Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene are associated with substantial clinical heterogeneity. Here, we report the first case of SYNE1 ataxia in Taiwan due to two novel truncating mutations. Our patient, a 53-year-old female, exhibited pure cerebellar ataxia with c.1922del in exon 18 and c. C3883T mutations in exon 31. Previous studies have indicated that the prevalence of SYNE1 ataxia among East Asian populations is low. In this study, we identified 27 cases of SYNE1 ataxia from 22 families in East Asia. Of the 28 patients recruited in this study (including our patient), 10 exhibited pure cerebellar ataxia, and 18 exhibited ataxia plus syndromes. We could not find an exact correlation between genotypes and phenotypes. Additionally, we established a precise molecular diagnosis in our patient’s family and extended the findings on the ethnic, phenotypic, and genotypic diversity of the SYNE1 mutational spectrum.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.