Ming‐Shiang Wu

CONTEXT: Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection. OBJECTIVE: To investigate the association between nucleoside analogue use and risk of tumor recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery. DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010. MAIN OUTCOME MEASURES: The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. RESULTS: The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765 [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%]; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89). CONCLUSION: Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.

OBJECTIVE: Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. METHODS: Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. RESULTS: Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03). CONCLUSIONS: This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.