Hepatitis B-infected Patients Research Articles

HLA Gene Polymorphism in Patients with Chronic HBV Infection. Fundeni Clinical Institute Experience

Introduction: Hepatitis B virus (HBV) infection is a serious health problem for the public health systems in many countries worldwide. According to the European Society for the Liver Study, more than 350 million people are diagnosed with hepatitis B virus infection. Chronic viral HBV infection could be caused by the inability of both the cellular and humoral immune systems to eliminate HBV. HLA genes control cellular and humoral immune responses and present the viral antigens to CD8+ (cytotoxic T cells) and CD4+ T (T helper cells). Aim: To look at the HLA allele polymorphisms in chronic hepatitis B-infected patients to search for significant HLA allele associations. Methods: We have included 240 patients with HBV infection from the Gastroenterology and Hepatology ward, at Fundeni Clinical Institute. As a control group, 300 unrelated healthy people with no hepatitis B infection were also included. We have genotyped the HLA class I and class II genes for both patients and the control group with Next Generation Sequencing Illumina (Immucor, Mia Fora NGS Flex, Norcross, GA, USA). Results: Our preliminary data showed that HLA-DQA1*01:02:02 and HLADRB5*02:02:01 alleles are associated with the risk of HBV infection persistence. Conclusions: Our study showed that a specific HLA genotype profile is associated with chronic HBV infection in our Romanian patients.

Cloning and periplasmic soluble expression of hepatitis B surface antigen gene in Escherichia coli.

The objective of this study was to clone and express the hepatitis B surface antigen gene (HBsAg) in Escherichia coli (E. coli), thereby aiming to develop potential local therapeutics for combating Hepatitis B virus (HBV) infection in the Pakistani community by producing HBsAg in E. coli. Blood serum samples were collected from hepatitis B-infected patients, and their genomic DNA was extracted. Real-time and nested polymerase chain reaction (PCR) was performed to amplify the HBsAg gene. The gene of interest was cloned into the pET20b expression vector and transformed into E. coli BL21 (DE3) using Isopropyl β-D-1-thiogalactopyranoside (IPTG) induction. The gene's precise size was confirmed with gene-specific external and internal primers (681 bp and 400 bp, respectively). The HBsAg gene was successfully sequenced and submitted to GenBank, exhibiting 98% homology with targeted HBV sequences worldwide. The expression of HBsAg protein was confirmed through silver staining, Coomassie staining, western blot, and dot blot analysis. The expressed protein clones are now available for further development as a local recombinant DNA vaccine to prevent hepatitis B viral infection in the local community.

A CASE OF THYROTOXIC PERIODIC PARALYSIS AND MODERATE TO SE- VERE GRAVE’S OPHTHALMOPATHY REQUIRING INTRAVENOUS STEROID THERAPY WITH A COMORBIDITY OF CHRONIC HEPATITIS B INFECTION

Grave’s disease is an autoimmune thyroid disease with several characteristic symptoms and signs. Grave’s ophthalmopathy, an inflammatory disease in the orbital area, is the primary extrathyroid manifestation of Grave’s disease. About 5% of Grave’s ophthalmopathy patients have moderate to severe severity requiring high doses of systemic corticosteroid therapy. Grave’s disease also has a few complications, one of which is thyrotoxic periodic paralysis characterized by hypokalemia and muscle paralysis. Chronic hepatitis B virus infection has the potential to be co-incidence with other diseases (e.g., Grave’s ophthalmopathy). The need for a high dose of corticosteroid therapy in treating Grave’s ophthalmopathy is a risk of reactivation in hepatitis B-infected patients. This paper presented a Grave’s disease patient complicated with Grave’s ophthalmopathy who developed limb muscle weakness. The patient will receive high doses of corticosteroids and prophylactic lamivudine therapy to prevent hepatitis B virus reactivation.

The Use of Statin Is Associated With Better Disease-Free Survival In Patients with Hepatitis B-Related Hepatocellular Carcinoma after Curative Treatment

Background and aims: The association of use of statins and risk of hepatocellular carcinoma (HCC) hepatitis B-infected (HBV) patients has been reported. This study aimed to examine the effect of statin on survival after curative treatment for HCC in HBV population.

Serological markers and molecular analysis of hepatitis B infection in a tertiary care hospital at Kathmandu, Nepal.

To analyze the serology and molecular markers of the hepatitis B-infected patients from the tertiary care hospital at Kathmandu in Nepal. A total of 399 blood samples of patients from Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu, were collected. Samples were tested for HBsAg, HBeAg, and IgM anti-HBc using ELISA method. The samples were further categorized as acute and chronic. The genotyping was performed by real-time polymerase chain reaction (real-time PCR) and further validated by sequencing. Out of 399 samples that were collected, 271 and 128 samples were acute and chronic cases respectively. Fifty-six samples were genotyped by qPCR, out of which 40 samples belonged to genotype D, 4 to C/D recombinant, 5 to genotype C, 3 to genotype B, and 4 were genotype A respectively. From these, 15 samples were used for sequencing of P (polymerase) gene and S (surface) genes. Thus, obtained sequences were used to construct neighbor-joining tree using Tamura-Nei model evolution and further validated by Bayesian analysis. A total of four sub-genotypes namely A1, C1, D1, and D5 were detected. Hepatitis B virus infection is a global health problem affecting about 257 million people worldwide. In Nepal, there are few reports on the molecular and phylogenetic analysis of this virus. In this study, we report the circulation of seropositive occult hepatitis as well as CD-recombinant genotype in Nepalese population.

Pre-Intervention Treatment, Screening, and Vaccination Rates in Hepatitis B-Infected Patients at an Urban Academic Center

Pre-Intervention Treatment, Screening, and Vaccination Rates in Hepatitis B-Infected Patients at an Urban Academic Center

Serum lincRNA-p21 as a potential biomarker of liver fibrosis in chronic hepatitis B patients.

Serum long non-coding RNAs (lncRNAs) are emerging as promising biomarkers for various human diseases. The aim of this study was to investigate the feasibility of using serum long intergenic non-coding RNA-p21 (lincRNA-p21) as a biomarker for chronic hepatitis B patients. Serum lincRNA-p21 levels were quantified using real-time PCR in 417 CHB patients and 363 healthy controls. The promoter methylation level of lincRNA-p21 was detected using bisulphite-sequencing analysis in primary hepatic stellate cells (HSCs). Sera from hepatitis B-infected patients contained lower levels of lincRNA-p21 than sera from healthy controls. Serum lincRNA-p21 levels negatively correlated with stages of liver fibrosis in infected patients. Receiver operating characteristic (ROC) curve analyses suggested that serum lincRNA-p21 had a significant diagnostic value for liver fibrosis in these patients. It yielded an area under the curve of ROC of 0.854 with 100% sensitivity and 70% specificity in discriminating liver fibrosis from healthy controls. There was additionally a negative correlation between serum lincRNA-p21 level and the markers of liver fibrosis including α-SMA and Col1A1. However, there was no correlation of serum lincRNA-p21 level with the markers of viral replication, liver inflammatory activity, and liver function. Notably, during primary HSCs culture, loss of lincRNA-p21 expression was associated with promoter methylation. Serum lincRNA-p21 could serve as a potential biomarker of liver fibrosis in CHB patients. Down-regulation of lincRNA-p21 in liver fibrosis may be associated with promoter methylation.

Using Various Serological Markers to Characterize Hepatitis B - Infected Patients Who Visit Clinical Analysis Laboratory, KNUST

Ghana is not an exception from developing countries suffering from hepatitis B infection. Research has shown that various communities have different prevalent rate as result of life style and socioeconomic levels. This study investigated the prevalence of the infection, possible risk factors, determined liver enzymes (AST and ALT) of infected respondents and serologically characterized the infected respondents in KNUST community. In a total of 85 respondents, 8 of them tested positive to the HBsAg indicating 9.41% prevalence. Males have higher prevalence (13.16%) than females (6.38%). Ages from 20-29 recorded the highest prevalence followed by 30-39 and 50-59. The mean values obtained for AST in U/l was (40.33±13.60) and ALT in U/l was (25.17±5.70). The mean values indicate normal health for liver cells. Three of the respondents reported of having a family history of HB virus, two claimed they had been blood-transfused and one was involved in sharing of devices. Therefore, age, sex, history of blood transfusion, use of shared items and blood contacts have much influence and could be major contributing factors to HBV infection. Serological evidence indicates that positive respondents to HBsAg fall within the inactive chronic hepatitis B carrier phase and so it can be concluded that the chronic hepatitis B-infected patients visiting the Clinical Analysis Laboratory are in the inactive phase.

THU-163 - On-treatment ALT flares are associated with HBsAg loss in genotype A chronic hepatitis B-infected patients treated with nucleotide analogue therapy

THU-163 - On-treatment ALT flares are associated with HBsAg loss in genotype A chronic hepatitis B-infected patients treated with nucleotide analogue therapy

Anxiety leads to up-regulation of CD36 on the monocytes of chronic hepatitis B-infected patients.

Introduction It has been hypothesized that mental disorders including depression and anxiety can affect immune responses. The study was done to evaluate the relation between depression and anxiety and expression levels of CD36, CD68, and CD9 on peripheral blood monocytes of chronic hepatitis B (CHB) patients. Methods Sixty CHB patients were selected with various ranges of depression and anxiety. Depression and anxiety were evaluated using a standard questionnaire by an expert psychiatrist according to BECK's Depression Inventory II and Hamilton Anxiety Rating Scale, respectively. The levels of CD36, CD68, and CD9 on the peripheral blood monocytes have been performed using flow cytometry technique. Results The results demonstrated that levels of CD36 were significantly increased on the peripheral blood monocytes of CHB patients when compared with CHB patients with no anxiety. Expression levels of CD68 and CD9 were not significantly altered on the CHB patients with various ranges of anxiety. Expression levels of CD36, CD68, and CD9 were also not significantly altered on the CHB patients with various ranges of depression. Discussion It seems that anxiety induces inflammation in the CHB patients by induction of alteration in several molecules including up-regulation of CD36. CD36 plays important roles in the induction of tissue damage; hence, it may be hypothesized that anxiety may participate in the induction of some hepatitis B complications.

Are serum quantitative hepatitis b surface antigen levels, liver histopathology and viral loads related in chronic hepatitis b-infected patients?

Background/Aims:Fluctuations in hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels complicate assessment of the phases of chronic hepatitis B (CHB) infection and correct identification of the inactive HBV carrier state. In this study, we aimed to examine the role of HBsAg quantification (qHBsAg) in the identification of the phases of HBV and to evaluate its association with liver histopathology.Patients and Methods:Inactive HBV carriers (IC) (n = 104) and CHB patients (n = 100) were enrolled in the study. Demographic characteristics of patients were evaluated; biochemical parameters and serum qHBsAg levels were studied, and liver biopsy and histopathology were assessed.Results:Serum qHBsAg levels were found to be significantly low in IC (5150.78 ± 8473.16 IU/mL) compared with the HBeAg-negative CHB (7503.21 ± 8101.41 IU/mL) (P = 0.001) patients. The diagnostic accuracy of qHBsAg to differentiate HBeAg-negative CHB from IC was found to be moderate (c-statistic: 0.695) and the cutoff level for qHBsAg in diagnosis was found as 1625 IU/mL (specificity: 80%; sensitivity: 49%). No correlation was noted between serum qHBsAg level and ALT, histologic activity index (HAI), and fibrosis in IC and CHB. A moderate and positive correlation was observed between the serum qHBsAg level and HBV-DNA in HBeAg-positive CHB patients.Conclusions:Serum qHBsAg levels may prove to be useful in the differentiation between IC and HBeAg-negative CHB when used in conjunction with HBV DNA. Furthermore, patients diagnosed solely on the basis of HBV DNA and ALT may present with higher grade and stage of liver histopathology than expected.

FRI-147 - Long-Term Follow-Up of European HBeAg-Negative Chronic Hepatitis B-Infected Patients on Antiviral Treatment

FRI-147 - Long-Term Follow-Up of European HBeAg-Negative Chronic Hepatitis B-Infected Patients on Antiviral Treatment

Aflatoxin levels in chronic hepatitis B patients with cirrhosis or hepatocellular carcinoma in Balıkesir, Turkey.

Aflatoxins, the secondary metabolites produced by species of naturally occurring Aspergilli, are commonly found in food such as cereals, dried fruits and juice, wine, beer and spices. They are hepatotoxic and are well known human carcinogens based on evidence from human studies. Aflatoxins are an environmental risk factor for the development of hepatocellular carcinoma (HCC). Chronic hepatitis B-infected patients are at increased risk of cirrhosis, hepatic failure and liver cancer. This study was designed to determine the serum aflatoxin B1 (AFB1 ), aflatoxin B2 (AFB2 ), aflatoxin G1 (AFG1 ) and aflatoxin G2 (AFG2 ) concentrations using high-pressure liquid chromatography (HPLC) in hepatitis B-infected patients with or without cirrhosis and liver cancer, alongside healthy controls in Balıkesir, Turkey. The mean AFB1 and total AF levels in patients without liver cancer and cirrhosis were significantly higher than healthy controls. The mean AFB1 and total AF levels in patients with chronic hepatitis B and HCC were significantly higher than infected patients with or without cirrhosis. These results suggest that patients with chronic hepatitis B who are exposed to AFs are at increased risk for developing HCC, which might be prevented by reducing consumption of contaminated foods.

Red blood cell distribution width levels correlate with liver fibrosis and inflammation: a noninvasive serum marker panel to predict the severity of fibrosis and inflammation in patients with hepatitis B.

We aimed to study whether red blood cell distribution width (RDW) could be one of the variables determining the extent of liver fibrosis and inflammation in patients with biopsy-proven hepatitis B.A total of 446 hepatitis B virus-infected patients who underwent liver biopsy were divided into 2 groups: absent or mild and moderate–severe according to the severity of liver fibrosis and inflammation. The independent variables that determine the severity of liver fibrosis and inflammation were explored.RDW values increased with progressive liver fibrosis and inflammation. After adjustments for other potent predictors, liver fibrosis (moderate–severe) was independently associated with RDW, platelet, and albumin (odds ratio = 1.121, 0.987, and 0.941, respectively), whereas increased odds ratios of significant inflammation were found for RDW, alanine aminotransferase, albumin, and PLT (odds ratio = 1.146, 1.003, 0.927, and 0.990, respectively). The sensitivity and specificity of model A were 70.0% and 62.9% for detection of significant liver fibrosis [area under the receiver-operating characteristic curve (AUC) = 0.713, P < 0.001]. The sensitivity and specificity of model B were 66.1% and 79.4% for predicting advanced liver inflammation (AUC = 0.765, P < 0.001). Compared with preexisting indicators, model A achieved the highest AUC, whereas model B showed a higher AUC than RDW to platelet ratio (0.670, P < 0.001) and FIB-4 (0.740, P = 0.32).RDW may provide a useful clinical value for predicting liver fibrosis and necroinflammation in hepatitis B-infected patients with other markers.

Management strategies for hepatitis B-infected patients undergoing immunomodulatory therapy: Is lamivudine enough?

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Toll-Like Receptor 4 and Hepatitis B Infection: Molecular Mechanisms and Pathogenesis

Hepatitis B virus (HBV) infection mainly causes liver disease, including inflammation, cirrhosis, and hepatocellular carcinoma (HCC). It has been documented that prolonged hepatitis B-infected patients are unable to clear HBV from hepatocytes completely. Previous investigations have suggested that various genetic and immunologic parameters may be responsible for the induction of prolonged infection forms. Toll-like receptors (TLRs), as members of pathogen recognition receptors (PRRs), play critical roles in the recognition of viruses and the induction of appropriate immune responses. Thus, TLRs may be considered as essential sensors for the recognition of HBV and the induction of immune responses against this virus. It has been documented that TLR4 plays key roles in the detection of several microbial pathogen-associated molecular pattern molecules, including bacterial lipopolysaccharide (LPS), as well as endogenous ligands (damage-associated molecular pattern molecules) and subsequently activates pro-inflammatory transcription factors in either MYD88 or TRIF dependent pathways. Previous investigations have proposed that TLR4 might be involved in appropriate immune responses against HBV. Therefore, the aim of this review is to present the recent data regarding the important roles of TLR4 in HBV recognition and regulation of immune responses against this virus, and also its roles in the pathogenesis of cirrhosis and HCC as complications of prolonged hepatitis B infections.

Lowered Serum Triglyceride Levels among Chronic Hepatitis B-Infected Patients in Ghana

Dyslipidemia is a common finding in most studies of liver diseases. Little is however known about the effect of the two pathological stages of chronic hepatitis B (CHB) infection – chronicsymptomatic and asymptomatic – on the distribution of serum lipids in CHB infection. We conducted a study on CHB-infected patients attending specialist care at the Gastro-Intestinal (GI) Clinic at the Komfo Anokye Teaching Hospital (KATH) during a 7-month period. 64 participants were randomly sampled over the period. On the basis of serological and liver enzyme assays, participants were categorised as chronic asymptomatic, chronic symptomatic and healthy individuals. The relationship between the hosts pathological stage of infection were evaluated with the indices of lipid metabolism – LDL, HDL, triglyceride, and total serum cholesterol using ANOVA. The 64 volunteers recruited in the study were found to consist of 18 patients (28.1%) who were chronic symptomatic, 35 patients (54.7%) who were chronic asymptomatic hepatitis B, and 11 (17.2%) were healthy subjects. Significant overall male dominance was observed among all categories of population enrolled (p=0.0063). Serum triglyceride levels decreased more among the CHB-infected population compared to the healthy individuals (p=0.0010) with value lowest among the chronic symptomatic population. Basal serum cholesterol, HDL, and LDL were unaffected by the disease. This work reveals that serum triglyceride is significantly lowered in CHB infection and that the extent of this decrease in host is independent of the pathological stage of the infection. Keywords: chronic hepatitis B, lipid metabolism, triglyceride, chronic symptomatic

CPC-130 Switching from Adefovir to Tenofovir in Hepatitis B-Infected Patients

BackgroundAdefovir disoproxil (ADF) was the second nucleoside analogue to be approved for Hepatitis B Virus (HBV) treatment. Later studies showed that tenofovir had better and more cost effective clinical outcomes...

Predictors of Histologic Severity in Chronic Hepatitis B-infected Patients

The role of liver biopsy in chronic Hepatitis B treatment guidelines remains incompletely defined. Our aim was to correlate histologic disease severity with demographic, biochemical and virologic parameters as currently used in Hepatitis B treatment guidelines. We conducted an Institutional Review Board (IRB) approved retrospective cross-sectional study of chronic Hepatitis B patients between January 2001 and July 2009. Patients with at least two Alanine Aminotransferase (ALT) values (6 months apart), with detectable Hepatitis B DNA quantitative levels at the time of initial evaluation, unchanged HBeAg status over a minimum of 6 months but no prior history of antiviral therapy, alcohol abuse, co-infection, hepatocellular carcinoma, iron overload or liver decompensation were reviewed. Advanced histological disease was defined as a METAVIR score of greater than or equal to stage and/or grade 3 (≥S/G 3). Multivariable binary logistic regression was used to determine the independent predictors of advanced histology. One hundred and twenty-eight patients met inclusion criteria. On multivariate logistic regression analysis, viral load was not an independent predictor. However, age ≥40, abnormal ALT and HBeAg(+) were independent predictors of ≥S/G3. Controlling for ALT and HBeAg status, patients ≥40 years old had 14.5 times the adjusted odds of ≥S/G3 (95% CI, 4.24–49.54) while 31% of HBeAg(-) /Low Viral load patients had ≥S/G3. Current HBV-treatment guidelines do not fully predict advanced histological disease. In the group where all the current guidelines recommend observation without treatment, one third had advanced histology on liver biopsy.

Urinary Metabolic Biomarkers of Hepatocellular Carcinoma in an Egyptian Population: A Validation Study

The advent of metabonomics has seen a proliferation of biofluid profiling studies of patients with hepatocellular carcinoma. The majority of these studies have been conducted in single indigenous populations making the widespread applicability of candidate metabolite biomarkers difficult. Presented here is a urinary proton nuclear magnetic resonance spectroscopy study of mainly hepatitis C virus infected Egyptian patients with hepatocellular carcinoma, which corroborates findings of a previous study from our group of mainly hepatitis B-infected Nigerian patients with hepatocellular carcinoma. Using multivariate statistical analysis, in the form of orthogonal signal-corrected partial least squared discriminant analysis, the sensitivity and specificity of the technique for distinguishing patients with tumors from healthy controls and patients with cirrhosis was 100%/94% and 81%/71%, respectively. Discriminatory metabolites included glycine, trimethylamine-N-oxide, hippurate, citrate, creatinine, creatine, and carnitine. This metabolic profile bears similarity to profiles identified in the Nigerian cohort of subjects indicative of tumor effects on physiology, energy production, and aberrant chromosomal methylation. This is the first study to identify similarly altered urine metabolic profiles of hepatocellular carcinoma in two etiologically and ethnically distinct populations, suggesting that altered metabolism as a result of tumorogenesis is independent of these two factors.