Implementing Adult Hepatitis B Immunization and Screening Using Electronic Health Records: A Practical Guide.

IMPORTANCE: Hepatitis B is a serious problem in the United States (US), with up to 2.4 million Americans living with a chronic infection. Only 26-32% of people living with hepatitis B in the US are diagnosed. Additionally, just 30% of all adults are vaccinated against the virus. In 2022, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) updated adult hepatitis B vaccination recommendations to include all adults aged 19-59 years and those 60 years and older with risk factors for hepatitis B. Subsequently, in 2023, the CDC recommended that all adults be screened at least one time in their lives. OBSERVATIONS: Electronic health record (EHR) tools (prompts, order sets, etc.) have proven to be an effective method of increasing hepatitis B screening and vaccination, but longstanding challenges and questions around hepatitis B vaccines and tests could prevent effectual EHR implementation. As the new recommendations directly impact providers who may have limited familiarity with hepatitis B, guidance on how to identify eligible patients and triggers, order sets to facilitate vaccine/test selection, and proper documentation and patient follow-up is necessary. CONCLUSIONS AND RELEVANCE: This communication offers a practical framework for health systems to build an effective EHR strategy for the updated adult hepatitis B recommendations. We also provide comprehensive responses to clinicians' questions that are frequently asked prior to screening or vaccinating for hepatitis B.

It Is Time for a Simplified Approach to Hepatitis B Elimination.

Background and Aims: Hepatitis B virus (HBV) infection continues to threaten millions of lives across the globe, despite universal vaccination efforts. Current guidelines for screening, vaccination, and treatment are complex and have left too many people undiagnosed or improperly managed. Antiviral therapy has been shown to significantly reduce the incidence of liver-related complications, including liver cancer. However, the complexity of existing guidelines can make it difficult to identify which patients to target for treatment, and recommendations that are difficult to implement in real-world settings pose a barrier to eligible patients to receive therapy and contribute to health disparities in HBV care. The goal of this global expert panel was to gain consensus on a streamlined approach to HBV care to facilitate implementation of HBV intervention and treatment, especially in the primary care setting. Methods: A group of 8 liver and infectious disease specialists attended a meeting in January 2021 with the objective of gaining consensus on a streamlined algorithm for HBV care that would encourage implementation of HBV intervention and treatment. Results: We have created a comprehensive perspective highlighting screening optimization, diagnostic workup, treatment, and monitoring. This treatment algorithm is designed to provide a streamlined visual pathway for risk stratification and management of patients with HBV that can be adapted in various care settings. Conclusion: Simplification of guidelines will be critical to achieving health equity to address this public health threat and achieve HBV elimination.

The Current Status of US and Global Access to Direct-Acting Antiviral Regimens for Hepatitis C Virus Infection.

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Localized US Efforts to Eliminate Hepatitis C.

The United States has national plans for the elimination of hepatitis C virus but much of US health care is organized on the state level and requires local solutions. This article describes the plans developed by New York, Massachusetts, and the city/county of San Francisco for hepatitis C virus elimination. Coalitions capitalize on existing resources and advocate for new resources to address barriers in hepatitis C virus care. Although each coalition has distinct plans, all share a commitment to groups that are disproportionately affected and are at risk for being excluded from advances in hepatitis C virus treatment and cure.

Price and affordability of direct-acting antiviral regimens for hepatitis C virus in the United States.

Hepatitis C virus is a serious infection causing cirrhosis, liver cancer, and death. The recent development of direct-acting antivirals has dramatically improved tolerability of treatment and rates of cure. However, the high price of these medications has often limited access to care and resulted in rationing of medications in the United States to those with advanced liver disease, access to specialist care, and without active substance use. This review assesses the way pharmaceutical prices are established and how pricing of directly acting antiviral regimens in the United States has impacted access to treatment for hepatitis C virus.

Access to New Medications for Hepatitis C for Medicaid Members: A Retrospective Cohort Study.

BACKGROUND: Sofosbuvir (SOF)- or simeprevir (SIM)-containing regimens are highly effective for treating chronic hepatitis C virus (HCV) infection. These regimens, however, are expensive. Most payers have implemented prior authorization (PA) requirements to ensure that patients who can benefit most have priority for these medications. While many Medicaid programs limit access to those with advanced disease or to members who do not have active substance use disorder (SUD), the Massachusetts Medicaid (MassHealth) Primary Care Clinician (PCC) plan does not limit access based on disease severity or presence of SUD. Evaluating PA requests for SOF and/or SIM among MassHealth members will offer a useful example of early uptake among Medicaid members and will identify patient groups who might face barriers to treatment at the provider or patient level. OBJECTIVES: To (a) evaluate the percentage of MassHealth PCC members with HCV who had a PA request, along with the percentage of requests approved, and (b) identify characteristics associated with PA requests for SOF or SIM among Massachusetts Medicaid (MassHealth) members with HCV. METHODS: This retrospective cohort study used enrollment, medical claims, and PA request data from MassHealth PCC members from December 6, 2012, to July 31, 2014. The sample included members with 1 or more claims with an ICD-9-CM code for HCV during this time who were continuously enrolled from December 6, 2013, to July 31, 2014. Enrollment and medical claims data for the cohort with HCV were linked to a database containing information collected from PA requests. The overall percentage of members with HCV and a PA request for SOF and/or SIM between December 6, 2013, and July 31, 2014, and the percentage of requests approved were calculated. Chi-square statistics were used to compare demographic and clinical characteristics among members with HCV who did and did not have a request. Logistic regression was used to estimate the strength of associations between patient characteristics and a PA treatment request, adjusting for clinical and demographic variables. RESULTS: Of 6,849 members identified with HCV, 346 (5.1%) had a PA request for SOF and/or SIM submitted to MassHealth. Compared with members with HCV who did not have a PA request for SOF or SIM, those with a PA request for these new treatments were more likely to be male (P = 0.01), older (P < 0.001), white race (P = 0.04), have standard MassHealth insurance (P = 0.01), and less likely to be homeless (P < 0.001). Members with a PA request were also more likely to have been treated for HCV in the past year and have advanced disease (hepatic decompensation, cirrhosis, or liver transplant) but less likely to have SUD (P < 0.001 for each). Ninety percent of requests for SOF or SIM were approved; few demographic or clinical characteristics were associated with approval. In adjusted analyses, predictors of PA request were aged 50-64 years (odds ratio (OR) = 2.0, 95% CI = 1.1-3.7 vs. aged < 30 years); hepatic decompensation (OR = 1.6, 95% CI = 1.2-2.3); cirrhosis (OR = 3.0, 95% CI = 2.2-4.1); liver transplant (OR = 3.0, 95% CI = 1.4-6.5); substance use (OR = 0.6, 95% CI = 0.5-0.8); recent HCV treatment (OR = 1.6, 95% CI = 1.0-2.6); comorbidity (OR = 0.95, 95% CI = 0.91-0.98) for 1-unit increase in Diagnostic Cost Group score; and care at a hospital outpatient department (OR = 2.0, 95% CI = 1.2-3.2 vs. group practice). CONCLUSIONS: Antiviral treatment with SOF and/or SIM was requested for a relatively small proportion of MassHealth members with HCV, with nearly all approved. Prescriber prioritization or patient barriers to care, rather than the PA process, determined access to treatment in this Medicaid population. Support may be needed to ensure patients with SUD benefit from advances in HCV treatment. DISCLOSURES: No outside funding supported this research. Internal funding was provided by the Commonwealth of Massachusetts. Lavitas has received compensation from University of Tennessee Advanced Studies in Medicine for development of CPE activity. Graham has consulted for the National Viral Hepatitis Roundtable and the Department of Health and Human Services, has received payment from Medscape for CME development, and is employed by Trek Therapeutics. Jeffrey has received payment for guest lectures at Boston University and Harvard University. Study concept and design were primarily contributed by Clark and Clements, along with Graham, Lenz, and Jeffrey. Kunte collected the data, which were interpreted by Graham, Lenz, and Jeffrey, with assistance from Lavitas, Clark, and Clements. The manuscript was written primarily by Clements, along with O'Connell and assisted by Graham, and revised by all the authors.

A path to eradication of hepatitis C in low- and middle-income countries.

We are entering a new era in the treatment of hepatitis C virus (HCV) infection and almost all patient groups in high-income countries have the potential to be cured with all-oral, highly potent combinations of direct-acting antiviral drugs. Soon the main barrier to curing hepatitis C, even in wealthy countries, will be the high price of these all-oral regimens. The gulf between the advances in HCV drug development and access to treatment for individual patients will be even greater in low- and middle-income countries (LMIC) where 80% of the global burden of HCV infection and mortality exists. Ensuring that people in LMIC have access to regimens against HCV will require a similar level of advocacy and public-private partnerships as has transformed the control of other global diseases such as HIV. Numerous challenges will need to be overcome. These include improving low-cost diagnostic tests, especially in sub-Saharan Africa where the false-positive rate is unacceptably high, reducing iatrogenic spread of HCV, addressing transmission among people who inject drugs (PWID), and ensuring affordable access to antiviral treatment for all people living with HCV infection in LMIC. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication."

Impact of hepatitis C virus on HIV response to antiretroviral therapy in Nigeria.

The effect of hepatitis C virus (HCV) on antiretroviral therapy (ART) response in patients in sub-Saharan Africa is unknown. We studied 1431 HIV-infected ART initiators in Jos, Nigeria, of whom 6% were HCV coinfected. A similar proportion of HIV/HCV-coinfected and HIV-monoinfected patients achieved HIV RNA <400 copies per milliliter after 24 and 48 weeks of ART (P > 0.05). Hepatotoxicity was uncommon (0.8% and 0.33% at 24 and 48 weeks, respectively) but was more common in the HIV/HCV-coinfected group at 24 (adjusted odds ratio = 19.3; 95% confidence interval: 4.41 to 84.4) and 48 weeks (adjusted odds ratio = 56.7; 95% confidence interval: 5.03 to 636.92). HCV did not significantly impact ART response in this Nigerian cohort.

Comparison of current US risk strategy to screen for hepatitis C virus with a hypothetical targeted birth cohort strategy.

OBJECTIVES: We compared the theoretical performance of a 1-time, birth cohort strategy with the currently recommended risk strategy for screening for hepatitis C virus (HCV) infection, which is undetected in an estimated 75% of 4 million affected people in the United States. METHODS: We applied current American Association for the Study of Liver Disease risk screening guidelines and a targeted birth cohort strategy to National Health and Nutrition Examination Survey data from 2003 to 2006 to estimate their performance in identifying HCV cases. RESULTS: Risk guidelines would recommend testing 25% of the US population aged 20 years or older and, if fully implemented, identify 82% of the projected HCV-exposed population. A targeted birth cohort (1946-1964) strategy would test 45% of the same population and identify 76% of the projected HCV population. CONCLUSIONS: In this ideal-world simulation, birth year and risk screening had similar theoretical performances for predicting HCV infection. However, actual implementation of risk screening has not achieved its theoretical performance, and birth cohort screening might increase HCV testing rates.

Noninvasive markers of liver fibrosis are highly predictive of liver-related death in a cohort of HCV-infected individuals with and without HIV infection.

OBJECTIVES: Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality. METHODS: We assessed the ability of two indices of liver fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child-Pugh-Turcotte (CPT) and model of end-stage liver disease (MELD) scores. RESULTS: A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86-0.96), CPT 0.91 (0.79-0.96), APRI 0.88 (0.80-0.93), Fib-4 0.87 (0.77-0.92), MELD 0.84 (71-0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT. CONCLUSION: Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD.

Predictors of treatment for hepatitis C virus (HCV) infection in drug users.

Documented treatment rates for Hepatitis C virus (HCV) infection are low. Within this cohort of HCV-infected patients (N = 373), participants who were not actively injecting drugs or not co-infected with HIV were most likely to initiate HCV treatment. Persons of white race and HIV-infected participants with a CD4 count above 200 were also more likely to have initiated HCV treatment. We defined five factors as potentially modifiable, and found almost all (90%) of the cohort had at least one such factor. Participants with more than one of these factors were least likely to initiate treatment. The proportion of patients receiving treatment increased as their number of modifiable risk factors decreased (p < 0.01, for trend). Focused strategies to overcome these potentially modifiable factors may be indicated to increase HCV treatment in affected populations.

Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor beta that can suppress HCV-specific T-cell responses.

Hepatitis C virus (HCV)-specific T-cell responses are rarely detected in peripheral blood, especially in the presence of human immunodeficiency virus (HIV) coinfection. Based on recent evidence that T-regulatory cells may be increased in chronic HCV, we hypothesized that functional blockade of regulatory cells could raise HCV-specific responses and might be differentially regulated in the setting of HIV coinfection. Three groups of subjects were studied: HCV monoinfected, HCV-HIV coinfected, and healthy controls. Frequencies of peripheral T cells specific for peptides derived from HCV core, HIV type 1 p24, and recall antigens were analyzed by gamma interferon (IFN-gamma) enzyme-linked immuno-spot assay. HCV-specific T-cell responses were very weak in groups with HCV and HCV-HIV infections. Addition of blocking antibodies against transforming growth factor beta1 (TGF-beta1), -2, and -3 and interleukin-10 specifically increased the HCV-specific T-cell responses in both infected groups; however, this increase was attenuated in the group with HCV-HIV coinfection compared to HCV infection alone. No increase in recall antigen- or HIV-specific responses was observed. Flow cytometric sorter analysis demonstrated that regulatory-associated cytokines were produced by HCV-specific CD3(+)CD8(+)CD25(-) cells. Enhancement of the IFN-gamma effect was observed for both CD4 and CD8 T cells and was mediated primarily by TGF-beta1, -2, and -3 neutralization. In conclusion, blockade of TGF-beta secretion could enhance peripheral HCV-specific T-cell responses even in the presence of HIV coinfection.