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.
Seroprevalence and factors associated with hepatitis B infection among the hill tribe adult population in Thailand: a cross-sectional study
BMC INFECTIOUS DISEASES
Authors: Upala, Panupong; Apidechkul, Tawatchai; Tamornpark, Ratipark; Chomchoei, Chalitar; Yeemard, Fartima
Abstract
BackgroundHepatitis B virus (HBV) infection is one of the greatest public health burdens, particularly for people living with several barriers to access to health care services, such as the hill tribe adult population in Thailand. People aged 25years and over who are out of the target population for HBV immunization under the national Expanded Program on Immunization (EPI) are at risk of HBV infection. The study aimed to estimate the prevalence and determine the factors associated with HBV infection among hill tribe adults aged 25years and over living in Chiang Rai Province, Thailand.MethodsA cross-sectional study design was used to collect information on hill tribe adults aged 25years and over living in 36 selected hill tribe villages in Chiang Rai Province. All people living in the selected villages who met the criteria were invited to participate in the study. A validated questionnaire and a 5-mL blood specimen were used as research instruments. Hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface (anti-HBs), and antibody to hepatitis B core (anti-HBc) were detected by using the Wondfo Test Kit(@), which has high sensitivity and specificity. Logistic regression was used to detect the associations between variables at the significance level of alpha =0.05.ResultsA total of 1491 individuals were recruited into the analysis; 60.8% were females, 81.3% were aged between 30 and 60years, and 86.0% were married. The majority were illiterate (54.9%), were Buddhist (55.7%), worked in agricultural sectors (87.3%), and had an annual income of less than 50,000 baht per year (72.9%). The overall prevalence of hepatitis B infection was 26.6%; 7.6% were positive for HBsAg, 19.2% were positive for anti-HBs, and 18.9% were positive for anti-HBc. In the multivariate analysis, three variables were found to be associated with hepatitis B infection: those who were in the Yao and Lisu tribes had a 1.64-fold (95% CI=1.08-2.49) and a 1.93-fold (95% CI=1.10-3.31) greater chance, respectively, of HBV infection than did those in the Karen tribe; those who were Christian had a 1.41-fold (95% CI=1.06-1.87) greater chance of HBV infection than did those who were Buddhist; and those who did not use alcohol had a 1.29-fold (95% CI=1.01-1.65) greater chance of HBV infection than did those who used alcohol.ConclusionsIt is necessary to develop and implement effective public health interventions among hill tribe adult populations who are not part of the EPI-targeted population, particularly Christians, those in the Lisu and Yao tribes, and those who do not use alcohol, to reduce the HBV infection rate, save lives and reduce medical expenses.