The inverse association of serum HBV DNA level with HDL and adiponectin in chronic hepatitis B infection

<p>Abstract</p> <p>BACKGROUND</p> <p>The natural history of hepatitis B virus (HBV) is complex and influenced by the level of viral replication and host factors. The hepatoprotective role of high density lipoproteins (HDL) and adiponectin as host factors on HBV persistence is less well understood.</p> <p>METHODS</p> <p>To investigate correlation between HBV DNA level with clinical parameters in patients with chronic hepatitis B, 92 male subjects with HBV infection without any risk factors for diabetes were enrolled in this study. Age and BMI of the study population were matched and HBV DNA, ALT, tumor necrosis factor alpha (TNF-α), adiponectin and lipid levels was measured.</p> <p>RESULTS</p> <p>Serum HBV DNA correlated inversely with serum HDL level (r = -0.23; P = 0.014). The median of log copies/ml for HBV DNA (3.67) was considered as cut off point. Patients with HBV DNA level higher than cut off point had lower adiponectin (8.7 ± 5.3 vs 10.7 ± 4.9 μg/ml p = 0.05). Also, adiponectin had a negative correlation with TNF-α (r = -0.21, P = 0.04) and positive correlations with HDL (r = 0.18, P = 0.043).Multivariate regression models show that serum HDL level is an independed factor to predict serum HBV DNA.</p> <p>CONCLUSION</p> <p>Our findings showed that higher HBV DNA levels are associated with lower HDL and adiponectin but induced TNF-alpha values.</p

Protein-x of hepatitis B virus in interaction with CCAAT/enhancer-binding protein α (C/EBPα) - an in silico analysis approach

<p>Abstract</p> <p>Background</p> <p>Even though many functions of protein-x from the Hepatitis B virus (HBV) have been revealed, the nature of protein-x is yet unknown. This protein is well-known for its transactivation activity through interaction with several cellular transcription factors, it is also known as an oncogene. In this work, we have presented computational approaches to design a model to show the structure of protein-x and its respective binding sites associated with the CCAAT/enhancer-binding protein α (C/EBPα). C/EBPα belongs to the bZip family of transcription factors, which activates transcription of several genes through its binding sites in liver and fat cells. The C/EBPα has been shown to bind and modulate enhancer I and the enhancer II/core promoter of HBV. In this study using the bioinformatics tools we tried to present a reliable model for the protein-x interaction with C/EBPα.</p> <p>Results</p> <p>The amino acid sequence of protein-x was extracted from UniProt [UniProt:Q80IU5] and the x-ray crystal structure of the partial CCAAT-enhancer α [PDB:<ext-link ext-link-id="1NWQ" ext-link-type="pdb">1NWQ</ext-link>] was retrieved from the Protein Data Bank (PDB). Similarity search for protein-x was carried out by psi-blast and bl2seq using NCBI [GenBank: <ext-link ext-link-id="BAC65106.1" ext-link-type="gen">BAC65106.1</ext-link>] and Local Meta-Threading-Server (LOMETS) was used as a threading server for determining the maximum tertiary structure similarities. Advanced MODELLER was implemented to design a comparative model, however, due to the lack of a suitable template, Quark was used for <it>ab initio </it>tertiary structure prediction.</p> <p>The PDB-blast search indicated a maximum of 23% sequence identity and 33% similarity with crystal structure of the porcine reproductive and respiratory syndrome virus leader protease Nsp1α [PDB:<ext-link ext-link-id="3IFU" ext-link-type="pdb">3IFU</ext-link>]. This meant that protein-x does not have a suitable template to predict its tertiary structure using comparative modeling tools, therefore we used QUARK as an <it>ab initio </it>3D prediction approach. Docking results from the <it>ab initio </it>tertiary structure of protein-x and crystal structure of the C/EBPα- DNA region [PDB:<ext-link ext-link-id="1NWQ" ext-link-type="pdb">1NWQ</ext-link>] illustrated the protein-binding site interactions. Indeed, the N-terminal part of 1NWQ has a high affinity for certain regions in protein-x (e.g. from Ala76 to Ser101 and Thr105 to Glu125).</p> <p>Conclusion</p> <p>In this study, we predicted the structure of protein-x of HBV in interaction with C/EBPα. The docking results showed that protein-x has an interaction synergy with C/EBPα. However, despite previous experimental data, protein-x was found to interact with DNA. This can lead to a better understanding of the function of protein-x and may provide an opportunity to use it as a therapeutic target.</p

A population based study on hepatitis B virus in Northern Iran, Amol.

BACKGROUND: Viral hepatitis is a major health problem worldwide. Change in transmission patterns of hepatitis B makes it necessary to re-evaluate its prevalence and risk factors. OBJECTIVES: We aimed to determine the prevalence of HBV infection and its related risk factors in Amol city, Northern Iran. PATIENTS AND METHODS: As a population based study, a cluster sampling approach was used and 6146 individuals from the general population of urban and rural areas of Amol, Iran, from both genders and different ages were enrolled. Inclusion criteria were willingness to participate in the study, being a lifelong resident in Amol city or its surrounding areas with Iranian nationality. Ten milliliters (10 mL) of blood was taken from each study subject and checked regarding hepatitis B markers including HbsAg, HBsAb and HBcAb using a third generation ELISA. The prevalence of HBV infections and its potential risk factors were recorded. RESULTS: The prevalence of HBsAg, HBsAb and HBcAb were estimated as 0.9%, 30.7% and 10.5%, respectively. The mean age of all participants was 43.9 (95% CI: 43.4, 44.3) in females and 55.6 in (n = 3472) males. In our study, there was a significant association between family history of hepatitis, rural residency and presence of HBsAg. There was also a positive correlation between HBcAb and family history of hepatitis, history of other types of hepatic diseases, history of tattooing, traditional phlebotomy, male gender and age. In backward logistic regression, a significant association was found between history of hepatitis in first-degree family members (OR = 13.35; 95% CI: 6.26, 28.47) and place of residence (OR = 2.32; 95% CI: 1.27, 4.22) with presence of HBsAg. There was also a positive correlation between history of hepatitis among first-degree family members (OR = 2.49; 95% CI: 1.52, 4.08), history of tattooing (OR = 2.13; 95% CI: 1.33, 3.42), history of previous hepatitis (OR = 1.87; 95% CI: 1.06, 3.28), male sex (OR = 1.36; 95% CI: 1.12, 1.66) and age (OR = 1.03; 95% CI: 1.03, 1.04) with presence of HBcAb. CONCLUSIONS: The prevalence of hepatitis B in Amol City and its surrounding areas was about one percent, a lower rate than other reports from Iran

The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH

Multimorbidity as an important issue among women: results of gender difference investigation in a large population-based cross-sectional study in West Asia

Objectives: To investigate the impact of gender on multimorbidity in northern Iran. Design: A cross-sectional analysis of the Golestan cohort data. Setting: Golestan Province, Iran. Study population: 49 946 residents (age 40–75 years) of Golestan Province, Iran. Main outcome measures: Researchers collected data related to multimorbidity, defined as co-existence of two or more chronic diseases in an individual, at the beginning of a representative cohort study which recruited its participants from 2004 to 2008. The researchers utilised simple and multiple Poisson regression models with robust variances to examine the simultaneous effects of multiple factors. Results: Women had a 25.0% prevalence of multimorbidity, whereas men had a 13.4% prevalence (p&#60;0.001). Women of all age-groups had a higher prevalence of multimorbidity. Of note, multimorbidity began at a lower age (40–49 years) in women (17.3%) compared with men (8.6%) of the same age (p&#60;0.001). This study identified significant interactions between gender as well as socioeconomic status, ethnicity, physical activity, marital status, education level and smoking (p&#60;0.01). Conclusion: Prevention and control of multimorbidity requires health promotion programmes to increase public awareness about the modifiable risk factors, particularly among women

The marginal causal effect of opium consumption on the upper gastrointestinal cancer death using parametric g-formula: An analysis of 49,946 cases in the Golestan Cohort Study, Iran

Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most common cancers in the world. Hence, the determination of risk factors of UGI helps to reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study, we examine the causal effect of opium use on the time to UGI cancer death. Based on the Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to the study for four years (2004–2008) and followed annually until July 2018. We used “parametric g-formula” to study the causal effect of opium use on the time to death due to UGI. In this study, the information of 49946 individuals due to missingness were analyzed. So the median of follow-up time was 144 months and the prevalence of opium use was 17% (about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula = 1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results showed a causal effect of opium use on the intensity of upper gastrointestinal cancer deat

Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- a cross-sectional analysis of 50,000 individuals.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. METHODS: We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. RESULTS: Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75) and opium use (OR 1.70, 95% CI 1.55-1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). CONCLUSION: GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere

Multimorbidity and associations with clinical outcomes in a middle-aged population in Iran: a longitudinal cohort study

BACKGROUND: As the populations of lower-income and middle-income countries age, multimorbidity is increasing, but there is little information on its long-term consequences. We aimed to show associations between multimorbidity and outcomes of mortality and hospitalisation in Iran, a middle-income country undergoing rapid economic transition. METHODS: We conducted a secondary analysis of longitudinal data collected in the Golestan Cohort Study. Data on demographics, morbidities and lifestyle factors were collected at baseline, and information on hospitalisations or deaths was captured annually. Logistic regression was used to analyse the association between baseline multimorbidity and 10-year mortality, Cox-proportional hazard models to measure lifetime risk of mortality and zero-inflation models to investigate the association between hospitalisation and multimorbidity. Multimorbidity was classified as ≥2 conditions or number of conditions. Demographic, lifestyle and socioeconomic variables were included as covariables. RESULTS: The study recruited 50 045 participants aged 40–75 years between 2004 and 2008, 47 883 were available for analysis, 416 (57.3%) were female and 12 736 (27.94%) were multimorbid. The odds of dying at 10 years for multimorbidity defined as ≥2 conditions was 1.99 (95% CI 1.86 to 2.12, p<0.001), and it increased with increasing number of conditions (OR of 3.57; 95% CI 3.12 to 4.08, p<0.001 for ≥4 conditions). The survival analysis showed the hazard of death for those with ≥4 conditions was 3.06 (95% CI 2.74 to 3.43, p<0.001). The number of hospital admissions increased with number of conditions (OR of not being hospitalised of 0.36; 95% CI 0.31 to 0.52, p<0.001, for ≥4 conditions). CONCLUSION: The long-terms effects of multimorbidity on mortality and hospitalisation are similar in this population to those seen in high-income countries

The role of mutations in core protein of hepatitis B virus in liver fibrosis

The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 ± 9 years old) with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL) epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 ± 0.8 vs 1.9 ± 1.4 for mean stage of fibrosis P = 0.05). Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both). Patients with mutation in C-terminal domain had higher serum ALT (62 ± 17 vs 36 ± 12 IU/l, p = 0.02). Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein