assigned to the biopsy proven cirrhosis results. 

The Bottom Line
The authors noted that the since the ICD-9 codes may not be the best codes to indicate the prevalence of cirrhosis and that there may be a ‘fourfold’ higher prevalence of cirrhosis in studies previously reported. 

Editorial Comment
This is an important study.  We need to understand the true prevalence of cirrhosis in this country.  It will help to push for better funding and making sure that people are treated sooner rather than waiting until people become sick. 

Article:  Chronic Hepatitis C Virus Infection Is Associated with Subclinical Coronary Atherosclerosis in the Multicenter AIDS Cohort Study (MACS): a Cross-Sectional Study—RA McKibben
  Source: J Infect Dis. 2015 Jul 27. pii: jiv396. [Epub ahead of print]

 

Results and Conclusions
Eighty-seven men with chronic hepatitis C were evaluated for the risk of cardiovascular disease (CVD).

Note: the study also looked at HIV and HIV/HCV coinfected men but did not find an association. 

The men were assessed for coronary plaque using non-contrast coronary CT and CT angiography and evaluated the associations of CHC with measures of plaque (substances that lead to hardening of the veins/arteries), prevalence, extent, and stenosis (narrowing of the veins). It was found that all types of plaques were significantly higher in men with chronic hepatitis C.

Bottom Line
This is not the first study that has shown that there are cardiovascular problems associated with hepatitis C.  But it is important to remember that this is a small study.  It also needs to be replicated in a larger patient population and in women with HCV. 

Editorial Comment:
As we come to understand more and more about hepatitis C it becomes clear how much damage hepatitis C causes to many organs outside of the liver.  Everyone with hepatitis C needs to be monitored on a regular basis.  In this case men and women need to be monitored for cardiovascular disease.  This is another reason why people with hepatitis C should be treated before these types of health issues are allowed to begin.

http://hcvadvocate.org/news/newsLetter/2015/advocate0815_mid.html#4

Future Treatment May Be Best for Kids with Hepatitis C

The best time to treat children infected with the hepatitis C virus may be off in the future when newer, better drugs with fewer side effects are expected to be approved for pediatric populations, according to the authors of a recent article in Clinical Liver Disease.   

Hepatitis C is a bloodborne virus that over time if left unchecked can severely damage the liver. But for children who are chronically infected, progression to advanced liver disease during their childhood years is uncommon, says lead author Christine Lee, MD.  

A major milestone in the treatment of hepatitis C is the recent development of direct-acting antiviral (DAA) agents and combination drug regimens, Lee stated in the article. These developments are likely to similarly revolutionize treatment of the virus in children in the near future however clinical trials are still being conducted.


Read more...

HealthWise: Children with Hepatitis C —Lucinda K. Porter, RN

Rick Nash has had hepatitis C his entire 29 years of life. He didn’t know about the infection until the summer prior to starting 7th grade. Rick wasn’t even a teenager, and he was already showing signs of advanced liver disease from chronic hepatitis C virus (HCV).

Rick acquired HCV when he was an infant. Approximately 6% of infants with HCV-positive mothers will acquire the virus perinatally: This is known as vertical transmission.  When Rick learned that he had hepatitis C, his mother was diagnosed too. Up to 4000 children in the U.S. contract HCV vertically every year.

According to NHANES-III, about 0.17% of 6-11 year olds (31,000) and 0.39% of 12-19 year olds (101,000) are HCV antibody-positive. This amounts to roughly 23,000 to 46,000 children in the US with HCV. Vertical transmission is the most common way children acquire HCV. Another frequent HCV transmission mode is via drug use, which is infecting adolescents at alarming rates.

Before going further, it is important to note that information about HCV in the pediatric population is disturbingly minimal. The best source of information comes from the practice guidelines by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) published in June 2012.  With no mention of the newest HCV treatments, the guidelines are outdated.

NASPGHAN admits that little is known about the pathophysiology of HCV in infants and children. “Infants may have certain defense mechanisms, possibly age-related, which explain the relative inefficiency of mother-to-infant HCV transmission.”¹ Nonetheless, HCV during childhood is still quite serious. There is a 26-fold increased risk of liver-related death associated with chronic HCV acquired in childhood.

Generally, HCV progression in children is not as severe or as rapid as it is in adults. However, significant fibrosis or cirrhosis may occur, as was the case with Rick. Pediatric liver transplantation from HCV is rare. Hepatocellular carcinoma (liver cancer) is extremely uncommon in HCV-positive children. 

Cognitive impairment has been observed in children with HCV. This includes developmental delay, learning disorders, and cognitive deficits. Children are less likely than adults to have HCV extrahepatic manifestations; cryoglobulinemia and lymphoma have not been reported. Glomerulonephritis (a kidney disease) may occur in children with chronic HCV.

 

Hepatitis C in Society
Hepatitis C doesn’t just affect the body; it affects social systems. A child with hepatitis C has complicated social systems. The child’s parents may be worried. Kids may not have the maturity to deal with the shifting sands of living with a chronic, infectious disease. Keeping others safe is a tricky issue, and these issues differ if you are five versus fifteen years old. Conversations about sex and drugs are more complicated when you have a potentially infectious virus. Telling an HCV-positive kid to avoid alcohol is an even more serious discussion than it already is.

In the middle of all this is stigma. The public isn’t kind, especially to children living with infectious diseases. Zachary is a second grader in Virginia who is struggling with hepatitis C.²  He contracted HCV at birth and was adopted into a loving family. His family had no experience with HCV, and his mother learned all she could about it. Zach is now six, and has already undergone combination therapy with interferon and ribavirin, but didn't respond.

Zach’s mother Kelly noticed a few changes relating to school. Zach revealed that he would be in trouble if he got a loose tooth at school. He was barred from using the school computer because of concerns that he might sneeze on the keyboard. All the students except Zachary were invited to join an after school wrestling program. This occurred despite the fact that Kelly has educated the teachers and officials at school about HCV transmission.

This is a common story. We saw it with HIV. Ryan White was kicked out of school because he had HIV. The family was constantly harassed and threatened. The Ray brothers, three boys with hemophilia, experienced the same horrors. They were banned from school in Arcadia, Florida. They fought and won the right to attend, but their house was burned to the ground because of arson. Blogger Shawn Decker was another hemophiliac who was dismissed from school because of his HIV status. He also had hepatitis B and C. He lived to share his story. Ryan White and two of the three Ray brothers are dead.   

Treating Children for Hepatitis C
Rick’s first glimpse at hepatitis C treatment was watching his mother go through it. “My mother would end up going on two hep C treatments while I was in school. Each treatment she went through gave me a glimpse of the insane side effects and pain she suffered from interferon. This wasn't just my mother’s pain; it was also mine.” Eventually, Rick’s mother would be cured. Rick was not as lucky.

As shocking as it may sound, the only FDA-approved HCV treatment for children is peginterferon plus ribavirin. Children with genotype 2 or 3 need 24 weeks of treatment; everyone else endures 48 weeks. Response rates are slightly more than 50%. Genotype 1 patients have the lowest rates (47%).

Side effects are common and can be quite severe. Neuropsychiatric side effects can be difficult to manage. Thinking back to my two interferon experiences, I was a wreck. I can’t imagine what it would be like if I was a youngster and didn’t have the coping skills that come with maturity.

Rick’s first treatment began when he was 18 years old. As an adult, he now had access to all the medications, however, at that time there wasn’t much. He started with interferon, a difficult treatment that did not work. He made his way down the menu of HCV treatments, and is now on his fifth attempt, using Harvoni. In the meantime, Rick struggles with decompensated cirrhosis. He has portal hypertension (high blood pressure in the liver), esophageal varices, hepatitis encephalopathy (mental confusion caused by high levels of toxins in the blood), ascites (accumulation of fluid in the abdomen), and jaundice (build-up of bilirubin in the blood which causes yellow skin and eyes, dark urine, and clay-colored stools).

If Rick were still a kid, his choices would be to use peginterferon/ribavirin, look for a clinical trial, or wait. Some pediatric hepatologists will prescribe HCV treatment off-label, but getting insurance companies to cover the cost of off label drugs is challenging. When this article was going to press, there were at least two trials for kids, but there aren’t many slots. (See ClinicalTrials.gov for more information.)

 

Coping
Coping with hepatitis C is hard, but coping with it when your child has it, or you yourself are a child, takes monumental strength. In his young life, Rick Nash has coped with fragile health and five HCV treatments. “My mother didn't know the risk when she had me, and she told me that in hindsight had she known, she would have been less likely to have taken the risk of having me. I told her that whatever the risk, I am glad of having been born, even if it meant I could have only done so having been given the virus. It is through this hardship I was able to better know myself, and better know my mother. Pandora opened the jar not knowing its contents, but within the dread, there was the greatest gift of all: hope.”

To keep up with Rick’s progress and see if he responds to Harvoni, visit Rick Nash’s Blog http://blogs.hepmag.com/ricknash/

Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of Free from Hepatitis C and Hepatitis C One Step at a Time. Her blog is www.LucindaPorterRN.com

Additional Resources

• NASPGHAN Practice Guidelines: Diagnosis and Management of Hepatitis C Infection in Infants, Children, and Adolescents – Cara L. Mack, et al. Journal of Pediatric Gastroenterology and Nutrition Volume 54, Number 6, June 2013
• PKIDS – Parents of Kids with Infectious Diseases – www.pkids.org

Endnotes

1. NASPGHAN Practice Guidelines
   
   
2. This story first appeared on Kim Bosseley’s blog at http://blogs.hepmag.com/kimbossley

http://hcvadvocate.org/news/newsLetter/2015/advocate0315.html#2