High HBV DNA Levels Research Articles

Predictive value of FibroScan in detecting liver fibrosis in HBeAg negative patients with chronic hepatitis B whose HBV DNA 2000-20000 IU/ml with ALT 1-2 times the upper limit of normal and those with HBV DNA >20000 IU/ml and normal ALT.

Objective:In hepatitis B infection, it is difficult to make a treatment decision in patients with slightly elevated transaminases and HBV DNA level between 2000 and 20000 IU/ml, and in those with normal ALT, despite high levels of HBV DNA. Objectives: In HBeAg negative patients whose HBV DNA levels were between 2000 and 20000 IU/ml with ALT 1–2 times the upper limit of normal (ULN) and those with HBV DNA >20000 IU/ml and normal ALT, the concordance between liver fibrosis in biopsy and liver stiffness measured by transient elastography with FibroScan® (FS) was investigated, and diagnostic value of FS to predict the liver fibrosis was tested.Methods:The patients were selected from the outpatient hepatology clinics between the dates of November 2014 and October 2016 among those who were taken liver biopsy. Transient elastography was obtained within 3 months after liver biopsy. The diagnostic value of FS in detecting advanced fibrosis or moderate to advanced (MTA) fibrosis was investigated for each group.Results:In 38 patients with HBV DNA 2000–20000 IU/ml and ALT 1–2×ULN, advanced fibrosis was detected in only one patient (2.6%) on liver biopsy, sensitivity of FS to show advanced fibrosis is 100%, specificity 78.3%, and diagnostic accuracy rate 79%. The area under curve was determined to be 0.892. In detecting MTA fibrosis, these values are 100%, 62%, 71%, and 0.810, respectively. Of 79 patients with HBV DNA >20000 IU/ml and normal ALT, five had advanced (5.5%) and 18 had MTA (23%) fibrosis. Sensitivity of FS in detecting advanced fibrosis was 100%, specificity 87.8%, and accuracy 88.6%, and these values for MTA fibrosis were 85.7%, 81%, and 82.3%, respectively.Conclusion:Because of false negativity in a few patients with HBV DNA >20000 IU/ml in detecting MTA, FS may be combined with other non-invasive techniques. Negative predictive values of FS in predicting advanced or MTA fibrosis were very high, while positive predictive values were low. However, FS may save several patients from liver biopsy.

Non Invasive Methods versus Liver Biopsy for Making Therapeutic Decisions in Chronic Hepatitis B Patients with High HBV DNA Levels and Mildly Elevated Transaminases

Introduction: Staging of liver fibrosis is essential for making therapeutic decisions in patients with Chronic Hepatitis B (CHB) having raised Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) levels (>2000 IU/ml) and normal or mildly elevated Alanine Transaminase (ALT). Though the gold standard for assessment of liver fibrosis has been liver biopsy, many non invasive models have been developed to mitigate the risks associated with liver biopsy and overcome its limitations. Aim: To evaluate the non invasive models predictive of significant fibrosis in this selected subgroup of Chronic Hepatitis B patients. Materials and Methods: Fifty-six CHB patients were evaluated. This longitudinal observational study was conducted at Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University from February 2017 to July 2018 on 56 patients. Liver Stiffness Measurement (LSM), Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI), FIBROSIS-4 (FIB-4) and Gamma-Glutamyl Transpeptidase (GGT) to platelet ratio (GPR) were estimated. Liver fibrosis staging was done using Metavir score. Significant fibrosis corresponds to Metavir score F2-F4 and advanced fibrosis as more than F3.The performance of non invasive methods was assessed using Receiver Operating Characteristic (ROC) curves. Z -test was used to compare Area Under ROC Curves (AUROCs). Results: Twenty-one patients (37.5%) had significant fibrosis, out of which seven had F3-F4 fibrosis. Patients with F2-F4 fibrosis had higher age, Hepatitis B e antigen (HBeAg) positivity, HBV DNA, ALT, AST, GGT, LSM, APRI, FIB-4 and GPR values than patients with F0-F1 fibrosis. Metavir fibrosis stages positively correlated with LSM values (r=0.831, p<0.0001), APRI (r=0.338, p=0.011), FIB-4 (r=0.375, p=0.003) and GPR (r=0.36, p=0.012). To predict advanced fibrosis, the AUROC of LSM had higher AUROC than APRI (0.956 vs 0.755, p=0.01), FIB-4 (0.956vs 0.786, p=0.01) and was comparable to GPR (0.956 vs 0.895, p=0.2). Conclusion: Transient Elastography (TE) is a reliable non invasive test for the diagnosis of liver fibrosis. GPR is a new model which is comparable to APRI and FIB-4 but inferior to TE.

Loss of HBsAg in Patients with High Levels of HBV-DNA During Treatment with Nucleoside or Nucleotide Analogs

Background: HBsAg is synthesized in the endoplasmic reticulum and is necessary for the formation of complete HBV particles. A decreased synthesis of this antigen leads to an intracellular inhibition of virus production. Methods: The study aimed to assess the incidence of HBsAg elimination among 1,290 patients who suffered from chronic HBV infection undergoing an antiviral treatment with nucleoside or nucleotide analogs (NAs). Furthermore, possible predictive factors for this elimination were analyzed. Results: A permanent HBsAg loss was confirmed in 3% of the patients, which was more frequent in men than in women (4.4% vs. 1.9%; P = 0.009). The HBsAg elimination occurred in 5% of HBeAg (+) patients and 2.8% of HBeAg (-) patients. The age of patients whose HBsAg was eliminated was higher than the age of the remaining patients (60 vs. 51 y/o). The effect of initially used pegylated interferon alfa (PEG-IFN) therapy on the HBsAg elimination was not observed. It occurred with the use of entecavir (ETV) and tenofovir (TDF); however, among patients treated with ETV, HBsAg was significantly more often eliminated in HBeAg (+) patients. Conclusions: The HBsAg elimination in patients undergoing antiviral treatment occurs more often in men, patients with positive HBeAg before treatment, individuals above 60 years, and patients treated with ETV.

Combination of quantitative hepatitis B core antibody (qHBcAb) and aspartate aminotransferase (AST) can accurately diagnose immune tolerance of chronic hepatitis B virus infection based on liver biopsy

Background and aimsImmune tolerance is defined as HBeAg positive, high hepatitis B virus load (HBV), persistent normal alanine aminotransferase (ALT), no or slight inflammation or fibrosis in liver histology. However, it is still unclear the threshold of high hepatitis B virus load and how to predict histology without liver biopsy. The aim of this study was to predict immune tolerance in HBeAg positive, alanine aminotransferase -normal populations with non-invasive indicators. MethodsTwo multi-center prospective cohort study recruited 907 treatment-naïve chronic hepatitis B (CHB) patients who had undergone liver biopsy in mainland China from August 2013 to September 2016 and April 2018 to June2019. Quantitative hepatitis B core antibody, AST and HBV DNA were investigated using commercial diagnostic assays and histological grading and staging was assessed by the Ishak scoring system. ResultsOne hundred and thirteen untreated CHB patients with HBeAg-positive, normal alanine aminotransferase (ALT) and high level of HBV DNA (≥5log10 IU/mL) were enrolled in this study. The area under the receiver operating characteristic curves (AUROCs) of qHBcAb, AST, HBV DNA and qHBcAb-AST index were 79.6%, 80.5%, 76.4% and 87.7%. Our novel qHBcAb-AST index, which combined qHBcAb and AST showed better performance with higher sensitivity (88.6% [95% confidence interval (CI) 72.3% – 96.3%]) and negative predictive value (NPV) (93.8% [95% CI 84.2% - 98.0%]). ConclusionsThe combination of qHBcAb and AST can more accurately predict the immune tolerance of people with HBeAg-positive, normal alanine aminotransferase (ALT).

IL-18 variant increases risk of enhanced HBV DNA replication in chronic hepatitis

BackgroundThe outcome ofhepatitis B (HBV) infection is influenced by immune responses and host genetics. Interleukin-18 (IL-18) is a determinant factor in controlling the balance of Th1/Th2 during antiviral response.Weexamine therole of two functional polymorphisms -607A/C and-137A/C inIL-18 gene with risk of chronic HBV infection. Methods and ResultsGenomic DNA isolates were obtained from 200 seropositive cases stratified according to their HBV DNA loads, and 200 blood donorsas a control population. Genotypes of the two polymorphisms were identified by ARMS-PCR method. The -607A allele, the-607AA and -607AC genotypes were associated with increased risk to develop chronic HBV infection (1.98, 5.11 and 3.5-fold risks, respectively). By contrast, the -137C minor allele and CG genotype had protected effects against chronic HBV infection.We found that -607A allele, -607AA and -607AC genotypes were significantly more frequent in patient’s group with high HBV DNA levels compared to patient group with low HBV DNA level. Additionally, they were associated with increased 1.72, 6.04 and 3.28-fold risk of high HBV DNA replication.Patients carrying “-607A/-137 C” or “-607A/−137 G” haplotypes presented a high risk to develop chronic HBV infection (OR = 3.27; OR = 4.32, respectively). ConclusionsTaken together, our data suggest that theIL-18 -607A/C functional polymorphism was associated with susceptibility to enhanced replicative form of HBV DNA in chronic infection.

The autophagy gene ATG16L1 (T300A) variant is associated with the risk and progression of HBV infection

Autophagy pathway genes variants that play crucial roles in immune responses are involved in many diseases but their role in viral diseases is ill-defined. ATG16L1 gene plays a crucial role in the autophagy process. In this study, we have investigated the role of ATG16L1 variant T300A in the risk of HBV infection. rs2241880 (T300A) variant in 551 HBV infected patients (at various stages of infection) and 247 healthy controls were genotyped applying PCR-RFLP. Data analysis revealed that mutant allele G contributes to the risk of hepatitis B infection. Mutant alleles were significantly associated the HBV risk in allelic (OR = 1.31; 95%CI = 1.06–1.63, p = .01) and homozygous (OR = 1.87; 95%CI = 1.17–2.99, p = .009) models. On stratifying HBV infected individuals according to the stage of infection, a significant association was observed in asymptomatic (allelic; OR = 1.52; 95%CI = 1.10–2.09, p = .01 and homozygous; OR = 2.30; 95%CI = 1.22–4.36, p = .01) and chronic (allelic; OR = 1.36; 95%CI = 1.07–1.73, p = .01 and homozygous; OR = 2.07; 95%CI = 1.22–3.53, p = .008) stages of infection. High HBV DNA levels were associated with mutant genotype GG in asymptomatic and chronic carriers. Significantly higher ALT levels were observed in the liver cirrhosis patients with mutant genotypes. In conclusion, our data suggest that rs2241880 mutant allele carriers (allelic and homozygous models) were associated with increased risk of hepatitis B virus infection in North Indian population.

The role of caesarean section and nonbreastfeeding in preventing mother-to-child transmission of hepatitis B virus in HBsAg-and HBeAg-positive mothers: results from a prospective cohort study and a meta-analysis.

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother-to-child transmission (MTCT) in HBsAg- and HBeAg-positive mothers via a cohort study and a meta-analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [("HBV" or "hepatitis b" or "hepatitis b virus") and ("mother-to-infant transmission" or "vertical transmission")]. Studies were screened, and data were extracted. The fixed-effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>108 IU/mL; RR=3.03, 95% CI: 1.41-6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR=0.61) and nonbreastfeeding (RR=0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR=0.58, 95% CI: 0.46-0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR=0.74, 95% CI: 0.56-0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg- and HBeAg-positive mothers who did not receive antiviral therapy during pregnancy.

Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients

The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33–2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24–9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85–13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01–0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05–6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06–0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.

Persistently elevated alpha-fetoprotein associated with chronic hepatitis B during chemotherapy for malignant ovarian germ cell tumors: a case series and a review of the literature

BackgroundAlpha-fetoprotein (AFP) plays a crucial role in the management of malignant ovarian germ cell tumors (MOGCTs) and is an important reference index for chemotherapy termination. However, a high level of AFP can also be caused by several benign diseases, causing confusion and impacting treatment decisions.Case presentationWe described four patients who were diagnosed with MOGCTs; the histologic subtype in two of them was mixed MOGCTs (yolk sac tumor with mature teratoma), while the rest was immature teratoma. The serum AFP level of each patient was abnormal before surgery, but it was still persistently elevated around 300 ng/ml even after additional cycles of chemotherapy. All patients were thoroughly evaluated, but we did not find any evidence of disease progression or residual tumors. Liver function tests were normal, whereas serum assays revealed positive of hepatitis B surface antigen, and two patients had a high level of HBV-DNA. They were chronic carriers of hepatitis B virus and never received relevant treatments. Then they were managed with tumor surveillance and the antiviral treatment. Thereafter, the AFP levels presented a slowly decreasing trend.ConclusionsFalse elevation of AFP in MOGCTs is a rare condition and should be assessed with a comprehensive evaluation to avoid unnecessary treatments.

P.319 Intravenous ketamine long-term use in two bipolar depression cases: 1-year follow-up

Hepatitis B (HBV) reactivation induced by chemotherapy is a problem currently encountered in the management of malignancies. HBV reactivation occurs particularly in patients who were not checked for HBV status, and therefore have not undergone antiviral prophylaxis. HBV reactivation may ultimately lead to fulminant liver failure (FLF). Liver transplantation (OLT), the only remaining effective treatment option, is generally denied for subjects with a recent history of malignancy.We described retrospectively three cases of FLF caused by HBV reactivation in two men and one woman undergoing rituximab-containing chemotherapy for malignant lymphomas: follicular, diffuse large B-cell and lymphoplasmacytic types. The two men reactivated after eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and the one woman after 13 cycles of rituximab monotherapy; their hematologic disease was in remission. All three patients were hepatitis B surface antigen (HBsAg)-positive with high HBV DNA levels. Neither man had been screened for HBV before chemotherapy; the woman had been treated with lamivudine (LAM) experiencing an HBV flare-up due to emergence of LAM resistance. All patients fulfilled King's College criteria for urgent OLT upon admission to the transplant center and underwent an urgent OLT. Their hemato-oncologic prognosis was considered to be favorable. All three patients are alive (54, 46, and 37 months post-transplantation), tumor-free and HBsAg negative on a standard HBV prophylaxis regimen: hepatitis B immunoglobulin and LAM + adefovir or tenofovir.Before chemotherapy appropriate prophylaxis for HBV reactivation should always be administered to at-risk patients. However, if reactivation with FLF occurs, OLT should not be generally denied. The prognosis of the hematologic malignancy should be assessed; OLT should be considered for patients in remission with a favorable long-term prognosis, for our data suggest acceptable survival.

Present and Future Therapies for Chronic Hepatitis B.

Chronic hepatitis B (CHB) remains the leading cause of liver-related morbidity and mortality across the world. If left untreated, approximately one-third of these patients will progress to severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC). High level of serum HBV DNA is strongly associated with the development of liver failure, cirrhosis, and HCC. Therefore, antiviral therapy is crucial for the clinical management of CHB. Current antiviral drugs including nucleoside/nucleotide analogues (NAs) and interferon-α (IFN-α) can suppress HBV replication and reduce the progression of liver disease, thus improving the long-term outcomes of CHB patients. This chapter will discuss the standard and optimization antiviral therapies in treatment-naïve and treatment-experienced patients, as well as in the special populations. The up-to-date advances in the development of new anti-HBV agents will be also discussed. With the combination of the current antiviral drugs and the newly developed antiviral agents targeting the different steps of the viral life cycle or the newly developed agents modulating the host immune responses, the ultimate eradication of HBV will be achieved in the future.

HBV DNA levels impact the prognosis of hepatocellular carcinoma patients with microvascular invasion.

To discuss the prognostic correlation between hepatitis B virus DNA (HBV DNA) level and HBV-related hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).Data from HCC patients undergoing hepatectomy with pathological evidence of MVI were retrospectively collected and 1:1 propensity scoring matching (PSM) analysis was performed. According to the HBV DNA levels before and after surgery, the disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the Cox proportional hazards regression was used to analyze the risk factors associated with the postoperative prognosis. After 1:1 PSM, 139 pairs of patients were enrolled in the high preoperative HBV DNA level group (H group) and low preoperative HBV DNA level group (L group), and after operation, patients with high preoperative HBV DNA levels were divided into the persistently high HBV DNA level group (P group) and the decreased HBV DNA level group (D group).According to the multivariate analysis, the HBV DNA level of 2000 IU/ml or greater before operation was significantly associated with the DFS (hazard ratio, 1.322; 95%CI, 1.016-1.721) and OS (hazard ratio, 1.390; 95%CI, 1.023-1.888). A persistent HBV DNA level of 2,000 IU/ml or greater after operation was also the independent risk factor of DFS (hazard ratio, 1.421; 95%CI, 1.018-1.984) and OS (hazard ratio, 1.545; 95%CI, 1.076-2.219).For the HBV-related HCC patients with MVI, preoperative high HBV DNA copies are prognostication of poorer prognosis, and effective antivirus treatment would significantly improve the patients' prognosis.

Antiviral therapy improves post-operative survival outcomes in patients with HBV-related hepatocellular carcinoma of less than 3 cm – A retrospective cohort study

BackgroundThe impact of antiviral therapy on long-term survival outcomes in patients with small HBV-related hepatocellular carcinoma (HBV-related HCC) after liver resection is still controversial, as the impact can be overshadowed by tumor-related factors. This study investigated this impact on recurrence and survival in patients with HCC of less than 3 cm. ObjectiveThis study was designed to further determine the impact of antiviral treatment on prognosis of patients with HCC after liver resection, to verify whether patients with cirrhosis still benefited from antiviral treatment, to study the impact of antiviral treatment on post-operative HCC recurrence, and to determine whether patients with a low preoperative HBV-DNA viral load should receive antiviral therapy. MethodsThe clinical data on patients who underwent curative liver resection for histopathologically confirmed small HCC (≤3 cm in diameter) were analyzed to determine factors which were related with HCC recurrence and survival. The disease-free and overall survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify the risk factors of long-term survival. ResultsOf the 795 patients in this study, patients with high preoperative HBV-DNA levels had significantly worse DFS and OS outcomes at 1-, 3- and 5- year after liver resection when compared with those with low HBV-DNA levels (86.1%, 60.8%, 46.6% vs 90.5%, 71.3%, 51.4%; and 98.5%, 89.3%, 75.2% vs 98.8%, 91.5%, 84%, respectively). Patients who received antiviral therapy had significantly better DFS and OS outcomes at 1-, 3- and 5- year after liver resection when compared with those without (91.6%, 69.5%, 55% vs 80.2%, 56%, 44.2%; and 99.6%, 93.5%, 87% vs 96.1%, 80.5%, 61.3%, respectively). Antiviral therapy significantly improved the OS but not DFS outcomes in patients with low HBV-DNA levels. The corresponding 1-, 3- and 5- year DFS and OS outcomes were 92.6%, 73%, 59.1% vs 87.1%, 68.5%, 57.9%; and 99.5%, 95.1%, 91.1% vs 97.6%, 85.5%, 72.4%, respectively. Antiviral treatment significantly prolonged DFS and OS in patients with cirrhosis. The corresponding 1-, 3- and 5- year DFS and OS were 90.2%, 66%, 49% vs 73.9%, 46.6%, 32.8%; and 100%, 93.6%, 85% vs 93.8%, 73.3%, 52.6%, respectively. ConclusionAntiviral therapy improved the prognosis of small HBV-related HCC of less than 3 cm. The survival benefit was also detected in patients with cirrhosis. Antiviral therapy should be considered a routine post-operative therapy for patients with HBV-related HCC.

Antiviral therapy to reduce hepatocellular carcinoma recurrence in patients with low HBV-DNA levels: A randomized controlled trial.

1510 Background: Despite antiviral treatment has been shown to reduce hepato- cellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. Methods: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were ran- domly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. Results: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P 1/4 0.016, P 1/4 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409– 0.884; P 1/4 0.010] and 0.509 (95% CI, 0.333–0.778; P 1/4 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recur- rence (hazard ratio [HR] 1/4 0.316, 95% CI 0.157 – 0.637; P 1/4 0.001) but not of early tumor recurrence (HR 1/4 0.782, 95% CI, 0.493–1.240; P 1/4 0.296). Conclusions: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection. Clinical trial information: ChiCTR-IPR-15006587.

SAT-177-Loss of HBsAg by patients with high levels of HBV-DNA during treatment with nucleoside or nucleotide analogues

SAT-177-Loss of HBsAg by patients with high levels of HBV-DNA during treatment with nucleoside or nucleotide analogues

Antiviral Therapy Reduces Hepatocellular Carcinoma Recurrence in Patients With Low HBV-DNA Levels: A Randomized Controlled Trial.

Despite antiviral treatment has been shown to reduce hepatocellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were randomly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.016, P = 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409-0.884; P = 0.010] and 0.509 (95% CI, 0.333-0.778; P = 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recurrence (hazard ratio [HR] = 0.316, 95% CI 0.157-0.637; P = 0.001) but not of early tumor recurrence (HR = 0.782, 95% CI, 0.493-1.240; P = 0.296). In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection.

DEPENDENCE OF GRAVITY OF LIVER DISEASE FROM REPLICATIVE ACTIVITY OF VIRUS HEPATITIS B AND D

The article is devoted to the study of the connection between the replicative activity of HBV DNA and HDV RNA with the formation of CP at all stages of development of chronic hepatitis of viral nature, evidence that a high level of HBV DNA is a pronounced predictor of liver cirrhosis (LC) progression. The purpose of the study is to study the dependence of the severity of liver damage on the replicative activity of the hepatitis B virus and D. Materials and methods. The study included 67 patients with cirrhosis of the liver in the outcome of viral hepatitis B and 140 patients with an outcome of cirrhosis against the background of chronic hepatitis B + D. The clinical stage of LC was determined according to the Child-Puy classification. Results. A direct link has been established between the increase in the viral load of HBV DNA and HDV RNA with the duration of the disease. A tendency was revealed to increase the severity of the disease in patients with LC of viral etiology with an increase in viral load. The biochemical indices of blood showed a tendency to an increase in the level of cytolytic enzymes against the background of high replicative activity of HBV DNA and HDV RNA. The conclusion. Thus, a high level of HBV DNA is a pronounced predictor of the progression of LC at all stages of the pathological proces

DEPENDENCE OF GRAVITY OF LIVER DISEASE FROM REPLICATIVE ACTIVITY OF VIRUS HEPATITIS B AND D

The article is devoted to the study of the connection between the replicative activity of HBV DNA and HDV RNA with the formation of CP at all stages of development of chronic hepatitis of viral nature, evidence that a high level of HBV DNA is a pronounced predictor of liver cirrhosis (LC) progression. The purpose of the study is to study the dependence of the severity of liver damage on the replicative activity of the hepatitis B virus and D. Materials and methods. The study included 67 patients with cirrhosis of the liver in the outcome of viral hepatitis B and 140 patients with an outcome of cirrhosis against the background of chronic hepatitis B + D. The clinical stage of LC was determined according to the Child-Puy classification. Results. A direct link has been established between the increase in the viral load of HBV DNA and HDV RNA with the duration of the disease. A tendency was revealed to increase the severity of the disease in patients with LC of viral etiology with an increase in viral load. The biochemical indices of blood showed a tendency to an increase in the level of cytolytic enzymes against the background of high replicative activity of HBV DNA and HDV RNA. The conclusion. Thus, a high level of HBV DNA is a pronounced predictor of the progression of LC at all stages of the pathological process.

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China.

BackgroundThe aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy.MethodsLiver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak’s fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out.ResultsOf the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30–39, 40–49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3).ConclusionOur results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

11. Factors predicting acute hepatitis B (AVH-B) versus chronic hepatitis B with acute exacerbation (CHB-AE)

Background and Aims: Differentiation of acute viral hepatitis-B (AVH-B) from chronic hepatitis B with acute exacerbation (CHB-AE) is a considerable diagnostic and therapeutic challenge. CHB-AE can lead to ACLF with high mortality and requires urgent treatment. Early recognition is must and there is no gold standard differentiating between the two conditions. We aim to analyse the clinical and laboratory factors differentiating AVH-B from CHB-AE. Materials and Methods: Thirty one patients presenting with acute hepatitis and HBsAg positive status were included in the study. Patient with co-infection with HAV and HEV were excluded. Cases of AVH-B versus CHB-AE labelled on basis of loss of HBsAg after 6 months of follow up. HBV DNA (IU/mL, by Real time PCR) and IgM anti HBc levels (Chemiluminescent microparticle immunoassay, >1 = Reactive) compared in both groups at baseline. [Results: Out of 31 patients 12 were CHB-AE. Mean ALT (IU/L) levels were 749.1 and 1035.5 in CHB-AE and AVH-B group respectively. Mean platelets (109/L) were 222.3 and 229.1 in CHB- AE and AVH-B group respectively. Difference in ALT and platelets levels was statistically non- significant. Mean IgM anti HBc levels were 9.68 and 19.2 in CHB-AE and AVH-B group respectively, was statistically significant [P = 0.008]. Diagnostic accuracy of HBV DNA > 15390 IU/ml had sensitivity of 75% and specificity of 42.1% for CHB-AE. IgM anti HBc level > 10.38 had sensitivity of 78.9% and specificity of 50% for diagnosis of AVH-B. Conclusions: Combination of low IgM anti-HBc titer and high HBV DNA level are useful in diagnosing CHB-AE. The authors have none to declare. TableTabled 1ParametersAVH-BCHB-AEP ValueALT (IU/L)1035.58 (669.05)749.17 (731.47)0.27Total Bilirubin (mg/dl)18.78 (10.32)22.94 (14.94)0.53Serum albumin (gm/dl)3.52 (0.44)2.97 (0.53)0.24Platelets (109/L)229.11 (75.63)222.33 (76.93)0.81HBV DNA (IU/mL)136318.58 (240576.74)19249376.33 (42565326.99)0.058IgM Anti HBc19.20 (10.23)9.68 (6.51)0.008 Open table in a new tab