Few reports have detailed mutation frequencies and mutation patterns in the entire X region according to clinical status. The aims of this study were to elucidate the relationships between mutation patterns and their frequencies in the X region and clinical status in a Korean cohort and determine specific X mutation types, related closely with liver disease progression. All X mutations were determined by direct sequencing in 184 patients with different clinical features. Mutation rates in the X region in patients with more severe liver disease, hepatocellular carcinoma (HCC) (3.6%) or liver cirrhosis (4%) were always significantly higher than in patients with corresponding less severe forms, chronic hepatitis (2.9%) or asymptomatic carriers (2.1%), but no significant difference in mutation rates was found in terms of HBeAg serostatus. All five mutation types (V5M/L, P38S, H94Y, I127T/N, and K130M and V131I) affecting the six codons were found to be related significantly to clinical severity. Among these, two mutation types (V5M/L and K130M and V131I) were observed more frequently in HBeAg negative patients than in HBeAg positive patients. In conclusion, the results suggest that an accumulation of mutations in the X region contributes to disease progression in chronic patients, at least Korean patients with genotype C. Specific mutation types appears to be related more to severe liver diseases such as HCC or liver cirrhosis. In particular, a novel mutation type (V5M/L) discovered firstly during the present study was found to be associated significantly with HCC.

Previous studies have found an association between serum albumin levels and cognitive function. However, the results of this association are inconsistent, and the effect of Apolipoprotein E (APOE) on the association is less clear. Using retrospective cohort data (2008–2020), we investigated whether chronic serum albumin was associated with cognitive performance in older adults. We further assessed how the APOE genotype modifies its relevance. A total of 2396 Korean veterans and their families who were aged 65 years or older in 2008 and who had both data of serum albumin and cognitive performance (assessed by the Mini-Mental State Examination, MMSE) were included for the current study. The serum albumin levels were divided into four groups by quartiles: Group 1 (<4.0 g/dL), Group 2 (4.0–4.19 g/dL), Group 3 (4.2–4.49 g/dL), and Group 4 (≥4.5 g/dL). APOE ε4 carriers were defined as the presence of at least one ε4 allele (ε2/4, ε3/4, ε4/4). After adjusting for age, sex, and medical conditions, serum albumin levels (assessed by the median serum albumin levels during the study period) were significantly associated with increases in the median MMSE scores (beta = 3.30, p < 0.0001). Compared with the lowest median albumin category (Group 1), the beta coefficients for the median MMSE score were significantly and gradually increased in Group 2 (beta = 2.80, p < 0.0001), Group 3 (beta = 3.71, p < 0.0001), and Group 4 (beta = 4.01, p < 0.0001), respectively. In the analysis of repeated albumin measures, similar patterns were observed in cognitive function. All regression coefficients were greater in ε4 carriers than in non-carriers. Our findings suggested that sustained lower serum albumin levels were associated with lower MMSE scores. This observation may be modified by APOE polymorphisms.

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