Hepatitis B virus DNA integration: Implications for diagnostics, therapy, and outcome

Journal of Hepatology, Год журнала: 2024, Номер 81(6), С. 1087 - 1099

Опубликована: Июль 5, 2024

HBV DNA integration originally recognized as a non-functional byproduct of the life cycle has now been accepted significant contributor to pathogenesis and HDV persistence. Integrated is derived from linear genomic present in virus particles or produced aberrantly processed relaxed circular following an infection, can drive expression HBsAg HBx. events accumulate over course viral infection ranging few percent during early phases nearly 100 infected cells after prolonged chronic infection. have primarily investigated context HCC development where they activate known oncogenes other growth promoting genes, cause chromosomal instability presumably epigenetic alterations tumor growth. More recent evidence suggests that integrated might contribute by attenuating immune response. provides source for envelope proteins required replication hence represents means Because responsible persistence absence it impacts established criteria resolution which relies on diagnostic marker. useful assessing turnover hepatocytes occurs all hepatitis B including initial phase historically termed tolerant. was also shown impact novel therapies targeting RNAs.

Язык: Английский

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Prospects for Controlling Hepatitis B Globally

Pathogens, Год журнала: 2024, Номер 13(4), С. 291 - 291

Опубликована: Март 29, 2024

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic B, and more than 800,000 patients die each year due to complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage suboptimal. In adults, sexual transmission by far most frequent route of contagion. The WHO estimates that 1.5 new infections occur annually. Oral nucleos(t)ide analogues entecavir tenofovir antivirals prescribed as therapy. Almost adherent medication achieve undetectable plasma viremia beyond 6 months monotherapy. However, less 5% anti-HBs seroconversion, viral rebound occurs following drug discontinuation. Therefore, need be lifelong. New long-acting formulations being developed will maximize treatment benefit overcome adherence barriers. Furthermore, antiviral agents in development, entry inhibitors, capside assembly modulators, RNA interference molecules. use combination therapy pursues a functional cure, meaning it negative both circulating HBV-DNA HBsAg. Even when this goal achieved, cccDNA reservoir within infected hepatocytes remains signal past infection, can reactivate under immune suppression. gene therapies, editing, eagerly pursued silence or definitively disrupt genomes and, way, ultimately cure B. At time, three actions taken push eradication globally: (1) expand universal newborn vaccination; (2) perform once-in-life testing adults identify susceptible persons could vaccinated (or re-vaccinated) unveil asymptomatic carriers treatment; (3) provide earlier carriers, aviremic reduces risk clinical progression transmission.

Язык: Английский

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Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(4), С. 364 - 364

Опубликована: Март 29, 2024

Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury its complications. It has hypothesized that high levels circulating HBV surface antigen(s) may lead immune tolerance against contribute carriership. Conversely, low-level HBsAg create a window reconstitution an HBV-specific response through vaccination control infection. Previous studies non-responders yeast-derived vaccines, using third-generation pre-S/S vaccine, led up 95% anti-HBs seroconversion. This report evaluates long-term outcome after experimental with vaccine intended as therapeutic intervention carriers. Four carriers (<500 IU/mL) were vaccinated three seven times 20 μg PreHevbrioR. Three out four eliminated completely seroconverted anti-HBs. One patient but remained borderline titer (10 IU/mL). Serum following repeated varied between 27 >1000 IU/L, respectively. Long-term observation (>6 years) showed discontinuing NUC at least two years, DNA negative positive titers ranging 80 IU/L. Based on our preliminary observations, there is rationale further evaluate role this agent.

Язык: Английский

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Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection

Viruses, Год журнала: 2024, Номер 16(9), С. 1386 - 1386

Опубликована: Авг. 30, 2024

Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in case B infection and only selected individuals, such reportedly Keith Richards, guitarist The Rolling Stones. present paper provides an updated narrative review research devoted to phenomenon order identify discuss demographic, lifestyle-related, clinical, viral genotype-related, host genetic factors underpinning SC occurrence. body evidence indicates that likelihood is decreased older men, Black people, HIV-coinfected subjects, intravenous drug alcohol users. In turn, HBV coinfection specific polymorphism genes encoding interferon lambda 3 (particularly rs8099917) 4 rs12979860)

Язык: Английский

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AAV-mediated gene therapies by miniature gene editing tools

Science China Life Sciences, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Язык: Английский

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Hepatitis B in Pediatric Population: Observational Retrospective Study in Romania

Life, Год журнала: 2024, Номер 14(3), С. 348 - 348

Опубликована: Март 7, 2024

Hepatitis B virus (HBV) is a frequent cause of chronic hepatitis worldwide, with an estimated 5.6 million children under 5 years being infected. In Romania, there are no available epidemiology reports on large cohorts in children. We aimed to assess the profile pediatric HBV infection southern Romania. conducted observational retrospective study 506 HBV-infected Based alaninaminotransferase (ALT), serology and viremia, we identified four states disease. correlated age, gender, household infection, coinfection other viruses laboratory parameters. Most patients were positive envelope antigen (HBeAg) immune-active state (65.4%). Age at diagnosis was significantly lower for those (p < 0.05). ALT values not different between or negative HBeAg = 0.780). higher D (HDV)-associated 0.001). Children had high viraemia more frequently when compared infected relative (79.3% vs. 67.4%) 0.001), but 0.21). (high ALT, viremia). The percentages HBV- HDV-associated infections high, than reported prevalence Romania general population.

Язык: Английский

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The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Авг. 15, 2024

Abstract The global burden of hepatitis B virus (HBV) infection remains high, with chronic (CHB) patients facing a significantly increased risk developing cirrhosis and hepatocellular carcinoma (HCC). ultimate objective antiviral therapy is to achieve sterilizing cure for HBV. This necessitates the elimination intrahepatic covalently closed circular DNA (cccDNA) complete eradication integrated HBV DNA. review aims summarize oncogenetic role integration significance clearing in cure. It specifically focuses on molecular mechanisms through which leads HCC, including modulation expression proto-oncogenes tumor suppressor genes, induction chromosomal instability, truncated mutant proteins. also highlights impact reducing preventing HBV-related HCC. Additionally, offers insights into future objectives treatment CHB. Current strategies inhibition include mainly therapies, RNA interference gene editing technologies. Overall, deserves further investigation can potentially serve as biomarker CHB

Язык: Английский

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In vivo liver targeted genome editing as therapeutic approach: progresses and challenges

Frontiers in Genome Editing, Год журнала: 2024, Номер 6

Опубликована: Авг. 23, 2024

The liver is an essential organ of the body that performs several vital functions, including metabolism biomolecules, foreign substances, and toxins, production plasma proteins, such as coagulation factors. There are hundreds genetic disorders affecting functions and, for many them, only curative option orthotopic transplantation, which nevertheless entails risks long-term complications. Some peculiar features liver, its large blood flow supply tolerogenic immune environment, make it attractive target in vivo gene therapy approaches. In recent years, genome-editing tools mainly based on clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) system have been successfully exploited context liver-directed preclinical or clinical therapeutic applications. These include knock-out, knock-in, activation, interference, base prime editing Despite achievements, important challenges still need to be addressed broaden applications, optimization delivery methods, improvement efficiency, risk on-target off-target unwanted effects chromosomal rearrangements. this review, we highlight latest progress development liver-targeted genome approaches treatment disorders. We describe technological advancements currently under investigation, overcome applicability, future perspectives technology.

Язык: Английский

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Functional cure of chronic hepatitis B-hope or hype?

World Journal of Hepatology, Год журнала: 2024, Номер 16(9), С. 1199 - 1205

Опубликована: Сен. 23, 2024

Chronic hepatitis B constitutes a substantial disease burden worldwide. The steps advocated by the World Health Organization in 2016 to eradicate 2030 has failed achieve significant progress, especially with respect immunization coverage and linkage care. lack of governmental public awareness regarding long-term implications cause underfunding developmental projects. presently approved treatment modalities have limited efficacy complete viral eradication, hence need for newer molecules functional cure (sustained undetectable surface antigen (HBsAg) virus DNA peripheral blood after finite period therapy). However, preliminary results from trials novel therapies show their inadequacy this end themselves but better performance low baseline serum HBsAg nucleos(t)ide analogues (NA) which be combined with/without pegylated interferon as an immunomodulator. Such therapy is cost adverse events incremental benefit over standard care (long-term NA therapy) drug toxicities, making development process tenuous. Thus, while such continue tested, strategies should still focus on prevention transmission non-pharmaceutical measures, vaccination increasing

Язык: Английский

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Advanced siRNA delivery in combating hepatitis B virus: mechanistic insights and recent updates

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 30, 2024

Hepatitis B virus (HBV) infection is a major health problem, causing thousands of deaths each year worldwide. Although current medications can often inhibit viral replication and reduce the risk liver carcinoma, several obstacles still hinder their effectiveness. These include resistance, prolonged treatment duration, low efficacy in clearing antigens. To address these challenges HBV treatment, numerous approaches have been developed with remarkable success. Among strategies, small-interfering RNA (siRNA) stands out as one most promising therapies for hepatitis B. However, naked siRNAs are vulnerable to enzymatic digestion, easily eliminated by renal filtration, unable cross cell membrane due large, anionic structure. Therefore, effective delivery systems required protect maintain functionality. In this review, we discussed promises siRNA therapy treating HBV, milestones systems, products that entered clinical trials. Finally, outlined future perspectives siRNA-based treatment.

Язык: Английский

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