간경변증은 간암 발생 위험이 매우 높다.

Research Summary & Abstract: BACKGROUND: Chronic hepatitis B (CHB) is a major cause of hepatocellular carcinoma (HCC). In patients receiving CHB treatment, coexistence of steatotic liver disease (SLD) and cardiometabolic risk factors (CMRFs) markedly influence HCC risk. This study explored hepatic and metabolic profiles, HCC predictors, and the modifying roles of SLD and CMRFs in CHB. METHODS: This study included 1012 patients receiving nucleos(t)ide analogs between 2004 and 2022. They were stratified into SLD (N = 702) or non-SLD (N = 310) groups. RESULTS: Over a 5.5-year follow-up period, 73 patients developed HCC. At baseline, the SLD group had younger age, higher body mass index values, lower fibrosis indices, and more severe metabolic dysregulation than did the non-SLD group. SLD conferred protection against HCC (adjusted hazard ratio: 0.43; p = 0.001). However, the presence of ≥2 CMRFs significantly increased HCC risk (adjusted hazard ratio: 1.93; p = 0.009). The highest HCC risk was observed in patients without SLD having ≥2 CMRFs (5-year incidence rate: 21.4%). The protective effect of SLD persisted after inverse probability of treatment weighting. It was most pronounced in older, cirrhotic, and high-metabolic-risk subgroups. Hepatitis B virus DNA suppression, hepatitis B surface antigen decline, and fibrosis score improvement during treatment were similar between the two groups. CONCLUSIONS: Among patients with CHB receiving nucleos(t)ide analogs, those without SLD having ≥2 CMRFs had the highest risk of HCC. Thus, steatosis and metabolic burden should be incorporated into precision risk stratification.

Research Summary & Abstract: Cyanobacteria are ubiquitous environmental bacteria capable of producing cyanotoxins, including potent liver tumor promoters. There is limited knowledge of exposure to cyanotoxins and their potential role in the pathogenesis of liver cancer The relationship of cyanotoxin exposure with two hallmarks of progressive liver disease-liver fibrosis and steatosis-was evaluated in a cross-sectional study of 399 adult residents of the state of Hawaii and the US territory of Guam without a history of cancer. Microcystins (MC), nodularins (NOD), cylindrospermopsin (CYN), and anabaenopeptins (AB) were analyzed in saliva, serum, and urine using direct competitive enzyme-linked immunosorbent assays. Liver fibrosis and steatosis were measured by transient elastography. Linear and non-linear associations of cyanotoxin levels with degree of fibrosis and steatosis were evaluated in multivariate generalized linear and additive models. One or more cyanotoxins were variably detected in all individuals. Moderate to severe fibrosis or cirrhosis was present in 18% and moderate to severe steatosis in 53%. Positive associations with fibrosis level were observed for salivary cyanotoxins: MC/NOD (linear: β = 9.07, 95% confidence interval [CI] 1.32-16.82, p = .022; non-linear p = .0011); CYN (linear: β = 24.21, 95% CI 14.12-34.30, p < .0001; non-linear p = .0001); AB (non-linear p = .0125). A positive association with steatosis level was observed for serum MC/NOD (non-linear p = .0120). Non-linear associations of cyanotoxins with fibrosis were specific to defined concentrations. Our novel findings suggesting that cyanotoxins are independent risk factors for liver disease are consistent with our prior study linking oral cyanobacteria to hepatocellular carcinoma and may have global implications for liver cancer prevention.