Vaccination status of the adult sickle cell anaemia population: The South Wales experience

The Sickle Cell Society have issued standards for additional immunisations that adults with sickle cell disease (SCD) require. These include annual influenza, 5-yearly pneumococcal conjugate vaccine (PPV23) and Hepatitis B vaccination. Patients who have not received their primary vaccination as part of the national schedule in the UK should also receive further additional vaccines. We reviewed whether adults with SCD in South Wales currently receive these. 49 adult patients were identified as having SCD under the care of the Hereditary Anaemia Service based in the University Hospital of Wales, Cardiff. GP records were not available for 5 patients leaving a final cohort of 44 patients to analyse. Average age was 33 years (range 17-67). Median age was 27 with the cohort predominantly lying in the 17-29 year category (52%). Results showed good compliance with the annual influenza vaccine in those over 40 (>80%). However, compliance for the 17-29 category and 30-39 categories were 37.5% and 42.8%, respectively. The improved compliance in those >40 was not seen with the 5-yearly pneumococcal vaccine. Compliance was worse in all age groups compared to the annual flu vaccine with only 23% compliance overall. However, when looking at those who had received a single dose of PPV23, the numbers improved to nearly 60%. Compliance with the SARS-CoV2 vaccination was highest at 61.3%. However, rates were lower in the 17-29 and 30-39 age groups in keeping with previous trends. Only 34.1% of patients had full hepatitis B cover. Again, trends in compliance mirrored previous with poorer rates in those under 40. Assessing compliance for the remainder of the standards was more challenging given that we could not confirm retrospectively how many of our cohort had received their primary vaccinations in other parts of the UK, thought to be around half. However, most of the cohort had not received any additional vaccines suggesting high non-compliance regardless. This review looked at data from 2020 and likely reflects the impact of the SARS-CoV2, whether positive or negative. The reduced compliance in 5-yearly pneumococcal compared to flu suggest better health-professional education is needed;if patients are attending for their annual flu vaccine, there is ample opportunity to administer other vaccines. The vaccination rate for our patient group is comparable to national rates by ethnicity although lower than the national average for age. Vaccination rates for the SCD population of South Wales are not adequate. Better education and engagement is needed.

Screening and monitoring patients with COVID-19 pneumonia treated with immunosuppressive agents for hepatitis B reactivation.

Immunosuppressive drugs are used for treating coronavirus disease 2019COVID-19pneumonia. This study examined the current status of screening and monitoring patients with COVID-19 pneumonia treated with immunosuppressive agents for hepatitis B virusHBVreactivation. Of 123 patients whose hepatitis B surface antigen level was measured, 2 were HBsAg-positive. Antihepatitis B core/surface antibodies were measured in all 121 HBsAg-negative patients. HBV DNA was measured in 31 of 32 patients who were positive for either or both antihepatitis B core/surface antibodies. Of 34 patients requiring regular monitoring, only 4 were monitored. The HBV monitoring rate at the initiation of COVID-19 treatment was high. How-ever, HBV monitoring after COVID-19 treatment was difficult because most patients were transferred to other hospitals or had their treatment terminated.Copyright © 2022 Takeshi Matsui et al.

A pre-existing case of HBV infection with elevated HBV DNA after COVID-19 pneumonia treatment.

The patient presented with fever and appetite loss. Computed tomography (CT) revealed a moderate grade 2 pneumonia. Besides, further blood examination showed his HB antigen as negative, anti-HBs/c anti-body as positive, and HBV DNA level as 1.0 LIU/mL. Therefore, he was diagnosed with COVID-19. Administered treatments comprised oxygen inhalation and steroid therapy, including pulses, remdesivir, and baricitinib, which improved pneumonia. Interestingly, one month posttreatment, his HBV DNA level in-creased to 1.4 LIU/mL, followed by a further increase to 1.7 LIU/Ml, showing an improvement. Tenofovir alafenamide fumarate was thus administered. In clinical practice, immunosuppressive therapy is used for patients with moderate-to-severe COVID-19 pneumo-nia. However, close attention should also be paid to the elevation of blood HBV DNA levels during and after treatment.Copyright © 2022 The Japan Society of Hepatology.

COVID-19 Incidence and its Clinical Course in Liver Transplant Recipients.

Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.

The Effect of FOXP3+Regulatory T Cells on Infectious and Inflammatory Diseases

CD4+CD25+FOXP3+regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.Copyright © 2021. All rights reserved.

19th Seminar on Tropical Pathology and Public Health 12th Biotechnology Week 1st Physical Therapy Week, Virtual, 23-25 November 2022

These proceedings comprise 85 articles spanning diverse fields such as bacteriology, molecular biology, biotechnology, dermatology, infectious and parasitic diseases, epidemiology, physiotherapy, immunology, mycology, parasitology, pathology, collective health, and virology. The articles delve into a wide range of research topics, from repurposing drugs for Mycobacterium abscessus complex infections to utilising artificial intelligence for SARS-CoV-2 diagnosis. In bacteriology, investigations explore the correlation between smoking and Helicobacter pylori infection in gastric adenocarcinoma patients, as well as the resistance profiles of Staphylococcus aureus and Pseudomonas aeruginosa in tracheostomised children. Molecular biology studies focus on gene polymorphisms related to diseases like paracoccidioidomycosis. Biotechnology research emphasises bioactive molecules in species like Croton urucurana and the development of computational models for cytotoxicity prediction. Dermatology articles address stability characterisation in vegetable oil-based nanoemulsions. The section on infectious and parasitic diseases encompasses studies on COVID-19 vaccine response in pregnant women and the impact of infection prevention measures in rehabilitation hospitals. Epidemiology investigations analyse trends in premature mortality, tuberculosis in diabetic patients, and public adherence to non-pharmacological COVID-19 measures. Physiotherapy research covers topics such as telerehabilitation through a developed game and the prevalence of congenital anomalies. Immunology studies explore immune responses in HIV and Leishmaniasis, whilst mycology investigates the biotechnological potential of fungi from the cerrado biome. Parasitology research evaluates treatment efficacy against vectors parasites such as Aedes aegypti and Toxoplasma gondii. Pathology articles discuss intentional intoxication in cattle and the influence of curcumin on acute kidney injury therapy. Collective health studies focus on intervention plan development in healthcare settings and pesticide use in horticulture. Lastly, virology research investigates parvovirus occurrence in hospitalised children during the COVID-19 pandemic, hidden hepatitis B virus infection in inmates, and the prevalence of HPV and HTLV-1/2 infections in specific populations.

Recommendations for the integral diagnosis of chronic viral hepatitis in a single analytical extraction. / Recomendaciones para el diagnóstico integral de las hepatitis virales crónicas en una única extracción analítica.

The Spanish Society of Digestive Pathology (SEPD), the Spanish Association for the Study of the Liver (AEEH), the Spanish Society of Infections and Clinical Microbiology (SEIMC) and its Viral Hepatitis Study Group (GEHEP), and with the endorsement of the Alliance for the Elimination of Viral Hepatitis in Spain (AEHVE), have agreed on a document to carry out a comprehensive diagnosis of viral hepatitis (B, C and D), from a single blood sample; that is, a comprehensive diagnosis, in the hospital and/or at the point of care of the patient. We propose an algorithm, so that the positive result in a viral hepatitis serology (B, C and D), as well as human immunodeficiency virus (HIV), would trigger the analysis of the rest of the virus, including the viral load when necessary, in the same blood draw. In addition, we make two additional recommendations. First, the need to rule out a previous hepatitis A virus (VHA) infection, to proceed with its vaccination in cases where IgG-type studies against this virus are negative and the vaccine is indicated. Second, the determination of the HIV serology. Finally, in case of a positive result for any of the viruses analyzed, there must be an automated alerts and initiate epidemiological monitoring.

A Hepatitis B Virus Reactivation Case Potentially Triggered by the Onset of Diffuse Large B Cell Lymphoma.

An 81-year-old man underwent rituximab-containing chemotherapy for chronic lymphocytic leukemia (CLL). Thirteen years after his last chemotherapy, he was diagnosed with hepatitis B virus (HBV) reactivation. He was then treated with entecavir, and improvement was seen in his liver injury. He developed diffuse large B cell lymphoma (DLBCL) after improvement in his hepatitis. Despite chemotherapy, he contracted the coronavirus disease 2019 (COVID-19) and died of COVID-19. We suspect that HBV reactivation was triggered by DLBCL. When HBV reactivation occurs a long time after chemotherapy has concluded, the onset of DLBCL should be considered.

Causal associations between chronic hepatitis B and COVID-19 in East Asian populations.

BACKGROUND: The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies. METHODS: We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively. RESULTS: Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01-1.07, P = 3.39E-03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06-1.13, P = 7.31E-08), and severe COVID-19 (OR = 1.16, 95%CI 1.08-1.26, P = 1.43E-04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02-1.11, P = 1.44E-03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07-1.16, P = 5.13E-07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB. CONCLUSIONS: This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry.

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

Background: The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. Patients and methods: A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire. Results: A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001). Conclusion: Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

Current status of guideline based screening and monitoring for HBV reactivation in patients with COVID-19 pneumonia treated with immunosuppressive agents

Background and Aim: Immunosuppressive agents (e.g., baricitinib [BAR], tricizumab [TCZ]) and steroids are used for treating coronavirus disease 2019 (COVID-19) pneumonia. These immunosuppressive agents are known to cause HBV reactivation. The current guidelines recommend HBV screening and HBV reactivation monitoring in Japan. However, the status of compliance among treated patients with COVID-19 pneumonia remains unclear. Herein, we report the status of compliance with the current guidelines on HBV reactivation. Method(s): We investigated the implementation of HBV screening and HBV reactivation monitoring for patients who received immunosuppressive agents in our hospital from April 2021 up to June 2021. Background factors related to the presence or absence of screening were analyzed. Result(s): There were 123 patients who received immunosuppressive agents in our hospital from April 2021 up to June 2021. The patients median age was 63 years old (31-95 years), and 90 patients were men. BAR/steroid therapy was given in 115 patients and TCZ/steroid therapy in 8 patients. Of the 123 patients in whom HBs antigen level was measured, 2 patients were positive for HBs antigen. Anti-HBc/ HBs antibodies were measured in all 121 HBsAg-negative patients according to the guidelines. Of 32 patients who were positive for either or both anti-HBc/HBs antibodies, HBV DNA was measured in 31 patients. Of 34 patients who required regular reactivation monitoring, 30 did not receive regular monitoring (6 died in the hospital, 11 were transferred to other hospitals, and 13 were terminated of their treatment early in the outpatient department of the hospital). Only 4 patients were monitored according to the guidelines. Of the 4 patients monitored, 1 was positive for HBs antigen and was given a nucleic acid analogue. In 1 patient, HBV DNA increased from signal-positive to 1.4 LIU/mL and then to 1.7 LIU/mL and nucleic acid analogue was started. The remaining 2 patients had undetectable HBV DNA or remained signal-positive. Conclusion(s): The HBV reactivation monitoring rate at the start of COVID-19 pneumonia treatment was high. However, HBV reactivation monitoring after the COVID-19 pneumonia treatment was difficult because most patients were transferred to other hospitals or had their treatment terminated.

Real-World Single-Centre Experience of Jak Inhibitor Use in Ra

Background/Aims The use of Janus Kinase Inhibitors (JAKi) has been gradually increasing overtime in the management of rheumatoid arthritis (RA) and other inflammatory arthritis and these appeal to patients. being oral agents. Nevertheless, rheumatologists have become cautious about their use since recent trials have shown safety concerns about VTEs, MACE and malignancies. Methods We decided to study use of JAKi at our centre in Princess of Wales Hospital Bridgend. The aim was to assess whether appropriate patients were selected (considering cautions about MACE, VTEs and malignancies). We also wanted to see whether all patients had required pretreatment safety testing and post-treatment monitoring performed. Results These were 70 patients;59 were females and 11 were males. All of them were diagnosed as RA. Average age was 61.1 years (20-85), average duration of disease 129.9 months (16-340) and average duration of treatment was 58.1 weeks. The most common JAKi being used was baricitinib (84%) followed by tofacitinib (12%) and upadacitinib (4%). 50% patient were on concomitant csDMARDs among whom two-thirds were on methotrexate. Looking at previous biologic use, 9 patients were biologic naive, 22 had one biologic, 15 had two biologics used in the past. All patients were appropriately selected (severe RA and no significant risk factors for MACE, VTEs and malignancies). All patients had pre-treatment Hepatitis B, Hepatitis C, latent TB, FBC and LFTs checked. All patients had FBC and LFTs monitored post treatment. No patient developed VTE, MACE or cancer on treatment. 84.2% patients had lipids tested before starting JAKi. 22.8% patients had abnormal lipids before Rx initiation and 62.5% of these were on lipid lowering Rx. All patients had lipids tested post treatment, but the timing was quite variable and only 62.5% of patients had lipids tested on the recommended time. There were 2 deaths recorded in this cohort. One of those was an 80-year-old RA patient on baricitinib 2mg OD, who died due to chest infection on the background of ILD. He was not on steroids or csDMARDs. The second patient was 63 years' old (on baricitinib 4mg OD), and died due to respiratory sepsis, and was also on azathioprine. She had RA with advanced ILD. The reasons for discontinuing JAKi were inefficacy (46%), side effects (39%) and both inefficacy and side effects (15%). 41.4%of patient experienced side effects due to JAKi. These included infection 28%, deranged lipids 17%, cytopenia 14%, deranged LFTs 14%, GI side effects 10%, skin rash 7% and varicella zoster 3%. Conclusion There has been steady increase in the use of tsDMARDs for RA and other rheumatic conditions. Due to short half-life, these drugs became a popular choice during COVID-19 pandemic but on the other hand safety monitoring became extremely challenging during this time.

Anti-hepatitis B surface antigen as a biomarker for immunity acquisition against SARS-CoV-2

Background: More than a year has passed since the first coronavirus vaccines were widely used. However, some healthcare workers are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite full vaccination. The immune effect of SARSCoV- 2 vaccines attenuates in a few months in contrast to other universal vaccines, such as the hepatitis B vaccine, which have an immune effect that lasts for a longer time. In addition, the neutralizing antibody (Ab) titers can be measured only in limited medical institutions. In this study, we aimed to investigate the factors that predict SARS-CoV-2 infection in healthcare workers after vaccination. Method(s): In this study, we enrolled one thousand one hundred and thirty-three healthcare workers (826 women, 307 men) after second inoculation of the BNT162b2 vaccine (Pfizer /BioNTech) in February- April 2021. Medical checkups and self-reported questionnaires were used to collect medical histories and demographic characteristics. The Alinity SARS-CoV-2 IgG II Quant (Abbott) quantitative IgG spike protein serology assay was examined in a cohort of participants 1, 4, 6 months after the second vaccination, and 1 month after the third vaccination of the BNT162b vaccine. Lower Ab titers were defined under median at each time point. The relationships between SARS-CoV-2 infection and these factors were analyzed. Result(s): The mean observation period was four hundred and fortyeight days. The median titers at 1, 4, 6 months after the second vaccination were 9293 U/mL (interquartile range [IQR], 5840-14392 U/mL), 1658 U/mL (IQR, 999-2676) and 832 U/mL (IQR, 523-1300), respectively. The risk factors for lower Ab titers were age (60 years older, odds ratio [OR], 2.08), presence of current illness (OR 1.52), smoking habit (OR 2.36), and no fever after the second vaccination (OR 2.44). The median titers at 1 month after the third vaccination was 13780 U/mL (IQR, 9085-22722), and the risk factor for lower Ab titers was hepatitis B surface Ab (HBsAb) negative (OR 1.38). The total 1-year cumulative infection rate was 4.9%. The median infection period was three hundred and twenty days (IQR, 298-365) after the second vaccination. The risk factors of infection were age (30 s and 40 s), and HBsAb negative. The 1-year cumulative infection rate of 30-40 s and other ages were 6.6% and 3.7%, respectively (p<0.01). The 1-year cumulative infection rate of HBsAb negative participants with 30-40 s and other age were 7.7% and 4.9%, respectively (p = 0.064), while that of HBsAb positive participants with 30-40 s and other age were 6.7% and 1.7%, respectively (p<0.01). Conclusion(s): HBsAb and age can become prognostic factors to be infected with SARS-CoV-2 after vaccination. Especially, HBsAb negative people under 50 years old should pay attention to SARSCoV- 2 infection even after second vaccination.

Countermeasures against viral hepatitis in Japan: road to HCV elimination

The World Health Organization (WHO) has set a goal of elimination of viral hepatitis by 2030. In Japan, the estimated people of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections were 1.7-2.2 and 1.3-1.5 million in 2000, respectively. Although the mortality due to hepatocellular carcinoma (HCC) had been increasing until around 2002, it has been gradually decreasing to date, and approximately 24,000 people died from HCC in 2021 in Japan. Japan has a national action plan for addressing viral hepatitis called, ''Basic Act on Hepatitis Measures'', established in 2009. ''Basic Guidelines for Promotion of Control Measures for Hepatitis'' was issued in 2011 and was updated in 2016 and 2022, comprising 9 principles in order to promote measures to prevent HBV and HCV. According to these guidelines, national and local government share screening costs for testing HBV and HCV for those residents who are over 40 years old. Thus, out-of-pocket expenses from examinees are free of charge or reduced to a minimum. In addition, for patients with chronic HBV or HCV infections treated with nucleotide analogues, interferon, and direct antiviral agents, the drug prices and examination expenses were covered by a medical-expenses support system for viral hepatitis. By these countermeasures against viral hepatitis, the estimated people of chronic HCV infection revealed a decrease to 1.0-1.6 million in 2011 (30-40% decrease from 2000 level) and 0.9-1.3 million in 2015 (40- 50% decrease from 2000 level). If the current situation had been continuing, the number of HCV patients is expected to decrease to 0.2-0.5 million (80-90% decrease from 2000 level and 60-80% decrease from 2015 level) by 2030. However, the COVID-19 pandemic since December 2019 is thought to have affected testing, linkage to care, treatment uptake, and follow-up, and new efforts that do not slow the progress to date toward HCV elimination, which is finally becoming visible, will be necessary in the future. In this lecture, I would also like to talk about the efforts at our hospital to achieve the sustainable development goal targeted by WHO.

Effect of the capsid assembly modulator (CAM) ALG-000184 on HBsAg Levels in subjects with HBeAg positive chronic hepatitis B (CHB)

Background: ALG-000184 is a prodrug of ALG-001075, a novel, potent, pan-genotypic Class II CAM. CAMs are thought to have two mechanisms of action (MoA). The primary MoA affects pgRNA encapsidation resulting in inhibition of HBV DNA/RNA replication, as confirmed in CHB subjects receiving ALG-000184. The secondary MoA, which occurs at higher concentrations, regulates the establishment and replenishment of cccDNA, resulting in lowering of HBsAg, an effect that has not been reported to date with ALG- 000184. Method(s): ALG-000184-201 is a multi-part, multicenter, doubleblind, randomized, placebo-controlled study. In healthy volunteers (HVs), single doses up to 500 mg and multiple doses up to 250 mg were well tolerated with linear PK (Gane E., HBV TAG and APASL 2021). In treatment naive (TN) subjects with CHB, daily oral doses of 10-100 mg ALG-000184 for 28 days were well tolerated with linear PK and were associated with profound reductions of DNA/RNA regardless of HBeAg status or dose (Yuen MF, EASL 2022). Plasma exposures required to engage the secondary MoA are expected to be achieved at the 300 mg dose level. Data from a 300 mg cohort treated for 28 days are described here. Data from another ongoing cohort treated with 300 mg for 12 weeks will be presented at the conference. Result(s): Ten subjects were randomized to 300 mg ALG-000184 for 28 days and two to placebo. Two subjects randomized to ALG- 000184 were replaced due to missing data due to Covid-19 lockdown. Subjects were Asian, HBeAg positive, and genotype B or C. Mean baseline HBV DNA and RNA levels were 8.4 log10 IU/mL and 7.3 log10 copies/mL, respectively. One subject experienced a serious adverse event (AE) of pneumothorax>8 weeks after last dose which was considered unlikely related to study drug. No subjects prematurely discontinued study drug. All treatment emergent AEs were Grade <= 2 except for 4 Grade >= 3 alanine aminotransferase (ALT) elevations, which an independent ALT Flare Committee assessed as not related to study drug toxicity. PK was similar to HBeAg negative and HV cohorts following body weight adjustment. Subjects dosed with 300 mg ALG-000184 experienced mean declines of 4.0 log10 IU/mL and 2.6 log10 copies/mL in HBV DNA and RNA levels, respectively, at Day 28. Three of 7 evaluable subjects who received ALG-000184 had HBsAg declines>0.2 log10 IU/mL (0.23-0.78 log10 IU/mL). One subject receiving ALG-000184 had unquantifiable HBsAg throughout the study. Additionally, one HBeAg positive subject in a prior 100 mg cohort had plasma exposures equivalent to the 300 mg dose level and experienced a 0.5 log10 IU/mL HBsAg decline. Conclusion(s): In TN HBeAg positive CHB subjects, 300 mg ALG- 000184 for 28 days was well tolerated, exhibited predictable PK and resulted in rapid and substantial declines in HBV DNA and RNA. Notably, 3 of 7 evaluable subjects from this cohort experienced HBsAg declines of up to 0.78 log10 IU/mL. These data suggest that ALG-000184 can engage the secondary MoA of CAM II. Cohorts evaluating 300 mg over longer durations are planned or ongoing.

Organ transplantation and vaccination

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic.Copyright © 2022 Journal of Zhongshan University. All Rights Reserved.

Tackling hepatitis B co-infection in PLHIV after COVID: an audit and updated guidelines

Background: 5-20% of people living with HIV (PLWH) are co-infected with Hepatitis B (HBV) and coinfection is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), incidence of which is 5 to 6 times higher. COVID-19 led to a lapse in surveillance of this population, warranting a reassessment. Method(s): BHIVA and EACS guidelines were combined to create a standard to audit against. All people under the care of the HIV team with co-infection were included, and analysed for the prior six months. Local ethics approval was granted. The results were then presented to clinicians, and local guidelines created to reflect the most recent research on co-infection which were shared with the department. A re-audit was then conducted against the modified guidelines. Result(s): 42 people were living with co-infection of HBV and HIV, with a 50:50 gender split;32 were of Black African ethnicity (76%). The median age was 50.5. Nobody had a HBV resistance profile done at baseline. 3 people did not have suppressed HIV viral load (VL), and 8 people did not have a suppressed HBV VL. In the previous 6 months only 26 (62%) had had a HBV VL, 20 (48%) had had an alfa-fetoprotein (AFP) check, and 21 (36%) had had an ultrasound liver. An US had been requested in 21 (50%) of patients. 100% were on a tenofovir-containing drug regimen. Following presentation and rewriting of guidelines, performance of investigations improved. An US had been requested in 26 (62%) cases although only performed in 16 (38%) and an AFP had been measured in 25 (60%). Vaccination of partners had also improved. Conclusion(s): The provision of care of those with coinfection was significantly impacted by the COVID pandemic, but reinforcement of information, and re-issuing of guidelines improved patient care. Attendance of appointments for blood tests and scans remains a major challenge for improving patient care. Literature aimed at our local population to reinforce the importance of HCC screening is being developed.

Week 48 results of a phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir 1 emtricitabine/tenofovir disoproxil fumarate (DTG 1 F/TDF) as initial treatment in HIV-1/HBV-coinfected adults (ALLIANCE)

Background/Aims: The clinical course of hepatitis B virus (HBV) infection in individuals with HIV-1 coinfection is marked by accelerated disease progression. A tenofovir-containing antiretroviral regimen is recommended in most people with HIV-1/HBV-coinfection, but there have not been randomized studies of tenofovir disoproxil fumarate (TDF) vs tenofovir alafenamide (TAF) in treatment- naive HIV-1/HBV-coinfected individuals. We report primary endpoint results from a Phase 3 study comparing bictegravir/emtricitabine/ TAF (B/F/TAF) vs dolutegravir + emtricitabine/TDF (DTG + F/TDF) at Week (W)48 in participants initiating treatment for both viruses. Method(s): Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG + F/TDF (with placebo). Primary endpoints were the proportion of participants with HIV-1 RNA<50 copies/mL (FDA Snapshot) and plasma HBV DNA<29 IU/mL (missing = failure) at W48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline cluster of differentiation 4 (CD4) count, proportion with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss/seroconversion, and alanine transaminase (ALT) normalization (AASLD criteria). Result(s): Participants (N = 243) were randomized and treated (B/F/ TAF [n = 121], DTG + F/TDF [n = 122]) from 11 countries in Asia, Europe, North, and Latin America. Baseline characteristics were median age of 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA>100,000 c/mL, 40% CD4<200 cells/lL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG + F/TDF at achieving HIV-1 RNA<50 copies/mL (95% vs 91%, difference 4.1%;95% CI -2.5%-10.8%;P = 0.21), with mean CD4 gains of + 200 and + 175 cells/lL, respectively. B/F/TAF was superior to DTG + F/TDF at achieving HBV DNA<29 IU/mL (63% vs 43%, difference 16.6%;95% CI 5.9%-27.3%;P = 0.0023). Participants treated with B/F/TAF vs DTG + F/TDF had numerically higher HBsAg loss (13% vs 6%;P = 0.059), HBeAg loss (26% vs 14%;P = 0.055), HBeAg seroconversion (23% vs 11%;P = 0.031), and ALT normalization (73% vs 55%;P = 0.066). The most frequent adverse events among participants treated with B/F/TAF vs DTG + F/TDF were upper respiratory tract infection (17% vs 11%), COVID- 19 (13% vs 11%), pyrexia (9% vs 12%), ALT increase (7% vs 11%), and nasopharyngitis (11% vs 4%). ALT flares (elevations at >= 2 consecutive postbaseline visits) occurred in 11 participants (7 B/F/ TAF, 4 DTG + F/TDF), and all resolved. Conclusion(s): Among adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG + F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.