HBV Infection Group Research Articles

Hepatitis B virus infection among hemodialysis patients in Aden-Yemen

HBV infection is one of major global health problems worldwide. It increases the morbidity and mortality rates among hemodialysis patients which make the management process more complicated. This study was aimed to determine the prevalence of HBV infection among hemodialysis patients and assessment the risk factors associated with infection. An analytical cross-sectional study was conducted on 50 HD patients. Blood samples were collected and serum HBsAg was analyzed using ELISA technique. The overall prevalence of HBV was 6 (12.0%). The males had highest rate. There were statistically significant recorded between the prevalence of HBV infection and age group 30 – 39 years and duration of hemodialysis from 1-2 years and more than 2 years (p=0.02, 0.001 and 0.001) respectively. It can be concluded that the HBV prevalent rate among HD patients was common and lower than that reported among most general population in Yemen. Increasing of the duration and long standing in hemodialysis unit may increase the risk of HBV infection. Hepatitis B vaccine should be given to all HBV negative HD patients before HD process and health education programs about the transmission routes of HBV and preventive measures should be implemented for general population.

Association of hepatitis B virus and thyroid hormones during pregnancy.

This study aims to evaluate the correlation between serum thyroid hormone levels and hepatitis B virus (HBV) DNA and HBV genotypes in pregnant women with chronic hepatitis B. A total of 96 pregnant women with chronic HBV-infected pregnant women between January 2020 and December 2022 were selected as the observational study subjects. About 50 HBV-uninfected pregnant women during the same period were selected as the control group. Serum thyroid hormone levels at different stages of pregnancy, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroperoxidase antibody (TPOAb), and thyroglobulin antibody (TGAb), were compared between the 2 groups. Thyroid hormones levels were also compared between HBV-DNA-positive and HBV-DNA-negative women in the HBV-infected pregnancy group, and to determine the correlation between thyroid hormones levels and HBV-DNA load and HBV genotype in HBV-DNA-positive pregnant women. The TSH levels in mid and late pregnancy and TPOAb levels in early, mid, and late pregnancy of HBV-infected pregnant women were higher than those in the same period in HBV-uninfected pregnant women (P < .05). The TPOAb and TGAb levels in early, mid, and late pregnancy of HBV-DNA-positive pregnant women were higher than those in the same period in HBV-DNA-negative pregnant women (P < .05). The HBV-DNA load and FT3 or FT4 levels were negatively correlated (P < .05), and the HBV-DNA load and TGAb levels were positively correlated (P < .05). However, there was no statistical difference in thyroid hormone levels between different HBV genotypes (P > .05). The thyroid hormone levels will change in pregnant women infected with hepatitis B virus, and there is a certain correlation between HBV-DNA load and thyroid hormone levels. Therefore, timely monitoring of thyroid hormones and HBV-DNA load can provide early prevention and treatment for HBV infection in pregnant women, ensuring the health of pregnant women and fetuses.

Effects of male hepatitis B virus infection and serostatus on sperm quality, pregnancy outcomes, and neonatal outcomes following intrauterine insemination.

To evaluate the impact of male hepatitis B virus (HBV) infection and serostatus on sperm quality, pregnancy outcomes, and neonatal outcomes following intrauterine insemination for infertility. We retrospectively analyzed data from 962 infertile couples undergoing intrauterine insemination treatment at a single center. The case group comprised 212 infertile couples with male HBV infection, and the control group comprised 750 noninfected infertile couples. The couples were further divided into subgroups according to their hepatitis B e antigen (HBeAg)/anti-HBe status: hepatitis B surface antigen (HBsAg)+HBeAg- (group A), HBsAg+HBeAg+ (group B), and HBsAg-HBeAg- (control group). The main outcome parameters, including the seminal parameters, clinical pregnancy rate, miscarriage rate, live birth rate, preterm delivery rate, multiple pregnancy rate, delivery type, birth weight, and sex ratio, were compared. A lower sperm acrosin activity, higher cesarean rate, and newborn sex ratio were observed in the HBV-infected group and group A in comparison with the control group (P < 0.05). However, the standard sperm parameters, clinical pregnancy rate, miscarriage rate, live birth rate, preterm delivery, and birth weight showed no statistically significant differences among the groups. Male HBV infection does not adversely impact standard sperm parameters or pregnancy outcomes but can influence sperm acrosin activity and some neonatal outcomes. Moreover, the effect may vary among different HBV serostatuses.

Deviations in the content of neurotransmitters amino acids in patients with chronic hepatopathies

Introduction. Some amino acids are neurotransmitters. These include glycine (Gly), gamma-aminobutyric acid (GABA), glutamate (Glu), and aspartate (Asp). The liver is an important organ for the metabolism of amino acids. Materials and methods. It was examined 24 patients with chronic hepatopathy: 12 patients with chronic HBV infection (group I) and 12 patients with hepatic steatosis (group II), the control group (CG) consisted of 12 practically healthy individuals. Quantitative determination of Asp, Glu, Gly and GABA in blood serum was carried out using liquid chromatography. Results. In most patients with chronic hepatopathy Gly and Asp levels were within the regional norms, GABA levels were higher, and Glu levels were below the reference values. In I-st group of patients the level of Gly was 18.76±1.45, GABA - 0.83±0.06, Asp - 5.56±0.97, and Glu - 6.34±0.70 mcM/ dL. In II-nd group: the level of Gly was 22.37±0.91, GABA 0.77±0.03, Asp - 5.16±0.74, and Glu - 7.87±1.47 mcM/dL. In CG: the level of Gly was 22.93±2.21, GABA - 0.55±0.06, Asp - 2.69±0.45, and Glu - 12.46±1.92 mcM/dL. Conclusion. A violation of neurotransmitter amino acids metabolism is found in chronic hepatopathy. A decrease in glycine and glutamate was observed in patients’ blood serum, with an increase in GABA and aspartate. These disorders are most profound in individuals with chronic viral infection B.

Lifetime Risk of Hepatorenal Events Assessed in Longitudinal Cohort of Renal Transplant Recipients with HBV Infection

Kidney transplantation is a treatment option for patients with end-stage renal disease (ESRD) who are infected with hepatitis B virus (HBV). However, the impact of nucleos(t)ide analogues usage on the clinical outcomes in HBV-infected ESRD patients undergoing kidney transplantation is not well understood. This study aimed to assess the outcomes of kidney transplant recipients with HBV infection using real-world data to provide insight into the disease course over time. A nationwide retrospective longitudinal population-level cohort study was conducted using the National Health Insurance Research Database. The study evaluated patient and allograft survival and kidney-related and liver-related events and identified factors contributing to these events. Of the 4838 renal transplant recipients in the study, there were no significant differences in graft survival between the HBV-infected and non-infected groups (P=.244). However, the HBV-infected group had suboptimal patient survival compared to the non-infected group (hazard ratio [HR] for overall survival, 1.80; 95% CI 1.40-2.30; P < .001). Diabetes mellitus was associated with a higher re-dialysis rate (HR, 1.71; 95% CI, 1.38-2.12; P < .001) regarding kidney-associated events. For liver-associated events, HBV-infected status (HR, 9.40; 95% CI, 5.66-15.63; P < .001), and age >60 years (HR, 6.90; 95% CI, 3.14-15.19; P < .001) were associated with increased incidence of liver cancer. Hepatitis B-infected renal transplant recipients have comparable graft survival but inferior patient survival outcomes due to pre-existing diseases and increasing liver-related complications. The findings of this study can help optimize treatment strategies and improve long-term outcomes for this patient population.

Restoration of IL-11 and IL-15 cytokine production post calcium modulators and ROS treatment can assist viral clearance both in vitro and in vivo.

Hepatitis B virus (HBV) infection alters the cytokines production to establish persistent infection. A reversion of cytokines back to their normal state can be a promising therapeutic approach to establish an optimal host immune response. We investigated the alteration in expression of IL-15 and IL-11 after HBV infection in vitro and in vivo in PBMCs of 63 individuals divided into various HBV-infected patient groups. The mRNA expression was evaluated post-anti-oxidant and calcium modulators treatment by Real-time qPCR. In vitro mRNA expression of both cytokines, post-infection was down-regulated considerably. Interestingly, in line with in vitro results, both cytokines' in vivo expression was intensively down-regulated in chronic HBV-infected individuals rather than healthy controls. Both cytokines' expression was up-regulated in cases of recovery compared with the inactive carriers and chronic HBV-infected individuals. IL-15 mRNA expression was significantly up-regulated in both cell lines post EGTA and Ru360 treatment while a significant increase was observed in the HepAD38 cell line with NAC and BAPTA treatment. IL-11 mRNA expression was significantly up-regulated in the HepG2 cell line after all modulator treatments, whereas in the HepAd38 cell line it was observed after BAPTA treatment. Our results thus indicate that viral infection tends to down-regulate the expression of cytokines and an in vivo up-regulation is an indication of recovery. Treatment of anti-oxidants and calcium modulators has resulted in the successful restoration of these cytokines thus pointing towards the use of calcium modulators to boost natural antiviral cytokine production.

Impact of hepatitis B virus infection on maternal and infant outcomes of women with gestational diabetes mellitus: A three-year retrospective study

AimsTo explore the impact of HBV infection on maternal and infant outcomes of GDM women. MethodsWe retrospectively identified 8126 women with GDM in China from July 2017 to June 2020, and divided them into GDM with HBV infection group (n = 483) and GDM with non-HBV infection group (n = 7643). Two sample t-test and Chi-square test were used to compare differences between groups. Logistic regression models were used to explore the association between HBV infection and maternal and infant outcomes. ResultsPlacental abruption (PA), (2.3% vs. 1.0%, P = 0.008), placenta previa (4.3% vs. 2.8% p = 0.044), intrahepatic cholestasis of pregnancy (ICP), (6.4% vs. 3.0%, P < 0.001), cesarean section (52.0% vs. 46.0%, P = 0.011), fetal chromosomal abnormalities (1.2% vs. 0.4%, P = 0.021), and neonatal hyperglycemia (1.9% vs. 3.6%, P = 0.047) were more likely to occur in GDM with HBV infection group. After adjusting for the covariates, HBV infection was found to be associated with ICP (aOR, 2.35; 95% CI: [1.58–3.50]), PA (aOR, 2.34; 95% CI: 1.22–4.47), and fetal chromosomal abnormalities (aOR, 2.88; 95% CI: 1.18–7.03). ConclusionsHBV infection was associated with part of maternal and infant outcomes in the GDM population.

Importance of miR-141-5p and miR-501-5P expression in patients with HBV infection.

MicroRNAs (miRNAs) as small RNA and post-transcriptional modulators are shown to have regulatory effects for different cellular activities and pathways, such as metabolism, virus replication and also cell growth. In addition, miRNAs can regulate the replication of the hepatitis B virus (HBV). Therefore, the expression profile of miRNAs was evaluated in HBV-infected patient groups and healthy controls. The expression levels of the following microRNAs (as noninvasive biomarkers) were compared in two experimental (those with various stages of HBV infection) and control groups to evaluate their diagnosis ability: mir141-5p and mir501-5p. RNA extraction was performed for 45 serum samples. The miRCURY LNA™ Universal RT-miRNA-PCR system and miRNA PCR panels were used for measuring microRNA expression profiles. To normalize quantitative values, the endogenous reference by UniSp6 expression was used. Serum mir141-5p and mir501-5 were significant None in patient in different stages of HBV infection(p<0.001) than in controls(p<0.01). Receiver operating characteristic (ROC) curve analyses suggested that serum has mir141-5p and mir501-5p none significant diagnostic value for HBV infection. Results suggest that mir141-5p and mir501-5 can not be used as diagnostic biomarkers for monitoring of HBV infection and other biomarkers in this disease need to be investigated.

Kinetics of quantitative hepatitis B surface antigen in patients with rheumatic disease and chronic hepatitis B receiving biologic agents.

The effect of biologic treatment on quantitative Hepatitis B surface Antigen (qHBsAg) levels and HBsAg clearance in rheumatic patients with chronic HBV infection has not been well studied. We prospectively followed rheumatic patients with HBeAg-negative chronic HBV infection (n=28) treated with biologics and oral antivirals, categorized into patients with chronic hepatitis B (CHB, group A n=13) and chronic HBV infection (group B n=15) and matched them to appropriate non-rheumatic controls. qHBsAg kinetics were serially measured and compared between groups. No HBV reactivation (HBVr) was recorded during the 108.25 patient-year follow-up. Among patients with CHB, the annual rapid qHBsAg decline (i.e. decline >0.5log10 IU/mL/year) as well as HBsAg clearance did not differ between rheumatic patients [n=4 (32.7%), n=1 (7.7%)] and controls [n=6 (28.4%), p=.726 and n=2 (7.7%), p=.818, respectively]. In contrast, there was a slower annual qHBsAg decline in rheumatic patients with chronic HBV compared to non-rheumatic controls (-0.04 vs -0.13log10 IU/mL at year 1, p=.019) with no cases of rapid qHBsAg decline or HBsAg clearance in rheumatic patients (0%) compared to a cumulative incidence of 24% and a rate of 20%, respectively in controls. In biologic-treated rheumatic patients with HBeAg-negative HBV receiving antiviral prophylaxis, there was slower qHBsAg decline, lower cumulative rates of rapid qHBsAg decline and HBsAg clearance compared to non-rheumatic controls.

Risk Factors for Hepatitis B Virus Transmission in Oman.

ObjectivesHepatitis B virus (HBV) is a major public health problem worldwide. The prevalence of HBV is dependent on the modes of transmission. Chronic hepatitis B (CHB) infection can progress to liver cirrhosis and hepatocellular carcinoma. Oman is regarded as an intermediate endemic region and has had a neonatal vaccine against HBV since 1990. However, little research has been conducted regarding risk factors for HBV transmission. Our study aimed to identify the prevalence of major risk factors for acquiring HBV in Oman.MethodsWe conducted a retrospective chart review of all adult Omani patients diagnosed with CHB at two tertiary hospitals in Oman, Sultan Qaboos University Hospital and Armed Forces Hospital, between February 2009 and July 2013. The prevalence of major risk factors was identified by interviewing CHB patients using a standard questionnaire during their follow-up visits to the hepatology clinic at both hospitals. The risk factor frequency was stratified by age, gender, and educational level.ResultsA total of 274 patients were interviewed; 52.2% of the participants were males. The median age for men was 35.9 years and 35.1 years for women, with 75.5% aged 20–39 years old. The antenatal screening was the most common means of identifying HBV infection in females, and pre-blood donation screening was the most common in males. Intra-familial contact with HBV infected persons and behavioral risks such as body piercing (females) and barber shaving (males) were more common than nosocomial risk factors. Knowledge about HBV infection was scarce among our participants. More than half of the participants had a positive family history of HBV infection. There was a significant association between HBV infection and age groups, and educational levels (p < 0.050 and p < 0.001, respectively). Among those who were infected due to intra-familial contact or behavioral risk, there was a significant difference between the two sexes (p < 0.020) and between the three age groups (< 23, 23–28, >28) of HBV positive mothers (33.3%, 14.3%, and 6.6%, respectively; p < 0.050). There was also a statistically significant difference among different educational levels (p < 0.050).ConclusionsDirect contact of infected individuals within a family and exposure to high-risk behaviors such as piercing and barber shaving are the main reported risk factors for HBV infection in Omani patients. Reducing the vertical and horizontal transmission of HBV in Oman could be improved by implementing routine antenatal screening of pregnant women and a greater focus on contact screening, respectively.

Assisted reproductive technology outcomes in women with a chronic viral disease.

The aim of this study was to evaluate the cumulative live birth rate in women undergoing in-vitro fertilization/intracytoplasmic-sperm-injection (IVF/ICSI) according to the type of chronic viral infection [HIV, hepatitis-B virus (HBV) and hepatitis-C virus (HCV)]. A cohort study. A tertiary-care university hospital. Women with a chronic viral illness HIV, HBV or HCV- were followed until four IVF/ICSI cycles had been completed, until delivery or until discontinuation of the treatment before the completion of four cycles. The primary outcome was the cumulative live birth rate after up to four IVF/ICSI cycles. A total of 235 women were allocated to the HIV-infected group (n = 101), the HBV-infected group (n = 114) and the HCV-infected group (n = 20). The cumulative live birth rate after four cycles was significantly lower in the HIV-infected women than in those with HBV [39.1%, 95% confidence interval (95% CI): 17.7-60.9 versus 52.8%, 95% CI: 41.6-65.5, respectively; P = 0.004]. Regarding the obstetrical outcomes, the mean birth weight was lower in the HIV-infected women than in those with HBV or HCV. Multivariate analysis indicated that the age, the anti-Müllerian hormone and the number of cycles performed were significantly associated with the chances of a live birth. HIV-infected women had lower cumulative live birth rate than women with chronic hepatitis, and this was due to less favourable ovarian reserve parameters. These findings underscore the need to better inform practitioners and patients regarding fertility issues and the importance of early fertility assessment. However, larger studies are necessary to gain more in-depth knowledge of the direct impact of HIV on live birth rates.

The Association between Interleukin-10 Gene Polymorphisms and Hepatitis B Virus: Evidence in Iran

Background and Aim: Hepatitis B virus (HBV) is a human carcinogenesis agent. Interleukin 10 (IL-10) is a key anti-inflammatory cytokine, and single nucleotide polymorphisms in IL-10 gene promoter are correlated with infections caused by HBV. This research intended to assess the prevalence and genotype of HBV as well as the association between the polymorphisms of -819 and -1082 in the IL-10 gene with HBV in individuals with HBV infection in Qom Province, Iran Methods: In this cross-sectional research, 360 individuals with chronic HBV infection and control group were involved between July 2018 and March 2019. HBV diagnosis was evaluated using ELISA and nested PCR assays. To determine polymorphisms in the IL-10 gene promoter in HBV positive and control samples, an allele-specific polymerase chain reaction technique was employed. Results: The constructed phylogenetic trees for the HBsAg gene revealed that all sequences under study belong to genotype D and also, the majority of HBV samples presented similar sequences to the Iranian samples. Genotype frequencies of TT, TC and CC (polymorphism -819) were 82.2%, 11.6% and 6.1% for patients and 85%, 10.5% and 4.4% in control groups, respectively. Also, frequency of genotypes of AA, AG and GG (polymorphism -1082) were 45%, 43.8% and 11.1% for patients and 42.2%, 46.1% and 11.6% in control groups, respectively. Conclusion: Here, we found no association among IL-10 gene polymorphisms in control and HBV-infected groups. However, more studies about the frequency of chronic HBV infection are necessary to be conducted. *Corresponding Author: Mohsen Zargar; Email: zargar@qom-iau.ac.ir Interleukins-10 Gene Polymorphism and Hepatitis B Virus: Evidence in Iran. Arch Med Lab Sci. 2021;7:1-7 (e7). https://doi.org/10.22037/amls.v7.33557

Effect of oxidative stress and calcium deregulation on FAM26F (CALHM6) expression during hepatitis B virus infection

BackgroundFamily with sequence similarity 26, member F (FAM26F) is an important innate immunity modulator playing a significant role in diverse immune responses, however, the association of FAM26F expression with HBV infection is not yet known. Thus, the current study aims to explore the differential expression of FAM26F in vitro in HepAD38 and HepG2 cell lines upon HBV infection, and in vivo in HBV infected individuals. The effects of antioxidant and calcium inhibitors on the regulation of FAM26F expression were also evaluated. The expression of FAM26F was simultaneously determined with well-established HBV infection markers: IRF3, and IFN-β.MethodsThe expression of FAM26F and marker genes was analyzed through Real-time qPCR and western blot.ResultsOur results indicate that the differential expression of FAM26F followed the same trend as that of IRF3 and IFN-β. The in vitro study revealed that, in both HBV infected cell lines, FAM26F expression was significantly down-regulated as compared to uninfected control cells. Treatment of cells with N-acetyl-L-cysteine (NAC), EGTA-AM, BAPTA-AM, and Ru360 significantly upregulated the expression of FAM26F in both the cell lines. Moreover, in in vivo study, FAM26F expression was significantly downregulated in all HBV infected groups as compared to controls (p = 0.0007). The expression was higher in the HBV recovered cases, probably due to the decrease in infection and increase in the immunity of these individuals.ConclusionOur study is the first to show the association of FAM26F with HBV infection. It is proposed that FAM26F expression could be an early predictive marker for HBV infection, and thus is worthy of further investigation.

Mortality in relation to hepatitis B virus (HBV) infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy.

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub-Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)-positive with HBV DNA≥2,000IU/ml; HBsAg-positive with HBV DNA<2,000IU/ml; isolated HBcAb-positive; resolved infection (HBsAb-positive/HBcAb-positive); and HBV non-immune/vaccinated (HBcAb-negative). We compared square-root CD4-cell count increases using mixed-effect, non-linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all-cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti-HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non-immune/vaccinated. We found no significant difference in CD4 cell increases between HBV-infection groups after adjustment (p=0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all-cause mortality (1.9/100 person-years, 95% Credibile Interval [CrI]=1.0-3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI=-79%, -13%), 60% (95%CrI=-82%, -12%) and 66% (95%CrI=-84%, -23%) in those who had isolated anti-HBcAb-positive, resolved HBV infection and HBV non-immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti-HBcAb-positive serology, much like HBV non-immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV-related management would not be necessary for these individuals.

Interaction analysis of IL-12A and IL-12B gene variants with chronic hepatitis B infection in Tunisian patients

Given the key role of interleukin-12 (IL-12) in the control of HBV, we investigated the possible correlation between IL-12A rs568408 and IL-12B rs3212227 polymorphisms and the risk of chronic HBV infection in Tunisian population.Two hundred patients with chronic HBV infection and two hundred healthy controls were genotyped using PCR-RFLP.A allele, AA and AG genotypes of IL-12A rs568408 were more represented in the chronic HBV infection group compared to the control group, and they were associated with 1.65-, 2.58- and 3.13-fold risks of developing this infection, respectively.Gene–gene interaction analysis showed that subjects carrying the IL-12A rs568408AA/AG and IL-12B rs3212227AA genotypes had a 3.16-fold increased risk of chronic HBV infection.This study suggested that IL-12A rs568408 and gene–gene interactions of IL-12A rs568408 and IL-12B rs3212227 contributed to the outcome of chronic HBV infection, meanwhile indicating their usefulness as a predictive and diagnostic biomarker of chronic HBV infection.

Distinct clinical and genetic characteristics of AFP-negative hepatocellular carcinoma patients infected by HBV or HCV.

e16620 Background: The serum level of alpha-fetoprotein (AFP) is a key biomarker in hepatocellular carcinoma (HCC) screening regardless of the high false-negative rates. Studies have characterized AFP negative HCC patients, however, the differences between HBV and HCV infected AFP negative HCC patients have not been discussed. Methods: The clinical profiles and whole-exome sequencing data of 243 patients were downloaded from the TCGA database. Patients were divided into 4 groups based on their virus infection status and serum AFP measurements as indicated in the table. The mutation profiles and clinical features of the patients were analyzed. Results: In the HBV infected groups, the AFP+ patients carried significantly larger tumors (n = 17, 85.88±11.87 mm) compared to the AFP- patients (n = 13, 49.08±8.933 mm, p = 0.026). The HBV+ AFP+ group exhibited the prevalence of vascular invasion (VI, 76%, 13/17) while less than half of the patients in the HBV+ AFP- group developed VI (46%, 6/13). The WES results identified shared mutations in more than 10% of patients in each group. It appeared that 126 shared mutations were restricted to the HBV+ AFP+ group, they are involved in the regulation of ion transmembrane transport (p &lt; 0.001) and interaction between L1 and Ankyrins (p &lt; 0.0001). Only 51 shared mutations were exclusive to the HBV+ AFP- group, they majorly affect developmental growth (p &lt; 0.001) and skeletal system development (p &lt; 0.01). In contrast, the tumor sizes of HCV+ AFP+ and HCV+ AFP- patients are similar (55.18±7.781 vs 48.19±5.564, p = 0.47), while the VI rate is higher in the HCV+ AFP- group (63%, 17/29, Table). In total, 11 shared mutations were restricted to the HCV+ AFP+ group, several of the genes were involved in the generation of precursor metabolites and energy (p &lt; 0.01) and activation of immune response (p &lt; 0.01). 27 shared mutations were exclusive to the HCV+ AFP- group, the enrichment analysis showed that they are related to the regulation of synapse organization (p &lt; 0.0001) and the regulation of chromosome organization (p &lt; 0.01). Conclusions: HBV and HCV infection were associated with distinct clinical features among the AFP positive and AFP negative patients. The differences were underpinned by the mutations exclusive to each group, and they were involved in distinct molecular and cellular functions. [Table: see text]

The mutation profiles of HBV or HCV infected hepatocellular carcinoma patients underlie the varied responses to second-line immunotherapy.

e16629 Background: HBV and HCV infections facilitate the development of hepatocellular carcinoma (HCC) via different mechanisms, given that the DNA sequence of HBV but not HCV can integrate into the host genome. However, it remains unclear that whether the altered genomic landscape of HCC patients caused by HBV or HCV infection may result in different responses to treatments. Methods: The MSK panel sequencing results and treatment data of 127 HCC patients were downloaded from the TCGA database (MSK, Clin Cancer Res 2018). Profiles of HBV positive and HCV positive patients were extracted. Based on the treatment received, those patients were classified to sorafenib treated groups and sorafenib + immunotherapy (IT) groups. The progression-free survival (PFS, months) and overall survival (OS, months) were compared, and the mutational profiles of patients were analyzed. Results: Among patients who received sorafenib treatment alone, the mean PFS of HBV positive patients (n = 12, 4.9 ±1.1) is similar to that of the HCV positive patients (n = 21, 5.1±1.8). However, the mean OS of HBV positive patients (n = 12, 18.3 ±6.6) was longer than the mean OS of HCV positive patients (n = 21, 10.0 ±1.9). Among the patients who received immunotherapy following sorafenib treatment, the mean IT PFS of HBV positive patients was (n = 5, 4.4 ±1.8), which was longer than the mean IT PFS of HCV positive patients (n = 5, 2.5 ±0.5). Consistently, the mean IT OS of HBV positive patients (n = 5, 10.9 ±4.4) was longer than the mean IO PFS of HCV positive patients (n = 5, 4.6 ±1.0). Overall it seems that the HBV positive patients responded better to second-line immunotherapy, despite the fact that these comparisons did not reach statistical difference due to the limited sample size. By comparing the MSK panel sequencing results, mutations exclusive to the HBV or HCV infected groups were identified. Enrichment analysis showed that 7/35 mutations exclusively found in the HBV positive group are responsible for lymphocyte activation (p &lt; 0.00001), which may underlie the better IT treatment outcome. Among the mutations restricted to the HCV infected group, 9/50 were involved in histone modification, 7/50 were involved in Hepatitis B pathways (p &lt; 0.0001), suggesting that HCV infection may interfere with diverse molecular processes. Conclusions: HBV and HCV infected HCC patients may respond differently to second-line immunotherapy. This difference is perhaps related to the altered genetic landscape of the patients resulted from virus infections by HBV or HCV.

Levels and Significance of Serum Adiponectin in Patients with Chronic HBV Infection at Different Clinical Stages

To analyze the serum APN levels of patients with chronic HBV infection in different clinical stages and their correlation with clinical laboratory examination indicators. A total of 120 HBV-infected patients are included in this study, including chronic HBV carriers, chronic hepatitis B (CHB) and compensated cirrhosis patients, 40 cases in each group, and 40 medical examinees as healthy controls. Compared with the healthy control group, the APN level in the chronic HBV infection group is significantly increased (p&lt;0.05), and the APN level in the cirrhosis group is significantly increased compared with the other two groups (p&lt;0.05). There is no significant difference between the chronic HBV carrier group and the CHB group. The ratio of people with high APN in the high DNA viral load group is higher (p = 0.002, χ2 = 9.143); the APN level of the liver cirrhosis group is significantly different from the non-cirrhosis group (P = 0.004, χ2 = 8.123). There is no significant correlation between APN level and ALT, AST and other indicators (P&gt;, 0.05). High serum APN may be used as a marker for the diagnosis of HBV-infected liver cirrhosis.

142P - Relation between Interleukin -4 (590C/T) gene polymorphism and hepatocellular carcinoma risk in HBV and HCV patients

BackgroundInterleukin-4 (IL-4) is an important modulator in the immune response of macrophages, B and T cells to stand in front of infections and malignancy. This study aimed to assess the association between IL-4 gene 590C\\T polymorphism and risk of hepatocellular carcinoma (HCC) on top of viral hepatitis. MethodsThis study was conducted on 220 patients and 60 apparently healthy individuals. One hundred and twenty patients with HCV infection (group 1) classified as sixty patients with liver cirrhosis and sixty with HCC, one hundred patients with HBV infection (group 2) classified as fifty with liver cirrhosis and fifty with HCC. Virus status of the patients was confirmed by measuring HBsAg, HCV antibodies and real time PCR. Liver cirrhosis was assessed by laboratory investigations, abdomino-pelvic ultrasound and CHILD score. Patients with HCC were diagnosed by triphasic CT, alphafeto-protein level (AFP) and biopsy. The studied groups were genotyped for IL-4 590C/T gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. ResultsIL-4 590C/T gene analysis detected significant variation between studied groups, regarding genotype and allele frequencies (p = 0.025 and p = 0.002 respectively). There were higher frequencies of CC genotype and C allele in HCC and cirrhotic hepatitis C patients than controls. C allele had higher prevalence in HCC than cirrhosis in HBV patients. CT+CC genotype carriers had an elevated HCC risk odd ratio (OR): 4.6 [95% CI: 1.5 –14] and OR 3.6 [95% CI: 1.1 –11.6], in HCV and HBV patients in contrast to controls. C allele was associated with increased cirrhotic and HCC risk in HCV infected patients with OR = 4 [95% CI: 1.8 – 8.8] and OR = 2.3 [95% CI: 1.1 – 5.2] versus control group. In HBV patients C allele showed higher HCC risk with OR = 4.2 [95% CI: 1.8 – 9.5] when compared to controls. ConclusionsIL-4 590C/T gene polymorphism may have a role in occurrence of HCC on top of liver cirrhosis. Legal entity responsible for the studyauthors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females

The relationship between females with low glucose-6-phosphate dehydrogenase activity level (LG6PD) and HBV infection is unclear. We conducted a cross sectional study of 124 406 reproductive-age Chinese females who participated in the National Free Pre-conception Check-up Projects to investigate the risk of HBV infection among females with LG6PD and its effect on liver enzyme. Based on HBV serological test results, the participants were divided into the susceptible, immunized, and HBV infected groups. The multivariable-adjusted odds ratios (ORs) for HBV infection in LG6PD participants were 1.71 (95% confidence interval (CI): 1.45–2.01) and 1.41 (95% CI: 1.23–1.62), respectively with the susceptible and immunized participants as references, compared to those without LG6PD. Participants with HBV infection only and combined with HBV infection and LG6PD had 184% and 249% significantly higher risks of elevated alanine transaminase (ALT) (susceptible participants as reference). If the immunized participants were used as reference, significant higher odds of elevated ALT occurred (3.48 (95% CI: 3.18–3.80), 4.28 (95% CI: 2.92–6.28)). Thus, reproductive-age females with LG6PD had a higher prevalence of HBV infection, and LG6PD might exacerbate ALT elevation in HBV infected females. Our findings underscore the need to explore collaborative management approaches for these two diseases among reproductive-age females for maternal and child health.