Focus on Hepatitis B: WHO's New Guidelines and Their Global Implications
At the 2024 Asian Pacific Conference for the Study of Liver Disease in Kyoto, the World Health Organization (WHO) introduced transformative guidelines for the prevention, diagnosis, care, and treatment of chronic Hepatitis B virus (HBV) infection. HBV is a major global health challenge affecting approximately 296 million people worldwide. If left untreated, it results in nearly 900,000 deaths annually from complications like liver disease and cancer.
The new guidelines aim to increase testing access and expand treatment eligibility, particularly in sub-Saharan Africa which accounts for 70% of all new HBV infections. They provide evidence-based recommendations based on updated scientific data about antiviral effectiveness, diagnostic test performance, and service delivery models. By simplifying testing and extending treatment eligibility, these guidelines address longstanding access barriers. They represent a significant step towards achieving the 2030 goal of eliminating HBV as a major public health threat.
Key Changes in the New Guidelines
The WHO's new guidelines focus on making HBV testing and treatment more accessible for those who need it most. Key changes include:
Simplified Testing Recommendations
The WHO's revisions highlight the importance of streamlined testing methods such as dried blood spot sampling and point-of-care viral load assessments. The goal is to expand early diagnosis. Coupled with community-based testing, these methods aim to enhance accessibility, particularly in areas with limited resources. They facilitate early intervention and aim to reduce the stigma associated with traditional diagnostic procedures.
There is also an emphasis on expanding testing among pregnant women to prevent transmission of HBV from mother to child during birth or through breastfeeding, which is the primary way the virus is transmitted.
Previous recommendations advised pregnant women with active HBV infection to receive temporary treatment until their child was fully vaccinated against the disease. The new guidelines take into account that not every health facility has the tests to determine if a woman has an active infection. They suggest that health care providers consider administering prophylaxis to pregnant women with HBV, even if they cannot determine the status of their infection.
Expanded Treatment Eligibility and Access
Nearly 300 million people currently live with HBV, and the disease causes approximately 820,000 deaths each year. Prior guidelines typically limited treatment to those with advanced liver disease or significant fibrosis, which made it challenging for patients to access care until their conditions had substantially deteriorated. The new guidelines propose a more inclusive treatment approach, expanding eligibility for antiviral therapy to millions more people. This change should increase the portion of people living with HBV eligible for treatment from the current 8% to 15% to around 50%. The World Health Organization now strongly recommends treatment for all people aged 12 and older who have chronic HBV and exhibit early signs of liver damage or other indicators, including co-infections such as HIV. The previous guidelines often recommended treatment only at more advanced disease stages and for patients above 30 years old, a significant hardship considering that 25% of infections in the region occur in people under 20.
The updated guidelines provide a more comprehensive approach to the management of hepatitis B virus (HBV) infection. These guidelines notably broaden the recommended treatments. Previously, the guidelines strongly advocated for single-drug therapies as the preferred treatment option. However, in recognition of the ongoing shortage of these single-drug therapies in some low- and middle-income countries, the updated guidelines now also endorse two dual regimens as alternate treatment options when the preferred monotherapies are not readily accessible.
This shift in treatment recommendations is a direct response to the pressing need to ensure that effective therapies are available in all regions, irrespective of their economic status. The scarcity of the preferred monotherapies in some parts of the world has necessitated the inclusion of the dual regimens in the guidelines.
Furthermore, the expansion of the recommended treatments is grounded in a growing body of scientific evidence. This evidence increasingly suggests that initiating treatment at an earlier stage of the disease can have a significant positive impact on long-term health outcomes for people living with HBV infection. Early intervention also has the potential to markedly reduce transmission rates. By taking this approach, we can address the global HBV burden more effectively and ensure a healthier future for those affected by this disease.
Improving Patient Support
Improvements in patient support mechanisms, such as the introduction of peer support and digital adherence tools, show a thorough and empathetic understanding of the many challenges faced by people living with chronic Hepatitis B virus (HBV) infection. These patient-focused initiatives, an evolution of the regulations that governed HIV testing and treatment, are based on real-world experiences and insights. They are carefully designed with two critical objectives in mind.
First, they aim to significantly enhance treatment adherence. This is crucial, as consistent adherence to prescribed treatment regimens is a key factor in the success of long-term antiviral therapy. Without proper adherence, the effectiveness of the treatment is compromised, potentially leading to less than optimal health outcomes for the people affected.
Second, these initiatives also aim to reduce the risk of drug resistance. Drug resistance is a major concern in managing chronic diseases like HBV, as it can make first-line treatments less effective over time. This can complicate the disease management process and potentially lead to worse health outcomes.
By addressing the dual challenges of treatment adherence and drug resistance, these improved patient support mechanisms represent a significant step forward in the comprehensive and patient-centered management of chronic HBV.
Integrating HBV into Existing Services
The guidelines suggest integrating existing HIV, tuberculosis, and primary care programs to offer streamlined services for Hepatitis B Virus (HBV). This leverages the existing infrastructures, resources, and patient engagement strategies of these programs, potentially resulting in early detection and effective management of HBV.
By making use of these existing programs, healthcare systems can effectively expand HBV services. This method ensures patients receive coordinated care for their various health needs, fostering a more holistic patient care approach. Not only does this integration yield immediate patient benefits, but it also presents long-term advantages for the entire healthcare system, aiding healthcare providers in efficient resource allocation and reducing overall costs. Additionally, the improved patient outcomes resulting from this integration could decrease the long-term expenses associated with managing chronic conditions.
Potential Impact of the Guidelines
The global impact of these guidelines could be transformative. By simplifying the diagnostic process and expanding treatment access, the WHO aims to significantly increase the rate of early HBV diagnoses. This method aims to improve health outcomes for people living with HBV, reducing liver cancer, cirrhosis, and other disease-related complications. Additionally, preventing HBV progression to severe liver diseases could substantially lessen the economic burden on global healthcare systems. This aligns with the WHO's goal of eliminating HBV as a public health threat by 2030. Experts anticipate:
Increased Diagnosis and Treatment: Expanded eligibility and easier testing could lead to more HBV diagnoses and access to lifesaving antiviral therapy.
Improved Health Outcomes: Earlier intervention and broader treatment may reduce rates of liver cancer, cirrhosis, and HBV-related deaths.
Reduced Healthcare Costs: Preventing long-term HBV consequences could alleviate strains on healthcare systems and lower economic burdens.
Considerations for the United States
The WHO's new Hepatitis B guidelines could have significant implications for U.S. healthcare policy. Domestic adoption could improve HBV management in the U.S. and demonstrate the country's commitment to global health initiatives. While the WHO guidelines provide a global framework, their implementation in the U.S. requires policy-level action. Advocates could focus on:
Streamlining Screening Programs: Encouraging community-based testing and simplifying recommendations could raise diagnosis rates, particularly in underserved populations.
Expanding Access to Treatment: Prioritizing the removal of insurance-based barriers and addressing treatment access disparities.
Implementing Supportive Care Models: Exploring strategies like peer support programs to improve patient adherence and ensure everyone benefits from treatment.
Aligning with the WHO's Hepatitis B guidelines requires substantial shifts in U.S. public health policy. This includes integrating streamlined testing protocols into existing healthcare frameworks for more accessible diagnostic services. Expanding treatment eligibility may require revising healthcare policies to include a broader range of HBV-affected populations. This could mean changes in insurance coverage and healthcare provider guidelines to implement broader treatment protocols.
The U.S. can lead global efforts in adopting these guidelines through its role in global health initiatives. By advocating for and implementing these guidelines, the U.S. can demonstrate the effectiveness of simplified and accessible HBV care, encouraging other nations to follow. This leadership role can include providing technical support, sharing best practices, and offering financial assistance to resource-limited countries, thereby enhancing global health security and moving closer to eliminating HBV as a public health threat by 2030. Researchers have estimated that $6 billion annually is needed to meet the global hepatitis targets in 67 low- and middle-income countries alone.
The WHO's revised guidelines for Hepatitis B management represents a significant step towards addressing this global health challenge. They provide a plan for simple, accessible, and effective HBV care, with a focus on early diagnosis and expanded treatment eligibility to enhance patient outcomes and reduce transmission.
A Different Booster: HBV Vaccines among PLWHA
Because of the shared transmission vectors between HIV and Hepatitis B (HBV), the rate of co-infection is about 10% in the United States, according to the Centers for Disease Control and Prevention (CDC). As a result, people living with HIV (PLWHA) are more likely to experience adverse health impacts including cirrhosis and certain types of liver cancers. A small study conducted in Chile took a look at the recommended HBV vaccine schedule among adults living with HIV and HBV antibody uptake and potentially finding cause for a “high dose” fourth shot to be added into the series for PLWHA.
A giant asterisk belongs on the study’s findings, labeled “deserves further study consideration”. Despite being double-blinded, the study’s greatest weakness included participant pool size (right around 100 participants) and clinical selection criteria (which remains an issue in clinical trial work, generally speaking). In order to be considered for the study, participants generally had to present with an undetectable HIV viral load and no other comorbidities, ruling out application of the resulting data to most PLWHA and especially most long-term survivors or people experiencing barriers to care or medication adherence concerns – or those most likely to be impacted by HIV and HBV co-infection.
The study sought to examine the need for revaccination among PLWHA. Of note, the CDC’s “Pink Book” on HBV does not recommend “boosters” unless a particular “low” threshold of HBV antibodies is met, nor does the publication recommend for routinized serological testing among people who have previously received a vaccine. Therein lies a program and policy problem. We’ll get to that in a moment.
As a result of selection bias favoring those with more ideal circumstances, few participants dropped out of the trial. The study itself found that a fourth and “stronger” dose of vaccine improved antibody responses among people with “well controlled” HIV with an improved HBV antibody response from 50.9% in the low-dose arm of the study to 72% among the high-dose arm of the trial. After a one-year follow up, 80% of participants of the high-dose arm still had sufficient antibody titers, whereas only 39% of the standard-dose arm still had sufficient antibodies for protection.
While Ryan White and CDC funded clinical care programs for PLWHA require HBV monitoring and vaccination efforts as part of their grant funding, few entities necessarily do and almost no private providers do. Federally-funded providers may screen upon intake or initial labs but maintenance screening is not a priority in terms of clinical data collected on a given patient. Even on-site audits from these funders can sometimes look like reviewing particular case files and discussing details but the HBV conversation is not pressing. Rather, a review of intake data can suffice depending on the clinical auditor/consultant (site-visits and audits are often conducted under the supervision of the funding agency but only actually audited by consultants, including staff from other funded clinics).
Public funders aiming to end HBV and the unjust circumstances in which PLWHA are not educated by their providers on the other risks to their health should shift some focus to emphasize the need for preventative care – especially vaccines. Provider education for these publicly funded clinics should include the need to routinize HBV antibody monitoring not just as a concern on behavioral risk factors continuing in a client’s life but because HBV immunity is clearly not necessarily a given, regardless of prior vaccination history.
While the study suggests the need for investigating further, with regard to efficacy of HBV vaccines among PLWHA, the larger question - given the nation-wide rush for another vaccine (and boosters) - creating more robust standards of care among a population known to have immunological “memory-loss” due to the particular cells “attacked” by HIV seems to be in order. Part and parcel to that is tying this level of necessary education to funding and licensure could improve the quality of care PLWHA receive, especially those of low-income and otherwise marginalized identities.
Rising Morbidity: Viral Hepatitis Co-Infection with HIV and Age All Associated with Increased Rates of Liver Cancer
In February, researchers associated with numerous universities across Canada and the United States published one of the most comprehensive data reviews thus far conducted on the incidence rates of the most common type of liver cancer among people living with HIV/AIDS (PLWHA) and PLWHA co-infected with viral hepatitis. The study reviewed data collected as part of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), conducted between 1996 and 2015, with clinical data from 109,283 participants. Conclusions from the study were fairly straight-forward: the combination of HIV status (mono-infection), co-infection with viral hepatitis (HBV and/or HCV) and age all correlated with an increased chance of developing liver cancer (hepatocellular carcinoma [HCC]). The hope of researchers, as evidenced in the study’s introduction was to “inform expectations for other regions with a substantial burden of HIV and HBV-HCV coinfection but with delayed cART [combination antiretroviral therapy] scale-up and limited access to viral hepatitis treatment”.
While most research papers wait to include study limitations at the end, I prefer to open with them as prefacing allows for contextualizing data. The first and primary limitation on the review is clinical information reviewed was necessarily from those people linked to care and correlations provided by the data in the study cannot be applied to the diagnosed-but-not-in-care or undiagnosed population. Second, researchers note, information on relevant, individual health factors were missing from significant portions of participants data (example: smoking and drinking habits, natural clearance of HCV, fibrosis score, and HIV exposure risk). Additionally, data collection was not uniform across all participating entities at the time of linkage to care, though a quality analysis was used to help even things out and ensure the integrity of data comparisons. This lack of uniform protocol also included certain sites not administering or participants not receiving HCV or HBV screening. The last, though likely most significant limitation of the study is the data were collected prior to the advent of curative direct acting agents (DAAs) for HCV, and conclusions cannot be made on the potential positive impacts of readily available DAAs.
A limitation not mentioned and data unassessed is any reference between older ART regimens and newer ones, in which toxicity and tolerability is commonly known to be considerably improved with newer regimens. Liver health monitoring is fairly standard, among other relevant patient labs, for PLWHA because of a relationship between ART and liver health. While it’s understandable researchers who generally enjoy significant funding from manufacturers may wish to avoid broaching this topic, not mentioning the issue, even to say “we can’t make any conclusions on cART tolerability and toxicity as an indicator for adherence or risk of developing HCC” misses an incredibly important elephant in the room for researchers, providers, and patients alike.
Instead, researchers chose to focus on cART “eras” (1996-2000 [A], 2001-2005[B], and 2006-2015[C]), in which there’s a positive correlation between age and era; or those aging with HIV were more likely to be diagnosed with HCC. Highest rates of HCC diagnosis by cART area are as follows: A – between 50 and 60 years-old (HBV co-infection with HIV), B – lower end 70-80 (HCV co-infection with HIV), and C – upper end 70-80 (HCV and HBV co-infection with HIV). This data is particularly valuable on its own, however, as the associated risk cohort shift appears to be very closely related to age (ie. those in the upper end of the C “era” are also those to first receive effective cART and the 20-year age gap between the C and A cART eras).
Ultimately, PLWHA were more than 3 times as likely as the general population to develop HCC and more than 20 times more likely to develop HCC if co-infected with viral hepatitis. HCC incidence among study participants fell along rather predictable lines in terms of HIV related clinical monitoring metrics; those with higher viral loads and lower CD4 counts were more likely to develop HCC.
The study’s finding highlight the need for ensuring access to DAAs and HBV vaccines, ready ART uptake upon linkage to care, and strengthening the integrity of AIDS Drug Assistance Programs, Medicaid Programs, and care provided to incarcerated persons – specifically, ensuring the inclusion of coverage of DAAs in these.
Advocates, providers, and patients can review DAA coverage inclusion in ADAPs and Medicaid and harm reduction policies impacting HIV and HCV with Community Access National Network’s quarterly HIV-HCV Co-Infection Watch report.
Ongoing Viral Hepatitis Outbreaks: Systemic Interventions
Viral Hepatitis outbreaks, namely Hepatitis A and Hepatitis B, have been in the news quite a bit during the last year. Could COVID-19 have contributed to them?
Annual surveillance data for the state of Florida found the 2017 Hepatitis A outbreak has shifted location from primarily South Florida to the Pensacola area, in Escambia County. Florida isn’t alone with persistent Hepatitis A outbreaks. According to the CDC’s Hepatitis A outbreak dashboard, as of February 5, 2021, almost 40,000 cases of Hepatitis A have been confirmed related to the outbreak beginning in 2017, with more than 25 states still in an active outbreak status. Florida, Indiana, Kentucky, Ohio, Tennessee, and West Virginia top the list for the most cases reported since the outbreak began.
These outbreaks are primarily attributed to an increase in homeless populations and populations experiencing housing instability and lack of access to sanitary conditions. Hepatitis A is primarily transmitted in close-contact settings by way of ingesting blood or stool particles from a person carrying the disease. While the disease is not always deadly, it can be. Indeed, the 2017 multi-state outbreak has resulted in at least 354 deaths, according to the CDC.
Additionally, in late 2020, Vermont reported outbreaks of Hepatitis A and B, with Vermont Health Commissioner, Dr. Mark levin, said the state had been anticipating an eventual outbreak because of existing outbreaks in New Hampshire and Massachusetts. Hepatitis B, much like Hepatitis C, is often attributed to injection drug use, long-term health care settings, and contact with bodily fluids containing the virus, including blood and semen.
In response to these outbreaks, the CDC has encouraged states to engage in more active community education and vaccination programs. Both Hepatitis A and Hepatitis B are preventable and post-exposure vaccine administration may be appropriate in some situations. However, as the COVID-19 pandemic has reminded us, other interventions are necessary to address both risk factors to infectious diseases and reduce barriers to care. Addressing the nation’s housing and homelessness crisis could potentially provide one, extraordinarily significant structural intervention to address these and other public health crises.
President Joe Biden made campaign promises relating to need for more equitable housing policies and expanding affordable housing to address social justice needs as well as health-related needs and is already working to establish a fairer housing environment for the country. From extending the eviction moratorium to ensuring housing protections are extended to all Americans regardless of sexual identity or gender orientation (a reversal of the previous Administration’s policies), first steps are already being laid in order to meet well-known housing needs. And none too soon, as we don’t yet have a full picture of exactly how the COVID-19 caused economic recession will impact rates of homelessness, but one study issued a rather dire warning last month, saying this recession would likely cause double the rate of homelessness than the 2008 crisis.
From Hepatitis A and B to COVID-19 and the Opioid Crisis, housing has become (always was) a preeminent intervention that remains largely inadequately addressed. Federal funding and state programming must move to invest in housing as a prevention strategy in order to get ahead of these outbreaks and stop the chains of transmission. Housing is not just a human necessity; it is a public health necessity and must be embraced with the vigor the moment demands.
For the most up-to-date information from the National ADAP Working Group (NAWG), Hepatitis Advocacy, Education, and Leadership blog, and the quarterly HIV-HCV Co-infection Watch Report, sign up for our listserv here.