Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection.

[Background]Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC HCC) has increased, its clinicopathologic characteristics remain unclear. [Methods]We retrospectively analyzed 518 HCC patients who underwent hepatic resection. Hepatitis B surface antigen- and hepatitis C antibody-negative patients were categorized into the NBNC HCC group (n = 145); others were categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided the etiologies of NBNC HCC according to alcohol intake and presence of steatosis. [Results]NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD) (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and hypertension was higher and hepatic function was better in the NBNC HCC group, which had significantly larger tumors than the BC HCC group. The entire NBNC HCC group displayed similar overall and disease-free survival as the BC HCC group. Among the subdivisions, NAFLD-associated HCC patients had significantly better disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33–3.96) and steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21–3.93) were associated with disease-free survival in NBNC HCC patients. [Conclusions]The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients

Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors

IntroductionImmune-checkpoint inhibitors are effective in various advanced cancers. Type 1 diabetes mellitus induced by them (ICI-T1DM) is a serious complication requiring prompt insulin treatment, but the immunological mechanism behind it is unclear.MethodsWe examined amino acid polymorphisms in human histocompatibility leukocyte antigen (HLA) molecules and investigated proinsulin epitope binding affinities to HLA molecules.Results and DiscussionTwelve patients with ICI-T1DM and 35 patients in a control group without ICI-T1DM were enrolled in the study. Allele and haplotype frequencies of HLA-DRB1*04:05, DQB1*04:01, and most importantly DPB1*05:01 were significantly increased in patients with ICI-T1DM. In addition, novel amino acid polymorphisms in HLA-DR (4 polymorphisms), in DQ (12 polymorphisms), and in DP molecules (9 polymorphisms) were identified. These amino acid polymorphisms might be associated with the development of ICI-T1DM. Moreover, novel human proinsulin epitope clusters in insulin A and B chains were discovered in silico and in vitro peptide binding assays to HLA-DP5. In conclusion, significant amino acid polymorphisms in HLA-class II molecules, and conformational alterations in the peptide-binding groove of the HLA-DP molecules were considered likely to influence the immunogenicity of proinsulin epitopes in ICI-T1DM. These amino acid polymorphisms and HLA-DP5 may be predictive genetic factors for ICI-T1DM