Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Enomoto, Hirayuki; Aizawa, Nobuhiro; Hasegawa, Kunihiro; Ikeda, Naoto; Sakai, Yoshiyuki; Yoh, Kazunori; Takata, Ryo; Yuri, Yukihisa; Kishino, Kyohei; Shimono, Yoshihiro; Ishii, Noriko; Takashima, Tomoyuki; Nishimura, Takashi; Nishikawa, Hiroki; Iwata, Yoshinori; Iijima, Hiroko; Nishiguchi, Shuhei
Abstract
Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0 x 10(-4)). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.
Combination of saikosaponin c and telbivudine synergistically enhances the anti-HBV activity
INFLAMMATION RESEARCH
Authors: Li, Xiaohe; Ke, Zhiyi; Lian, Dongli; Yuan, Jing; Pan, Yanchao
Abstract
Objective The present study was undertaken to obtain data using the combination of SSc and lamivudine (LAM), entecavir (ETV) or telbivudine (LdT) in HepG2.2.15 cells to explore whether SSc acts as a potent adjuvant of nucleoside analogues in anti-HBV treatment. Methods HepG2.2.15 cells were incubated with either SSc combined with any one of three nucleoside analogues (NAs) LAM, ETV, LdT or only one of them for 48 h. The expression profiles of HBV DNA, HBsAg, HBeAg, and HBcAg were examined by real-time quantitative PCR, ELISA, and western blot. Results Compared with mono-drug treatment, the combination of SSc and any of the three nucleoside analogues significantly promoted additional reduction on HBV DNA level. Declined levels of HBsAg, HBeAg, and HBcAg were observed in SSc and LdT combination group. Conclusion These in vitro results indicated that SSc acted as a promising nucleoside analogue adjuvant, especially for telbivudine in the therapeutic strategies against HBV infection.