METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19.
RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p
APPROACH AND RESULTS: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p
APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings.
CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.
Materials and methods: We developed a mathematical model based on the susceptible-infectious-recovered model to simulate the HBV-induced infection in children under the age of five at three different vaccination rates: 80, 90, and 95%. Additionally the impact of current vaccination coverage was assessed on HBV-induced death rates in the future. Moreover, we took advantage of the mathematical model to investigate the impact of negative bias toward girls in vaccination program on HBV-induced infection and death rates.
Results: The model simulations revealed that 10% increase in the vaccination rate from 80 to 90% can potentially contribute to the significant lowering (around 40%) of HBV-induced infection rate among children. When increased by 5% of vaccination rate from 90 to 95%, the HBV-infection rate is likely to be decreased by another 22%. Likewise, 44% reduction in HBV-induced death rate in the future (2050 onward) can potentially be achieved by 10% increase in the current vaccination rate from 80 to 90%, whereas 5% increase in the current vaccination rate (90-95%) may lead to 24% further reduction of death rate. These results underscored the significant impact of vaccination in reducing HBV-induced infection among children and future death rates in adults. Moreover, at 90% vaccination coverage, the negative bias of vaccination toward girls contributes to an increase of 15 and 12% of HBV-induced infection and death rates, respectively, in female subjects compared to their male counterparts.
Conclusion: The current vaccination coverage (80-90%) is further aggravated by untimely vaccination, dropouts from vaccination program, and negative bias toward girls in vaccination program. Therefore, if the current situation persists, it will not be possible to accomplish the required reduction in HBV-induced infection and death rates by 2030, according to the SDG guidelines. Moreover negative bias in the vaccination program may intensify the HBV-induced infection and death rates in the future.
Clinical significance: In light of the mathematical model, we suggest that the vaccination coverage should be increased to 95% without any negative bias toward girls. To accomplish this, the concerning authorities must ensure timely and full completion of the HBV vaccine schedules, reducing dropouts from vaccination program, and lastly preventing negative bias toward girls to uplift vaccination coverage to more than 95% with gender equality. Without these strategies, the necessary reduction in the HBV-induced infection and death rates in Bangladesh may not be attained per SDG directives.
How to cite this article: Chakraborty S, Chakravorty R, Alam S, et al. A Dynamic Mathematical Modeling Revelation about the Impact of Vaccination on Hepatitis B Virus-induced Infection and Death Rate in Bangladesh. Euroasian J Hepato-Gastroenterol 2019;9(2):84-90.