Chronic Hepatitis Patients Research Articles

Chronic hepatitis in patients with hemophilia A: histologic studies in patients with intermittently abnormal liver function tests

AbstractRecent studies in multiply transfused patients with hemophilia A and persistent liver function abnormalities have shown a high incidence of chronic active hepatitis. The purpose of the present study was to determine the severity of liver disease in multiply transfused patients with intermittent liver enzyme abnormalities. Fifteen patients with elevated enzymes on two or three out of four determinations at 6-mo intervals were studied. None had signs or symptoms of chronic liver disease. Thirteen had serologic evidence of prior exposure to the hepatitis B virus. Liver biopsy performed on these patients after replacement therapy with factor VIII showed chronic persistent hepatitis or other mild forms of liver disease in 14 of the 15 patients. Patients with chronic persistent hepatitis had significantly higher mean liver enzymes at time of biopsy than patients with milder forms of hepatic inflammation, but there was no relationship between liver histology and hepatitis B serology or the amount of factor VIII used in the 6 mo preceding biopsy. These findings support the continued use of factor VIII concentrates in patients with hemophilia.

Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection

Biomarkers for early diagnosis of hepatocellular carcinoma (HCC) are needed in chronic hepatitis B virus (HBV) infection, a leading cause of HCC. We evaluated whether measurement of serum pentraxin 3 (PTX3) could improve diagnosis of HCC in chronic HBV infection. Data from patients with HBV-related chronic hepatitis (n = 159), cirrhosis (n = 99) and HCC (n = 107), and healthy controls (n = 151) were analyzed. Serum PTX3 concentration was measured by immunoassay. Area under the receiver operating characteristic curve (AUC) was applied to assess diagnostic accuracy. PTX3 levels were significantly higher in HBV patients than in healthy controls (P < 0.001) and in HCC than in chronic hepatitis (P < 0.001) or cirrhosis patients (P < 0.001). PTX3 was an independent risk factor of HCC [odds ratio (OR) 1.617, P < 0.001] and could distinguish HCC in chronic HBV infection [cutoff 9.231 ng/mL, AUC 0.929 with 95% confidence interval (CI) of 0.898–0.953], including α-fetoprotein (AFP) negative [cutoff 8.985 ng/mL, AUC (95%CI) 0.947 (0.908–0.973)] and early-stage HCC [cutoff 9.359 ng/mL, AUC (95%CI) 0.920 (0.885–0.947)]. Combination of PTX3 with AFP improved the discrimination of early HCC from chronic HBV infection [AUC (95%CI) 0.948 (0.918–0.970)]. In short, PTX3 measurement could identify HCC, including AFP-negative and early-stage HCC, in chronic HBV infection.

The role of serum bile acid profile in differentiation between nonalcoholic fatty liver disease and chronic viral hepatitis

BackgroundBile acids are essential organic molecules synthesized from cholesterol in the liver. They have been utilized as indicators of hepatobiliary impairment because synthesis of BAs and their metabolism are influenced by liver diseases. We aimed to investigate the role of serum bile acid level and composition in differentiation between nonalcoholic fatty liver disease (NAFLD) and chronic viral hepatitis. An ultra-performance liquid chromatography coupled with mass spectrometry assay was used to measure the serum level of 14 bile acids in chronic viral hepatitis and NAFLD patients beside normal healthy control subjects.ResultsThe mean serum levels of 11 out of the 14 bile acids (two primary, six conjugated, and three secondary) were significantly higher in viral hepatitis compared to control. Only 4 bile acids [2 primary, one glycine conjugated (GCDCA), and one secondary (LCA)] had statistically significant increase in their mean serum bile acid level in NAFLD compared to control. Comparing viral hepatitis group against NAFLD group revealed that the mean serum levels of five conjugated and one secondary bile acid (DCA) were significantly higher in viral hepatitis group. Receiver operating characteristic (ROC) curve analysis revealed that LCA had the best diagnostic performance for viral hepatitis followed by TCA and GCDCA. ROC curve for the combined three parameters had better sensitivity and specificity (70.55% and 94.87% respectively).ConclusionBA compositions including primary, secondary, and conjugated ones could differentiate between chronic viral hepatitis and NAFLD patients, and they might be potential distinguishing biomarkers for this purpose.

Tfr-Tfh index: A new predicator for recurrence of hepatocellular carcinoma patients with HBV infection after curative resection

BackgroundT follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells were newly identified as the subsets of cluster of CD4+ T cells. As major components of human immune system, they were found in tumor microenvironment and reported to play vital roles in the progression of cancer. But their clinical significance in Hepatocellular carcinoma (HCC) was not elucidated. Thus, this research aimed to investigate their prognostic value in HCC. Materials and methodsA total of 210 subjects (including 110 HCC patients, 50 chronic hepatitis patients and 50 healthy individuals) were enrolled in the research. Tfh, Tfr cells and Treg cells from peripheral blood were measured by flow cytometry. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of Tfr-Tfh Index (TTI) in early HCC and relapse status. Its further prognostic valve was assessed by Kaplan-Meier survival estimate and log rank tests. ResultsTfh cells, Tfr cells, Treg cells and TTI were all higher in HCC patients than in chronic hepatitis patients and healthy control. TTI was found to have positive correlation with the load of HBV. The AUC of TTI for early HCC and relapse status was better than other clinical indices in HBV positive patients. An optimal cutoff point for the TTI stratified the HCC patients into high (>21.96) and low index (≤21.96) groups. High TTI was significantly correlated with recurrence. Univariate and multivariate analyses revealed TTI could be a predictor for recurrence. Moreover, it retained prognostic performance for patients with lower recurrence risk. ConclusionOur research showed that TTI could be a promising indicator for early recurrence in HCC patients with HBV infection.

Serum Hepcidin Levels in Diabetic and Non-diabetic Chronic Hepatitis C Patients and Its Relation with Serum Iron Levels

&lt;p&gt;&lt;strong&gt;Background and Objective:&lt;/strong&gt; Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver. Research shows that HCV infection leads to a marked reduction of serum&amp;nbsp; hepcidin levels which might be a factor in causing systemic iron overload. The present study was aimed to&amp;nbsp; determine the cause of iron overloadwhich might be due to reduced levels of serum hepcidin in chronic&amp;nbsp; hepatitis C patients.&lt;br /&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This cross-sectional study was conducted in Department of Physiology at University of Health Sciences, Lahorefrom January 2012 to January 2014. A total of 54 male patients of chronic hepatitis C were recruited for this study and divided into two groups, group A (CHC with diabetes) and group B (CHC without diabetes). Both groupswere tested for serum hepcidin, serum iron and serum ferritin levels. ELISA technique was used to measure serum hepcidin. Serum ferritin levels were measured via CODA analyzer. Serum iron levels were measured by colorimetric method. Frequencies and percentages were calculated for serum hepcidin, serum iron and serum ferritin levels in group. The data was analyzed using SPSS (Statistical Package for Social Sciences) version 20.0. Data was considered significant where P-value was &amp;le; 0.05.&lt;br /&gt;&lt;strong&gt;Results:&lt;/strong&gt; Patients in both groups showed less serum hepcidin levelsalong with less serum iron levels in 93% cases of both groups. The patients in group A showed raisedferritin levels in 26% cases and normal ferritin levels in 63% cases. Whereas in group B 04% cases showed raisedferritin levels and 92% patients hadnormal ferritin levels; which could be a marker of ongoing chronic inflammation in CHC patients. Non-significant negative correlation was observed between serum iron and serum hepcidin inCHC population.&lt;br /&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Hepatitis C virus and decreased serum iron levels in study population may be the reason of less serum hepcidin levels. Raised/normal ferritin reflects chronic inflammation in patients. Non-significant negative correlation between serum iron and serum hepcidin leads the focus towards increasing the sample size in further studies to see any significant negative correlation between studied parameters.&lt;/p&gt;

Three-dimensional CT texture analysis of anatomic liver segments can differentiate between low-grade and high-grade fibrosis

BackgroundCT texture analysis (CTTA) has been successfully used to assess tissue heterogeneity in multiple diseases. The purpose of this work is to demonstrate the value of three-dimensional CTTA in the evaluation of diffuse liver disease. We aimed to develop CTTA based prediction models, which can be used for staging of fibrosis in different anatomic liver segments irrespective of variations in scanning parameters.MethodsWe retrospectively collected CT scans of thirty-two chronic hepatitis patients with liver fibrosis. The CT examinations were performed on either a 16- or a 64-slice scanner. Altogether 354 anatomic liver segments were manually highlighted on portal venous phase images, and 1117 three-dimensional texture parameters were calculated from each segment. The segments were divided between groups of low-grade and high-grade fibrosis using shear-wave elastography. The highly-correlated features (Pearson r > 0.95) were filtered out, and the remaining 453 features were normalized and used in a classification with k-means and hierarchical cluster analysis. The segments were split between the train and test sets in equal proportion (analysis I) or based on the scanner type (analysis II) into 64-slice train 16-slice validation cohorts for machine learning classification, and a subset of highly prognostic features was selected with recursive feature elimination.ResultsA classification with k-means and hierarchical cluster analysis divided segments into four main clusters. The average CT density was significantly higher in cluster-4 (110 HU ± SD = 10.1HU) compared to the other clusters (c1: 96.1 HU ± SD = 11.3HU; p < 0.0001; c2: 90.8 HU ± SD = 16.8HU; p < 0.0001; c3: 93.1 HU ± SD = 17.5HU; p < 0.0001); but there was no difference in liver stiffness or scanner type among the clusters. The optimized random forest classifier was able to distinguish between low-grade and high-grade fibrosis with excellent cross-validated accuracy in both the first and second analysis (AUC = 0.90, CI = 0.85–0.95 vs. AUC = 0.88, CI = 0.84–0.91). The final support vector machine model achieved an excellent prediction rate in the second analysis (AUC = 0.91, CI = 0.88–0.94) and an acceptable prediction rate in the first analysis (AUC = 0.76, CI = 0.67–0.84).ConclusionsIn conclusion, CTTA-based models can be successfully applied to differentiate high-grade from low-grade fibrosis irrespective of the imaging platform. Thus, CTTA may be useful in the non-invasive prognostication of patients with chronic liver disease.

Commonly used non-invasive markers do not reliably predict liver fibrosis in those patients of chronic hepatitis B who really need it: a prospective multi-centre study

Commonly used non-invasive markers do not reliably predict liver fibrosis in those patients of chronic hepatitis B who really need it: a prospective multi-centre study

The Impact of COVID-19 Pandemic on Treatment, Follow-up and Behavioral Characteristics of Chronic Viral Hepatitis Patients

Objectives: It has been not yet fully understood whether chronic liver diseases may be considered as risk factors for critical course of Coronavirus disease-2019 (COVID-19) Considering the importance of managing with COVID-19, we aimed to investigate the impact of the COVID-19 pandemic on treatment, follow-up and behavioral characteristics of chronic viral hepatitis (CVH) patients Materials and Methods: Patients followed-up in our clinic with diagnosis of chronic hepatitis B or C were screened retrospectively and a total 213 adults included in the study We performed a telephone survey with patients Results: The mean age of participants was 49 9±13 4 years Of the participants, 62% were male Totally 75 (35 2%) patients disrupted their follow-up visits due to COVID-19 pandemic The only risk factor for disruption in follow-up was found as anxiety The vast majority of CVH patients paid attention to prevention measures for COVID-19 Conclusion: We can say that CVH patients' awareness about COVID-19 and application of control measures were well enough Continuity of treatment can be provided in patients with chronic illness during crisis period with informing patients in a way not to cause anxiety and efficient implementations in healthcare system

Real-word efficacy of sofosbuvir, velpatasvir plus ribavirin therapy for chronic hepatitis patients who failed to prior DAA therapy with NS5A-P32 deletion mutated HCV infection.

The hepatitis C virus (HCV) NS5A-P32 deletion (P32del) confers potent resistance to NS5A inhibitors. Chronic hepatitis C patients in whom NS5A-P32del variants had emerged during prior direct-acting antiviral (DAA) therapy with an NS5A inhibitor show poor response to DAA retreatment. Here, we report three patients with HCV NS5A-P32del infection who were treated with sofosbuvir, velpatasvir plus ribavirin (SOF/VEL + RBV) in a real-world setting. The patients developed HCV NS5A-P32del, L31F + P32del, or L31V + P32del variants following failure of daclatasvir plus asunaprevir (DCV/ASV) therapy. One of the patients failed to respond to subsequent DCV/ASV and beclabuvir therapy, and the remaining two patients failed to respond to subsequent glecaprevir and pibrentasvir therapy. All three patients completed 24-week SOF/VEL + RBV therapy. Serum HCV RNA became negative at the end of the therapy in all three patients. Two patients with NS5A-P32del and NS5A-L31F + P32del achieved sustained virological response 12weeks after completion of treatment (SVR12), but HCV relapsed in the remaining NS5A-L13V + P32del patient. Direct sequence analysis detected no additional variants within either the NS5A or NS5B regions at the time of relapse. In conclusion, three patients with prior NS5A-P32del-associated DAA treatment failure received 24weeks of SOF/VEL + RBV therapy, and two of the patients achieved SVR12.

Noninvasive Transient Elastography identifies initial stage liver fibrosis &amp; cirrhosis in Hepatitis B patients

Background: Among the many non-invasive techniques performed on patients with Hepatitis B Virus (HBV) related fibrosis, the most appropriate results have been obtained using Transient Elastography (FibroScan) to measure liver stiffness. The accurate diagnosis of fibrosis related to HBV is essential for prognostic and therapeutic decisions and offset the limitations of liver biopsy.&#x0D; Objective: To evaluate Transient Elastography (FibroScan) for detecting and staging hepatic fibrosis by comparing it with hepatic histopathology in patients with Hepatitis B at a tertiary care hospital of Peshawar.&#x0D; Materials &amp; Methods: A descriptive study was done in March-April 2020 at Rehman Medical Institute, Peshawar, based on retrospective data from May 2016 to March 2020 on 145 HBV positive patients with various stages of hepatic fibrosis who had undergone non-invasive FibroScan during their first visit. Routine demographic, clinical and laboratory parameters were analyzed to predict the existence or absence of advanced fibrosis. At the end of the evaluation, the samples were categorized as F0 (No fibrosis), F1 (Initial fibrosis without septa), F2 (Fibrosis with septa), F3 (Advanced fibrosis) and F4 (Severe fibrosis with cirrhosis, C1). Descriptive data analysis was done by SPSS 17.0.&#x0D; Results: Out of 145 included patients of chronic hepatitis B, 110 were males and 35 were females. At initial stages the existing laboratory tools diagnosed chronic HBV-infected patients correctly, with minor fibrosis and cirrhosis. Independent indicators of liver fibrosis included platelet count, age, AST, ALT values and albumin; 80% of the patients were not affected by the disease, which means F0 was 80%. Yet some patients had fibrosis at different stages F1, F2, F3, F4 and C1. The FibroScan assessment revealed that out of 145 patients, only 11% patients were at stage F1 whereas the diagnostic value for F2, F3, F4, and C1 are ≤3% with F2=3%, F3=1%, F4=2%, and C1=2%.&#x0D; Conclusion: FibroScan is an effective method to detect HBV-related fibrosis and cirrhosis; it provided accurate distinction between various stages of fibrosis in Hepatitis B patients.&#x0D; Keywords: Cirrhosis, Liver; Hepatitis B; Liver Fibrosis; Carcinoma, Hepatocellular.

Expression and Significance of Insulin Receptor Substrate 1 in Human Hepatocellular Carcinoma.

Background Insulin receptor substrate 1 (IRS-1) is an important molecule of the insulin signal transduction pathway and has been associated with the occurrence and development of many tumors, including hepatocellular carcinoma (HCC). Our study was designed to determine the expression and significance of IRS-1 in human HCC. Methods Two hundred and forty specimens were drawn from 140 patients, including 100 HCC tissues and 100 paracancerous (PC) tissues from 100 HCC patients, 20 liver cirrhosis (LC) tissues from 20 LC patients, and 20 chronic hepatitis (CH) tissues from 20 CH patients. Baseline and pathological characteristics were included, and the expression of IRS-1 was examined by immunohistochemical (IHC) staining. Binary logistic regression model calculation was used for multivariate analysis. Results The total positive rates of IRS-1 expression were 41.0%, 17.0%, 15.0%, and 10.0% in HCC, PC, LC and CH tissues, respectively. IRS-1-positive signals were brown in color and located in the nucleus and cytoplasm. Compared with PC, LC, and CH tissues, a significantly increased expression was observed in human HCC tissues (P < 0.001, P = 0.028, and P = 0.008). Eight of the total 240 specimens had the strong immunostaining of IRS-1 expression, and all of them were HCC tissues. After control of the age, gender, and HBV and HCV infection, IRS-1 expression was independently associated with the diagnosis of HCC (OR 6.60, 95% CI 2.243-19.425, P = 0.001). Conclusions Positive expression of IRS-1 in HCC was increased significantly and may play an important role in the occurrence and development of human HCC.

Differences in Theophylline Clearance Between Patients With Chronic Hepatitis and Those With Liver Cirrhosis.

Theophylline, a xanthine derivative drug, is used for the treatment of respiratory diseases, such as asthma, and is primarily eliminated by hepatic metabolism. There is marked interindividual variability in theophylline clearance. Therefore, the aim of this study was to evaluate the influence of chronic hepatitis (CH), liver cirrhosis (LC), and other covariates on theophylline clearance by population pharmacokinetic (PPK) analysis. The authors retrospectively obtained 496 trough concentrations of theophylline at steady state from 226 adult patients with bronchial asthma. The liver functions of the patients were classified into 3 categories: normal hepatic function, CH, and LC. The PPK analysis was performed using the NONMEM program. CH, LC, age, smoking status, coadministration of clarithromycin (CAM), and sex were considered as covariates that affected theophylline clearance. Theophylline clearance (CL/F per kg) was significantly influenced by CH, LC, smoking, and CAM. The final model of theophylline clearance was as follows: CL/F (L/h·kg) = 0.0484 × 1.40 × 0.861 × 0.889 × 0.557. Smoking is a well-known factor that markedly enhances CL/F through the induction of CYP1A enzymes, whereas CAM has been reported to inhibit CYP3A4. The final model for hepatic function showed that CL/F in CH and LC patients was 0.043 and 0.027 L/h/kg, respectively, and it was lower than that in patients with normal hepatic function. As theophylline clearance depends on intrinsic hepatic clearance, lower CL/F in patients with LC than in those with CH may be due to a decrease in the metabolic enzymatic capability of LC patients. Differences exist in theophylline clearance between CH and LC patients as per the PPK analysis.

Association of LIN28B polymorphisms with chronic hepatitis B virus infection

BackgroundLIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown.MethodsThis study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated.ResultsLIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491–0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561–0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439–0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503–0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445–0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019).ConclusionsThese results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.

Golgi Protein 73 as a Diagnostic Tool for Hepatocellular Carcinoma in Cirrhotic Hepatitis C Patients

Background and study aim: Hepatocellular carcinoma (HCC) is the commonest primary liver cancer originating from the hepatocytes. HCC nowadays considered the 3rd cause of malignancy related mortality allover the world. Small HCC, means that size of hepatic focal lesions did not exceed 5 centimeters in patients with solitary hepatoma, typically have no clinical manifestations. This makes cirrhotic liver patients a perfect target population for HCC surveillance.This study was designed to evaluate the clinical use of serum GP73 levels as a good diagnostic biomarkers for malignant liver tumours in cirrhotic patients due to HCV infection. Subjects and Methods: The study was designed as a Descriptive - Analytic study at Suez Canal University Hospital. The study included 87 individuals who were divided into four groups (healthy, chronic hepatitis, cirrhosis and HCC patients). All patients were clinically evaluated, had routine laboratory investigations and measurements of circulating levels of AFP and GP73. Abdominal ultrasonography and Triphasic CT abdomen was done for detection of hepatic focal lesions and hepatobiliary system. Results: The maximum cutoff levels for GP73 was 534.5 ng/L and in comparison the cutoff AFP level was 32 ng/mL. For GP73, the sensitivity was 88% and specificity 88% while the sensitivity of AFP was 72% and the specificity of AFP was 80%. The +v predictive value of GP73 and the -ve predictive value of GP73 were 84.6% and 87.5% while the same values of AFP were 75% and 73.1%, respectively. Conclusion: It was found that serum GP73 was up-regulated in HCC and we can use it as a good biomarker for early detection and for screening of malignant liver lesions in cirrhotic patients due chronic HCV infection and it would be more accurate and effective tool than serum AFP in discriminating the malignant liver lesion from the chronic hepatitis.

Golgi Protein 73 versus Alpha-Fetoprotein as a New Biomarker in Early Diagnosis of Hepatocellular Carcinoma.

BackgroundScreening of early hepatocellular carcinoma (HCC) diagnosis is the greatest challenge for hepatologists. Alpha-fetoprotein (AFP) is the most common non-invasive biomarker used in HCC diagnosis.Objectives and AimsTo make a comparison between the new biomarker Golgi protein 73 (GP73) versus the standard biomarker AFP in the diagnosis of HCC.MethodsOur study was a case–control study, and 60 patients were included in the study. They were divided into two groups: 1) HCC patients with either chronic HBV or HCV infection (n=30); and 2) non-HCC patients with HBV or HCV infection who had either chronic hepatitis or liver cirrhosis (n=30). In addition, 30 healthy volunteers were included as a control group. Patients were subjected to liver function tests, kidney function tests, serum Golgi protein 73 and AFP levels. Imaging diagnosis of HCC was done by computed tomography (CT) or magnetic resonance imaging (MRI) based on American Association for the Study of Liver Diseases (AASLD) practice guidelines.ResultsStatistically significant differences between groups in terms of serum AFP (p<0.001) and GP73 (p<0.001) were found. Non-HCC patients (chronic hepatitis and liver cirrhosis) and HCC patients had significantly higher AFP and GP73 than the control group. In addition, patients with HCC had significantly higher AFP and GP73 than chronic hepatitis and cirrhotic patients. GP73 had higher diagnostic performance than AFP. At a cut-off value of ≥8.4 ng/mL, GP73 yielded a sensitivity of 86.7% and specificity of 89% for the discrimination between HCC and normal populations. Similarly, at a cut-off value of ≥8.45 ng/mL, GP73 yielded a sensitivity of 83.3% and specificity of 84% for the discrimination between HCC patients and non-HCC patients. On the other hand, AFP at a cut-off value of ≥2.4 ng/mL yielded a sensitivity of 75.4% and specificity of 90% for the discrimination between HCC and normal populations; and at a cut-off value of ≥20.85 ng/mL, AFP yielded a sensitivity of 72.2% and specificity of 86.2% for the discrimination between HCC and non-HCC patients.ConclusionGolgi protein 73 is a promising and accurate biomarker for early detection of HCC.

The Study of Correlation Between Serum Vitamin D3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients.

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20–30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9 ± 5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (β:−6.2, 95% CI: −10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.

Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Regulates Host Gene PPM1A Related to Hepatocellular Carcinoma.

Hepatitis B is a liver infection disease caused by the Hepatitis B Virus (HBV) that can become chronic and develop into hepatocellular carcinoma. HBV was classified as a double-stranded DNA virus. Currently, there is a report showing that HBV virus-encoded miRNA called HBV-miR-3 controls the replication of HBV. However, the regulation of HBV-miR-3 in host cells remains unclear. This study aimed to investigate the regulation of HBV-miR-3 in host gene target which is related to chronic HBV infection and HCC process. In this study, we analyzed the read count of HBV-miR-3 from next-generation sequencing of chronic hepatitis patients in Pegylated interferon alpha-2a (PEG-IFN-α-2a) treatment. To understand the regulation of HBV-miR-3 in host cells, the HBV-miR-3 recognition sites were predicted in host target genes using miRDB. The effect of HBV-miR-3 in host cells was examined using qPCR and 3' UTR dual luciferase assay. The read count of HBV-miR-3 was found in chronic hepatitis patients before treatment. Moreover, the decrease of HBV-miR-3 was correlated with response group of chronic hepatitis patients after treatment. On the other hand, the abundance of HBV-miR-3 showed no difference in nonresponse group of chronic patients after PEG-IFN-α-2a treatment. To study the role of HBV-miR-3 in patients, four HBV-miR-3 target regions from Protein phosphatase 1A (PPM1A) and DIX domain containing 1 (DIXDC1) were identified in the human genome using miRDB. Interestingly, we found that HBV-miR-3 hybridized with PPM1A mRNA. The mRNA expression from RT-qPCR showed no difference between HepG2 transfected with pSilencer_scramble or pSilencer_HBV-miR-3. However, the reporter assay showed that PPM1A mRNA was suppressed by HBV-miR-3. The protein expression of PPM1A showed a decrease in cells overexpressing HBV-miR-3. Finally, the HBV-miR-3 can promote cell proliferation in cells overexpressing HBV-miR-3. This study is the first report showed the HBV encoded miRNA can regulate host gene expression. HBV-miR-3 silenced PPM1A by inhibiting the translation process of PPM1A. The downregulation of PPM1A promotes cell proliferation related to HCC development.

The Distribution of Hepatitis C Virus Genotypes, Viral Load and Antibody Titer among Iraqi Chronic Hepatitis Patients

Background: The infection by hepatitis C virus causedliver diseases such as:chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The current study aims to investigate the rate of HCV genotypes, subtypes, viral load and antibody immune response among Iraqi chronic hepatitis patients.Methodology: During 2012-2017 period seventy-hundred and twenty tow hepatitis patients were referred to Middle East Laboratory from Baghdad and other provinces asking for HCV viral load, its genotype and anti-HCV antibody determination.Results: A cross six years records, HCV genotype 4 was the most prevalent among Iraqi chronic hepatitis patients (46.68%), then genotype 1 (37.12%).There is notable changes in HCV genotypes distribution especially during 2017, where the genotype 1 predominantly found (52.63%). Although, these genotypes were none significantly associated with gender, age, viral load or anti-HCV antibody.Conclusion: This recordindicates a recent change in the rate of HCV genotype 1 over genotype 4 infection in Iraqi chronic hepatitis patients.

HEPATITIS B AND C: FREQUENCY, MODES OF TRANSMISSION AND RISK FACTORS ALONG WITH SOME UNORTHODOX ROUTES OF SPREAD

Background: Pakistan's being a country placed in intermediate endemicity zone of HBV and HCV, with rising population, there is lack scarcity of knowledge about transmission of risk factors specially unorthodox and frequency of this health challenge. Methods: A retrospective case control study where case records of all patients aged from 18 - 70 years from 2012 to 2017 with either gender diagnosed as chronic hepatitis B and C were included. Information about shave from barber-shop, sharing of toothbrush at home, tattooing, cautery, and ear piercing were collected. Information about unorthodox risks for transmission of HBV and HCV, like skin branding, cupping of blood, circumcision by the barber, sharing of tooth brushes and leech therapy was collected. Results: Among 1134 patients of chronic hepatitis B (HBV) and chronic hepatitis C (HCV), Age &gt; 35 years, shave from barber and dental treatment were found to be risk factor for both HCV and HBV transmission. Amongst unorthodox risk factors like skin branding, cupping of blood, circumcision by the barber, sharing of tooth brushes and leech therapy, only cupping of blood (Hijama) was a significant risk for transmission of both HBV and HCV. Conclusion: Viral related chronic hepatitis is frequently reported problem in this part of the world where HCV supersedes HBV. Socieodemographic factor like age &gt; 35 year, shave from barbers and dental treatment were risk factors for transmission of both HCV and HBV. Among orthodox routes of transmission blood cupping (hijama) has shown as a significant transmission risk for both HCV and HBV.

Circulating CTLA-4 levels and CTLA4 polymorphisms associate with disease condition and progression and hepatocellular carcinoma patients' survival in chronic hepatitis B virus infection

BackgroundCTLA-4 is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating CTLA-4 levels and CTLA4 polymorphisms with disease condition and progression in chronic HBV infection. MethodsSerum CTLA-4 levels and CTLA4 rs231775 and rs5742909 polymorphisms were determined in patients with various HBV-related diseases [53 asymptomatic HBV carrier status (ASC), 147 chronic hepatitis, 130 cirrhosis and 102 HCC] and nearly a 10-year follow-up. ResultsSerum CTLA-4 levels were stepwisely increased from ASC, chronic hepatitis, cirrhosis to HCC and independently associated with HCC (OR 2.628, P < 0.001). HCC patients had lower frequencies of rs231775 genotype GA, genotype AA and allele A than ASC, chronic hepatitis and cirrhosis patients. Rs231775 genotype GG was independently associated with HCC (OR 2.324, P = 0.010) and higher CTLA-4 levels in patients with HBV infection. In the follow-up, higher baseline CTLA-4 levels and CTLA4 rs231775 genotype GG significantly associated with disease progression from chronic hepatitis to cirrhosis (OR 2.561, P = 0.011 and OR 2.799, P = 0.015, respectively) or from cirrhosis to HCC (OR 2.673, P = 0.008 and OR 2.097, P = 0.023, respectively) and with a shorter overall survival in HCC patients (HR 0.317, P = 0.018 and HR 0.682, P = 0.026, respectively). Rs5742909 had no significant association with CTLA-4 levels and disease progression. ConclusionCTLA-4 levels and CTLA4 rs231775 polymorphism associate with the disease condition and progression and HCC development in chronic HBV infection and their determination may be used for monitoring disease progression and predicting patient prognosis.