Background Pyroptosis is a unique inflammatory‐related cell death process, and inflammation is considered to be a key factor in hepatocellular carcinoma (HCC). However, the pyroptosis landscape in HCC has not been thoroughly studied. Methods Clinical data and RNA sequencing data of HCC patients were collected from The Cancer Genome Atlas database, and differentially expressed genes (DEGs) associated with pyroptosis were discovered. The relationship between DEGs and prognosis was studied. Using The Cancer Genome Atlas cohort, a least absolute shrinkage and selection operator regression model was built on the basis of pyroptosis‐related DEGs, which was then verified by the Gene Expression Omnibus (GEO) cohort. Functional enrichment analysis and immunological states were also studied between distinct risk subgroups. Finally, the potential tumor suppressive function of NLRP6 in HCC was analyzed. Results In total, 26 pyroptosis‐related DEGs were identified. Consensus clustering results showed patients with high levels of pyroptosis were associated with higher tumor stage, grade, and poor prognosis. The least absolute shrinkage and selection operator risk model was built using six genes linked with prognosis ( GSDMC, GSDME, NOD2, NLRP6, CASP8, and SCAF11 ). Risk score was an independent risk factor that suggested shortened overall survival in both the training cohort (HR: 3.52, 95% CI: 1.351–9.193) and validation cohort (HR: 3.31, 95% CI: 1.435–7.617). Meanwhile, the low‐risk population had higher immunological activity. We also found a novel potential tumor suppressor gene NLRP6, which may negatively regulate the E2F and MYC pathways and be associated with higher immune cell infiltration levels, which lead to better prognosis. Conclusions This study revealed the pyroptosis landscape of HCC and provided a promising clinical prognosis evaluation model. Additionally, some new targets related to prognosis such as NLRP6 are proposed for further study.

Aims Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019 (COVID‐19) than healthy individuals, and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an effective prevention strategy. This meta‐analysis aimed to assess the effectiveness and safety of SARS‐CoV‐2 vaccines in patients with chronic liver disease (CLD) and post‐liver transplantation (LT). Methods The PubMed, Embase, and Cochrane databases were searched. A random‐effects model meta‐analysis was used to determine the seropositivity rates of SARS‐CoV‐2 antibodies, odds ratio (OR) compared with healthy controls (HC), risk ratio (RR) between the booster and standard vaccination regimen, and the rate of adverse reactions (ADR). Results In the standard vaccination regimen analysis, 17 controlled articles were included for effectiveness analysis, and six articles for ADR analysis. The pooled seropositivity rates of SARS‐CoV‐2 antibodies in patients with CLD and post‐LT were 93.3% (95% confidence interval [CI]: 89.0%–97.6%) and 69.1% (95% CI: 63.0%–75.3%), respectively. Both rates were lower than those in HC (p < 0.001). The differences remained significant after sorting by detection interval, vaccine type, antibody type, or CLD type. LT recipients showed much lower seropositivity rates of antibodies than patients with CLD (69.1% vs. 93.3%) or HC (OR: 0.055). The pooled total ADR rate of patients was 24.0% (95% CI: 16.2%–31.8%). In the booster vaccination regimen analysis, 11 prospective studies were enrolled, and the seropositivity rates of antibodies after the booster dose were increased by 27% compared with those of the standard vaccination regimen (RR: 1.27, 95% CI: 1.15–1.41, p < 0.001). Conclusion Patients with CLD and post‐LT can gain protection against COVID‐19 from standard vaccines, demonstrating a potentially weaker immunogenic response than HC. Booster vaccines can compensate for this deficiency. Therefore, patients with CLD and post‐LT should be prioritized for receiving the COVID‐19 booster vaccine.