Progression Of Chronic Hepatitis Research Articles

Machine-learning methodologies to predict disease progression in chronic hepatitis B in Africa

Background: Little is known about the determinants of disease progression among African patients with chronic HBV infection. Methods: We used machine-learning models with longitudinal data to establish predictive algorithms in a well-characterized cohort of Ethiopian HBV-infected patients without baseline liver fibrosis. Disease progression was defined as an increase in liver stiffness to >7.9 kPa or initiation of treatment based on meeting the eligibility criteria. Results: Twenty-four of 551 patients (4.4%) experienced disease progression after a median follow-up time of 69 months. A random forest model based on a combination of available laboratory tests (standard hematology and biochemistry) demonstrated the best predictive properties with the AUROC ranging from 0.82 to 0.88. Conclusion: We conclude that combined metrics based on simple and available laboratory tests had good predictive properties and should be explored further in larger HBV cohorts.

MiR-302 targets PAK5 and prevents the transition from chronic hepatitis B to liver cirrhosis

Objective: To determine and compare the levels of p21-activated kinase 5 messenger ribonucleic acid and micro-ribonucleic acid 302 in the serum of patients with chronic hepatitis B, liver cirrhosis and healthy individuals, and to analyse the roles and correlation of p21-activated kinase 5 messenger ribonucleic acid and micro-ribonucleic acid 302 in the progression of chronic hepatitis. Method: The observational, clinical, case-control study was conducted at the Department of Laboratory Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou, China, from February 2021 to January 2022. Peripheral blood serum samples were collected from healthy individuals undergoing physical examinations, as well as from patients with chronic hepatitis B and hepatitis B-related liver cirrhosis. Total ribonucleic acid was isolated and purified using the magnetic bead method, and the relative expression levels of micro-ribonucleic acid 302 and p21-activated kinase 5 messenger ribonucleic acid were determined using quantitative real-time polymerase chain reaction. Clinical test results were retrospectively analysed, and differences between the groups were assessed. Data was analysed using SPSS 22. Results: Of the 70 participants, 18(25.71%) were healthy individuals with median age 33 years (interquartile range: 25-36.25 years), 18(25.71%) were patients with chronic hepatitis B having median age 34 years (interquartile range: 26-42 years), and 34(48.57%) were patients with cirrhosis having median age 54 years (interquartile range: 44-62 years). Overall, there were 50(71%) males and 20(29%) females with mean age 42.7±13.8 years. Median albumin (p=0.0365) and platelet (p=0.0116) levels were significantly lower in cirrhosis group compared to chronic hepatitis B group. Median aspartate aminotransferase level (p=0.0400) and aspartate aminotransferase/platelet ratio (p=0.0053) of chronic hepatitis B group were significantly higher than the healthy group (n=18). The expression of p21-activated kinase 5 was significantly increased in cirrhosis group compared to chronic hepatitis B group (p=0.0444) and healthy controls (p=0.0089). Compared to the healthy individuals, the expression of micro-ribonucleic acid 302 was significantly increased in both chronic hepatitis B (p=0.0237) and cirrhosis groups (p=0.0428). Conclusions: P21-activated kinase 5 represented a promising therapeutic target for liver disease, and micro-ribonucleic acid 302 could serve as a therapeutic small molecule if an appropriate delivery system is available, particularly for liver fibrosis caused by hepatitis B virus infection. Key Words: MicroRNA, miR-302, PAK5, HBV, Liver fibrosis, Cirrhosis.

Mutations in the X Gene of the Hepatitis B Virus and Their Influence on Outcome CHB Infection in Three-Generations in the Family

Background: The occurrence of specific mutations within the Hepatitis B virus (HBV) genome is associated with the progression of chronic hepatitis B infection towards more severe outcomes. Objectives: This study aimed to investigate mutational patterns in the X-gene and their influence on the outcome of chronic HBV infection (CHB) across three generations in a family. Methods: Ninety CHB patients, meeting the inclusion criteria, were recruited from cases referred to the Center of Hepatology at Golestan University of Medical Sciences between September 2020 and January 2021. The HBx gene was amplified using semi-nested PCR from serum samples and then subjected to sequencing. Results: A comparison of the sequences from CHB patients indicated that children and mothers in the two-generation group exhibited the highest similarity (79.3%) in the X-gene, with the lowest mutation rate (20.7%). The N-terminal region of the X-gene showed the highest mutation frequency in the three-generation group, including C1491G (25%), G1613T (23.9%), C1500T (43.4%), and G1658T (33.4%). The mutation rate was notably higher in HBeAg-negative patients across the three groups compared to HBe-Ag-positive CHB patients, with a statistically significant difference (P = 0.03). A1762T/G1764A mutations were observed in 15.6% of patients, and their presence showed a significant difference (P = 0.03). Additionally, in the three-generation group, a silent mutation (A1727G, 10%) and a missense mutation (A1727T, 30%) were detected. Conclusions: Specific mutational patterns in the HBx gene may be valuable in predicting clinical outcomes in CHB patients and could serve as warning indicators for increased susceptibility to hepatocellular carcinoma (HCC).

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients

Objective Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. Methods A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. Results The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). Conclusion MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B.

The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively. Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC = 0.834, 95% CI 0.800-0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742-0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.

A Mendelian randomization study investigating causal links between gut microbiota or metabolites and chronic hepatitis B.

This study aimed to explore the potential causal relationship between the gut microbiota and/or its metabolites and the progression of chronic hepatitis B (CHB). The gut microbiota was used as the exposure factor. The training set exposure data were obtained from the China Nucleotide Sequence Archive (CNSA). Genome-wide association study (GWAS) data from Asia were used as the outcome variables. Outcome data for both the training and validation sets were sourced from the GWAS Catalog database. A dual-sample Mendelian randomization approach was used to analyze the causal relationships, with the inverse variance-weighted method serving as the main analytical strategy. Sensitivity analysis was conducted to assess the robustness of Mendelian randomization analysis results. In the training set database, analysis using the inverse variance-weighted method revealed a positive correlation between Fusobacterium varium and chronic hepatitis B [OR = 1.122, 95% CI (1.016, 1.240), p = 0.022]. Conversely, Veillonella parvula exhibited a negative correlation with chronic hepatitis B [OR = 0.917, 95% CI (0.852, 0.987), p = 0.021]. Sensitivity analysis revealed no evidence of pleiotropy and heterogeneity. No gut microbiota metabolites with a causal effect on chronic hepatitis B were identified. Additionally, no associations between the gut microbiota and the progression of chronic hepatitis B were found in the validation data from the European cohort. This study suggests that F. varium may facilitate the progression of chronic hepatitis B, whereas V. parvula may impede it. No causal relationships between gut microbiota metabolites and chronic hepatitis B were established.

Metabolic disorders and hepatitis: Insights from a Mendelian randomization study.

Hepatitis is a systemic disease that often results in various comorbidities. Meta-bolic disorders, the most common comorbidities in clinical practice, were selected for this study. To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes. A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases. A two-sample Mendelian randomization (MR) was performed to investigate causality between exposure [type 2 diabetes mellitus (T2D), hyperlipidemia, and hypertension] and outcome (chronic hepatitis B or C in-fections). The data supported the causal relationship between comorbidities and hepatitis infections, which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers. All three exposures showed a link with progression of both hepatitis B (T2D, P = 0.851; hyperlipidemia, P = 0.596; and hypertension, P = 0.346) and hepatitis C (T2D, P = 0.298; hyperlipidemia, P = 0.141; and hypertension, P = 0.035). The results of MR support a possible causal relationship between different ex-posures (T2D, hyperlipidemia, and hypertension) and chronic hepatitis progression; however, the potential mechanisms still need to be elucidated.

Metabolic dysfunction-associated steatotic liver disease increases hepatocellular carcinoma risk in chronic hepatitis B patients: a retrospective cohort study.

Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients. Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics. Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007-7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327-24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with <2 and ≥2 cardiometabolic risk factors (CMRFs), between those with <3 and ≥3 CMRFs, or between those with <4 and ≥4 CMRFs (p = 0.110, p = 0.087, p = 0.066, and p = 0.490, respectively). Conclusion: The presence of MASLD is associated with a higher risk of HCC in patients with CHB. Notably, this higher risk is present in patients with MASLD, irrespective of the presence or absence of overweight or the number of CMRFs they have.

Serum hepatitis B virus spliced RNA proportion increases with liver disease progression in patients with chronic hepatitis B.

Serum hepatitis B virus (HBV) spliced RNAs (spRNAs) are ubiquitous in HBV-infected patients; however, their clinical significance remains unknown. Therefore, we aimed to explore the relationship between HBV spRNAs and liver disease progression in chronic hepatitis B (CHB) patients; in vitro cell line assessment was also performed. The serum HBV wild-type RNA (wtRNA) and spRNA levels were individually quantified in a cohort of 279 treatment-naïve, hepatitis B e antigenpositive CHB patients with or without cirrhosis. The spRNA proportion was determined as (spRNA × 100%)/(spRNAs + wtRNA). 20 patients'serum samples underwent spRNA species profiling using next-generation sequencing. Serum spRNA species 1, 2, 3, 4, and 5 were the most common variants. The spRNA proportion varied from 0.00% to 19.02%, with higher levels in HBV genotype C patients than in those with genotype B (1.76% vs. 0.84%, p < 0.001). The spRNA proportion was positively associated with the alanine aminotransferase levels (r = 0.144, p = 0.053) and significantly higher in cirrhotic than in non-cirrhotic patients (1.69% vs. 1.04%, p = 0.001). Multivariate analysis revealed a 2.566-fold higher risk of cirrhosis in patients with elevated spRNA proportion (p = 0.024). In vitro experiments confirmed that spRNAs contributed to hepatic stellate cell activation, which is critical in liver fibrosis development. Therefore, increased HBV spRNA expression poses a risk for liver disease progression. Quantifying serum HBV spRNAs can aid in monitoring liver disease progression. Furthermore, the therapeutic targeting of spRNAs may improve the prognosis of patients with CHB.

Mendelian randomization supports causality between gut microbiota and chronic hepatitis B.

Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation. Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program. According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR] = 0.046), genus Family XIII AD3011 group (OR = 0.60; 95% CI, 0.39-0.91; FDR = 0.026), genus Prevotella 7 (OR = 0.73; 95% CI, 0.56-0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03-3.12; FDR = 0.061), genus Eggerthella group (OR = 1.34; 95% CI, 1.04-1.74; FDR = 0.043), genus Eubacterium ventriosum group (OR = 1.59; 95% CI, 1.01-2.51; FDR = 0.056), genus Holdemania (OR = 1.35; 95% CI, 1.00-1.82; FDR = 0.049), and genus Ruminococcus gauvreauii group (OR = 1.69; 95% CI, 1.10-2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs). In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.

SAT-166 - Similarly low risk of chronic kidney disease (CKD) progression in chronic hepatitis B patients with Stage 2 CKD on tenofovir alafenamide versus entecavir

SAT-166 - Similarly low risk of chronic kidney disease (CKD) progression in chronic hepatitis B patients with Stage 2 CKD on tenofovir alafenamide versus entecavir

Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers

The study enrolled 284 patients with chronic hepatitis B virus infection. Participants included people with mild fibrotic lesions (32.5%), moderate to severe fibrotic lesions (27.5%), cirrhotic lesions (22%), hepatocellular carcinoma (HCC) in 5%, and people with no fibrotic lesions in 13%. Eleven SNPs within DIO2, PPARG, ATF3, AKT, GADD45A, and TBX21 were genotyped by mass spectrometry. The rs225014 TT (DIO2) and rs10865710 CC (PPARG) genotypes were independently associated with susceptibility to advanced liver fibrosis. However, cirrhosis was more prevalent in individuals with the GADD45A rs532446 TT and ATF3 rs11119982 TT genotypes. In addition, the rs225014 CC variant of DIO2 was more frequently found in patients with a diagnosis of HCC. These findings suggest that the above SNPs may play a role in HBV-induced liver damage in a Caucasian population.

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment.

T cells play an important role in the clearance of hepatotropic viruses but may also cause liver injury and contribute to disease progression in chronic hepatitis B and C virus infections which affect millions of people worldwide. The liver provides a unique microenvironment of immunological tolerance and hepatic immune regulation can modulate the functional properties of T cell subsets and influence the outcome of a virus infection. Extensive research over the last years has advanced our understanding of hepatic conventional CD4+ and CD8+ T cells and unconventional T cell subsets and their functions in the liver environment during acute and chronic viral infections. The recent development of new small animal models and technological advances should further increase our knowledge of hepatic immunological mechanisms. Here we provide an overview of the existing models to study hepatic T cells and review the current knowledge about the distinct roles of heterogeneous T cell populations during acute and chronic viral hepatitis.

Serum total IgE as immunological marker in patients with chronic hepatitis B Virus infection, and hepatitis B related hepatocellular carcinoma

This study evaluated the efficacy of IgE in predicting disease progression in chronic hepatitis B virus (HBV) and HBV related hepatocellular carcinoma (HCC) compared to normal controls. The study included 60 HBV-infected patients. Of these, 30 patients with chronic hepatitis B but not related to HCC and 30 patients with related HCC. Serum level of IgE was measured by ELISA. Serum level of IgE was higher in HCC patients than non-HCC patients (p < 0.005). Significant correlations were detected between IgE, transaminases (ALT, AST), alpha-fetoprotein and severity scores in chronic hepatitis B (CHB) patients. The level of IgE was correlated with HB viral load. Stronger correlations were evident between IgE, prothrombin time and total bilirubin. In conclusion, IgE levels may be considered as non-invasive markers for monitoring liver disease progression in CHB.

Hepcidin Level in Sera of Patients with Chronic Hepatitis B Virus in Babylon Province

Background: The most prevalent disease in the world, is chronic hepatitis B virus (CHB). It has several causes like, drugs, alcohol consumption, toxicity and auto-immune disease, but in most cases it is caused by hepatitis viruses (viral hepatitis). Hepcidin regulates the body iron negatively by binding to the cellular iron exporter ferroportin in target cells, like macrophages, enterocytes and making its internalization and deprivation, thus reducing iron efflux into plasma causing decrease serum iron level and an elevated in intracellular iron. Materials and Methods: One hundred subjects; 50 diagnosed with chronic hepatitis B virus and 50 healthy subjects were enrolled in this study. Age ranged between (20–60) years (for patients and control). Hepcidin and ferritin level in serum were estimated by enzyme- linked immunosorbent assay (ELISA) technique, while serum iron concentration was calculated by the Siemens Dimension by Direct method (Ferene). Results: In chronic hepatitis B virus group serum hepcidin, ferritin and iron levels significantly elevated compared with control group (P &lt; 0.01). On the other hand, the current study observed significant (p value &lt;0.05) positive correlation for hepcidin with ferritin and iron in (CHB) patients. Conclusion: Among chronic hepatitis B patients in Babylon province, increase the level of some iron regulatory parameters; indicate the significant linked with the progression of chronic hepatitis B virus.

Baseline Circulating miR-125b Levels Predict a High FIB-4 Index Score in Chronic Hepatitis B Patients after Nucleos(t)ide Analog Treatment.

The regulatory role of microRNAs (miRNAs) in HBV-associated HCC pathogenesis has been reported previously. This study aimed to investigate the association between serum miR-125b and liver fibrosis progression in chronic hepatitis B (CHB) patients after nucleos(t)ide analog (NA) treatment. Baseline serum miR-125b levels and other relevant laboratory data were measured for 124 patients who underwent 12-month NA therapy. Post-12-month NA therapy, serum miR-125, platelet, AST, and ALT levels were measured again for post-treatment FIB-4 index calculation. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for a higher post-treatment FIB-4 index. Results showed that baseline miR-125b levels were inversely correlated with the post-treatment FIB-4 index (ρ = -0.2130, p = 0.0082). In logistic regression analyses, age (OR = 1.17, p &lt; 0.0001), baseline platelet level (OR = 0.98, p = 0.0032), and ALT level (OR = 1.00, p = 0.0241) were independent predictors of FIB-index &gt; 2.9 post-12-month treatment. The baseline miR-125b level was not significantly associated with a higher post-treatment FIB-4 index (p = 0.8992). In 59 patients receiving entecavir (ETV) monotherapy, the alternation of serum miR-125b in 12 months and age were substantially associated with a higher post-treatment FIB-4 index (&gt; 2.9), suggesting that miR-125b is a reliable biomarker for detecting early liver fibrosis under specific anti-HBV NA treatments (e.g., ETV).

Association between the HLA-DQB1 Gene Polymorphism and Chronic Progression of Hepatitis B in Indonesia

BACKGROUND: The progression of hepatitis B is affected by the activity of T lymphocytes. Activation of T lymphocytes requires a primary signal originating from the presentation of antigen by HLA molecules to T cell receptors. HLA-DQB1 gene polymorphisms can affect the ability of HLA to bind and present viral antigens to T cells, thus affecting T cell activation and potentially associated with the progression of chronic hepatitis B. AIM: We aimed to investigate the polymorphisms of the HLA-DQB1 gene and its influence on chronic hepatitis B progression of chronic hepatitis B patients in Indonesia. METHODS: This cross-sectional research studied chronic hepatitis B patients at the Internal Medicine Department, Arifin Ahmad Hospital, Pekanbaru, from January 2018 to December 2018. Subjects were grouped into three categories: (1) Inactive chronic hepatitis B, (2) active chronic hepatitis B, and (3) end stage liver disease (ESLD) which consisted of patients with liver cirrhosis and hepatocellular carcinoma. Examination of the HLA-DQB1 gene polymorphism was performed with the SSP-PCR method and sequenced to verify the PCR results. Analysis results of p &lt; 0.05 were considered statistically significant. RESULTS: The most common allele in patients with chronic hepatitis B was the HLA-DQB1 0301. The HLA-DQB1 0301 allele found primarily in the inactive chronic hepatitis B group. The DQB1 0501 allele found to be more abundant in patients with active chronic hepatitis B. The HLA DQB1 0502 allele only found in patients with chronic hepatitis B with ESLD. CONCLUSIONS: The HLA-DQB1 gene polymorphism is associated with the progression of chronic hepatitis B in chronic hepatitis B patients in Indonesia.

Differential proteomic analysis of plasma-derived exosomes as diagnostic biomarkers for chronic HBV-related liver disease

Hepatitis B virus (HBV) infection is still a major public health problem worldwide. We aimed to identify new, non-invasive biomarkers for the early diagnosis of chronic HBV-related diseases, reveal alterations in the progression of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Here, exosomes were isolated and characterized through size exclusion chromatography and nanoparticle tracking analysis. Profiles of differentially expressed proteins (DEPs) were analyzed through liquid chromatography-tandem mass spectrometry (LC–MS/MS), Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Results showed that the DEPs, including CO9, LBP, SVEP1, and VWF levels in extracellular vesicles (EVs) were significantly higher in CHB than in healthy controls (HCs). VWF expression levels in EVs were significantly lower in CHB than in those with LC. KV311 expression levels in EVs were significantly higher, whereas LBP levels were significantly lower in patients with CHB than in those with HCC. All biomarkers seemed to exhibit a high diagnostic capacity for HBV-related liver disease. Patients with HBV-induced chronic liver disease exhibit characteristic protein profiles in their EVs. Thus, serum exosomes may be used as novel, liquid biopsy biomarkers to provide useful clinical information for the diagnosis of HBV-related liver diseases at different stages.

Association study of TAP and HLA-I gene combination with chronic hepatitis C virus infection in a Han population in China.

Host immune system genes play key roles in the progression of chronic hepatitis C virus (HCV) infection. Transporters associated with antigen processing (TAP) play an important role in the loading of viral peptides onto MHC class I molecules. This study aimed to investigate the association between TAP gene polymorphisms and chronic HCV in a Chinese Han population. A total of 232 chronic hepatitis C (CHC) patients and 362 healthy individuals were recruited from the Han population in Yunnan province in southwest China, and a TaqMan SNP genotyping assay was used to detect six single nucleotide polymorphisms (SNPs) of TAP1 and three SNPs of TAP2 genes. The association of the TAP gene with CHC was analysed at the allele, genotype, and haplotype levels. There were no significant differences in the allele and genotype frequencies of these SNPs in the TAP gene between CHC patients and controls after Bonferroni correction. A novel TAP1 allele (TAP1*unknown_1: rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: G-G-A-G-G-G) was only present in the CHC group, and this allele significantly increased susceptibility to CHC (p=.005, odds ratio [OR]=11.105. 95% confidence interval [CI]: 1.362-90.558). Homozygous TAP1*03:01/TAP1*03:01 was observed only in the CHC group that exhibited an obvious risk for CHC (p=.002, OR=9.637, 95% CI: 1.153-80.574). And the haplotype TAP1*unknown_1-TAP2*01:01 was only present in the CHC group and indicated a significant risk for CHC (p=.002, OR=9.498, 95% CI: 1.140-79.149). We observed significant interactions among HLA-A, -B,C, TAP1, and TAP2 alleles, and combination analysis revealed that the combination of TAP1*01:01-TAP2*01:01-HLA-B*35:01 was only present in the control group (2.2%) and resulted in significantly increased resistance to CHC (p=.002, OR=0.096, 95% CI: 0.012-0.759). Whereas, the combination of TAP1*01:01-TAP2*01:01-HLA-C*07:02 and TAP1*03:01-TAP2*01:01-HLA-C*01:02 increased the susceptibility to CHC significantly (p=.001, OR=2.016, 95% CI: 1.309-3.106 and p=.002, OR=8.070, 95% CI: 1.018-63.997, respectively). Our results indicated that TAP and HLA-I may exert a combined effect on CHC susceptibility in the Chinese Han population.

MiRNome profiling of circulating extracellular vesicles in patients with chronic hepatitis delta treated with pegylated interferon alpha

Introduction: MicroRNAs (miRNAs) are short noncoding RNAs involved in the epigenetic regulation of multiple signalling pathways including modulation of viral replication and host immune antiviral response. Specific circulating miRNAs profiles have been associated both with the progression of chronic hepatitis C and with the response to interferon (IFN) treatment in chronic hepatitis B patients. However, data in patients with chronic hepatitis delta virus (HDV) infection are missing.