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Hepatitis B: A Review

Author/s: 
Wen-Juei Jeng, Terry Cheuk-Fung Yip, Anna S. Lok

Importance: Hepatitis B virus (HBV) infection affects an estimated 254 million people worldwide and causes approximately 1.1 million deaths annually. In 2022, there were approximately 1.2 million new HBV infections worldwide and 14 000 in the US.

Observations: HBV is a DNA virus transmitted through percutaneous or mucosal exposure to infected blood, semen, or body fluids. Mother-to-child transmission, which is the principal cause of chronic HBV infection globally, occurs in 70% to 90% of infants born to mothers who are hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive and in 5% to 20% of those born to HBsAg-positive/HBeAg-negative mothers. However, HBV vaccination and administration of hepatitis B immune globulin within 12 to 24 hours of birth prevent approximately 94% of perinatal infections, and adding antiviral therapy in pregnant women with high HBV DNA reduces transmission to less than 1%. Although universal birth-dose HBV vaccination is the most effective strategy for eliminating HBV infection, global birth-dose HBV vaccine coverage was only 45% in 2024. The risk of developing chronic infection (HBsAg positive for more than 6 months) is 90% if HBV infection occurs during infancy, 30% in children aged 1 to 5 years, and less than or equal to 5% in immunocompetent adolescents and adults. HBV infection is diagnosed by serologic testing: HBsAg indicates ongoing infection, antibody to HBsAg indicates immunity, and antibody to hepatitis B core antigen indicates ongoing or past infection. Serum HBV DNA levels quantify virus-replication activity. Assessment of liver inflammation and fibrosis with alanine aminotransferase (ALT) and noninvasive tests such as Fibrosis-4 index and liver elastography guide treatment decisions. Chronic HBV infection may progress to cirrhosis and hepatocellular carcinoma (HCC); the 5-year cumulative risk of cirrhosis is 8% to 15% in untreated chronic HBV infection, and annual HCC incidence is 3% to 5% among patients with cirrhosis. Antiviral therapies-pegylated interferon alfa and nucleos(t)ide analogues (entecavir or tenofovir)-suppress HBV DNA replication and reduce the risk of HCC by approximately 50%. Antiviral treatment is recommended for all patients with chronic HBV and cirrhosis and for those without cirrhosis who have high HBV DNA with elevated ALT or significant inflammation/fibrosis. Patients at high risk of HCC should undergo surveillance with ultrasonography and alpha-fetoprotein testing every 6 months.

Conclusions and relevance: HBV infection causes approximately 1.1 million deaths annually worldwide. Universal HBV vaccination, particularly birth-dose administration, is the most effective strategy to prevent HBV infection. Among patients with HBV infection, antiviral therapy decreases progression to cirrhosis and liver failure and reduces the risk of HCC.

Keywords 
hepatitis hepatitis B Hepatitis B Core Antigens Hepatitis B Surface Antigens Antiviral Agents Liver Failure vaccination

Preexposure Prophylaxis (PrEP) for HIV

Author/s: 
Matthew A Spinelli, Kenneth Ngure, Monica Gandhi

Preexposure prophylaxis (PrEP) involves use of antiviral medication for HIV prevention in HIV-negative adults or adolescents at risk for HIV through sex or injection drug use. The United Nations Programme on HIV/AIDS (UNAIDS) recently set a goal for 95% of people at risk of HIV (approximately 10 million people worldwide) to have access to and use PrEP in 2025, although only 3.5 million individuals at risk of HIV were receiving PrEP as of 2023. The UNAIDS 2024 global AIDS update reported no decrease in HIV incidence since 2021, with an estimated 1.3 million new infections reported globally in 2023.

Keywords 
prophylaxis Anti-HIV Agents HIV

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

Author/s: 
Gregory A., Ovsyannikova , Inna G., Kennedy, Richard B.

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies. A mere 11 months ago, the canvas we call COVID-19 was blank. Scientists around the world have worked collaboratively to fill in this blank canvas. In this Review, we discuss what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 and relate this knowledge to the COVID-19 vaccines currently in phase 3 clinical trials.

Keywords 
COVID-19 SARS-CoV-2 COVID-19 vaccine Immunity

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial

Author/s: 
Butler, CC, van der Velden, AW, Bongard, E, Saville, BR, Holmes, J, Coenen, S, Cook, J, Francis, NA, Lewis, RJ, Godycki-Cwirko, M, Llor, C, Chlabicz, S, Lionis, C, Seifert, B, Sundvall, PD, Colliers, A, Aabenhus, R, Bjerrum, L, Jonassen Harbin, N, Lindbæk M, Glinz, D, Bucher, HC, Kovacs, B, Radzeviciene Jurgute, R, Touboul Lundgren, P, Little, P, Murphy, AW, De Sutter, A, Openshaw, P, de Jong, MD, Connor, JT, Matheeussen, V, Ieven, M, Goossens, H, Verheij, TJ

BACKGROUND:

Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups.

METHODS:

We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921.

FINDINGS:

Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group.

INTERPRETATION:

Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner.

FUNDING:

European Commission's Seventh Framework Programme.

Keywords 
influenza flu Tamiful oseltamivir
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