Hepatitis B Virus Load Research Articles

Association between khat chewing and high viral load in chronic hepatitis B infection

Background and aims: chronic hepatitis B infection (CHB) is a worldwide health threat that has moderate to high prevalence in Yemen. There is accumulating evidence of the hepatotoxicity of khat, which is commonly and habitually chewed in Yemen and elsewhere, but little is known in CHB. This study aimed to examine the association between khat chewing and hepatitis B virus (HBV) serum DNA level (viral load) in such cases. Methods: Between January and December 2016, a cross-sectional study was carried out on consecutively consenting 210 CHB participants (khat chewers and non-cutters) attending the hepatology clinics of two major hospitals in Sana’a city. After a structured interview, blood samples were collected for the determination of HBV markers and HBV load. Results: the study population, residing different cities in Yemen, had a median age of 36y (range = 20-72) with a 2.9:1 male to female ratio. Viral load was significantly (P<0.001) higher among khat chewers than non chewers: median (Interquartile range) = 1308 (531.5-5916.5) vs 177 (60-627) IU/ml. Khat chewing was observed, via multivariate logistic regression analysis, to be significantly (pThe0.001) and independently associated with a clinically significant high HBV load (>2000 IU/ml) even after adjustment for the studied socio-demographic and laboratory factors. Conclusion: This study suggests khat chewing, especially on a daily basis, as a potential risk factor for high viremia and, therefore, be prudently discouraged in CHB.

Viral Load of HBV and HCV Correlation to Torque Teno Virus (TTV) Co-Infection in Iraqi Patients

Abstract Background: While hepatitis viruses A–E are established, emerging evidence points to additional, novel viral hepatitis agents. The torqueteno virus (TTV) has garnered interest due to its prevalence among patients with hepatitis, suggesting potential hepatotropism. Aim: This study was conducted to detect TTV antigens in individuals infected with chronic hepatitis B (HBV) and/or C (HCV) using molecular diagnostics and to explore any associations between TTV presence and demographic characteristics of the cohort. Materials and Methods: The current study was conducted from the period of September 2022 to April 2023, the investigation involved Iraqi patients aged between 32 and 83 years and diagnosed with HBV and HCV in National Iraqi Central Laboratories, Virology Section. We employed real-time PCR to quantify HBV and HCV viral loads and conventional PCR for TTV DNA detection. Results: TTV DNA was detected in 17 of the 60 patients (28.3%) with chronic HBV and HCV infections. Viral load distribution was found to be similar for both HBV and HCV. An age-related increase in viral load was noted, suggesting a trend where older individuals exhibited higher concentrations. However, no significant variation was observed that could link alterations in HBV and HCV viral loads to TTV status directly. Statistical analysis indicated a positive correlation between age and the likelihood of presenting with the virus, aligning with observed trends in other age-associated chronic conditions, such as Type 2 diabetes mellitus and chronic kidney disease. Conclusion: The presence of TTV in patients with enduring HBV or HCV infection could implicate the virus as a contributing factor to hepatitis pathology. Studies such as this are pivotal for elucidating the age-associated risk profiles for various pathologies and shaping corresponding public health policies and preventative approaches.

HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

QUANTIFICATION OF HEPATITIS B AND HEPATITIS C VIRAL LOAD BY REAL-TIME PCR AND ASSESSMENT OF COINFECTION OF HBV AND HCV AMONG HIV-POSITIVE PATIENTS IN A TERTIARY CARE HOSPITAL

bjective: To assess the prevalence of coinfection of HIV-HBV and HIV-HCV and to estimate the viral load of HBV and HCV in PLWH.
 Methods: A retrospective study was conducted from November 2021 to October 2022 among patients attending ICTC. 5 ml of blood sample collected aseptically was tested for HIV, HBV and HCV using rapid immunochromatographic tests, ELISA and viral load estimated by Real-time PCR.
 Results: Out of 5087 samples tested for HIV, 666 samples (13.09%) were found to be positive. Prevalence of HIV-HBV and HIV-HCV coinfection was 15.6%(104 cases) and 1.5% (10 cases), respectively. Out of which, males were predominant (62.28%). This is clinically significant with a p-value of * 0.05. HIV-HBV and HIV-HCV coinfections were predominant in 41-50 y age group. Among104 HIV-HBV coinfected, viral load at the time of diagnosis is ‘below detection level’ in 25(24.04%), <250 in 15(14.42%), 251-500 in 9(8.65 %), 501-1000 in 13(12.5 %), 1001-10,000 in 23(22 %) and>10, 000 copies/ml in 19(18.26%). In 10 HIV-HCV coinfected cases, the viral load is ‘below detection level’ in 2(20%), <250 in 1(10%), 251-500 in 1(10 %), 501-1000 in 1(10 %), 1001-10,000 in 4(40%) and>10,001-100,000 copies/ml in 1(10%).
 Conclusion: Monitoring the viral load in HBV or HCV infected at the time of diagnosis of HIV or testing for protective levels of antibodies post-vaccination in uninfected people will help in limiting the progression of chronic HBV or HCV to cirrhosis, end-stage liver disease or hepatocellular carcinoma.

A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study.

The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

Contagious order as a risk factor for liver fibrosis progression in co-infection with human immunodeficiency virus, hepatitis B and C viruses

In triple co-infection with HIV/HCV/HBV, the prognosis is significantly poorer and life expectancy is lower because of the rapid progression of liver fibrosis or development of hepatocellular carcinoma. The aim of this study was to test the hypothesis that one of the risk factors for the unfavorable course of HIV/HCV/HBV co-infection is contagious order and the interval between coinfections. The study analyzed anamnestic data and the results of direct follow-up of 97 patients co-infected with HIV/HCV/HBV for 1-2 years. Patients were divided into three study groups: (1) HIV as the first pathogen, (2) HCV as the first pathogen, and (3) HBV as the first pathogen. For each patient, the period (in years) between the acquisition of the first and subsequent pathogens was considered. During the fol-low-up period, viral HIV, HCV, and HBV load was assessed by PCR, and annual transient liver fibro-elastometry was performed to determine the fibrosis stage using the METAVIR scoring system. The risk of progressive liver fibrosis in HIV/HCV/HBV co-infection is higher when HIV or HBV is the first pathogen, but the interval between the acquisition of HBV and other viruses is 10 years. Meanwhile, a stable course of liver fibrosis is associated with an HBV viral load of &gt;7,200 copies/ml. In the risk group, the most effective antiretroviral therapy was a combination of reverse transcriptase inhibitors, HIV protease inhibitors, and direct antiviral (anti-HCV) drugs. Therefore, the order of infection and intervals between pathogen acquisition in triple co-infection with HIV/HCV/HBV have a significant effect on liver fibrosis progression, which requires specific approaches to the organization of diagnostic tests and the control of antiretroviral therapy.

Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-induced Immunotolerance

Background & AimsThe immune tolerance induced by Hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. MethodsWe utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including HBsAg, HBeAg, HBcAg, HBV DNA, and HBV RNA. ResultsOur study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an HBsAg vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. ConclusionThe current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/ STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.

Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus(HBV) functional receptor sodium taurocholate cotransporting polypeptide(NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients.Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed.A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males.NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Perilipin2 inhibits the replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions.

Chronic hepatitis B virus (HBV) infection is often associated with increased lipid deposition in hepatocytes. However, when combined with non-alcoholic fatty liver disease or hyperlipidemia, it tends to have a lower HBV deoxyribonucleic acid (DNA) load. The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood. To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms. 1603 HBsAg-seropositive patients were included in the study. We first explored the relationship between patients' lipid levels, hepatic steatosis, and HBV DNA load. Also, we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro. By knocking down and overexpressing Plin2, we observed whether Plin2 regulates autophagy and HBV replication. By inhibiting both Plin2 and cellular autophagy under high lipid stimulation, we examined whether the Plin2-autophagy pathway regulates HBV replication. The results revealed that serum triglyceride levels, high-density lipoprotein levels, and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group. Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load. Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAg-positive and HBeAg-negative groups. An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism. The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg, HBeAg, and HBV DNA load. Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins. Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy. Knocking down Plin2 and blocking autophagy with 3-methyladenine (3-MA) inhibited HBV DNA replication. In conclusion, lipid metabolism is a significant factor affecting HBV load in patients with HBV infection. The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.

Difference of gut microbiota between patients with negative and positive HBeAg in chronic hepatitis B and the effect of tenofovir alafenamide on intestinal flora.

Severe liver diseases, such as liver fibrosis, cirrhosis, and liver cancer, are mainly caused by hepatitis B virus (HBV). This study investigated the differences between gut microbiota in HBeAg-positive and negative groups of patients with chronic hepatitis B (CHB) and investigated the effect of tenofovir alafenamide (TAF) on gut microbiota. This prospective study included patients with CHB not taking nucleoside antivirals (No-NAs group, n = 95) and those taking TAF (TAF group, n = 60). We divided CHB patients into two groups according to the HBeAg status of the subjects on the day of data collection. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients. We investigated the improvement of clinical symptoms by TAF, as well as differences in gut microbiota between different groups by 16S rRNA high-throughput sequencing. Gut microbiota demonstrated significant differences between patients with HBeAg-positive and -negative CHB. Both the No-NAs and TAF Phase 2 subgroups demonstrated significantly increased microbiota richness and diversity, showing greater heterogeneity. Additionally, the Phase 2 subgroup exhibited a low abundance of pathways associated with glucose metabolism and amino acid metabolism. The TAF group demonstrated a significantly decreased HBV load, alanine aminotransferase, and aspartate aminotransferase and a significant increase in prealbumin compared with the No-NAs group. No significant difference was found in uric acid, creatinine, blood calcium, inorganic phosphorus, eGFR, and β2-microglobulin concentrations between the two groups. Additionally, the urea level in the TAF group was significantly lower than that in the No-NAs group, but with no significant effect on other indicators such as eGFR and β2-microglobulin. This study revealed significant differences in gut microbiota composition and function between patients with HBeAg-positive and -negative CHB.

Correlation between Hepatic Enzymes and Viral Load of HBV in Hepatitis B patients

Background: Hepatitis B virus is a causative agent of hepatitis B, and it is a severe global health issue. Aim: To investigate the increased level of aminotransferases and its association with viral load of HBV infected patients and to find the most sensitive and reliable technique for identification of HBV infection. Methods: This cross-sectional study included 198 patients of HBV. Blood samples were collected from these patients in serum tubes for detection of HBV by different techniques such as Immunochromatographic (ICT), Enzyme linked immunosorbent assay (ELISA), and whole blood was collected which was further processed for DNA extraction and real time PCR. Results: There were 64 female and 134 males in this study. All the patients were positive for HBV by the ICT method and also by ELISA method but for the RT-PCR out of these 198 patients 89(45%) were positive and 109 (55%) were negative. This study demonstrates no significant correlation between liver enzymes with viral load. The ICT test method is active and simple but not a precise and unique test also has no statistical correlation with viral load, but ELISA is correlated with viral load recognized by real time PCR. (P value=˂0.001, 95% Cl=0.40-0.69, r value =0.56). Conclusion: Our results concluded that the immunochromatographic technique is fast and easily available but not a precise and definitive test and has no statistical correlation with viral load, but ELISA is associated with viral load proved by RT-PCR. Real time polymerase chain reaction is the gold standard test for the detection of Hepatitis B virus infection. The practical implication of this study is that ICT technique is no longer a reliable technique for the diagnosis of HBV infection and the patients positive on ICT should be confirmed for HBV in PCR for both diagnostic and prognostic purposes. Keywords: Hepatitis B Virus, Liver enzymes, Immunochromatographic, Viral load, Enzyme linked immunosorbent assay

Determination of the Relationship Between C-Reactive Protein (CRP) Levels and Hepatitis B Surface Antigen

The relationship between hepatitis B virus (HBV) infection and C-reactive protein (CRP), which is an inflammatory biomarker, is limited in studies on the general population. Thus, this study aimed at determining the relationship between CRP levels and Hepatitis B surface antigen in patients with hepatitis B. A total of 70 samples were screened for the presence of hepatitis surface antigen by one step hepatitis B Surface antigen test strip (serum/plasma) package insert. The samples were further subjected to ELISA test and quantitative real time PCR to determine the viral load. The performance of the assay on the 70 samples showed 17 (24.29%) patients were positive and 53 (75.71%) patients were negative for serological test. Out of the 17 samples which were positive for HBV, CRP was positive in 5 patients while 12 patients were negative for CRP. While out of 53 patients who were negative for HBV, 9 were positive for CRP and 44 were negative for CRP. For the significance of viral load for clinical monitoring, three titer groups were presented. Among the 70 samples tested for viral load of HBV, 50% (35/70) of samples showed low titer by the Ct˂30, while only 15.71% (11/70) of samples were detected with high viral load by Ct˃30. Statistical analysis showed insignificant relationship between CRP and HBV. Positive predictive value of CRP was lower;it is revealed that the presence of HBV infection cannot be predicted on the basis of CRP analysis only. The reason behind lower CRP concentration in HBV positive cases remains unclear but there is a perception that high CRP levels in the blood can be a marker of inflammation.

Differential Viral Load Indicates HDV Influences HBV Replication in HBV/HDV Coinfected Patients

Viral Hepatitis causing approximately 1.4 million deaths every year. HBV is a partially double stranded DNA virus and belongs to the family Hepadnaviridae. HDV is a sub satellite virus which infects patients that are already infected by HBV because it depends on HBV surface antigen for its replication. HDV causes super infection with different complexities as compared to sole HBV infection.To compare viral load of HBV and HDV to check possible influence on each others replication.A cross-sectional analytical study was conducted on 907 samples. HBV DNA was detected and quantified by Abbott HBV Quantification kit and HDV RNA was detected and amplified by RoboGene®. Screening of HDV RNA and HBV DNA by PCR and results were analyzed using SPSS. Out of 907 patients, 33% were HBV/HDV co-infected, 35% were HBV, 18% were infected with HDV &amp; 14% were HBV/HDV negative.Out of these, 75.7% were males and 24.3% were females. The patients were divided into three age groups: 5-20 years, 21-40 years &amp; 41-80 years. Overall levels of HBV DNA PCR &lt; 1000 IU/ml was found in 74% HBV/HDV co-infected patients as compared to 30.8% HBV mono infected. This study indicates that the absence or the low viral load of HBV in HDV positive patients might be due to possible subdue of HBV by HDV in HBV/HDV co-infected patients.Age group of 20-40 years and male gender is comparatively at high risk for these viral infections.

Cell-based cccDNA reporter assay combined with functional genomics identifies YBX1 as HBV cccDNA host factor and antiviral candidate target

ObjectivesChronic hepatitis B virus (HBV) infection is a leading cause of liver disease and hepatocellular carcinoma. A key feature of HBV replication is the synthesis of the covalently close circular...

Virological responses to tenofovir-alafenamide-containing antiretroviral therapy in people living with HIV co-infected with lamivudine-resistant or lamivudine-susceptible hepatitis B virus

BackgroundData on the effectiveness of tenofovir alafenamide (TAF) against lamivudine-resistant (LAM-R) hepatitis B virus (HBV) among patients co-infected with human immunodeficiency virus (HIV) and HBV are limited. MethodsBetween April and December 2018, HIV-positive patients co-infected with LAM-R or lamivudine-susceptible (LAM-S) HBV who switched from tenofovir-disoproxil-fumarate-containing antiretroviral therapy (ART) to TAF-containing ART were followed for 96 weeks. Plasma HBV and HIV loads, HBV serological markers, and liver function before and after the switch were analysed. ResultsIn total, 182 patients co-infected with HIV and HBV were included in this study: 45 with LAM-R HBV and 137 with LAM-S HBV. At baseline, 28.9% and 7.4% of patients in the LAM-R and LAM-S groups, respectively, tested positive for hepatitis B virus envelope antigen (HBeAg) (P<0.001), and the respective percentages of patients who had achieved plasma HBV DNA <20 IU/mL were 95.5% and 97.1%. At weeks 48 and 96, 100% and 94.9% of patients in the LAM-R group, respectively, and 97.1% and 95.6% of patients in the LAM-S group, respectively, maintained plasma HBV DNA <20 IU/mL. Lamivudine resistance of HBV and baseline hepatitis B virus surface antigen (HBsAg) level were associated with HBsAg decrement at week 96 at a degree of 0.25 log10 IU/mL [95% confidence interval (CI) 0.059–0.246] and 0.22 log10 IU/mL (per 1-log10IU/mL increase, 95% CI 0.018–0.101), respectively. At week 96, 2.2% (4/182) of patients had HBsAg loss; no patients in the LAM-R group and 25.0% (2/8) of patients in the LAM-S group had HBeAg seroconversion. ConclusionsSwitching to TAF-containing regimens maintained high rates of HBV viral suppression in patients co-infected with either LAM-R or LAM-S HBV. The decrease in HBsAg was minimal, and HBsAg seroconversion occurred infrequently.

The Incidence and the Clinical Significance of the Gray Zone in the Clinical Phases of Chronic Hepatitis B Virus Infection

Background: five clinical phases were described in patients with chronic (HBV) infection: HBeAg- positive HBV infection, HBeAg- positive CHB, HBeAg negative HBV infection, HBeAg-negative CHB and occult HBV infection.&#x0D; Aim: This study aimed to determine the incidence of the unclassified phase (gray zone) in chronic hepatitis B patients and its significant in the clinical practice. &#x0D; Patients and methods: The study was conducted retrospectively on 109 patients' who have HBsAg positive for more than 6 months. The data recorded include; HbeAg and anti-HBe Ab, ultrasound of the abdomen, HBV DNA load and alanine aminotransferase (ALT), accordingly; we classify the patients to known clinical phases. Patients who were unfit one of these phases considered to be in the gray zone and subsequently sent for liver fibroscan to determine the fibrosis stage. &#x0D; Results: The mean age of our patients was 34.25 (±13.9) years with 54.12% being males. The mean viral load was 5,885,490 IU/ml and mean ALT was 56.22 (±89.88) U/L. eight patients (7.3%) were in the HBeAg+ve HBV infection, 13 patients (11.9%) were in HBeAg+ve CHB . Thirty four patients (31.1%) were in the HBeAg-ve HBV infection and 23 (21.1%) were in HBeAg-ve CHB phase, both were showed a significant statistical relationship with age&gt; 35 years. Thirty one (28.4%) further patients failed to identify with any of the four phases (normal ALT with HBV load &gt; 2000 IU/ml), this group also showed significant relation to age above 35 years and 12 patients (38.8%) had significant fibrosis on fibroscan.&#x0D; Conclusions: A considerable number of patients with chronic HBV infection have persistently normal ALT levels, despite elevated levels of viral load; this is known as the "grey zone" phase. These patients merit close follow up with short-interval measurement of liver enzymes, liver fibroscan and biopsy may be considered.

Increased ILT2 expression contributes to dysfunction of CD56dimCD16+NK cells in chronic hepatitis B virus infection

Natural killer (NK) cells play a crucial role in the control of human viral infections but their activity is significantly impaired in patients infected with chronic hepatitis B (CHB). The mechanism that contributes to NK cell dysfunction in CHB needs further elucidation. In this study, we analyzed the expression and function of the novel inhibitory receptor immunoglobulin-like transcript-2 (ILT2) on NK cells from 131 CHB patients and 36 healthy controls. We observed that ILT2 expression on circulating CD56dimCD16+NK cells was increased in immune-tolerant, immune-active and HBeAg-negative hepatitis patients compared with inactive carriers and controls. The frequency of ILT2+CD56dimNK cells was positively correlated with serum viral load in immune-tolerant patients. The percentage of ILT2+CD56dimNK cells decreased along with HBV load in CHB patients who received antiviral therapy. Functional analysis showed that ILT2+CD56dimNK cells in CHB patients had significantly reduced degranulation and IFN-γ production. Upregulation of ILT2 was associated with high levels of apoptosis in CD56dimCD16+NK cells from CHB patients. ILT2 blockade was shown to increase the cytotoxicity and IFN-γ production of CD56dimNK cells in some CHB patients. Finally, ILT2 was found to be moderately upregulated by TGF-β1, which was increased in immune-tolerant, immune-active and HBeAg-negative hepatitis patients. Our results show that chronic HBV infection increases the levels of the inhibitory receptor ILT2 on CD56dimNK cells and inhibits their functions, providing a new mechanism of NK-cell disability in CHB patients.

Interaction between baseline HBV loads and the prognosis of patients with HCC receiving anti-PD-1 in combination with antiangiogenic therapy undergoing concurrent TAF prophylaxis

BackgroundA high baseline hepatitis B virus (HBV) load has always been listed as an exclusion criterion for programmed cell death-1 (PD-1) inhibitor-associated therapy in clinical trials, as the interaction between HBV load and anti-PD-1/PD-L1 therapy with anti HBV therapy remains controversial.MethodsWe retrospectively enrolled 70 unresectable HCC patients who were seropositive for HBsAg and accepted tenofovir alafenamide fumarate (TAF) therapy before anti-PD-1 in combination with an antiangiogenic treatment. Patients were divided into a low HBV DNA group (≤ 2000 IU/ml) and a high HBV DNA group (> 2000 IU/ml) according to the baseline HBV DNA levels. Tumour response and progression-free survival (PFS) were compared, and univariate and multivariate Cox analyses were performed to identify potential risk factors for PFS. The incidences of HBV reactivation and HBV-associated hepatitis were also recorded.Results48 patients were assigned to the low group and the remaining 22 patients were assigned to the high group. The objective response rates (ORRs), disease control rates (DCRs), and PFS between the two groups showed no significant difference (P = 0.761, 0.552, and 0.784, respectively). The results of Cox analyses revealed that there was no relationship between baseline HBV load and PFS. Additionally, HBV reactivation occurred in only 2 patients (2.9%), and no patient experienced HBV-related hepatic impairment when given a continuous TAF treatment.ConclusionsBaseline HBV loads do not affect the prognosis of HCC patients receiving anti-PD-1 in combination with an antiangiogenic therapy, while PD-1 inhibitors do not aggravate HBV reactivation and hepatic impairment in patients simultaneously subjected to TAF prophylaxis.

Seroprevalence and mutations in the major hydrophilic region of hepatitis B virus among pregnant women in Huzhou, China.

Mother-to-child transmission (MTCT) is the main cause of hepatitis B virus (HBV) infections in China. However, there is a paucity of information on seroprevalence and mutations in HBV surface genes among pregnant women in Huzhou, China. In this retrospective cross-sectional study, serum markers of 31681 pregnant women were collected and analysed. The surface genes were amplified and directly sequenced. Mutations in the major hydrophilic region (MHR) were analysed in 171 randomly selected subjects. The seroprevalence of HBV infection was 3.32% (1053/31681). The predominant HBV genotypes were B (57.4%) and C (42.6%). Pregnant women ≥30y of age exhibited a higher hepatitis B surface antigen-positive rate than those <30y of age. MHR mutations were found in 42.6% (72/169) of the subjects, several of which were escape mutations. The mutational frequencies in the a-determinant and first loop (AA124-137) were higher in genotype C than genotype B. Pregnant women with MHR mutations showed increased alanine transaminase, aspartate transaminase and gamma-glutamyl transpeptidase levels and decreased HBV loads. The HBV seroprevalence among pregnant women in Huzhou was intermediate. MHR mutations occur and the risk of MTCT still persists. Therefore, early screening, intervention and care for HBV-infected pregnant women should be strengthened to minimize or prevent MTCT of HBV.