(Focus - Malaysia)
Hepatitis is a minacious liver disease, and it can be self-limiting or progress to fibrosis (scarring), cirrhosis, or liver cancer if not diagnosed and treated on time. WHO has set a goal to eliminate Hepatitis globally by 2030. World Hepatitis Day (July 28) helps reach this goal by acting as a platform to address the lack of awareness about Hepatitis.
We at decodeMR contribute to this cause through our Act to Impact approach, wherein we connect with HCPs, discuss different topics of interest, and publish in our interview series blog. Here we bring you an interview with Dr. Su Yin LAU, a renowned Hepatologist, and Gastroenterologist from Malaysia.
Dr. Su Yin LAU is a Fellow of the Royal Australasian College of Physicians (FRACP), currently serving as a Medical Lecturer at the University Putra Malaysia (UPM), Selangor, and working as Hepatologist and Gastroenterologist at Hospital Pengajar UPM, Selangor, Malaysia.
There are two things to reduce the risk of transfusion-transmitted Hepatitis B: One is to reduce the prevalence of Hepatitis B infection in our population, and the other would be a meticulous screening of blood donors. There is a long list of deferral criteria to exclude potentially high-risk donors. For example, individuals with a history of sexually transmitted infections (STIs) would be deferred permanently and would not be able to donate blood in the longer term.
What impact does COVID 19 have on the management of Hepatitis B patients?
Dr. Su Yin - The question should be what impact COVID-19 does not have in this world. Before the pandemic, in 2016, the WHO released a global health sector strategy on viral Hepatitis. One of the goals is to eliminate Hepatitis B as a public health problem by the year 2030. Strategies include prevention of transmission, early detection, and treatment of patients with chronic Hepatitis B infection.
As you would imagine, COVID-19 has disrupted many medical services worldwide. Reports showed that up to 90% of viral Hepatitis services were disrupted globally. For example, routine immunization programs, antenatal screening, access to diagnostic tests, and antiviral therapy were all affected.
Unfortunately, it will not stop here; there will be longer-term repercussions such as:
Vertical transmission of infection due to lack of screening and treatment of mothers, increasing the incidence of chronic hepatitis B infection
Undiagnosed individuals and patients who have decided to stop treatment would have progression of their liver disease leading to liver cirrhosis and hepatocellular (liver) cancer.
Transfusion-transmitted Hepatitis B viral infection can be reduced using serology and viral nucleic acid testing (NAT). However, the low viral DNA level in donors' blood remains a challenge in detecting Hepatitis B [1].
What can be done to reduce the risk of transfusion-transmitted Hepatitis B?
Dr. Su Yin - There are two things. One is to reduce the prevalence of Hepatitis B infection in our population, and the other would be a meticulous screening of blood donors. There is a long list of deferral criteria to exclude potentially high-risk donors. For example, individuals with a history of sexually transmitted infections (STIs) would be deferred permanently and would not be able to donate blood in the longer term.
The donated blood is then quarantined and screened. In Malaysia, blood screening is done at the transfusion microbiology lab for transfusion-transmitted infections, including HIV, Hepatitis B, Hepatitis C, and Syphilis. Rapid diagnostic tests are not allowed for blood product screening. I believe a combination of Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), and Hepatitis B viral DNA (HBV DNA) detection would be ideal for testing donor blood.
Is there any advancement in serology tests to eliminate the risk of Hepatitis B transmission during blood transfusion?
Dr. Su Yin - Screening donor blood for Hepatitis B started in the early 1970s. Over the years, a lot has changed. There are two different tests to detect the presence of Hepatitis B: serology for antigens and antibodies, and nucleic acid tests for the presence of HBV DNA in the blood.
These assays have been developed to be more sensitive where they can detect lower levels of HBsAg and HBV DNA in donors.
The use of immunosuppressive therapies reactivates Hepatitis B viral infection [2]. In this context, what are the challenges associated with co-managing Hepatitis B and rheumatoid arthritis patients?
Dr. Su Yin - Although these are less common nowadays, the main challenge would be remembering to screen for chronic Hepatitis B infection before starting these medications. Hepatitis B is interesting compared to chronic Hepatitis C infection because not all patients found to have chronic Hepatitis B will be started on treatment. There are individuals out there who have very low levels of Hepatitis B viruses without having any liver damage, for example, inflammation of the liver, liver scarring, or liver cirrhosis. These patients will only need to be monitored but do not require antiviral therapy. Individuals with low HBV DNA levels who are not on treatment are very vulnerable to reactivation if immunosuppressive medications are given.
According to you, what approaches can be taken to reduce the risk of Hepatitis B reactivation in rheumatoid arthritis patients who receive immunosuppressive agents?
Dr. Su Yin - The Asia Pacific Association for the Study of Liver (APASL) guidelines have been developed specifically to address this concern on Hepatitis B reactivation in patients commencing on immunosuppressive agents. Patients should be screened for Hepatitis B by testing HBsAg, anti-HBc antibodies and checking their immune status by looking at surface antibody (anti-HBs) titres. Risk stratification is done to categorize them as high risk, moderate risk, or low risk for Hepatitis B reactivation. Depending on what medication they will be started on, they are categorized under one of the risk groups.
For example, if they were started on infliximab, adalimumab, or high-dose steroids for more than four weeks, they will be deemed moderate or high risk. In that case, they will require antiviral therapy, such as tenofovir or entecavir. Lamivudine is less used these days due to its low barrier to resistance.
Studies have shown that people living with HIV would be more likely to develop a protective immunological response to vaccination if they had a higher CD4 count and low or undetectable HIV viral load at the time of vaccination. Some reports have recommended deferring vaccination for six months after starting antiretroviral therapy, but at the same time, balancing the risk of getting infected during that period.
We understand that there is an effective vaccine against Hepatitis B infection. However, people with HIV are less likely to develop a protective immunological response to vaccination [3]. What is the reason for the lower success rate of Hepatitis B vaccines in HIV-infected patients?
Dr. Su Yin - As we know, people living with HIV have a weakened immune system. So, they are unable to mount an immune response when injected with vaccines containing Hepatitis B surface antigen proteins.
According to you, what can be done to achieve durable protection against Hepatitis B infection in HIV-positive patients?
Dr. Su Yin - Studies have shown that people living with HIV would be more likely to develop a protective immunological response to vaccination if they had a higher CD4 count and low or undetectable HIV viral load at the time of vaccination. Some reports have recommended deferring vaccination for six months after starting antiretroviral therapy, but at the same time, balancing the risk of getting infected during that period.
In the case of HIV patients who do not achieve durable protection against Hepatitis B infection via vaccination, do you see any role of the double dose of Hepatitis B vaccine in achieving immunity against Hepatitis B infection?
Dr. Su Yin - There is a very recent study conducted in Chile answering just that question. People living with HIV who had not previously responded to Hepatitis B vaccination were randomized to receive the standard 3-dose regime of 20 mcg or double dose regime of 40 mcg at 0, 1, and 2 months.
Patients in the double-dose group were found to have a better immune response (72% response rate compared to 51% in the standard-dose group), higher antibody levels (80% compared to 50% in the standard-dose group), and had a more sustained response at 1 year (80% compared to 39% in the standard-dose group).
As a closing note, what would be your message to the public in order to prevent Hepatitis B transmission?
Dr. Su Yin - The important message would be to get screened and vaccinated and encourage your friends and family to get screened and vaccinated, thereby enabling us to eliminate Hepatitis B as a major health problem by 2030, as suggested by WHO.
Thank you very much, doctor. It was an excellent discussion with you.
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