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BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

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BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Asunto(s)

Antivirales , Carcinoma Hepatocelular , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Neoplasias Hepáticas , Carga Viral , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Masculino , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Femenino , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Antivirales/uso terapéutico , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Adulto , Taiwán/epidemiología , Virus de la Hepatitis B , Hong Kong/epidemiología , República de Corea/epidemiología , Estudios de Cohortes , Tenofovir/uso terapéutico , Guanina/análogos & derivados , Guanina/uso terapéutico , ADN Viral/sangre , Incidencia , Factores de Riesgo

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BACKGROUND: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC. METHODS: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses. RESULTS: Of 6942 records, 52 studies with at least 100 patients were analysed; ∼70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8-12 months (75.0% (95% CI 56.4-87.4%)). CONCLUSIONS: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.

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COVID-19 , SARS-CoV-2 , Humanos , Síndrome Post Agudo de COVID-19 , Progresión de la Enfermedad , Disnea

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BACKGROUND: Children who live with a parent with a substance use disorder (SUD) are more likely to experience adverse health outcomes, including mental health disorders. We assessed whether residing with anyone who used substances was associated with children's anxiety and/or depression, and whether these associations differed by the children's age or sex. METHODS: We analyzed nationally representative cross-sectional data from the 2019 National Health Interview Survey (n = 6642). The associations between ever residing with someone who used substances and caregiver-reported children's anxiety and depression frequency (never/a few times a year/monthly/weekly/daily) were estimated using multinomial logistic regression models, adjusted for children's age, children's sex, children's race/ethnicity, annual household income, and highest educational attainment by an adult in the household. We assessed whether the associations differed based on the children's age (5-11/12-17 years) or sex. RESULTS: Children who had resided with someone who used substances were more likely to be reported by their caregiver as having daily anxiety (risk ratio (RR) = 2.84; 95% confidence interval (CI) = 2.04, 3.95; referent = never anxious) and daily depression (RR = 3.35; 95% CI = 1.98, 5.67; referent = never depressed). Associations with more frequent anxiety were stronger among adolescents than younger children. Associations between residing with someone who used substances and depression frequency differed based on children's age and sex. CONCLUSIONS: Our results suggest that residing with someone who used substances is associated with children's anxiety and depression. Our findings can help inform screening and treatment efforts for anxiety and depression among children, as well as for the person using substances.