高齢者C型慢性肝炎患者に対するダクラタスビル＋アスナプレビル併用療法の安全性と有効性

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Efficacy of radiofrequency ablation for initial recurrent hepatocellular carcinoma after curative treatment: Comparison with primary cases

a b s t r a c t Objective: To determine the efficacy of radiofrequency ablation (RFA) for initial recurrence of small hepatocellular carcinoma (HCC; ≤3 nodules, each nodule ≤3 cm in diameter) after curative treatment and identify prognostic factors affecting therapeutic outcome, we compared clinical and outcome factors between patients with primary HCC and those with initial recurrent HCC who underwent RFA. Methods: In this retrospective cohort study, 211 HCC patients who underwent RFA were enrolled and comprised two groups: primary group (n = 139) and initial recurrent group (n = 72). We compared local tumor progression, overall survival (OS), disease-free survival (DFS), and RFA safety between the groups. Results: Median follow-up was 53 months. Local tumor progression rate was 5.8% in the primary group and 4.2% in the recurrent group. OS rates at 5 years and 10 years were 63.2% and 25.5% in the primary group and 54.5% and 33.4% in the recurrent group, respectively. Corresponding DFS rates were 30.7% and 14.6% and 19.2% and 11.0%. DFS was significantly shorter in the recurrent group (hazard ratio [HR] = 1.81; 95% confidence interval [CI], 1.27-2.57; P = 0.001). In the recurrent group, time from primary HCC development to recurrence was a determinant of OS (≤2 years; HR = 3.42; 95% CI, 1.52-7.72; P = 0.003). Conclusion: Although local tumor control and OS were similar between the groups, the recurrent group had shorter DFS than the primary group. Time from primary HCC development to recurrence was a prognostic factor for recurrence of HCC

The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy

<div><p>The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10–196) and 23 (range 4–78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.</p></div

Sequential changes of serum alfa-fetoprotein (AFP).

<p>Serum AFP levels before therapy and six months after the end of the treatment in patients treated with peg-interferon plus ribavirin (PEG-IFN/RBV) or daclatasvir plus asunaprevir (DCV/ASV). In these box-and-whisker plots, lines within the boxes represent median values; the upper and lower lines of the boxes represent the 75th and 25th percentiles, respectively; the upper and lower bars outside the boxes represent the 90th and 10th percentiles, respectively.</p

Characteristics of propensity score-matched patient treated with PEG-IFN plus RBV or daclatasvir plus asunaprevir.

<p>Characteristics of propensity score-matched patient treated with PEG-IFN plus RBV or daclatasvir plus asunaprevir.</p

Clinical characteristics of 398 patients.

<p>Clinical characteristics of 398 patients.</p

Cumulative hepatocellular carcinoma (HCC) development.

<p>Patients who achieved viral eradication by peg-interferon and ribavirin (PEG-IFN/RBV) or daclatasvir plus asunaprevir (DCV/ASV) therapies were analyzed.</p