Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.

Establishment and Validation of a nomogram for Predicting the Risk of Liver Fibrosis in Chronic HBV Infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant fibrosis in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical University from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected.131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization.The patients were divided into non-significant fibrosis and significant fibrosis groups in the modeling group.To collect the clinic information,serological examination,liver elastography and liver histopathology results and to establish a rosette model to predict the risk of chronic HBV infection with significant fibrosis.Results:A total of 180 patients with chronic HBV infection were included,and 113 patients(62.7%)had significant fibrosis.In the modeling set,84 patients(64.1%)had significant fibrosis.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,ALB,PAB,IL-6,HA,PⅢP,CIV,L.N and LSM for non-significant fibrosis and significant fibrosis showed statistically significant differences.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 4.988 and 0.527,respectively,corresponding to P values of 0.08 and 0.77,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant fibrosis after HBV infection for the modelling and validation groups was 0.843[95%CI(0.775-0.910)]and 0.776[95%CI(0.714-0.838)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that ALB,HA,PⅢP,LSM and IL-6 were more closely associated with the occurrence of significant fibrosis after HBV infection,and a visualization of the occurrence of significant fibrosis column line graph model was established by comprehensive assessment,and validation was given that all were superior to the traditional models FIB-4 and APRI.

Establishment and validation of a nomogram for predicting the risk of liver inflammation in chronic HBV infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant inflammation in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical College from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected,and to prevent overfitting of the model,131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization,to collect the clinic information,serological examination,liver elastography and liver histopathology results.The patients were divided into non-significant inflammation and significant inflammation groups in the modeling group.The R 4.1.1 package and the rms package were used to build the column line graph model,while the Bootstrap method was applied to repeat the sampling 1000 times for internal and external validation,and the H-L goodness of fit test and ROC curve were used to assess the calibration and discrimination of the column line graph model respectively.Results:A total of 180 patients with chronic HBV infection were included,and 92 patients(51.1%)had significant inflammation.In the modeling set,67 patients(51.1%)had significant inflammation.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,GGT,PAB,H.A,PⅢP,CⅣ,L.N,IL-6,LSM and HBeAg for non-significant inflammation and significant inflammation showed statistically significant differences(P<0.05).Nomogram were obtained using stepwise regression analysis to establish a predictive model for the risk of significant inflammation following chronic HBV infection.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 0.279 and 2.098,respectively,corresponding to P values of 0.87 and 0.35,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant inflammation after HBV infection for the modelling and validation groups was 0.895[95%CI(0.843-0.948)]and 0.760[95%CI(0.622-0.897)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that PLT,Ln(HBV-DNA),AST,C桇and LSM were more closely associated with the occurrence of significant inflammation after HBV infection,and a visualization of the occurrence of significant inflammation nomogram was established by comprehensive assessment,and the effectiveness was good.

New perspective on the natural course of chronic HBV infection

Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

The Expression of CD2 in Chronic HBV Infection

It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression level of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection. Cellular ＆ Molecular Immunology.

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

BACKGROUND 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.AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.METHODS 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.RESULTS 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 HBeAgpositive 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.CONCLUSION 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.

Antiviral Therapy of Liver Cirrhosis Related to Hepatitis B Virus Infection

Hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide,with 75% of those affected distributed in the Asia-Pacific region.Approximately one million HBV-infected patients die of liver cirrhosis and hepatocellular carcinoma (HCC) each year.If left untreated,6-20% of chronic hepatitis B (CrHB) patients will develop cirrhosis over five years.The cumulative incidence of HBV-related cirrhosis,disease progression,and prognosis are closely associated with serum HBV DNA levels.Antiviral therapy in HBV-related cirrhosis has been documented by several long-term cohort studies to decrease disease progression to hepatic decompensation and HCC.The approval and availability of oral antiviral agents with better safety profiles has greatly improved the prognosis for HBV-related cirrhosis.Here,we discuss the significance of antiviral therapy for HBV-related cirrhosis and the management of HBV-related diseases in the future.

Macrophage Phenotypes and Hepatitis B Virus Infection

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.

Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model

Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.

Fitting logistic regression models to assess vitamin D deficiency with clinical parameters in chronic hepatitis B patients

Statistical models provide a quantitative structure with which clinicians can evaluate their hypotheses to explain patterns in observed data and generate forecasts.In contrast,vitamin D is an important immune modulator that plays an emerging role in liver diseases such as chronic hepatitis B(CHB).Therefore,we quantified 25(OH)D_(3) serum levels in 292 CHB patients tested for their association with clinical parameters.Of 292 patients,69(63%),95(47%),and 39(19%)had severe vitamin D deficiency(25(OH)D_(3)<10 ng/mL),vitamin D insufficiency(25(OH)D_(3)10 and<20 ng/mL),or adequate vitamin D serum levels(25(OH)D_(3)20 ng/mL),respectively.In both univariate and multivariate analyses,zinc serum level was a strong predictor of low 25(OH)D_(3) serum levels(P<0.001).Results of fitted models showed that lower vitamin D levels were significantly associated with:younger age,lower uric acid levels,HBeAg-positive status,lower calcium levels(p<0.05).Vitamin D deficiency(<20 ng/ml)or severe deficiency(<10 ng/ml)was observed more frequently among HBV patients(52%).Vitamin D deficiency was observed in most CHB patients.Generally,our results recommend that substitution of vitamin D can be a substitution method in the treatment of patients with HBV-associated disorders.