Treatment Of CHB Research Articles

Lymph node-targeted STING agonist nanovaccine against chronic HBV infection

Chronic hepatitis B virus (HBV) infection is a global health problem that substantially increases the risk of developing liver disease. The development of a novel strategy to induce anti-HB seroconversion and achieve a long-lasting immune response against chronic HBV infection remains challenging. Here, we found that chronic HBV infection affected the signaling pathway involved in STING-mediated induction of host immune responses in dendritic cells (DCs) and then generated a lymph node-targeted nanovaccine that co-delivered hepatitis B surface antigen (HBsAg) and cyclic diguanylate monophosphate (c-di-GMP) (named the PP-SG nanovaccine). The feasibility and efficiency of the PP-SG nanovaccine for CHB treatment were evaluated in HBV-carrier mice. Serum samples were analyzed for HBsAg, anti-HBs, HBV DNA, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg, accompanied by an analysis of HBV-specific cellular and humoral immune responses during PP-SG nanovaccine treatment. The PP-SG nanovaccine increased antigen phagocytosis and DC maturation, efficiently and safely eliminated HBV, achieved a long-lasting immune response against HBV reinjection, and disrupted chronic HBV infection-induced immune tolerance, as characterized by the generation and multifunctionality of HBV-specific CD8+ T and CD4+ T cells and the downregulation of immune checkpoint molecules. HBV-carrier mice immunized with the PP-SG nanovaccine achieved partial anti-HBs seroconversion. The PP-SG nanovaccine can induce sufficient and persistent viral suppression and achieve anti-HBs seroconversion, rendering it a promising vaccine candidate for clinical chronic hepatitis B therapy.

Point-of-care ultrasound to inform antiviral treatment initiation in chronic hepatitis B virus infection in low-resource settings – the PUSH protocol

BackgroundChronic Hepatitis B (CHB) is prevalent worldwide and most related deaths occur in low-resource settings. Antiviral treatment of CHB is indicated in those with significant liver disease and markers of viral replication. However, recommended diagnostics such as elastography (a non-invasive imaging measure of fibrosis/cirrhosis) or HBV viral load are often lacking in these settings, which creates barriers to treatment. Point-of-care clinical B-mode ultrasound (US) has potential to overcome implementation barriers in HBV care programs in low-resource settings.MethodsWe describe a Point-of-care US protocol for Hepatitis (“PUSH”) to check for signs of cirrhosis and hepatocellular carcinoma in the liver of people with CHB. We performed a prospective observational study applying the protocol, first by trainee clinicians and then by trainers, in consecutive patients referred to our clinic for CHB treatment eligibility assessment. All patients additionally underwent physical examination, liver function tests (LFTs) and platelet counts. We describe the PUSH training approach and performance of the protocol.ResultsFour clinicians and 111 adult patients with HBV infection were included in the development of PUSH. Using US, liver complications of HBV were documented in 31 (27.9%) patients; including cirrhosis in 15 patients, HCC with cirrhosis in 13, and HCC without cirrhosis in 3. Patients with sonographic findings had significantly more clinical symptoms also their LFTs were higher and more frequently indicative for HBV treatment. Of 28 patients with sonographic diagnosis of cirrhosis, 23 (82.1%) showed a nodular liver surface, 24 (85.7%) a coarse echotexture, 20 (71.4%) scarce vessels, and 9 (32.1%) an enlarged caudate lobe. Overall concordance of the findings between assessment of trainees and experienced sonographers was high, ranging from 90 to 95%; trainees were not blinded to clinical and laboratory findings.ConclusionUltrasound can facilitate same-day initiation of antiviral therapy for chronic HBV monoinfection in a resource-limited setting and a streamlined protocol-driven liver ultrasound can be feasibly used by front line clinicians managing HBV.

The co-existence of NAFLD and CHB is associated with suboptimal viral and biochemical response to CHB antiviral therapy: a systematic review and meta-analysis

Background and aimsChronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are leading causes of liver-related morbidity and mortality. The interaction between these two disease processes is poorly defined and the impact of NAFLD on HBV-related cirrhosis and HCC remains unclear. The aim of this study was to evaluate the impact of NAFLD on response to antiviral CHB therapy to inform the debate on changing CHB treatment thresholds for these comorbid patients.MethodsStudies with a minimum of 50 adult CHB patients on nucleoside analogue therapy with or without concurrent NAFLD were identified from PubMed/Medline and EMBASE to February 21, 2023. Data extraction from each study included HBeAg and treatment status, diagnostic method of NAFLD, frequency of monitoring intervals, patient age, gender, grade of hepatic steatosis, BMI and metabolic comorbidities. The outcomes of interest, complete virological response (CVR), biochemical response (BR) and HBeAg loss/seroconversion, were recorded at each available monitoring interval. Comparing CHB-NAFLD and CHB-only groups, pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using random- or fixed-effects models depending on heterogeneity.ResultsFrom a search of 470 citations, we identified 32 potentially relevant papers. Overall, 11 studies, comprising 2580 unique patients, met the inclusion criteria of the meta-analysis. CHB-NAFLD patients exhibited significantly lower rates of CVR compared to CHB-only patients. This was demonstrated by an OR of 0.59 (0.38-0.93, p=0.001, I2 = 72%) at 12 months, which tapered off to an OR of 0.67 (0.48-0.95, p=0.02) at 60 months. CHB-NAFLD patients also exhibited significantly lower rates of BR compared to CHB-only patients, as demonstrated by ORs of 0.39 (0.24-0.62, p<0.0001, I2 = 53%) at 12 months and 0.33 (0.17-0.63, p=0.0008) at 24 months.ConclusionPatients with concurrent CHB and NAFLD experience delayed CVR to antiviral therapy and more persistent biochemical abnormalities in comparison to patients with CHB only. This supports the argument for earlier antiviral therapy in order to avert CHB complications in these multi-morbid patients, as the global disease burden of NAFLD continues to increase.

AWARENESS AND KNOWLEDGE OF VIRAL HEPATITIS PREVENTION AND TRANSMISSION IN HEALTHCARE WORKERS

The objective of this study was to evaluate the knowledge and awareness of healthcare workers about the prevention and transmission of hepatitis B virus. The study was conducted in Nishtar Medical Hospital, Multan, from January 2023 to September 2023 and included 300 healthcare workers, such as doctors and nurses. The participants were asked to fill out a 50-question questionnaire designed to test their knowledge about hepatitis B. The questionnaire was in English, but assistance was provided if needed. The questions were related to the virus, behaviors, and medical practices when treating infected patients, and it took an average of 30 minutes to complete. The results showed that 74% of the healthcare workers knew the consequences and possible complications of acquiring HBV infection. Between 69% and 80% of the respondents answered correctly about the transmission routes. However, only 24% of the HCWs knew the age distribution of the infections and that neonates were at the highest risk of developing it through mother-to-child transmission. Respondents answered wrongly about transmission through food and cutlery with the infected (69%), through sneezing and coughing (81%), prevention of infection by thorough cleaning (50%), and not sharing food and cutlery with the infected (55%). Only half of the workers knew about disposing of needles and syringes correctly. The average knowledge score was 24 ± 5 with a median score of 24 (10-33). Respondents performed the worst when answering questions about CHB monitoring and treatment. In conclusion, this study found that the awareness and knowledge about hepatitis B prevention and transmission among healthcare workers in Pakistan is poor. Therefore, it is recommended to make training programs mandatory for professionals to improve disease management.

Intrahepatic homeobox protein MSX-1 is a novel host restriction factor of hepatitis B virus.

Chronic hepatitis B virus (HBV) infection (CHB) is a risk factor for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Covalently closed circular DNA serves as the sole transcription template for all viral RNAs and viral transcription is driven and enhanced by viral promoter and enhancer elements, respectively. Interactions between transcription factors and these cis-elements regulate their activities and change the production levels of viral RNAs. Here, we report the identification of homeobox protein MSX-1 (MSX1) as a novel host restriction factor of HBV in liver. In both HBV-transfected and HBV-infected cells, MSX1 suppresses viral gene expression and genome replication. Mechanistically, MSX1 downregulates enhancer II/core promoter (EnII/Cp) activity via direct binding to an MSX1 responsive element within EnII/Cp, and such binding competes with hepatocyte nuclear factor 4α binding to EnII/Cp due to partial overlap between their respective binding sites. Furthermore, CHB patients in immune active phase express higher levels of intrahepatic MSX1 but relatively lower levels of serum and intrahepatic HBV markers compared to those in immune tolerant phase. Finally, MSX1 was demonstrated to induce viral clearance in two mouse models of HBV persistence, suggesting possible therapeutic potential for CHB.IMPORTANCECovalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo, and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.

A glycoengineered therapeutic anti-HBV antibody that allows increased HBsAg immunoclearance improves HBV suppression in vivo.

Introduction: The effective and persistent suppression of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection (CHB) is considered to be a promising approach to achieve a functional cure of hepatitis B. In our previous study, we found that the antibody E6F6 can clear HBsAg through FcγR-mediated phagocytosis, and its humanized form (huE6F6 antibody) is expected to be a new tool for the treatment of CHB. Previous studies have shown that the glycosylation of Fc segments affects the binding of antibodies to FcγR and thus affects the biological activity of antibodies in vivo. Methods: To further improve the therapeutic potential of huE6F6, in this study, we defucosylated huE6F6 (huE6F6-fuc-), preliminarily explored the developability of this molecule, and studied the therapeutic potential of this molecule and its underlying mechanism in vitro and in vivo models. Results: huE6F6-fuc- has desirable physicochemical properties. Compared with huE6F6-wt, huE6F6-fuc- administration resulted in a stronger viral clearance in vivo. Meanwhile, huE6F6-fuc- keep a similar neutralization activity and binding activity to huE6F6-wt in vitro. Immunological analyses suggested that huE6F6-fuc- exhibited enhanced binding to hCD32b and hCD16b, which mainly contributed to its enhanced therapeutic activity in vivo. Conclusions: In summary, the huE6F6-fuc- molecule that was developed in this study, which has desirable developability, can clear HBsAg more efficiently in vivo, providing a promising treatment for CHB patients. Our study provides new guidance for antibody engineering in other disease fields.

Silencing SIRT1 promotes the anti-HBV action of IFN-α by regulating Pol expression and activating the JAK-STAT signaling pathway

PurposeThe purpose this study is to investigate the impact of SIRT1 on the anti-HBV activity of IFN-α and further elucidate its underlying mechanism. MethodsHepG2.2.15 cells stably transfected with HBV virus were chosen as the primary study subject. IFN-α was used to stimulate the cells and regulate the expression of SIRT1, and the JAK-STAT pathway and HBV-related indices were measured by qRT-PCR, Western blotting and ELISA. Immunofluorescence (IF) was used to detect the nuclear translocation of STAT1 and STAT2. Coimmunoprecipitation (Co-IP) was used to detect the binding of SIRT1 to HBV Polymerase (Pol). ResultsIn HepG2.2.15 cells, we found changes in SIRT1 expression. We show that silencing SIRT1 promotes the IFN-α-triggered Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and consequently enhances the antiviral effects of IFN-α against HBV replication. Importantly, SIRT1 can interact with Pol and increase JAK-STAT activity by regulating Pol expression. Additionally, the inhibition of SIRT1 activity by treatment with the SIRT1 inhibitor selisistat enhanced the anti-HBV effect of IFN-α and JAK-STAT pathway activity. ConclusionIn conclusion, our results demonstrate that silencing SIRT1 activates the JAK-STAT pathway and enhances the anti-HBV activity of IFN-α by inhibiting Pol expression. This would be a promising therapeutic target to improve the efficacy of IFN-α in the treatment of CHB.

Antiviral drug resistance rates among patients with chronic hepatitis B infection

Introduction and aim. Chronic hepatitis B infection (CHB) affects millions of people around the world. Many clinicians find it challenging to choose therapeutic agents due to the mutations that occur in the hepatitis B virus (HBV) that cause drug resistance. Thus, the aim of this study was to determine the HBV resistance rates against the currently recommended first-line therapies in the region of our country where HBV prevalence is high. Material and methods. A total of 96 patients (56 men and 40 women) with HBV infection were enrolled in the study. The serum samples collected from those were analyzed with real-time polymerase chain reaction analysis followed by pyrosequencing (PyroStar HBV Drug Resistance Test, Altona Diagnostics, Germany) for drug resistance mutations associated with lamivudine, adefovir, telbivudine, entecavir, and tenofovir. Results. HBV drug-resistance mutations were investigated in 80 treatment-naïve and 16 treatment-experienced patients (6 entecavir, 4 PEGylated-interferon, 4 tenofovir, 2 lamivudine). None of the HBV-DNA samples had mutations cause to drug resistance were detected in any codons regions that were analyzed. Conclusion. Antiviral resistance poses serious obstacles for clinicians in the treatment of CHB. Determining whether antiviral resistance exists in HBV is critical to choose the appropriate treatment agent.

Impact of treatment compliance in chronic hepatitis B

The incidence rate of chronic hepatitis B remains high in China. Antiviral therapy can significantly reduce the risk of progressive liver disease and hepatocellular carcinoma in patients with chronic hepatitis B. However, all current antiviral treatments can only inhibit HBV replication and not completely eliminate the hepatitis B virus, so antiviral therapy for chronic hepatitis B is probably a long-term or even lifelong treatment. Antiviral therapy compliance is essential for achieving long-term clinical benefits and preventing nucleot(s)ide drugs resistance. Herein, we analyzed the relevant factors of antiviral therapy compliance and their impact on CHB treatment and explored feasible programs that can improve compliance with nucleot(s)ide drug treatment by conducting a literature search using PubMed and Scopus with search terms including hepatitis B, compliance, nucleot(s)ide drugs, antiviral therapy, viral suppression, and drug resistance.

Comparing the efficacy and safety of tenofovir and adefovir or combined drug treatment for the treatment of chronic hepatitis B infection: a systematic review and meta-analysis.

BackgroundChronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV). However, the efficacy of monotherapy drug treatment is inconclusive, the safety and efficacy of TDF remain unclear, more data are needed to be included and combined drug treatment is considered to exhibit higher efficacy. To explore this issue, we performed a current literature review and meta-analysis to compare the efficacy and safety of ADV vs. TDF, TDF vs. ADV + lamivudine (LAM); TDF vs. ADV + entecavir (ETV).MethodsWe systematically searched China National Knowledge Infrastructure, the Cochrane Library, Embase, PubMed, Chinese VIP, and Wanfang Data, for relevant clinical trials since July 2015, all included studies were based on PICOS principles and evaluated independently by the reviewers in accordance with the Cochrane Handbook (Rob2.0). A meta-analysis was performed by using Review Manager 5.4.ResultsWe included a total of 32 studies, including 31 randomized controlled trials and one retrospective study involving 2,473 patients. The results revealed a low risk of bias in included studies, that the virologic response of TDF was superior to ADV (P<0.05). And TDF was also superior to ADV in Serum creatinine levels, Immunologic function, and safety profile. However, when ADV was combined with other medications, it was superior to TDF in alanine aminotransferase (ALT) level and Tbil level and adverse reactions, but on other indicators, TDF was superior to drug combination therapy.ConclusionsResults showed that TDF was superior to ADV in the parameters of ALT, hepatitis B virus (HBV)-DNA reduction, HBeAg-negative conversion rate, safety, and total bilirubin levels in patients with CHB. However, when ADV was combined with LAM or ETV, they often showed the same therapeutic effect as TDF in parameters such as ALT level and Tbil level and combined therapy can effectively reduce the occurrence of adverse reactions. In this study, because the sample source countries were limited, a greater number of global studies are needed in the future to verify the current findings.

Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study.

BACKGROUNDChronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIMTo investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODSA total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTSA positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR.CONCLUSIONIn pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.

Exploring the teaching mode about clinical laboratory diagnostic pathway for chronic hepatitis B

Exploring a new teaching mode of CHB laboratory diagnostics to improve the teaching quality through establishment a teaching model covered the whole process of CHB disease diagnosis and differential diagnosis, treatment, drug selection, the toxicity and side effects prediction, effect monitoring, and prognosis evaluation. According to the CHB clinical diagnosis and treatment guidelines, formulated the laboratory examination and detection strategies related to different stages of CHB, and established CHB clinical laboratory diagnostic pathway. Compared the classroom teaching effect by the questionnaire between the 2016 and 2017 eight-year undergraduates from the First Clinical College of Wuhan University. In this study,the CHB clinical laboratory diagnostic pathway was established and approved by clinicians, which covered the whole process of CHB disease diagnosis and differential diagnosis, treatment, drug selection, the toxicity and side effects prediction, effect monitoring, and prognosis evaluation. The teaching quality evaluation indicators and the scores on the class test had been greatly improved with the clinical diagnostic pathway teaching mode in the classroom teaching of 2017 clinical medicine undergraduates compared with the traditional teaching mode in the 2016 clinical medicine undergraduates. In summary, the medical students not only could realize the organic integration of laboratory diagnostics and clinical medicine, but also improves overall understanding of various laboratory tests in CHB diagnosis and treatment from the teaching model of laboratory diagnostics based on the CHB clinical laboratory diagnostic pathway,and the quality of teaching for CHB has been significantly improved.

Health care resources utilization and costs associated with different clinical stages of chronic hepatitis B in Egypt

IntroductionChronic hepatitis B (CHB) is associated with many serious clinical and social consequences. Despite Egypt being classified as a country of low endemicity, the infection is associated with a 15–25% risk of premature death from liver cancer or end-stage liver disease. The national committee of treatment and control of viral hepatitis has already offered a high-quality service for the diagnosis and treatment of CHB on a free basis. The current study aims to estimate the health care resources utilization and the annual direct medical cost associated with different clinical stages of CHB-related disease in Egypt.MethodologyThe data was retrieved through record review for three months in the General Administration of Hepatitis Viruses Control, Egypt. Then, the data was extrapolated to the population level by multiplying the prevalence in Egypt with a focus on the productive age groups (25–59 years).ResultsThe cost and utilization of different health care resources increase with disease progression. The total annual direct medical costs due to CHB in Egypt is 21.3 L.E. Billion (4.7 Int$ billion/year) for the management of estimated 1,420,700 CHB patients. The direct medical costs among the productive age group (25–59 years) constitute more than half of the total cost (57%). The highest disease burden is encountered among (25–29 years) age group; 2.695 L.E. billion (0.59 Int$ billion/year). Despite liver transplantation phase being associated with the highest annual cost/patient, the number of patients in this stage is the lowest. Then, it only constitutes 0.04% of the disease direct medical cost in the country. The chronic hepatitis clinical stage constitutes 57.26% of the disease direct medical cost in Egypt’s working age group.ConclusionStrengthening the preventive and control measures is mandatory to alleviate the disease’s direct medical costs. Close monitoring of the chronic hepatitis stage is mandatory to prevent disease progression. Enhancement of vaccination efforts will lower the disease prevalence and its cost. The universal health insurance system which is gradually implemented in Egypt nowadays will be a cornerstone in relieving the economic stresses by allowing more access to high-quality health care services.

Clinical Diagnostic Value of Quantitative Hepatitis B Virus Core Antibody Test in Chronic Viral Hepatitis B.

The level of CHB virus (HBV) core antibody (HBcAb) is different in four stages of chronic HBV infection and may be used for differential diagnosis of the natural history of chronic HBV infection. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose different stages of chronic HBV infection. The quantitative detection of HBcAb, hepatitis B surface antigen (HBsAg), HBV DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet count (PLT) were determined in the serum of 73 cases of low-replicative phase (LR), 46 cases of immune-tolerant phase (IT), 44 cases of immune clearance phase (IC), and 57 cases of HBeAg-negative hepatitis (ENH). Differentiating performance of these serum protein levels was analyzed by receiver operating characteristic (ROC) curve analysis. Our results showed that the levels of HBcAb, ALT, and AST levels were significantly higher in IC and ENH than those in LR and IT (both P ≤ 0.001). The levels of HBV DNA and HBsAg were higher in IC and IT than those in LR and ENH (both P ≤ 0.001). Logistic regression models showed that HBcAb, HBsAg, HBV DNA, ALT, and AST were the independent variables, respectively, and when combined, they provided high diagnostic accuracy for the staging of CHB. To sum up, HBcAb quantification is a new index, which can reflect whether the liver is in the immune activation state of HBV infection, and is related to the inflammatory state of the host liver. The combined detection of HBcAb quantification and other indicators has showed promising efficiency for staging of IC and ENH and can assist the diagnosis and treatment of CHB.

Cost-Effectiveness of 1-Time Universal Screening for Chronic Hepatitis B Infection in Adults in the United States.

An estimated 862 000 to 2.4 million people have chronic hepatitis B infection (CHB). Hepatitis B screening is recommended for pregnant women and populations with increased CHB risk. However, diagnosis rates remain low, with only 33% of people with CHB aware of their infection. This study aimed to assess the cost-effectiveness of universal adult screening for CHB. We used a Markov model to calculate the costs, population health impact, and cost-effectiveness of 1-time universal screening and CHB monitoring and treatment compared with current practice. Sensitivity analysis was performed on model parameters to identify thresholds for cost-saving or cost-effectiveness based on a willingness to pay of $50 000/quality-adjusted life-year. The analysis assumed testing would be performed during routine healthcare visits and that generic tenofovir or entecavir would be dispensed for treatment. Testing costs were based on Medicare reimbursement rates. At an estimated 0.24% prevalence of undiagnosed CHB, universal hepatitis B surface antigen (HBsAg) screening in adults aged 18-69 years is cost-saving compared with current practice if antiviral treatment drug costs remain below $894/year. Compared with current practice, universal screening would avert an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 hepatitis B virus-related deaths at a saving of $263 000/100 000 adults screened. Universal HBsAg screening of adults in the US general population for CHB is cost-effective and likely cost-saving compared with current CHB screening recommendations.

Low Rates of Hepatitis B Virus Treatment Among Treatment-Eligible Patients in Safety-Net Health Systems.

Timely initiation of antiviral therapy in chronic hepatitis B virus (CHB) reduces risk of disease progression. We evaluate overall treatment rates and predictors of treatment among treatment-eligible safety-net CHB patients. We retrospectively evaluated adults with CHB from 2010 to 2018 across 4 large safety-net health systems in the United States. CHB was identified with ICD-9/10 diagnosis coding and confirmed with laboratory data. Treatment eligibility was determined using American Association for the Study of Liver Diseases (AASLD) guidelines. Comparison of CHB treatment rates among treatment-eligible patients were performed using χ2 testing, Kaplan Meier methods and log-rank testing. Adjusted multivariate Cox proportional hazards models evaluated independent predictors of receiving treatment among eligible patients. Among 5157 CHB patients (54.7% male, 34.6% African American, 22.3% Asian), 46.8% were treatment-eligible during the study period. CHB treatment rates were 48.4% overall and 37.3% among CHB patients without human immunodeficiency virus. Significantly lower odds of treatment were observed in females versus males (odds ratio: 0.40, 95% confidence interval: 0.33-0.49, P<0.001) and patients age 65 years or above versus age below 45 years (odds ratio: 0.68, 95% confidence interval: 0.51-0.92, P=0.012). Conversely, significantly greater odds of treatment were observed in African American and Asians versus non-Hispanic whites, CHB patients with indigent care versus commercially insured patients, and non-English speaking versus English speaking patients. Among a large multicentered, safety-net cohort of CHB patients, 46.8% of treatment-eligible CHB patients overall and 37.3% of treatment-eligible CHB patients without human immunodeficiency virus received antiviral therapy. Improving CHB treatment rates among treatment-eligible patients represents "low hanging fruit," given the clear benefits of antiviral therapy in mitigating disease progression.

Antiviral Therapy Reduces Risk of Cirrhosis in Noncirrhotic HBV Patients Among 4 Urban Safety-Net Health Systems.

To evaluate the impact of chronic hepatitis B virus infection (CHB) treatment on risk of cirrhosis, liver-related outcomes, and death among a diverse CHB cohort with a large proportion of African Americans. Adults with noncirrhotic CHB without human immunodeficiency virus from 2010 to 2018 were retrospectively evaluated across 4 US safety-net health systems. CHB was identified with International Classification of Diseases, Ninth Revision/Tenth Revision diagnosis coding and confirmatory laboratory data. Propensity-score matching, Kaplan-Meier methods, and adjusted Cox proportional hazards models were used to evaluate impact of CHB treatment on risk of cirrhosis, hepatocellular carcinoma (HCC), death, and composite of cirrhosis, HCC, or death. Among 4,064 CHB patients (51.9% female, 42.0% age <45 years, 31.6% African American, 26.6% Asian, 26.7% Hispanic), 23.2% received CHB antiviral therapy and 76.8% did not. Among the propensity score-matched cohort (428 treated and 428 untreated), CHB treatment was associated with lower risk of cirrhosis (hazards ratio 0.65, 95% confidence interval 0.46-0.92, P = 0.015) and composite of cirrhosis, HCC, or death (hazards ratio 0.67, 95% confidence interval 0.49-0.94, P = 0.023). Females vs males and African Americans vs non-Hispanic whites had significantly lower risk of cirrhosis. When treatment effects were stratified by age, sex, and ethnicity, the benefits of antiviral therapies in reducing risk of cirrhosis were seen primarily in CHB patients who were females, age <45 years, and of Asian ethnicity. Our propensity score-matched cohort of noncirrhotic CHB patients demonstrated significant reductions in risk of cirrhosis due to CHB treatment.

Hepatocellular carcinoma risk in patients with HBV-related liver disease receiving anti-viral therapy

Hepatitis B virus is a major health problem worldwide, with approximatively 240 million people living with a chronic HBV infection. HBV chronic infection remains the major cause of hepatocellular carcinoma worldwide, with more than half of HCC patients being chronic HBV carriers, even if underlying mechanisms of tumourigenesis are not totally understood. HBV-related HCC can be prevented by reducing the exposure to HBV by vaccination or by treatment of CHB infection. Current treatment of CHB are Peg-IFN alpha and oral NUCs. Treating HBV infection, either with IFN or NUCs, substantially reduces the risk of HCC development, even if anti-viral therapy fails to completely eliminate HCC risk. Among treated patients, cirrhosis, HBeAg negative at baseline, and failure to remain in virological remission were associated with an increased risk of HCC. The reduction of the risk of developing HCC during anti-viral therapy is largely dependent upon the maintenance of virological remission, since viral load is found to be the most important factor leading to cirrhosis and its complications, including liver cancer development. The question whether Peg-IFN-alpha is superior to NUCs and whether there is a superior agent among NUCs is still controversial. Several studies demonstrated that anti-viral therapy with NUCs could reduce the risk of HCC recurrence after curative treatment of HBV-related HCC.

Hepatocellular carcinoma risk in patients with HBV-related liver disease receiving antiviral therapy.

Hepatitis B virus (HBV) is a major health problem worldwide, with approximatively 240 million people living with a chronic HBV infection. HBV chronic infection remains the major cause of hepatocellular carcinoma worldwide, with more than half of HCC patients being chronic HBV carriers, even if underlying mechanisms of tumorigenesis are not totally understood. HBV-related HCC can be prevented by reducing the exposure to HBV by vaccination or by treatment of CHB infection. Current treatment of CHB are Peg-IFN alpha and oral NUCs. Treating HBV infection, either with IFN or NUCs, substantially reduces the risk of HCC development, even if antiviral therapy fails to completely eliminate HCC risk. Among treated patients, cirrhosis, HBeAg negative at baseline and failure to remain in virological remission were associated with an increased risk of HCC. The reduction of the risk of developing HCC during antiviral therapy is largely dependent upon the maintenance of virological remission, since viral load is found to be the most important factor leading to cirrhosis and its complications, including liver cancer development. The question whether Peg-IFN-alpha is superior to NUCs and whether there is a superior agent among NUCs is still controversial. Several studies demonstrated that antiviral therapy with NUCs could reduce the risk of HCC recurrence after curative treatment of HBV-related HCC.

The treatment dynamics assessment among patients with chronic viral hepatitis B, infected with human immunodeficiency virus

Introduction: the article represents prospective study results of the treatment dynamics among patients with chronic viral hepatitis B, infected with human immunodeficiency virus. Particularly, the role of qHBsAg dynamics in the serum concerning CHB treatment effectiveness of CHB/HIV coinfected patients as well as clinical and laboratory factors influencing on this marker.The study purpose: To assess treatment dynamics of CHB/HIV coinfected patients basing on quantitative HBsAg determination and other clinical and laboratory test applying. Material and methods: 60 coinfected patients were examined – the main group, 60 CHB monoinfected patients – comparison group to reach established study purpose. Diagnosis of HIV and chronic hepatitis B were verified. A clinical, laboratory, serological, molecular-genetic methods were used. Statistical processing of results was held with applying parametric and nonparametric methods for the data analysis.Research results: There was a slight increase by 1.10 times in serum ALT in “a period of ≤ 6 months of antiviral therapy” with a subsequent decrease by 1.20-1.46 times in “a period of ˃ 6 months of therapy”. There was a decrease in the serum qHBsAg of coinfected patients in accordance with the duration of therapy by 1.56-21.10 times, and in case of the presence of "ALT flare" by 1.31-72.72 times. The greatest decrease in serum qHBsAg by 1.63-42.00 times during HAART was also observed in patients with an initial CD4 + count &lt;350 cells / μl. A serum qHBsAg was 11.24 times lower after ˃ 12 months of therapy in the group of CHB/HIV coinfected patients with ΔCD4 + ˃100 cells / μl compared with the group of patients with ΔCD4 + 0 - 100 cells / μl.Conclusions: A serum qHBsAg possibly to be decreased by 2 log10 among CHB/HIV coinfected patients after starting HAART with dual activity against HBV and HIV which includes nucleoside reverse transcriptase analogs (Tenofovir Disoproxil Fumarate (TDF) and lamivudine (3TC)). Defined main influencing factors on qHBsAg decreasing included: “ALT flare”, CD4+ count, ΔCD4+ as a result of monofactorial analysis. It is necessary to conduct further multifactorial analysis to determine complex of factors which could influence on further HBsAg by 2 log10 and HBsAg clearance.