HRI London 2023: The Homeopathy Research Community Reunites after a 4-Year Hiatus, Sparking Fresh Collaborations between Researchers 'Old and New'.

The Homeopathy Research Institute's (HRI) 5th international research conference took place in the heart of London, from 16th to 18th June 2023. With 230 attendees from 27 countries, HRI's conferences remain truly international. HRI London 2023 will be remembered for its inspiring blend of 'old and new', with a programme notable for the maturity of the evidence presented by experienced names drawing on decades of work, as well as the enthusiasm and skill of up-and-coming researchers who took the floor to present their new findings. In this report, we present scientific highlights from the event.

Gathering expert consensus to inform a proposed trial in chronic nonbacterial osteomyelitis (CNO).

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO.

The impact of obstructive sleep apnea on exercise capacity in a cardiac rehabilitation program.

PURPOSE: Cardiac rehabilitation (CR) improves clinical outcomes in patients with cardiovascular disease (CDV). Patients with CVD often have multiple comorbidities, including obstructive sleep apnea (OSA), potentially affecting their ability to participate and achieve functional improvement during CR. We aimed to test the hypothesis that OSA reduces peak exercise capacity (EC) in patients undergoing CR and to explore if OSA treatment modifies this relationship. METHODS: Data from a retrospective cohort of CR patients was analyzed. OSA was defined as a respiratory event index > 5/h or physician diagnosis. Patients with OSA were considered "treated" if using continuous positive airway pressure regularly during the CR period. Change in METs was the primary study outcome. RESULTS: Among 312 CR patients, median age of 67 years, 103 (33%) had known OSA (30 treated, 73 untreated). Patients with OSA vs. those with no OSA were more likely to be obese and male; otherwise, groups were similar. Compared with the no OSA group, patients with OSA had lower pre-CR METs (3.3 [2.9-4.5] vs. 3.9 [3.1-5], P = .01) and lower post-CR METs (5.3 [4-7] vs. 6 [4.6-7.6], P = .04), but achieved a similar increase in METs post-CR (1.8 [0.6-2.6] vs. 2.0 [0.9-3], P = .22). Furthermore, compared to no OSA, pre-CR and post-CR METs tended to be similar in patients with treated OSA, but lower in untreated patients, with similar increases in METs across all groups, even when adjusting for covariates via multivariable regression. CONCLUSION: OSA is prevalent in patients with CVD undergoing CR. CR substantially improves exercise capacity independent of OSA status, but screening for-and treatment of-OSA may improve the absolute exercise capacity achieved through CR.

HRI Online 2022: Leading International Experts Illustrate the Positive Impact of Increased Collaboration in Homeopathy Research.

The Homeopathy Research Institute (HRI) welcomed more than 450 people from 35 countries to their first online event on June 25, 2022. The one-day programme featured an excellent line-up of international speakers and provided a unique interactive platform in keeping with the theme of the event - Key Collaborations in Homeopathy Research. Scientists from a range of different research fields gave an exceptional insight into the current status of homeopathy research. Here we give an overview of the most significant findings in both clinical and basic research presented during HRI Online 2022.

Expansion of immature, nucleated red blood cells by transient low-dose methotrexate immune tolerance induction in mice.

Biological treatments such as enzyme-replacement therapies (ERT) can generate anti-drug antibodies (ADA), which may reduce drug efficacy and impact patient safety and consequently led to research to mitigate ADA responses. Transient low-dose methotrexate (TLD-MTX) as a prophylactic ITI regimen, when administered concurrently with ERT, induces long-lived reduction of ADA to recombinant human alglucosidase alfa (rhGAA) in mice. In current clinical practice, a prophylactic ITI protocol that includes TLD-MTX, rituximab and intravenous immunoglobulin (optional), successfully induced lasting control of ADA to rhGAA in high-risk, cross-reactive immunological material (CRIM)-negative infantile-onset Pompe disease (IOPD) patients. More recently, evaluation of TLD-MTX demonstrated benefit in CRIM-positive IOPD patients. To more clearly understand the mechanism for the effectiveness of TLD-MTX, non-targeted transcriptional and proteomic screens were conducted and revealed up-regulation of erythropoiesis signatures. Confirmatory studies showed transiently larger spleens by weight, increased spleen cellularity and that following an initial reduction of mature red blood cells (RBCs) in the bone marrow and blood, a significant expansion of Ter-119+ CD71+ immature RBCs was observed in spleen and blood of mice. Histology sections revealed increased nucleated cells, including hematopoietic precursors, in the splenic red pulp of these mice. This study demonstrated that TLD-MTX induced a transient reduction of mature RBCs in the blood and immature RBCs in the bone marrow followed by significant enrichment of immature, nucleated RBCs in the spleen and blood during the time of immune tolerance induction, which suggested modulation of erythropoiesis may be associated with the induction of immune tolerance to rhGAA.

What is the demand for out-of-hours dermatology? A UK-based region-wide survey of dermatology demand and provision during the evenings and at weekends.

BACKGROUND: Little is known about the demand for out-of-hours (OOH) dermatology in the UK, and this can make commissioning of acute services difficult. The East Midlands region has a population of 4.5 million people, with variable access to OOH dermatology services. AIM: We sought to investigate the provision of, and demand for, OOH dermatology services across the region with a view to informing commissioning decisions for the future. METHODS: We contacted all dermatology departments in the East Midlands region to establish what level of service was commissioned at evenings and weekends. At the sites providing any form of OOH service, we recorded all requests for advice received after 17.00 h on weekdays, or at any time during weekends and bank holidays over a 3-month period from October to December 2019. RESULTS: The OOH services provided ranged from 24 h/day cover 7 days/week at one site, to no formal provision across much of the rest of the region. In total, 125 calls were received during the study period, averaging 1 call per day on weekday evenings, and 2 calls per day at weekends and on bank holidays. Of these 125 calls, 11 patients (9%) were prioritized and seen by the on-call dermatologist on the day of referral, and 9 of these had potentially life-threatening skin conditions. A further 39 (31%) were deemed to need review within 24 h and 22 (18%) within 48 h. The remaining 42% were given appointments within 7 days or dealt with by telephone advice. CONCLUSION: The demand for OOH dermatology across the East Midlands is low, but access to timely dermatology advice is essential in some situations. Commissioning of a regional dermatology OOH service incorporating digital technology may help to improve the equity of access for all patients across the region.

Toxic epidermal necrolysis-like lupus.

Toxic epidermal necrosis (TEN)-like lupus is a rare condition characterized by epidermal loss and mucosal ulceration occurring in patients with acute severe flares of systemic lupus erythematosus. The clinical picture may mimic drug-induced Stevens-Johnson syndrome/TEN; however, the absence of a suitable culprit drug, and the context of acute lupus point to the correct diagnosis. In a case series of three patients, further discriminating features included a slower onset of epidermal loss, more limited mucosal ulceration and a lack of ocular involvement when compared with drug-induced TEN. Histology may show similar features, including basal layer vacuolation, apoptosis and full-thickness epidermal necrosis. Patients with TEN-like lupus may have additional features of lupus, and a lupus band on direct immunofluorescence. It is important to identify this condition correctly, so that these patients can be appropriately managed with early input from Rheumatologists and prompt treatment with high-dose combined immunosuppressant therapy.

Treatment of acne with spironolactone: a retrospective review of 395 adult patients at Mayo Clinic, 2007-2017.

BACKGROUND: Few large studies have assessed spironolactone treatment of adult female acne. OBJECTIVES: To explore the role of spironolactone in the treatment of adult female acne. METHODS: We performed a retrospective case series assessing the efficacy of spironolactone treatment of a cohort of women evaluated at Mayo Clinic in Rochester, Minnesota, from 2007 through 2017. RESULTS: In total, 395 patients (median age, 32 years) received a median spironolactone dose of 100 mg daily. Approximately two-thirds of patients (66.1%) had a complete response; 85.1% had a complete response or a partial response greater than 50%. Median times to initial response and maximum response were 3 and 5 months. Efficacy was observed across all severity subtypes of acne, including those with papulopustular and nodulocystic acne. Patients received long-term treatment with spironolactone (median duration, 13 months) and had few adverse effects. CONCLUSIONS: Spironolactone is a safe and effective treatment of acne for women.

HRI London 2019: 10 Years of Excellence in Homeopathy Research.

The Homeopathy Research Institute's (HRI's) 4th International Research Conference took place in the heart of London from 14 to 16 June 2019. With 352 attendees from 38 countries, this was HRI's largest and most international conference to date. HRI London 2019 will be remembered for the highest quality scientific programme so far, combined with a vibrant, positive atmosphere throughout, making it the perfect way to celebrate HRI's 10th Anniversary. Here we summarise the science presented during the intense 2.5-day programme.

Homeopathy for treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder that leads to decreased health-related quality of life and work productivity. A previous version of this review was not able to draw firm conclusions about the effectiveness of homeopathic treatment for IBS and recommended that further high quality RCTs were conducted to explore the clinical and cost effectiveness of homeopathic treatment for IBS. Two types of homeopathic treatment were evaluated in this systematic review: 1. Clinical homeopathy where a specific remedy is prescribed for a specific condition; 2. Individualised homeopathic treatment, where a homeopathic remedy based on a person's individual symptoms is prescribed after a detailed consultation. OBJECTIVES: To assess the effectiveness and safety of homeopathic treatment for IBS. SEARCH METHODS: For this update we searched MEDLINE, CENTRAL, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), the Cochrane IBD Group Specialised Register and trials registers from inception to 31 August 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs), cohort and case-control studies that compared homeopathic treatment with placebo, other control treatments, or usual care, in adults with IBS were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. The primary outcome was global improvement in IBS as measured by an IBS symptom severity score. Secondary outcomes included quality of life, abdominal pain, stool frequency, stool consistency, and adverse events. The overall certainty of the evidence supporting the primary and secondary outcomes was assessed using the GRADE criteria. We used the Cochrane risk of bias tool to assess risk of bias. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous outcomes and the risk ratio (RR) and 95% CI for dichotomous outcomes. MAIN RESULTS: Four RCTs (307 participants) were included. Two studies compared clinical homeopathy (homeopathic remedy, asafoetida or asafoetida plus nux vomica) to placebo for IBS with constipation (IBS-C). One study compared individualised homeopathic treatment (consultation plus remedy) to usual care for the treatment of IBS in female patients. One study was a three armed RCT comparing individualised homeopathic treatment to supportive listening or usual care. The risk of bias in three studies (the two studies assessing clinical homeopathy and the study comparing individualised homeopathic treatment to usual care) was unclear on most criteria and high for selective reporting in one of the clinical homeopathy studies. The three armed study comparing individualised homeopathic treatment to usual care and supportive listening was at low risk of bias in four of the domains and high risk of bias in two (performance bias and detection bias).A meta-analysis of the studies assessing clinical homeopathy, (171 participants with IBS-C) was conducted. At short-term follow-up of two weeks, global improvement in symptoms was experienced by 73% (46/63) of asafoetida participants compared to 45% (30/66) of placebo participants (RR 1.61, 95% CI 1.18 to 2.18; 2 studies, very low certainty evidence). In the other clinical homeopathy study at two weeks, 68% (13/19) of those in the asafoetida plus nux vomica arm and 52% (12/23) of those in the placebo arm experienced a global improvement in symptoms (RR 1.31, 95% CI 0.80 to 2.15; very low certainty evidence). In the study comparing individualised homeopathic treatment to usual care (N = 20), the mean global improvement score (feeling unwell) at 12 weeks was 1.44 + 4.55 (n = 9) in the individualised homeopathic treatment arm compared to 1.41 + 1.97 (n=11) in the usual care arm (MD 0.03; 95% CI -3.16 to 3.22; very low certainty evidence).In the study comparing individualised homeopathic treatment to usual care, the mean IBS symptom severity score at 6 months was 210.44 + 112.4 (n = 16) in the individualised homeopathic treatment arm compared to 237.3 + 110.22 (n = 60) in the usual care arm (MD -26.86, 95% CI -88.59 to 34.87; low certainty evidence). The mean quality of life score (EQ-5D) at 6 months in homeopathy participants was 69.07 (SD 17.35) compared to 63.41 (SD 23.31) in usual care participants (MD 5.66, 95% CI -4.69 to 16.01; low certainty evidence).For In the study comparing individualised homeopathic treatment to supportive listening, the mean IBS symptom severity score at 6 months was 210.44 + 112.4 (n = 16) in the individualised homeopathic treatment arm compared to 262 + 120.72 (n = 18) in the supportive listening arm (MD -51.56, 95% CI -129.94 to 26.82; very low certainty evidence). The mean quality of life score at 6 months in homeopathy participants was 69.07 (SD 17.35) compared to 63.09 (SD 24.38) in supportive listening participants (MD 5.98, 95% CI -8.13 to 20.09; very low certainty evidence).None of the included studies reported on abdominal pain, stool frequency, stool consistency, or adverse events. AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the effectiveness and safety of homeopathy for the treatment of IBS can be drawn. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy for IBS compared to placebo or usual care.

Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic Treatment.

BACKGROUND: This study focuses on randomised controlled trials (RCTs) of individualised homeopathic treatment (IHT) in which the control (comparator) group was other than placebo (OTP). AIMS: To determine the comparative effectiveness of IHT on health-related outcomes in adults and children for any clinical condition that has been the subject of at least one OTP-controlled trial. For each study, to assess the risk of bias and to determine whether its study attitude was predominantly 'pragmatic' or 'explanatory'. METHODS: Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2015, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether they examined IHT as an alternative treatment (study design Ia), adjunctively with another intervention (design Ib), or compared with a no-intervention group (design II). For each RCT, we identified a 'main outcome measure' to use in meta-analysis: 'relative effect size' was reported as odds ratio (OR; values >1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy). RESULTS: Eleven RCTs, representing 11 different medical conditions, were eligible for study. Five of the RCTs (four of which in design Ib) were judged to have pragmatic study attitude, two were explanatory, and four were equally pragmatic and explanatory. Ten trials were rated 'high risk of bias' overall: one of these, a pragmatic study with design Ib, had high risk of bias solely regarding participant blinding (a bias that is intrinsic to such trials); the other trial was rated 'uncertain risk of bias' overall. Eight trials had data that were extractable for analysis: for four heterogeneous trials with design Ia, the pooled OR was statistically non-significant; collectively for three clinically heterogeneous trials with design Ib, there was a statistically significant SMD favouring adjunctive IHT; in the remaining trial of design 1a, IHT was non-inferior to fluoxetine in the treatment of depression. CONCLUSIONS: Due to the low quality, the small number and the heterogeneity of studies, the current data preclude a decisive conclusion about the comparative effectiveness of IHT. Generalisability of findings is limited by the variable external validity identified overall; the most pragmatic study attitude was associated with RCTs of adjunctive IHT. Future OTP-controlled trials in homeopathy should aim, as far as possible, to promote both internal validity and external validity.

HRI Malta 2017-Cutting Edge Research in Homeopathy: HRI's Third International Research Conference in Malta.

The third international conference on "Cutting Edge Research in Homeopathy" organised by the Homeopathy Research Institute (HRI) was held on the inspiring and historic island of Malta from 9th to 11th of June, 2017. One hundred and two abstracts underwent peer review by the HRI Scientific Advisory Committee and external experts to produce the programme of 36 oral presentations and 37 posters, presented by researchers from 19 countries. The 2.5-day programme covered a diverse range of topics, including quantitative and qualitative clinical research, basic research, veterinary research, and provings. These intensive plenary and parallel sessions were interspersed with multiple opportunities for delegates to discuss and exchange ideas, in particular through interactive panel discussions and a pre-conference workshop. The continuing commitment of the homeopathy research community to generate high-quality studies in this rapidly evolving field was clear. In this conference report, we present highlights from this memorable event.

Cutting Edge Research in Homeopathy: HRI's second international research conference in Rome.

Rome, 3rd-5th June 2015, was the setting for the Homeopathy Research Institute's (HRI) second conference with the theme 'Cutting Edge Research in Homeopathy'. Attended by over 250 delegates from 39 countries, this event provided an intense two and a half day programme of presentations and a forum for the sharing of ideas and the creation of international scientific collaborations. With 35 oral presentations from leaders in the field, the scientific calibre of the programme was high and the content diverse. This report summarises the key themes underpinning the cutting edge data presented by the speakers, including six key-note presentations, covering advancements in both basic and clinical research. Given the clear commitment of the global homeopathic community to high quality research, the resounding success of both Barcelona 2013 and Rome 2015 HRI conferences, and the dedicated support of colleagues, the HRI moves confidently forward towards the next biennial conference.

Safety, tolerability, and pharmacokinetics of 6-month daily dosing of an oral formulation of cyclosporine (ATOPICA for cats®) in cats.

Cyclosporine was proven efficacious in the treatment of feline hypersensitivity dermatitis. This target animal study was conducted to evaluate the safety, tolerability, and pharmacokinetics of ATOPICA for Cats® (cyclosporine oral solution, USP) MODIFIED following 6-month daily dosing in cats. Forty healthy cats (four cats/sex/group) received 0, 8 (1×), 16 (2×), 24 (3×), or 40 (5×) mg/kg cyclosporine once daily for 6 months (183 days). Body weight, food consumption, ophthalmoscopic, physical examinations including neurological assessments, blood pressure, electrocardiography, clinical pathology (hematology, coagulation, clinical chemistry, urinalysis), organ weights, and macroscopic and microscopic examinations were performed and assessed. In addition, blood concentrations of cyclosporine were measured at the pretreatment trough on Days 1, 2, 7, 14, 31, 91, 154, and 182, and post-treatment on Days 1, 31, and 182. Adverse effects possibly related to treatment included prolonged APTT and one report each of bone marrow hypocellularity and lymphoma; all occurred in cats treated with doses more than 16 mg/kg. There was no significant accumulation of cyclosporine beyond the first week of treatment. Results confirm that ATOPICA for Cats is safe and well tolerated in cats without unexpected accumulation beyond the first week of treatment when administered as directed.

Not just in man's best friend: A review of Staphylococcus pseudintermedius host range and human zoonosis.

Staphylococcus pseudintermedius is one species in the commensal staphylococcal population in dogs. While it is commonly carried on healthy companion dogs it is also an opportunistic pathogen associated with a range of skin, ear, wound and other infections. While adapted to dogs, it is not restricted to them, and we have reviewed its host range, including increasing reports of human colonisation and infections. Despite its association with pet dogs, S. pseudintermedius is found widely in animals, covering companion, livestock and free-living species of birds and mammals. Human infections, typically in immunocompromised individuals, are increasingly being recognised, in part due to improved diagnosis. Colonisation, infection, and antimicrobial resistance, including frequent multidrug resistance, among S. pseudintermedius isolates represent important One Health challenges.

The curious case of the hypothalamic-pituitary-gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): No apparent role of opioids and glucocorticoids.

The naked mole-rat (Heterocephalus glaber) is a unique model mammal in which to study socially induced inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Naked mole-rat groups exhibit a high degree of reproductive bias in which breeding is restricted to one female (the queen) and one male, with subordinate non-breeding colony members rarely, if ever, having the opportunity to reproduce due to a dysfunctional HPG axis. It is posited that aggression directed at subordinates by the queen suppresses reproduction in these subordinates, yet the underlying physiological mechanisms causing this dysfunction are unknown. This study aimed to investigate the possible factors contributing to the dysfunction of the HPG axis in subordinate female naked mole-rats with a specific focus on the role of ovarian feedback and stress-related factors such as circulating glucocorticoid and endogenous opioid peptides. The results showed that stress-related factors appear to not mediate the suppression of reproductive function in subordinate female naked mole rats. Indeed, in some cases, the activation of the stress axis may lead to reproductive activation instead of deactivation. At the same time, the role of ovarian sex steroid feedback in reproductive suppression is likely limited and not clearly delineated. This study highlights the need for detailed studies to elucidate the mechanism of reproductive suppression in this unique model mammalian species which may shed light on, and reveal novel mechanisms, in the social regulation of reproduction.

Diagnostic findings in sinonasal aspergillosis in dogs in the United Kingdom: 475 cases (2011-2021).

OBJECTIVES: To describe the diagnostic tests used and their comparative performance in dogs diagnosed with sinonasal aspergillosis in the United Kingdom. A secondary objective was to describe the signalment, clinical findings and common clinicopathologic abnormalities in sinonasal aspergillosis. MATERIALS AND METHODS: A multi-centre retrospective survey was performed involving 23 referral centres in the United Kingdom to identify dogs diagnosed with sinonasal aspergillosis from January 2011 to December 2021. Dogs were included if fungal plaques were seen during rhinoscopy or if ancillary testing (via histopathology, culture, cytology, serology or PCR) was positive and other differential diagnoses were excluded. RESULTS: A total of 662 cases were entered into the database across the 23 referral centres. Four hundred and seventy-five cases met the study inclusion criteria. Of these, 419 dogs had fungal plaques and compatible clinical signs. Fungal plaques were not seen in 56 dogs with turbinate destruction that had compatible clinical signs and a positive ancillary test result. Ancillary diagnostics were performed in 312 of 419 (74%) dogs with observed fungal plaques permitting calculation of sensitivity of cytology as 67%, fungal culture 59%, histopathology 47% and PCR 71%. CLINICAL SIGNIFICANCE: The sensitivities of ancillary diagnostics in this study were lower than previously reported challenging the clinical utility of such tests in sinonasal aspergillosis. Treatment and management decisions should be based on a combination of diagnostics including imaging findings, visual inspection, and ancillary testing, rather than ancillary tests alone.

Chronic hepatitis B virus (HBV) infection in children: 25 years' experience.

Whereas e-seroconversion represents the loss of hepatitis B e-antigen (HBeAg) followed by gain of antibody to HBeAg (anti-HBe), 'inactive chronic infection' extends this concept to include e-seroconversion with decreased serum viral load and biochemical remission. These events must be well-characterized before treatment outcomes can be evaluated. We examined the rates of e-seroconversion and achievement of inactive chronic infection among children with chronic HBV infection. Children who were HBsAg positive >6 months were identified retrospectively between 1983 and 2008 from the Hospital for Sick Children Liver Clinic. Inactive chronic infection was defined as loss of HBeAg, serum ALT ≤40 IU/mL, and HBV DNA <10(6 ) IU/mL. Both e-seroconversion and achievement of inactive chronic infection were characterized using survival analysis. The effect of transmission route, treatment, age at diagnosis, ethnicity, gender and baseline ALT on these rates was evaluated with univariate and multiple regression. Of 252 HBeAg-positive cases, 59.9% had HBV-infected mothers, 77% were Asian, and 33 received interferon-α. Untreated children were younger at last follow-up (mean 14.5 vs 17.6 years), had lower ALT (median 60 vs 116 IU/mL) and had shorter follow-up (6.6 vs 9.1 years, all P < 0.002) compared to treated children. Crude e-seroconversion rate was 41.7% over 0.5-19.1 years of follow-up, and this was not affected by transmission route (P = 0.93), gender (P = 0.62) nor treatment (P = 0.08). 49% achieved inactive chronic infection by age 19 years. Being non-Asian, age at diagnosis<3 years, and ALT ≥40 IU/mL were associated with a higher rate of e-seroconversion and achieving inactive chronic infection (P < 0.0001). Almost 50% of children achieved inactive chronic infection by early adulthood.