Background and Aims Little is known about the association between non‐alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. Methods We conducted a nationwide cohort study involving 4 031 948 subjects aged 40–69 years who underwent ≥2 health check‐ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non‐NAFLD (HSI <30 at all check‐ups) and NAFLD (HSI >36 at one or more check‐ups). Dementia defined by ICD‐10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. Results At baseline, 31.3% had NAFLD. During the median follow‐up of 9.5 years, 138 424 in NAFLD group and 69 982 in non‐NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non‐NAFLD group on multivariable‐adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity‐score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non‐obese NAFLD subjects (BMI <25 kg/m2, HR, 1.09; p < .001) than obese NAFLD subjects. Conclusions This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non‐obese NAFLD subjects.

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BACKGROUND It is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen–positive (HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB). METHODS We conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log 10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels. RESULTS During a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log 10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00–5.99 log 10 IU/mL ( P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log 10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00–7.99 log 10 IU/mL, 6.00–6.99 log 10 IU/mL, or 5.00–5.99 log 10 IU/mL were 2.48 ( P = 0.03), 3.69 ( P = 0.002), and 6.10 ( P < 0.001), respectively. CONCLUSION On-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log 10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log 10 IU/mL) may maintain the lowest risk of HCC for those patients. FUNDING Patient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow-up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30-3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg-interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.