Viral hepatitis elimination in 2024: have we moved forward?- Dr Erika Duffell

There are approximately 5.4 million people living with chronic hepatitis B and C (HBV and HBC) in 30 EU/EEA countries. As per the recent estimates, there is a decline in prevalence of HBV and HCV across around two thirds of the countries within EU. This is in line with global estimates that indicate reduction in overall prevalence for HBV and HCV. Studies indicate that the prevalence of HBV is highest among some migration populations such as refugee populations. High estimates are also seen in people in prison and those who inject drugs. For HCV, high prevalence is seen in people who inject drugs, people who are in prison and migrant populations. Based on recent analysis, it can be estimated that for HBV migrant populations overall across the whole region account for just under a third of the total burden of hepatitis. According to 2022 data, only 10 out of the 25 countries achieved the target of 95% vaccine coverage. All EU/EEA countries reported universal antenatal screening programmes for HBV and 12 out of 15 countries with data reached the 90% target.  4 out of 5 countries with a universal birth dose policy achieved the target of vaccinating 90% of infants born to mothers with HBV. All countries with a targeted birth dose policy achieved the target of vaccinating 90% infants born to mothers with HBV. The control targets for HBV include- 95% coverage with 3 doses of vaccine, 90% coverage with interventions to prevent perinatal transmission and <0.5% HBsAg prevalence in cohorts born after introduction of universal vaccination. In the EU/EEA, only Italy and the Netherlands have validated achievement of these targets. None of the four countries reporting data achieved the WHO 2025 diagnosis target of 60% of people living with chronic HBV infection are diagnosed. Three of the four countries reporting data achieved the WHO 2025 diagnosis target of 60% of people living with chronic HCV infection are diagnosed. Median estimates indicate 8% of HBV cases and 6% of HCV cases are diagnosed late. Late diagnosis includes decompensated cirrhosis or hepatocellular carcinoma. There is a general downward trend, but in some countries 1 in 6 HBV/HCV cases is diagnosed late. 11 of 30 countries reported restrictions on access to treatment for undocumented migrants (8 countries), current/former injectors and people in prison. The cost of screening tests and PCR tests are also a huge barrier in achieving targets. Based on data from the Global burden of disease study for 2019, 8 countries achieved WHO target of combined HBV and HCV mortality rate of <6/100,000 per year. WHO has set a goal to have <10% of people living with hepatitis and key populations experiencing stigma. Stigma and discrimination creates a barrier that can hinder an individual’s access to healthcare. Strong measures need to be taken to achieve the target of eliminating hepatitis. These include further scaling of harm reduction, minimizing vertical transmission through development of robust and well-monitored mother to child transmission programme, removal of testing barriers rolling out approaches such as self-testing, ensuring treatment widely accessible through integrated programmes, better linkage to care for diagnosed cases and strong community engagement to identify solutions to tackling stigma.

Simplified approaches for screening and diagnosis of HCV, HBV, HDV infections- Simona Ruta

The chronic infections with hepatitis B,C and Delta viruses remain a great burden for the public health due to progressions to cirrhosis and hepatocellular carcinoma, despite the fact that there is very efficient vaccine against HBV and HDV and there is a curative treatment for HCV. Liver-related deaths have increased between 2019 and 2022 i.e approximately 1.3 million deaths in 2022. This is due to lack of awareness and access to healthcare services. In the USA, CDC has introduced universal screening for HBV for all adults aged > 18 years at least once during a lifetime. This screening is done with a triple panel using HBS antigen, total anti HBc antibodies as a marker of past infection and anti-HBs antibodies as marker of result infection. Reflex testing for HDV can be added to this triple panel for all those who are positive for HBS antigen. The simplified algorithms for HCV are more widely implemented all over the world and there are policies for testing and treating with hepatitis C antibody testing, universal testing, birth cohort based testing or risk based testing. But for all those who are positive, it will be reflex HCV RNA testing and will be directly linked to treatment with pan genotyping direct detecting antivirals (DDA) and follow up for a sustained virological response at 8-12 weeks after the cure. Point of care (POC) serologic tests have already been used largely worldwide. They are lateral flow immunoassays which give results in less than 20 minutes with reduced costs and no cold chain required. There are several diagnostics tests such as LFA for anti HDV antigen that can be used for screening and diagnosis. On-site POC testing is very important because it offers broader access for vulnerable populations and better linkage to care. The treatment uptakes are much higher (77%-81%) as compared to those who are diagnosed or screened by standard laboratory testing (53%). These tests are bringing services closer to communities, which is very important and several countries have used this type of mobile units to introduce POC testing. Rapid POC are used to determine level of liver fibrosis for the advanced liver fibrosis. An ideal POC test will have to be affordable, sensitive, specific, user-friendly, rapid and robust, equipment -free and deliverable. In 2019, 2 more criteria were added to this- real-time connectivity and ease of sample collection. Alternative sampling methods allow for easier collection transportation, storage and have very low costs and are represented by dried blood spots that can allow one sampling. There are also tests which can be performed on oral fluids which can be further used for self-testing. This can increase access to hard to reach populations while keeping confidentiality. Real time connectivity refers to result interpretation and remote monitoring acquiring optimization of instrument placement, storage and supply management. This can be acquired by using microfluidic devices which are paper-based analytical devices. These are environmentally-friendly that can be used together with a dongle to connect a smartphone to read the microfluidic disc. Integrated testing refers to integrated laboratory testing that will allow the use of a common infrastructure, procurement, sample transportation, storage and data management. This should also be included in primary care models. Egypt is the first country to achieve gold tier status on the path to eliminating HCV. 

The best we can do with the treatments we have: is it enough to eliminate HCV, HBV, HDV?- Adriana Vince

HBV is still a huge global burden with over 250 million people affected with this and around 1,100,000 die annually from HBV related cirrhosis and HCC. High viral load is associated with increased incidence of liver cancer and there is a link of viremia to development of cirrhosis. According to EASL, the main goal of therapy is to improve survival and quality of life by preventing disease progression and consequently HCC development. As per the guidelines, treatment is required for patients who have viremia higher than 2000 units. Some of the treatment options available are long-term virus suppressing therapy with nucleotide analogues and pegylated interferon can be considered for mild and moderate hepatitis. The current NA treatments efficiently suppress HBV DNA replication, decrease liver inflammation and fibrosis, decrease risk of cirrhosis, HCC and liver-related deaths and have a good safety profile. However, HBsAg loss rarely occurs. The optimal goal of HBV cure strategies is to achieve durable off-treatment HBsAg loss with or without seroconversion to anti-HBs antibodies. It implies the profound suppression of replication of HBV and suggests reduced overall expression from cccDNC and integrated viral genomes. Sterilizing cure is complete clearance of intrahepatic cccDNA and/or integrated HBV DNA. The most important biomarker besides HBV DNA is qHBsAg and it reflects the transcriptional activity of ccc DNA as well as integrated DNA. It is a predictor of HBsAg loss after cessation of NAS. In a systematic review and meta-analysis of 28 studies, seroclearance of HBsAg is associated significantly with improved patient outcomes. The safe cessation of NA therapy remains one of the most controversial topics in the clinical management of CHB. New therapies like virus targeting agents decrease the pool of cccDNA by more efficiently blocking new rounds of infection and the intracellular recycling of the virus. Immunomodulating therapies include immune modulators like TLR7/8 agonists, checkpoint inhibitors and therapeutic vaccines. The HBV vaccine for infants had been introduced nationwide in 190 member states by the end of 2022. Global coverage with 3 doses of hepatitis B vaccine is estimated at 84%. Around 50 million people are living with HCV globally. HDV affects globally 5% of people with chronic HBV infection. Every HCV RNA positive person should receive treatment like pegylated interferon- 48 weeks course leads to 23-28% undetectable HDV RNA. NAs should be added in patients with cirrhosis. The key actions to advance a public health approach to viral hepatitis include- expanding access to high-quality affordable testing and diagnostic services; shifting from policies to implementation for equitable access to treatment and cure; strengthening investment in primary prevention of viral hepatitis; simplifying and decentralizing the delivery; mobilizing innovative financing from all sources and improving data, community engagement and innovation towards hepatitis B cure. 

Hepatitis E in vulnerable populations- Zeinab Nabil Ahmed Said

Hepatitis E virus is the fifth known cause of human viral hepatitis and it is the most common etiologic agent of acute hepatitis and jaundice globally. Every year there are an estimated 20 million HEV infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. WHO estimates that hepatitis E caused approx. 44000 deaths in 2015. In developing countries, HEV mainly infects young adult males (15-30 years) and is asymptomatic, causes mild systemic illness or icteric acute hepatitis that can be fulminant or lead to acute liver failure. Vulnerable groups are at higher risk of developing severe complications from HEV infection. The challenges in diagnosing HEV in vulnerable groups leads to underreporting and inadequate management. Poor sanitation and limited access to clean water contribute to the high prevalence of HEV in vulnerable populations. Consumption of undercooked or contaminated food poses a significant risk for HEV transmission. HEV3 and HEV4 persist in vulnerable populations. Chronic hepatitis may progress to cirrhosis in 10% of infected patients. Fulminant hepatitis is more frequent in groups with pre-existing liver disease and in pregnant women. HEV causes high maternal mortality in pregnant women, especially in their trimester. It is associated with approx. 70,000 deaths and 3000 stillbirths globally every year. HEV1 and 2 infections in pregnancy can progress to ALF. 3 weeks post infection, HEV RNA becomes detectable in blood and stool. Simultaneous detection of anti-HEV IgM and anti-HEV IgA supports the diagnosis of acute hepatitis E. RT-PCR and nucleotide sequencing can help in diagnosing HEV. Most cases of acute HEV infection are self-limiting and require supportive care. Pegylated interferon alpha, mycophenolic acid, sofosbuvir/ribavirin combination therapy are some treatment options for HEV. Good sanitation and hygiene practice helps in prevention of HEV. Conduction of risk assessment for transfusion or transplantation related HEV transmission is recommended especially for risk groups. 

34th Annual Congress of European Society of Clinical Microbiology and Infectious Diseases(ESCMID), April, 2024