Fortunately, direct-acting antiviral (DAA) treatments have revolutionised the management of hepatitis C viral infection, and in April 2020, age restrictions were removed for three of the DAA medications subsidised in Australia by the Pharmaceutical Benefits Scheme (PBS). Early treatment of hepatitis C in children is cost-effective and reduces the lifetime impact of chronic liver disease and its after-effects
Recently, a study (published in the Medical Journal of Australia) was conducted to examine outcomes for children under 18 years of age with hepatitis C infection, and treated with DAAs during between April 2018 and April 2022 at five children’s hospitals in Australia.
Cases were identified by a retrospective medical record review of all children treated for hepatitis C during the study period. The study found that DAA treatments were well-tolerated and highly effective in children consistent with their efficacy in children and adolescents in clinical trials.
Out of the 54 children with hepatitis C infection who commenced DAA treatment at the five participating hospitals during the study period, 50 children completed treatment and were followed up. The median alanine transaminase (ALT) level declined significantly after treatment, indicating a clinically significant improvement. Four children had foetal alcohol spectrum disorder, and nine patients were Aboriginal or Torres Strait Islander people. Perinatal viral transmission was suspected in 51 cases.
DAA treatments are now attainable in Australia in normal practice for children with hepatitis C infection, using standard oral preparations, as outlined in the recent Australasian Society for HIV, Viral Hepatitis, and Sexual Health Medicine guidelines. Screening infants and children at particular risk should be the priority, with a focus on early referral to tertiary specialists with experience in treating hepatitis C infection in children.
Treating infected Australians early in life will minimise the risk of their lost to medical follow-up, reducing liver-related morbidity, social stigmatisation, and the risks of vertical and horizontal viral transmission prior to adolescence when activities that increase hepatitis C infection risk increase.
The benefits of DAA therapy for children with hepatitis C infection are now within reach in Australia in normal practice, which can only help us reach the World Health Organization’s ambitious target of eliminating hepatitis C globally by 2030.
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John (name changed for privacy reasons) had hepatitis C as a child and cleared the virus naturally. He talked about his experience.
“It was in the early 1980s and not much was known about hep C at the time. I was a kid, around 9 or 10 years old, when I started passing dark brown urine, like tea. My parents thought that wasn’t right and sent me off to hospital. They ran tests and diagnosed that I had what was called non-A non-B hepatitis.
“I lost heaps of weight during that time and was very jaundiced and yellow. I can’t remember how long I was crook for, but I was in hospital for two or three weeks. After that I had to get back up to strength and put weight back on and try to get back to normal.”
Although John and his parents didn’t speak much about it over the years, he found out later that his time in hospital was traumatic for all of them.
“I recall it being a bit like COVID times. I was in isolation in my own room and wasn’t really allowed visitors. My room had a glass window and my parents could only wave to me or speak to me from the outside of the window. The nurses and doctors were masked up as well.
“It was very daunting and scary as a kid. I was so young and didn’t know if I was going to survive the whole ordeal. And I still have mixed emotions when I think about how I got the virus through my blood products. You take a certain treatment for an illness that you think is going to save your life, and then you end up with another life-threatening virus or condition because of it. But I am probably one of the lucky ones. Other people got HIV. I cleared hep C naturally and I didn’t get HIV as well.”
Many years later, when John was celebrating a personal milestone, his normally stoic father was overwhelmed by the contrast between the happy occasion and the memory of John’s hepatitis C scare. His father broke down.
“He said he wasn’t sure I was going to survive,” said John.
Although John isn’t sure when he cleared the virus, he has had several occasions where his HCV RNA tests have confirmed that he no longer has the virus in his bloodstream.
“I had to obtain a few doctor’s reports for one reason or another, and they specified that I was diagnosed with hep C in my childhood but had cleared the virus spontaneously and this was verified in blood tests.”
One of the tests for hepatitis C came during preparation for in-vitro fertilisation, when John and his wife were undertaking pre-genetic diagnosis for haemophilia before becoming pregnant. John explained that the IVF doctors identified that he had been exposed to hepatitis C, but could also see that he had cleared the virus.
Stigma relating to hepatitis C remains an issue for many affected people with bleeding disorders. For John, there is often no good reason to tell other people that he had hep C as a child.
“I cleared it naturally. It’s a thing in the past and doesn’t affect my day-to-day life any more.”
However, he is conscious that he has told very few people in his life—only very close family and family friends—because of the stigma. This was influenced greatly by his experiences as a child.
“I was in primary school when it all came out in the news that haemophiliacs had been infected with HIV or hep C through blood products. Obviously, my classmates knew I had haemophilia, and there was the stigma of them thinking do I have HIV or hep C? I didn’t disclose having hep C at the time to my classmates. It was a bit daunting, and I was worried whether I would be treated as an outcast, and by their parents as well. So that wasn’t a very pleasant time.
“I kept it to myself. My parents probably told a few close friends but that was it. It was never spoken about outside that circle. And I thought their friends were a bit stand-offish towards me after that. The stigma is a big thing, even in this day and age.”
Keeping on top of his liver health is something that John takes seriously. There are several factors that contribute to liver health, not just the effects or after-effects of hepatitis C: for example, being overweight or drinking a lot of alcohol, or living with certain other health conditions. And even those who have cleared hep C will need ongoing liver health monitoring if they have already developed more severe liver scarring like cirrhosis.
John encouraged others to have any tests that are recommended for them individually, and to have hep C treatment if they haven’t already.
“Liaise with your treating doctor and see if you need more tests, because there are treatments now that can cure hep C in a short time if you still have the virus. Treatment has definitely come a long way from the early days!
“Keep an eye on your liver. Even though you might have been exposed to hep C 30 or 40 years ago, and you might have cleared the virus, it can still have some ramifications later in life. So it’s good to keep an eye on your liver and get any tests that you need, just to make sure there are no long-term consequences.”
This story was first published on the Haemophilia Foundation Australia website in July 2022, and is reprinted with permission.
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Hepatitis B isn’t common in young Australians because children born here are routinely immunised against it as part of the National Immunisation Program. The first of four free vaccination shots is usually given within a week of birth, with the others following at 2, 4 and 6 months of age (often in combination with other vaccinations). Babies who are born very prematurely or have a low birth weight get an additional free hepatitis B vaccine at 12 months.
If a pregnant woman has hepatitis B, she is usually given medicine to reduce the chance of passing the virus on to her baby. At birth, the baby might also get a extra injection of antibodies against hepatitis B, given within the first 12 hours, as well as the standard hepatitis B immunisation. Women who have hepatitis B can safely breastfeed unless their nipples are cracked or bleeding, as the virus can be transmitted in blood.
Hepatitis C is also rare in Australian children, due to to the fact that is is usually quite hard to transmit: it can only happen when blood containing the virus enters another person’s bloodstream. Household contact could lead to this happening, for example if a child uses a toothbrush belonging to an adult living with hepatitis C, or if they receive a needlestick injury after finding injecting equipment belonging to an adult. There is also a small risk of transmission if the mother breastfeeds with cracked or bleeding nipples.
What about the risks of transmitting viral hepatitis during pregnancy, birth or breastfeeding? In Australia, it is recommended that all pregnant women should be tested for hepatitis B and C. Testing in pregnancy allows arrangements to be made for vaccinating the newborn if the mother is found to have hepatitis B, or for precautions to be taken to prevent transmission of hepatitis C to the baby after birth. If a pregnant woman is found to have hepatitis C, plans can also be set up for her to start treatment once she is no longer breastfeeding. If hepatitis testing has not taken place for some reason, hepatitis C testing of pregnant women who are to have a planned invasive procedure — such as a Chorionic villus sampling (CVS) — has also been recommended, due to the small risk of blood-to-bloodstream hepatitis C transmission to the baby.
For hepatitis B, mother-to-child transmission can happen either in the uterus, through placental leakage, or through exposure to blood or blood-contaminated fluids at or around the time of birth. Perinatal transmission (transmission which takes place during or soon after the time of birth) is believed to account for between a third and a half of all hepatitis B infections.
If a pregnant woman is living with hepatitis C, it is actually extremely unlikely that she will pass on the virus to her child in utero: the risk is less than 5%. The greatest risk during birth is if a medical intervention is needed: for example, forceps can scratch a child’s skin, allowing blood-borne transmission. If the mother is known to have hepatitis C, then any interventions can be adjusted with this in mind to reduce risk as much as possible. Identifying women who have hepatitis C during pregnancy means that interventions that increase the risk of transmission to the baby can be avoided and effective treatments commenced after the birth or cessation of breastfeeding.
Because children with hepatitis B often don’t have symptoms, transmission between children may easily occur during play or fight through cuts and scratches.
If a child is living with viral hepatitis, what can be done? Clinical trials have recently shown that treatment of hepatitis C infection in children with the same medications used for those over the age of 18 is safe and effective, and these treatments have a cure rate of more than 97%.
Hepatitis C treatments listed on the Pharmaceutical Benefits Schedule can now be prescribed to children over three years old. However, they should be referred to a paediatrician who has experience with hepatitis C treatment, to discuss therapy options.
When children become infected with hepatitis B, some will recover from the virus within weeks or months without any medical intervention, and indeed may not even feel any effects from the infection. A majority (about 90%) of younger children who contract hepatitis B will develop chronic hepatitis B and will live with the virus long-term. This can put them at risk of liver scarring, liver failure and liver cancer in the future, so it is vital that children with chronic hepatitis B have liver and general health checks every 6-12 months depending on the advice of medical professionals. Although there is currently no cure for hepatitis B, there are some safe and effective anti-viral medicines to ameliorate its effects.
Any pregnant women or children living with viral hepatitis should be put in touch with a liver health nurse or specialist, in order to make sure that the best decisions are made for their health. It’s also extremely important to make all tests and services easily available for Aboriginal or Torres Strait women or women born overseas, as they are statistically more likely to have been exposed to viral hepatitis in the course of their lives.
If you have any concerns about your health or your child’s health, always remember to talk to your GP with any questions you might have, or you can call Hepatitis SA on 1800 437 222 or chat to us via the webchat icon at the bottom of our homepage.
Further reading:
https://www.schn.health.nsw.gov.au/fact-sheets/hepatitis-b-virus-infection-in-infants-and-children
https://www.schn.health.nsw.gov.au/fact-sheets/hepatitis-c-virus-infection-in-children
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The most common symptoms of the mysterious hepatitis are vomiting and jaundice: jaundice is a well-known symptom of serious hepatitis, as damaged livers can lead to high levels of bilirubin (a yellowy-orange bile pigment) in the body, which turns the skin and the whites of the eyes a yellow colour. At the time of writing, the Royal Australian College of General Practice (RACGP) had reported that at least five of the infected children have died.
Lab tests on all of those infected have excluded hepatitis viruses A, B, C, D (where applicable, as D only exists in some people living with hepatitis B) and E. Notably, a number of patients (at least 15%) have had severe COVID-19 infections, but given the overall high rate of infection in the UK generally, it is possible that this could well be coincidence instead of cause. Both COVID-19 and the unknown hepatitis being new viruses developing at around the same time may mean they are linked, or it may be a confusing case of bad luck.
Importantly, there is no sign of any link to COVID-19 vaccination: indeed, the majority of affected children are under five years old, and so too young to have received any COVID-19 vaccine.
One study found that an adenovirus—a type of common virus that typically causes mild cold- or flu-like illness—was present in around two-thirds of the infect UK children. In this case it was usually adenovirus 41, which more commonly causes diarrhea in children. A number of the cases which did not show the adenovirus being present were not properly tested, so its presence cannot be ruled out.
However, since it is very unusual to see hepatitis develop following an adenovirus infection in previously well children, clinical investigations are continuing into other factors which may be contributing, though no other epidemiological risk factors have been identified to date, including recent international travel. Some media outlets claimed research found that cases were linked with exposure to dogs, but the evidence for this is very weak and not well supported.
Though the first cases were found in March, retrospective testing of children who had shown similar health problems has found cases going back to October 2021. Laboratory testing for additional infections, chemicals and toxins is underway for the identified cases.
Dr Renu Bindra, Senior Medical Advisor at the UK Health Security Agency (UKHSA), said, “It’s important that parents know the likelihood of their child developing hepatitis is extremely low. However, we continue to remind everyone to be alert to the signs of hepatitis—particularly jaundice, look for a yellow tinge in the whites of the eyes—and contact your doctor if you are concerned.
“Our investigations continue to suggest that there is an association with adenovirus infection, but investigations continue to unpick the exact reason for the rise in cases.”
The UKHSA, the US Centers for Disease Control and other national health agencies continue to monitor the spread of the infection as they try to learn more about its cause and health effects.
In April, Gastroenterological Society of Australia (GESA) paediatric hepatologist Professor, Winita Hardikar, said that although each year in Australia, a small number of children present with unexplained hepatitis, with some requiring a liver transplant, there had not been an unusual spike.
In its media statement, GESA said cases of mystery hepatitis in Australian children “is a rare occurence”, and ongoing surveillance in Australia is occurring.
“Practise thorough handwashing, including supervising children,” the GESA statement advised. “Cover mouth and nose when coughing or sneezing.”
It advised parents to be alert to symptoms — which may include nausea, vomiting, abdonimal pain, loss of appetite, fever. jaundice, dark urine and pale faeces — and to contact their doctor if they have any concerns.
For more information, contact GESA on gesa@gesa.org.au
]]>Unlike other blood-borne viruses such as HIV and hepatitis B, the risk of a baby being infected with hepatitis C during the mother’s pregnancy or during birth is very low. Only about 5% of babies born to mothers who have hepatitis C are themselves infected by the disease.
A possible reason for this low figure is that the baby’s immune system has already destroyed the virus
before birth. A new study from researchers at Sweden’s Karolinska Institutet, published in the journal Gut, reveals clear adaptations of the uninfected babies’ immune system that may now lead the way to new treatment methods.
“The immune system of the [exposed but non-infected] babies shows similar changes to that in babies infected with hepatitis C,” explained Niklas Björkström, a doctor and researcher at the Institutet. “This could suggest that the immune cells have encountered the virus in the womb and managed to eliminate it before birth.”
The study was conducted in collaboration with a maternity hospital in Saint Petersburg, Russia. Of the 55 pregnant women participating, 40 had an active hepatitis C infection, while the others had been cured, but still tested positive for hepatitis C antibodies.
The babies born to women with an active infection were all considered exposed to the virus; despite this, only three of these 40 babies developed hepatitis C.
All the infants were monitored up to the age of 18 months through regular testing, and to increase the volume of comparable data, samples were added from 18 infants who had been infected with hepatitis C at birth.
This is particularly important research in the quest for a vaccine for hepatitis C.
The study showed that both the babies born with an infection and the babies who had been exposed to the virus by an infected mother had similar changes in their adaptive immune system, with clear adaptations of the body’s B lymphocytes, the role of which is to produce antibodies able to discover and identify alien microbes, such as viruses, bacteria and parasites.
“A possible explanation is that most babies exposed to the virus in utero manage to deal with it, which we can later see by the B lymphocytes,” said Dr Björkström. “One interesting hypothesis is that these cells can contain novel information that we can use to protect ourselves against hepatises C in the future.”
This is particularly important in the quest for a vaccine for hepatitis C. “This is why we need to continue researching,” Dr Björkström said. “We need to understand what it’ll take to obtain lasting protection against the virus. Only then can we attain the WHO goal of elimination.”
The researchers will now be investigating whether other immune cells in the infants have changed in a similar way. You can see the study here.
This article first appeared in issue 86 of the Hepatitis SA Community News.
]]>The study results, based on data collected from 44 patients, support entecavir as a safe and effective treatment for adolescents with chronic hepatitis B.
Believed to be the first long-term study on hepatitis B treatment for children and adolescents, the research also found that duration of entecavir therapy was an important factor in achieving successful outcomes. On average, the odds of undetectable hepatitis B DNA increases by about five per cent with each additional month of therapy.
Results
Outcomes were measured by HBV DNA levels, hepatitis B e antigen seroconversion (i.e. development of hepatitis B e antibodies) and ALT activity (liver function).
Researchers found that those who had undetectable HBV DNA at six months and twelve months of treatment were more likely to have a sustained response rate (SRR) at three years. SRR is defined as undetectable hepatitis B DNA, loss of hepatitis B e antigen and restoration of normal liver function.
Predictors of sustained response rate: age at infection & DNA results at 6th &12th month of treatment.
The study also found that adolescents who were 10 years old or more when they were infected were three times more likely to achieve undetectable hepatitis B DNA than those who were younger at infection.
Overall, data from the study showed that after four years 89.7% of the entecavir-treated adolescents had undetectable hepatitis B DNA (<20 IU/mL), 55.4% achieved hepatitis B e antigen seroconversion and there was a high of ALT normalization rate of 95.45%.
None of the people reported any significant side effects from the treatment.
Controversial
Children infected with hepatitis B during birth or in the first year of life have a high risk of developing chronic hepatitis B with potentially severe consequences such as liver cirrhosis or liver cancer.
Despite the availability of a hepatitis B vaccine, some children may not have access to it or have not completed the full course of vaccinations. Others may have contracted the virus prior to vaccination or were born to mothers with hepatitis B and did not receive immuno-prophylaxis at birth.
There are also about five per cent of infants who contract hepatitis B from their mothers despite having received the appropriate immunoglobulin injections and vaccinations.
The goal of hepatitis B treatment is to reduce virus replication and minimise damage to the liver. Treatments currently used for treating hepatitis B are interferon-alpha, lamivudine, adefovir, entecavir and tenofovir.
Hepatitis B infection progresses through an immune-tolerant phase during which treatment is not effective. Children and adolescents are often in the immune-tolerant stage. This, together with risks of developing resistance, makes the treatment of chronic hepatitis B in children and adolescents controversial. Some children with chronic hepatitis B required treatment to prevent cirrhosis and liver cancer. This is especially so where there is co-existing liver disease and a family history of cirrhosis or liver cancer.
The data from this study is similar to numerous studies on treatment of adults using entecavir. The study was published in PLoS ONE on 29 September. Read the full report.
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