Background We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. Methods Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. Results One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01–2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26–3.08), early recurrence (HR = 6.62, 95% CI:3.79–11.6) and late recurrence (HR = 3.75, 95% CI:1.99–7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. Conclusion Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

There has been no clear consensus on the optimal consolidation periods following HBeAg seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients. Our study aimed to prospectively compare relapse rates between 12 months’ and 18 months’ consolidation periods to see whether or not there is beneficial durability of tenofovir disoproxil fumarate (TDF) therapy with longer consolidation periods. We enrolled a total of 137 HBeAg-positive Asian CHB patients treated with TDF monotherapy. Forty-six patients achieved HBeAg SC. Then, they were randomly assigned to consolidation period of either 12 months (group A) or 18 months (group B). After stopping TDF therapy, all patients were followed up for 12 months. Thirteen patients (56.5%) relapsed in group A and 12 patients (52.2%) relapsed in group B after 12 months’ follow-up ( P = .958). Pretreatment HBsAg level is the only significant predictor for off-therapy recurrence by univariate analysis ( P = .024). Baseline HBeAg >1000 S/CO in group B patients were significantly less likely to relapse than those of group A ( P = .046). Baseline alanine aminotransferase (ALT) >133 U/L could significantly predict occurrence of HBeAg SC ( P = .008; 95% CI: 0.545–0.763; AUC: 0.654). Overall, a prolonged consolidation period has no positive effect on TDF therapy on sustained viral suppression in HBeAg-positive Asian CHB patients. However, a prolonged consolidation period was beneficial to patients with high baseline semi-quantitative HBeAg levels in terms of off-treatment durability. Baseline ALT > 133 U/L could significantly predict the occurrence of HBeAg SC.

Background A gender difference in hepatocellular carcinoma (HCC) that men have higher incidence than women—has long been noted and can be explained by the cross-talk between sex hormones and HBV/HCV virus. Whether metabolic factors yield similar sexual difference in non-HBV/HCV-HCC remains elusive. Methods 74,782 HBsAg/anti-HCV negative residents participating in the Keelung Community-Based Integrated Screening program were followed in 2000-2007. Incident HCC was identified by linkage to the Taiwan Cancer Registry. Cox proportional hazards regression models were used to estimate the association between metabolic factors and HCC stratified by sex. All statistical tests were two-sided. Results With 320,829 follow-up person-years, 99 developed HCC. The adjusted hazard ratios were 2.10 (95% CI = 1.07-4.13) and 3.71 (95% CI = 2.01-6.86) for prediabetes and diabetes, respectively, in males. The corresponding aHRs were 1.16 (95% CI = 0.48-2.83) and 1.47 (95% CI = 0.65-3.34) in females. Compared to normal weight (BMI 23-25), underweight (BMI&lt;21, HR = 3.56, 95% CI = 1.18-10.8) and overweight (BMI 25-&lt;27.3, HR = 3.81, 95% CI = 1.43 – 10.2 were associated with an elevated risk in men. The statistically significant gradient relationship per advanced BMI category was noted in females (adjusted HR = 1.41, 95% CI = 1.07-1.87). The HCC/fasting glucose (p = 0.046) and HCC/BMI (p = 0.03) associations were significantly modified by sex. Elevated AST, APRI fibrosis index and habitual alcohol consumption were related to HCC only in men while increased ALT and lower platelet levels predicted HCC risk in women. Conclusions We found that BMI-HCC association were U-shape for men and linear for women, and the elevated HCC risk began from glucose impairment in men only. Whether good glycemic and weight control can reduce HCC risk warrants further investigation.

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