A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

BACKGROUND: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. METHODS: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). RESULTS: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. CONCLUSIONS: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.

Four Years Since COVID-19 Day Zero: A Time to Evaluate Past and Future Pandemic Control Policies and Practices in Sub-Saharan Africa?

Four years after the first case of COVID-19, the world is still determining how best to prevent and control the long-term effects of SARS-CoV-2 infection. Non-pharmaceutical interventions (NPIs) were employed at the start of the pandemic as the only available options, prior to effective vaccines and antiviral agents. The World Health Organization recommended dual vaccination for 70% worldwide as the threshold for a return to "normal" community life. Immunization rates needed to increase in all global regions, irrespective of socioeconomic status, necessitating more equitable access. During the pandemic, wealthier countries hoarded vaccine supplies even when their citizens were immunized. This highlights the already enormous difficulties in healthcare provision faced by low-income sub-Saharan African countries, which remain at risk as industrialized nations have progressed to a post-pandemic era. Thus, in addition to redoubling vaccination efforts public health policymakers should consider ongoing and future use of NPIs. In this narrative account, we advocate that various NPI practices should not be shelved; rather, more research is needed to evaluate their impact in parallel with booster vaccination. This especially applies to so-called "long COVID". Lessons learned from implementing best practices in resource-limited settings should be incorporated into preparedness guidelines for future infectious disease outbreaks.