LLV observed during entecavir monotherapy was associated with a higher risk of HCC, especially for those with cirrhosis, indicating that LLV during potent antiviral therapy is consequential. (Hepatology 2017;66:335-343).

Acute hepatitis A (AHA) involves severe CD8 T cell-mediated liver injury. Here we showed during AHA, CD8 T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8 T cells. TCR-independent activation of non-HAV-specific CD8 T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8 T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8 T cells and the innate-like cytolytic activity of CD8 T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8 T cells, a result with implications for acute viral diseases.

The present study aimed to analyse the treatment outcome of four cycles of CHOP (cyclophosphamide-vincristine-doxorubicin-prednisolone) followed by involved field radiation therapy (IF RT) for the treatment of stage I-II nasal natural killer (NK)/T-cell lymphoma. From March 1995 to December 1999, 17 patients (median age 41 years; range 30-66) with localized nasal NK/T-cell lymphoma were enrolled. B symptoms were noted in five patients (31%). Sixteen of seventeen patients (94%) were of low risk when classified according to the International Prognostic Index (IPI). The treatment plan consisted of four cycles of CHOP chemotherapy followed by IF RT of 45 Gy. Two patients received radiation during the first or second cycle of CHOP because of bleeding from the primary tumour site. Both patients achieved complete responses (CRs). In the remaining 15 patients, after 4 cycles of CHOP, 6 CRs and 3 partial responses (PRs) were achieved (53% of response rate). IF RT was given to six patients (four in CR, one in PR and one in PD), and all six patients achieved CR. Overall, CR was achieved in 10 of 17 patients (58%). The planned sequential chemoradiotherapy was completed in only 6 of 17 patients (35%) because of the progression during chemotherapy. None of the patients who achieved CR experienced relapse of lymphoma during follow-up. The estimated overall three-year survival rate was 59%. In univariate analysis, B symptoms and stage were significant prognostic factors for response and overall survival (P < 0.05). The present study suggests that four cycles of CHOP followed by IF RT is not satisfactory for treating patients with localized nasal NK/T-cell lymphoma, and that further exploration for improved therapy is needed.

This randomised multicentre phase II study was conducted to investigate the activity and safety of two oral fluoropyrimidines, capecitabine or S-1, in elderly patients with advanced gastric cancer (AGC). Elderly (X65 years) chemo-naive patients with AGC were randomly assigned to receive capecitabine 1250 mg m À2 two times daily on days 1 -14 every 3 weeks or S-1 40 -60 mg two times daily according to body surface area on days 1 -28 every 6 weeks. Ninety-six patients were enrolled and 91 patients were randomised to capecitabine (N ¼ 46) or S-1 (N ¼ 45). Overall response rate, the primary end point, was 27.2% (95% CI, 14.1 -40.4, 12 of 44 assessable patients) with capecitabine and 28.9% (95% CI, 15.6 -42.1, 13 of 45) with S-1. Median times to progression and overall survival in the capecitabine arm (4.7 and 9.5 months, respectively) were similar to those in the S-1 arm (4.2 and 8.2 months, respectively). The incidence of grade 3 -4 granulocytopenia was 6.8% with capecitabine and 4.8% with S-1. Grade 3 -4 nonhaematologic toxicities were: asthenia (9.1% with capecitabine vs 7.1% with S-1), anorexia (6.8 vs 9.5%), diarrhoea (2.3 vs 0%), and hand -foot syndrome (6.8 vs 0%). Both capecitabine and S-1 monotherapies were active and tolerable as first-line treatment for elderly patients with AGC.