Inactive Hepatitis B Virus Carriers Research Articles

Hepatitis B Virus-related Membranous Nephropathy with Crescentic Formation in an Inactive Carrier of Positive Hepatitis B Surface Antigen with Undetectable DNA under Anti-viral Treatment.

A man who was an inactive hepatitis B virus (HBV) carrier with positive hepatitis B surface antigen (HBs antigen) and undetectable HBV-DNA under anti-viral treatment developed nephrotic syndrome at 52 years old, and a renal biopsy revealed advanced membranous nephropathy (MN) with focal cellular crescents, interstitial hemorrhaging, and peritubular capillaritis. Immunofluorescence studies demonstrated granular IgG deposition and HBs antigen-positivity along the capillaries. Glomeruli were negative for phospholipase A2 receptor 1. There were no clinical findings of systemic vasculitis. We considered MN combined with small-vessel vasculitis due to HBV infection. These results suggest that HBV-related kidney disease should be considered even in patients with an inactive HBV carrier status under treatment.

Mitochondrial HIGD1A inhibits hepatitis B virus transcription and replication through the cellular PNKD-NF-κB-NR2F1 nexus.

Hepatitis B Virus (HBV) replication has been reported to be restricted by the intrahepatic host restriction factors and antiviral signaling pathways. The intracellular mechanisms underlying the significant viremia difference among different phases of the natural history chronic HBV infection remain elusive. We herein report that the hypoxia-induced gene domain protein-1a (HIGD1A) was highly expressed in the liver of inactive HBV carriers with low viremia. Ectopic expression of HIGD1A in hepatocyte-derived cells significantly inhibited HBV transcription and replication in a dose-dependent manner, while silence of HIGD1A promoted HBV gene expression and replication. Similar results were also observed in both de novo HBV-infected cell culture model and HBV persistence mouse model. Mechanistically, HIGD1A is located on the mitochondrial inner membrane and activates nuclear factor kappa B (NF-κB) signaling pathway through binding to paroxysmal nonkinesigenic dyskinesia (PNKD), which further enhances the expression of a transcription factor NR2F1 to inhibit HBV transcription and replication. Consistently, knockdown of PNKD or NR2F1 and blockage of NF-κB signaling pathway abrogated the inhibitory effect of HIGD1A on HBV replication. Mitochondrial HIGD1A exploits the PNKD-NF-κB-NR2F1 nexus to act as a host restriction factor of HBV infection. Our study thus shed new lights on the regulation of HBV by hypoxia-related genes and related antiviral strategies.

Evulation of prolidase enzyme, and galectin levels as a marker for fibrosis in patients with chronic hepatitis B.

The fibrosis can be detected using non-invasive methods including prolidase activity, proline levels and galectin-3 (GAL-3) detection in the serum. The aim of this study was to investigate the liver fibrosis through non-invasive methods in chronic hepatitis B patients. This prospective case control study includes 56 patients with Chronic Active Hepatitis B (CAHB), 57 patients with Inactive Hepatitis B (IHB), and 60 healthy matched control subjects. The first group included the CAHB [hepatitis B surface antigen (HBsAg): positive; HBV DNA >2,000 IU/mL; normal or high alanine aminotransferase (ALT) value] undergo a liver biopsy, while the second group included the IHB (HBsAg: positive; HBV DNA: negative; normal ALT value). The third group comprised the healthy controls. Serum prolidase enzyme activities (SPEA), proline and galectin-3 levels were measured for each group. Patients with CAHB had significantly higher SPEA levels (1,004.3±186.8 IU/L) than did the controls (196.5±306 IU/L) (p<0.001). Significantly higher serum GAL-3 levels were found in the CHB group compared with HBV carrier and the control groups (27.4±32.2 ng/mL, 6.5±13.4 ng/mL, 3.1±5.7 ng/mL, respectively, p<0.001). The relationship between serum prolidase activity, hidroxiprolyne and fibrosis (p<0.05). There were no significant differences in ALT levels between inactive HBV carriers and the control groups (p>0.05). We suppose that hidroxiprolyne levels and prolidase enzyme activity might be an indicator as a marker for fibrosis in CAHB and the evaluation of response to treatment.

ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation, Regardless of HBV Genotype.

Hepatitis B virus (HBV) biomarkers have been used for a better categorization of patients, even though the lack of simple algorithms and the impact of genotypes limit their application. Our aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers (ICs) in a single-point evaluation and to design a predictive model for their identification. This retrospective-prospective study included 343 consecutive HBeAg-negative individuals. Clinical, analytical, and virological data were collected, and a liver biopsy was performed if needed. Subjects were classified at the end of follow-up as ICs, chronic hepatitis B and gray zone.A predictive model was constructed, and validated by 1000-bootstrap samples. After 39 months of follow-up, 298 subjects were ICs, 36 were chronic hepatitis B CHB, and nine were gray zone. Eighty-nine (25.9%) individuals required a liver biopsy. Baseline HBV DNA hazard ratio (HR) 6.0, p<0.001), HBV core-related antigen (HBcrAg) (HR 6.5, p<0.001), and elastography (HR 4.6, p<0.001) were independently associated with the IC stage. The ACE score (HBV DNA, HBcrAg, elastography), obtained by bootstrapping, yielded an area under the receiver operating characteristics (AUROC) of 0.925 (95% CI: 0.880-0.970, p<0.001) for identification of ICs. The AUROC for genotype D was 0.95, 0.96 for A, 0.90 for E, and 0.88 for H/F. An ACE score of <1 had a positive predictive value of 99.5%, and a score ≤12 points had a diagnostic accuracy of 93.8%. Low baseline HBV DNA, HBcrAg, and liver stiffness were independently associated with the IC phase. A score including those variables identified ICs at a single-point evaluation, and might be applied to implement less intensive follow-up strategies.

Noninvasive Evaluation of Liver Fibrosis in a Sample of Putative Inactive HBV Carriers in Rome, Italy.

Background Noninvasive methods are useful for investigating patients with chronic HBV infection. The severity of liver disease in inactive HBsAg carriers can be noninvasively assessed by transient elastography (TE) alone or in association with biochemical markers of fibrosis. Objectives The study evaluates the effectiveness of the TE compared to common fibrosis scores (FSs), APRI, Forns Index, and FIB4, for identifying significant fibrosis in Italian and foreigner HBsAg carriers. To investigate the risk of progression of the liver disease, liver stiffness (LS) and HBV-DNA were monitored over time. Methods Viral load, biochemical parameters, and LS have been retrospectively evaluated in 125 putative inactive HBV carriers, who visited two outpatient departments (Colleferro Hospital and INMP) from 01/03/2014 to 31/12/2019. Differences in clinical, biochemical, and demographic variables between Italians and foreigners were analyzed. 66 of 125 patients were followed up for 24 months by monitoring liver stiffness and HBV-DNA. Results Mean overall LS was 5.55 ± 1.92 kPa; 18 (14.4%) patients had a LS ≥7.5 kPa. Mean of APRI, Forns, and FIB4 was 0.29 ± 0.11, 4.15 ± 1.63, and 1.16 ± 0.59, respectively. FS did not differ between the patients with LS <7.5 kPa and those with LS ≥7.5 kPa. Italians displayed a significant lower ALT (0.53 ± 0.18 vs. 0.67 ± 0.33, p < 0.05) and AST (0.59 ± 0.16 vs. 0.70 ± 0.21, p < 0.01) value than foreigners. No differences in LS and HBV-DNA levels were observed. In 66 patients followed up for 24 months, HBV-DNA increased by ≥2000 UI/ml after 12 months in 15 individuals and remained ≥2000 UI/ml after 24 months in 10/15 individuals. 7/10 patients showed LS ≥ 7.5 kPa after 24 months, and 4 of them underwent antiviral therapy for HBV. Patients with HBV-DNA <2000 IU/ml had a significantly lower LS than those with HBV-DNA ≥2000 IU/ml (5.30 ± 1.43 vs. 7.69 ± 1.07, p < 0.0001). Conclusions Analysis shows lower effectiveness of FS vs. TE in the assessment of putative inactive HBV carriers. Furthermore, using FibroScan® and HBV-DNA can identify “false” inactive carriers.

Lower Somatic Mutation Levels in the λ Light-Chain Repertoires with Chronic HBV Infection

To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals.

Hepatitis B Surface Antigen Decline during Sofosbuvir and Ribavirin Therapy in Hepatitis B Inactive Carriers Who Were Co-infected with Hepatitis C.

Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.

Vitamin D Levels and Vitamin D Receptor (VDR) Gene Polymorphisms in Inactive Hepatitis B Virus Carriers.

To evaluate the vitamin D receptor (VDR) gene polymorphisms and vitamin D levels in inactive hepatitis B virus (HBV) carriers. A cross-sectional analytical study. From March to September 2017 at the Izmir Katip Celebi University (İKCU) Ataturk Training and Research Hospital, Izmir, Turkey. Eighty-six inactive hepatitis B carriers and 86 control individuals were included in the study. Individuals with diseases or under medication that could affect vitamin D levels were excluded from the study. Serum vitamin D concentration of >30 ng/mL was considered as sufficient, between 20-30 ng/mL as insufficient, <20 ng/mL as deficiency and <10 ng/mL as severe deficiency. VDR gene Bsm I, Fok I, Apa I and Taq I polymorphisms were identified by the polymerase chain reaction-fragment length polymorphism (PCR-RFLP) method. When vitamin D levels were examined, 52.3% (n = 45) of the inactive HBV carriers had severe deficiency, 38.4% (n = 33) deficiency, 7% (n = 6) insufficiency; 45.3% (n = 39) of the control group had severe deficiency, 43% (n = 37) deficiency, and 7% (n = 6) insufficiency. There was no statistically significant relationship between VDR gene and Bsm I, Fok I, Apa I, Taq I polymorphisms and vitamin D levels in inactive hepatitis B carriers and control group (p>0.05). Vitamin D deficiency is highly prevalent both among control population as well as in chronic hepatitis patients. Key Words: Inactive HBV carrier, Vitamin D, Polymorphism, Vitamin D receptor (VDR).

Decrease of Clone Diversity in IgM Repertoires of HBV Chronically Infected Individuals With High Level of Viral Replication.

High-throughput antibody sequencing allows in-depth insights into human antibody repertoires. To investigate the characteristics of antibody repertoires in patients with chronic HBV infection, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of B lymphocytes from healthy adults and the HBV carriers with high or low level of viral replication. The comparative study revealed high levels of similarity between the IgM and IgG repertoires of the HBV carriers and the healthy adults, including the somatic mutations in V regions, the average CDR3 length, and the occurrence of junctional modifications. Nevertheless, the diversity of the unique clones decreased and some clusters of unique clones expanded in the IgM repertoire of chronic HBV carriers (CHB) compared with healthy adults (HH) and inactive HBV carriers (IHB). Such difference in clone diversity and expansion was not observed in the IgG repertoires of the three populations. More shared antibody clones were found between the IgM repertoires of IHB and HH than that found between CHB and HH (7079 clones vs. 2304 clones). Besides, the biased used IGHD genes were IGHD2-2 and IGHD3-3 in CHB library but were IGHD3-10 and IGHD3-22 in IHB and HH library. In contrast, for IgG repertories, the preferred used VDJ genes were similar in all the three populations. These results indicated that low level of serum HBV might not induce significant changes in BCR repertoires, and high level of HBV replication could have more impacts on IgM repertories than IgG repertoires. Taken together, our findings provide a better understanding of the antibody repertoires of HBV chronically infected individuals.

Evaluation of the Relationship between Insulin Resistance and HBV DNA Level in Patients with HBeAg-negative Chronic HBV Infection (Natural Course Phase 3).

Background and aimsChronic hepatitis B (CHB) infection is an important cause of morbidity and mortality worldwide with an increased risk of liver failure, cirrhosis, and hepatocellular carcinoma. Hepatitis B virus (HBV) DNA level, the marker of viral load in the host, is a parameter affected by host factors. In this study, we investigated the relationship between HBV DNA level and insulin resistance as a host factor.MethodsIn this study, 146 patients diagnosed with “HBeAg-negative chronic HBV infection” (natural course phase 3, inactive carrier) according to the European Association for the Study of the Liver (EASL) 2017 guidelines were retrospectively analyzed and demographic, anthropometric, histopathological, radiological and laboratory data of the patients were recorded. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) levels of the patients were calculated, and according to the value, the patients were divided into two groups as insulin resistant and non-insulin resistant. All parameters, including HBV DNA, were evaluated and compared between the two groups.Results77 patients (52.7%) were insulin resistant with a HOMA-IR value of 2.5 or more. The remaining 69 patients (47.3%) whose HOMA-IR value less than 2.5 were non-insulin resistant. The median HBV DNA was 410 IU in the insulin-resistant group and 350 IU in the other group, and there was no statistical significance between the two groups (p: 0.537). HBV DNA level was only positive correlated with HBsAg level and negatively correlated with anti-Hbs level and age (p < 0.005). Compared to the non-insulin resistant group, body mass index (BMI), presence of hepatosteatosis on ultrasonography (USG), fasting blood sugar, fasting insulin, total protein, gamma glutamyl transferase (GGT), triglyceride (TG), very-low-density lipoprotein (VLDL), uric acid level, triglyceride/high-density lipoprotein (HDL) ratio were significantly higher and HDL levels were significantly lower in the insulin-resistant group (p < 0.005). GGT levels and TG/HDL ratio were found to be higher in patients with hepatosteatosis on ultrasonography than in patients without hepatosteatosis (p < 0.005). TG/HDL ratio was found to be an independent factor in predicting insulin resistance and every 1 unit increase of this ratio increases the risk of developing insulin resistance 2.1 times.ConclusionIn this study, no significant relationship was found between insulin resistance and HBV DNA levels in chronic inactive HBV carriers. In addition, insulin resistance was observed more frequently in these patients compared to the general population, and insulin resistance was found to be associated with high BMI, hepatosteatosis rate, VLDL, TG, GGT, total protein, uric acid, TG/HDL ratio, and low HDL. TG/HDL ratio was found to be successful in predicting insulin resistance.How to cite this articleSenoymak MC, Ozkan H. Evaluation of the Relationship between Insulin Resistance and HBV DNA Level in Patients with HBeAg-negative Chronic HBV Infection (Natural Course Phase 3). Euroasian J Hepatogastroenterol 2020;10(2):85–91.

Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers.

Many mutation analyses of the HBV genome have been performed in the search for new prognostic markers. However, the Kozak sequence preceding precore was covered only infrequently in these analyses. In this study, the HBV core promoter/precore region was sequenced in serum samples from European inactive HBV carriers. Quadruple mutation GCAC1809-1812TTCT was found with a high prevalence of 42% in the Kozak sequence preceding precore among all HBV genotypes. GCAC1809-1812TTCT was strongly associated with coexistence of basal core promoter (BCP) double mutation A1762T/G1764A and lower HBV DNA levels. In vitro GCAC1809-1812TTCT lead to drastically diminished synthesis of pregenomic RNA (pgRNA), precore mRNA, core, HBsAg, and HBeAg. Calculation of the pgRNA secondary structure suggests a destabilization of the pgRNA structure by A1762T/G1764A that was compensated by GCAC1809-1812TTCT. In 125 patients with HBV-related cirrhosis, GCAC1809-1812TTCT was not detected. While a strong association of GCAC1809-1812TTCT with inactive carrier status was observed, BCP double mutation was strongly correlated with cirrhosis, but this was only observed in absence of GCAC1809-1812TTCT. In conclusion, our data reveal that GCAC1809-1812TTCT is highly prevalent in inactive carriers and acts as a compensatory mutation for BCP double mutation. GCAC1809-1812TTCT seems to be a biomarker of good prognosis in HBV infection.

Patients with SARS-CoV-2 and HBV co-infection are at risk of greater liver injury

To date, it remains unclear if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection exacerbates liver injury in patients with chronic hepatitis B virus (HBV) infection. In this study, we present a retrospective study of 133 hospitalized confirmed mild coronavirus disease 2019 (COVID-19) cases, including 116 patients with COVID-19 with negative serum hepatitis B antigen and 17 HBV inactive carriers with COVID-19. We found that there were no significant differences for the discharge rate or duration of hospitalization between the two groups. However, inactive HBV carriers with SARS-CoV-2 co-infection are at a higher risk of abnormal liver function tests. The enhanced liver injury induced by SARS-CoV-2 and HBV co-infection was identified as the hepatocyte type rather than the cholangiocyte type. Moreover, the inflammatory response, including abnormal lactate dehydrogenase, D-dimer and interleukin-6 production, may contribute to this injury following SARS-CoV-2 co-infection. Collectively, SARS-CoV-2 and HBV co-infection exacerbates liver function of the patients with COVID-19.

Genetic polymorphisms of interleukin-6 influence the development of hepatitis B virus-related liver cirrhosis in the Han Chinese population

BackgroundInterleukin-6 (IL-6) plays an important role in chronic inflammation. Thus, we aimed to investigate the effects of IL-6 polymorphisms on predicting the progression of hepatitis B virus (HBV)-r elated liver cirrhosis. MethodsA cross-sectional study was conducted to analyse IL-6 polymorphisms and serum levels of IL-6 in HBV-infected patients at different clinical phases and in healthy controls. IL-6 polymorphisms were detected by the TaqMan PCR method, and plasma IL-6 levels were assessed by ELISA. ResultsOur analysis included 182 chronic hepatitis B (CHB) patients, 190 HBV-infected liver cirrhosis cases, 125 inactive HBsAg carriers, and 246 healthy controls. Seven SNPs in IL-6 including rs10499563, rs17147230, rs1800796, rs2069837, rs1524107, rs2066992, and rs2069852 were analysed. In a haplotype analysis between HBV-infected liver cirrhosis cases and CHB patients, inactive HBV carriers or healthy controls, haplotype CT in block 1 and haplotype GGCGG in block 2 were associated with liver cirrhosis (P <0.05). Moreover, the genotype or allele frequencies were significantly different in IL-6 rs10499563 and rs2069837 when HBV-infected liver cirrhosis patients were compared with CHB patients, inactive HBV carriers or healthy controls. A further study found that compared with that in the healthy controls, inactive HBV carriers or CHB patients, plasma IL-6 was elevated in HBV-infected liver cirrhosis patients. ConclusionIn conclusion, the IL-6 rs10499563 and rs2069837 polymorphisms are associated with incidence of liver cirrhosis may through their effects on IL-6 expression and these two single nucleotide polymorphisms can be used as potential prognostic markers of HBV-related liver cirrhosis.

2427 A Case of Hepatitis B Virus-Related Membranous Nephropathy in an Adult With Low Hepatitis B Viral Load

INTRODUCTION: Hepatitis B virus (HBV) infection is an important etiologic factor for secondary membranous nephropathy (MN), especially in regions with endemic HBV infection. Though an uncommon occurrence, it is crucial to recognize HBV-related MN as it may progress to renal failure in untreated adults. In patients with HBV infection, it is critical to exclude other secondary causes of MN. This case describes a case of HBV-related MN in a HBeAg-negative patient with low HBV viral load. CASE DESCRIPTION/METHODS: Mr C is a 64 year old gentleman who has underlying chronic HBV infection and Stage 3b chronic kidney disease. He presented with bilateral lower limb swelling. He was found to have hypoalbuminemia and nephrotic range proteinuria associated with microscopic hematuria. He was in “inactive chronic HBV carrier infection” phase with negative hepatitis B e antigen (HBeAg), positive anti-HBe and low HBV viral load 2.68 log IU/ml with positive antinuclear antibody and low complement C3. Other workup for secondary causes of membranous nephropathy was unyielding. Renal biopsy showed membranous nephropathy with focal proliferative glomerulonephritis. Immunofluorescence was not suggestive of lupus nephritis and staining for antiphospholipase A2 receptor was negative. He was diagnosed as HBV-related MN and he was treated with Tenofovir Alafenamide. Six months after HBV treatment, his proteinuria has improved with stable renal function. HBV viral load was suppressed to less than 1.3 log IU/ml but he still had high titer of HBsAg (7000 IU/ml) as expected. DISCUSSION: In HBV-related MN, HBV treatment is recommended as previous studies showed that HBV treatment and HBeAg clearance are associated with remission of MN. However, treatment endpoint remains unclear. The pathogenesis of HBV-related glomerular disease is due to the deposition of HBV antigens immune complexes in the glomerulus, especially to HBeAg. Therefore, MN can occur in patients with low HBV viral load. In HBeAg-positive patients, it may be reasonable to consider stopping antiviral following clearance of HBeAg. In HBeAg-negative patients, HBsAg immune complexes may contribute to MN. As in this case, it may be prudent to continue with HBV therapy as he has persistently high HBsAg titer. Future research is needed to find reliable HBV markers to guide management and define clinical end points for patients with HBV-related MN.

Patchy echogenicity of the liver in patients with chronic hepatitis B does not indicate poorer elasticity.

PurposeThis study was conducted to investigate whether the presence of patchy echogenicity in the liver of patients with chronic hepatitis B (CHB) is predictive of liver stiffness.MethodsA total of 200 CHB patients with and without patchy echogenicity of the liver were assigned to two groups, with 100 patients in each group, and 32 of them underwent liver biopsy. Additionally, 80 healthy subjects, 100 inactive HBV carriers, and 100 patients with decompensated hepatic cirrhosis were assigned to the control groups. Laboratory tests and clinical data were collected, and shear wave velocity (SWV) of the liver was measured for all 480 subjects.ResultsThe median SWV in patients with a normal liver, inactive hepatitis B virus carriers, CHB patients with and without patchy echogenicity, and decompensated hepatic cirrhosis were 1.07 m/sec, 1.08 m/sec, 1.16 m/sec, 1.16 m/sec, and 2.02 m/sec, respectively; there was no significant difference in SWV values between CHB patients with patchy echogenicity and those without patchy echogenicity. Furthermore, among CHB patients with and without patchy echogenicity, no significant difference in SWV was found according to fibrosis stage.ConclusionThe presence of patchy echogenicity of the liver does not indicate a higher degree of liver stiffness.

Association between hepatitis B virus infection and chronic kidney disease: A cross-sectional study from 3 million population aged 20 to 49 years in rural China.

Hepatitis B virus (HBV) infection can lead to different types of chronic kidney diseases (CKD) in clinical practice. However, HBV infection has been observed to have no significant association with CKD indicators in some epidemiological surveys. This research aims to estimate CKD prevalence in HBV infection population and clarify the relationship between HBV infection status and CKD.The participants aged 20 to 49 years were selected by multistage random sampling from January 1, 2010 to December 31, 2012 across 31 provinces and regions in rural China. The data was collected by standard questionnaire and physical check-up. Status of HBV infection was diagnosed as immune tolerant phase, hepatitis B envelope antigen -positive chronic HBV infection, inactive HBV carrier, hepatitis B envelope antigen -negative chronic HBV infection and resolved HBV infection based on serological markers, and the level of hepatic function, respectively.In total, 2,969,502 subjects were included in the study. In population aged 20 to 49 years in rural China, prevalence of HBV infection was 12.17%. Prevalence of proteinuria, hematuria, estimated glomerular filtration rate less than 60 mL/min/1.73m2 and CKD was 0.94%(95% CI = 0.91–0.97%) vs. 0.65%(95% CI = 0.64–0.66%), 1.92%(95% CI = 1.87–1.96%) vs. 1.19% (95% CI = 1.18–1.21%), 1.02%(95% CI = 0.99–1.06%) vs. 0.77% (95% CI = 0.76–0.78%), and 3.85%(95% CI = 3.78–3.91%) vs. 2.60%(95% CI = 2.58–2.62%) in population with HBV infection and without infection, respectively. Prevalence of CKD and indicators was higher in population in every status of HBV infection than in population without infection, respectively (all P < 0·0001). Every HBV infection status was a risk factor for CKD.CKD prevalence was higher in population in every status of HBV infection than without infection. HBV infection was a risk factor for CKD in population aged 20 to 49 years in rural China.

Effect of hepatitis B virus infection status on liver metastasis of nasopharyngeal carcinoma: a cohort study.

BackgroundThe impact of hepatitis B virus (HBV) infection status on liver metastasis of nasopharyngeal carcinoma (NPC) has not been thoroughly elucidated to date. This study aimed to determine how HBV infection status influences liver metastasis of NPC through the analysis of clinical samples.MethodsA total of 1,367 patients with pathologically diagnosed NPC who received systemic treatment at Nanfang Hospital or Zhujiang Hospital between January 2005 and December 2015 were enrolled in this retrospective study. Based on their HBV infection status, these patients were separated into four groups: negative infection (n=492), chronic HBV infection (n=123), inactive HBV carrier (n=175), and resolved HBV infection (n=577). The relationship between HBV infection status and liver metastasis of NPC was examined.ResultsCompared with the negative infection group, we observed that an inactive HBV carrier status was related to liver metastasis in patients with NPC (HR: 0.392; 95% CI: 0.178–0.863; P=0.020). The resolved HBV infection group had a lower risk of liver metastasis than the negative infection group (HR: 0.621; 95% CI: 0.402–0.959; P=0.032). There was no direct association between HBV infection status and distant metastasis of NPC.ConclusionsInactive HBV infections and resolved HBV infections are highly associated with a decreased risk of liver metastases in NPC patients compared with patients without HBV infections.

Dynamic Differences Of Red Cell Distribution Width Levels Contribute To The Differential Diagnosis Of Hepatitis B Virus-related Chronic Liver Diseases: A Case-control Study.

Objective: This study aims to clarify the changes and clinical significance of red cell distribution width (RDW) during HBV-related chronic diseases, including inactive hepatitis B virus (HBV) carriers, HBV immune tolerant individuals, chronic hepatitis B (CHB) patients and HBV-related hepatocirrhosis patients.Methods: RDW was measured 288 CHB patients, 100 patients with hepatitis B e antigen(HBeAg)-negative chronic HBV infection (inactive carriers), 92 patients with HBeAg-positive chronic HBV infection (immune tolerant), and 272 patients with HBV-related hepatocirrhosis. Their RDW changes were compared with 160 healthy controls. Correlations between RDW and clinical indicators were conducted. For HBeAg+ CHB patients, RDW was measured before and after antiviral therapy. The efficiency of RDW to distinguish hepatocirrhosis from CHB and/or inactive carriers was evaluated by receiver operating characteristic (ROC) curves.Results: RDW was higher in hepatocirrhosis patients than other groups of patients and healthy controls. Besides, HBeAg+ CHB patients possessed higher RDW than HBeAg- CHB patients. For HBeAg+ patients that underwent HBeAg seroconversion after antiviral therapy, RDW was decreased. RDW was positively correlated with total bilirubin and Child-Pugh scores and negatively correlated with albumin among hepatocirrhosis patients. The areas under the curve (AUC) of ROC curves to distinguish hepatocirrhosis from CHB patients was 0.7040 for RDW-standard deviation (RDW-SD) and 0.6650 for RDW-coefficient of variation (RDW-CV), and AUC to distinguish hepatocirrhosis from inactive carriers was 0.7805 for RDW-SD and 0.7991 for RDW-CV.Conclusions: RDW is significantly increased in HBeAg+ CHB patients and patients with HBV-related hepatocirrhosis and could reflect their severity. RDW could help to distinguish hepatocirrhosis from CHB patients and inactive HBV carriers.

Molecular Diagnosis in Differentiating Active and Inactive Forms of Hepatitis B Virus Carriers

Background &amp; objectives: Introducing a nucleic acid test program is aimed to diagnose and reduces the risk of viral infection or transmission. DNA assay for HBV can detect infection in the windows period, chronic occult infection and can discriminate between active and inactive HBV infection. This cross-sectional study designed to diagnose, analyze HBV infection and to differentiate active from inactive infection based on viral DNA detection. Methods: Blood samples were collected from 256 patients previously diagnosed on the clinical ground as hepatitis B seropositive in Erbil Central Lab. The viral nucleic acid quantitative assessment was done for the collected samples using RT-PCR. Q-square was performed for statistical analysis. Results: Out of 256 collected blood samples 93 (36.3%) showed HBV-DNA positive titers above 50 IU/ml. Among positive subjects, 67 (72.04%) was categorized as inactive carriers (˂ 2000-20.000 IU/ml HBV-DNA titers). Conclusions: The data produced from this study confirmed the importance of the RT-PCR technique in sensitivity and reliability as a superior diagnostics tool specifically in differentiating active from inactive HBV carriers.

The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease.

Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.