Low HBV DNA Research Articles

1033 Quality Metrics Adherence Assessment for Patients With Chronic Hepatitis B Virus Seen in Gastroenterology Clinics

INTRODUCTION: The American Association for the Study of Liver Disease (AASLD) guidelines for hepatitis B management have progressed over time. However, adherence to quality metrics for chronic hepatitis B (CHB) care needs to be evaluated, especially in settings where liver specific clinics are not part of the system. Our study aims to evaluate the adherence to quality of care metrics in CHB patients in a predominately African American patient population general Gastroenterology clinic in an academic medical center. METHODS: We performed a cohort chart review on 92 patients with ICD 9 or 10 codes for CHB. Patients co-infected with HIV were excluded from analysis as they were treated by Infectious Disease clinics. We identified 45 patients following up with our Gastroenterology clinic for CHB with a visit between 2017 and 2018. We gathered demographic data. Adherence metrics were collected including HAV vaccination, treatment guideline relevant metrics, timely measurement of alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), platelets and hepatitis B virus DNA level check to monitor for treatment response HBV status. Hepatocellular carcinoma screening measure. RESULTS: Our patient population was 65% African American,17% Asian,13% Caucasian and 5% other races. All treated patients had >2000 in HBV DNA levels and high ALT prior to treatment, whereas untreated patients had low HBV DNA and normal ALT with the exception of 1 patient under consideration for treatment. Hepatocellular cancer screening adherence was significantly high in both treated (80%) and untreated (84%) patients with 6 monthly imaging studies. Both treated and untreated patient had relatively high compliance (68%) with HAV vaccination. All the patients had ALT, AST and platelets so that APRI score could be checked every 6 months to provide an indirect assessment of fibrosis. Timely evaluation of fibrosis specific assessments has not been completed in most of the cases, and there was no consensus with respect to the preferred method for assessing fibrosis. CONCLUSION: Our finding reflects satisfactory adherence with AASLD guidelines particularly in areas of treatment indications, regular laboratory check, hepatocellular carcinoma screening and compliance with HAV vaccination. However, fibrosis evaluation was suboptimal according to guidelines. Given the access to Fibroscan in our practice, once yearly assessment is being recommended for our patients. Supported in part by an Investigator Initiated Grant from Gilead Sciences.

Increased Coffee Intake Reduces Circulating HBV DNA and HBsAg Levels in HBeAg-Negative Infection: A Cohort Study.

Coffee is hepatoprotective and potentially antiviral; however, its anti-hepatitis B virus (anti-HBV) property is not known in humans. This study investigated the influence of coffee drinking behaviour as well as clinical and biochemical profiles of hepatitis B e antigen (HBeAg) negative participants on circulating HBV DNA and hepatitis B surface antigen (HBsAg) levels at a 24-week interval. Exactly 114 chronically HBV-infected adult participants were enrolled from the University of Malaya Medical Centre (UMMC), Malaysia. A significant reduction of HBV DNA level was observed in those drinking three or more cups of coffee per day, with a median reduction of 523 IU/mL (P = 0.003). Reduction of HBsAg level was observed in those drinking two cups per day, with a median reduction of 37 IU/mL (P < 0.001). Multivariate analysis showed that increased coffee intake (P = 0.015) and lower ALT level (P = 0.033) were the significant predictors for a lower HBV DNA level, whereas increased coffee intake (P = 0.002) and having a family history of HBV infection (P = 0.021) were the significant predictors for a lower HBsAg level. These data suggest that drinking three cups or more coffee per day reduces circulating HBV DNA and HBsAg levels.

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.

HBV pol/S gene mutations in chronic hepatitis B patients receiving nucleoside/nucleotide analogues treatment

Chronic hepatitis B (CHB) is an important public health problem affecting over 240 million people all around the world. The aim of the treatment in chronic hepatitis B is to prevent progression to cirrhosis and liver cancer. Interferons (standard and peginterferon) (Peg-IFN) and nucleoside/nucleotide analogues (NAs) are widely used in the treatment of CHB. The use of long-term therapy can however result in drug resistant mutations, which can lead to treatment failure. In patients with chronic hepatitis B, in addition to primary drug resistance mutations in the pol gene, compensatory mutations were reported. The genom of HBV polymerase (pol) gene overlaps with the envelope (S) gene. Nucleoside/nucleotide analogue (NA) resistance mutations in the pol gene of HBV, either from selection of primary or secondary resistance mutations, typically result in changes in HBsAg. Recent studies have conferred a new acronym for these HBV pol/S gene overlap mutants; ADAPVEMs, for antiviral drug-associated potential vaccine-escape mutants. The aim of this study was to investigate clinically and epidemiologically significant HBV pol/S gene mutations in NA treated CHB patients. In the study, a total of 100 patients who received nucleoside/nucleotide analogue therapy for one year or more were included. The levels of HBV DNA from serum samples were detected by the commercial real-time PCR assay and the mutations ofpol/Sgenes by direct sequencing. Sixteen samples with low HBV DNA levels (> 200 IU/ml) could not be interpreted by sequencing due to insufficient amplification. Of the remaining 84 patients that could be sequenced HBV pol gene of HBV, 53 (63.09%) were males and 31 (36.91%) were women and the mean age was 47 ± 14.99 years (range: 20-67). Primary/secondary drug mutations (rtM204I/V, rtI169S, rtL180M, rtT184L, rtA194V, rtM204I/rtL91I, rtQ149K, rtQ215H/S, rtN238D) were detected in 38 (45.2%) of the patients. Because of the HBVpol/S gene overlapping,in 27 patients immun-selected amino acid substitutions (sI110L, sT127P, sS114A, sT123A), in nine patients HBIg selected escape mutants (sP120R, sT123N, sE164D, sY134F, sQ129H, sT118A, sP127K), in seven patients vaccine escape mutants (sT126I, sP120S, sG145A, s S193L) and in one patient misdiagnosis of HBsAg (sT131I) were detected. In addition, antiviral drug-associated potential vaccine-escape mutants were detected in 13 (15.4%) patients. In patients with chronic HBV, NAs including commonly used lamivudine were observed to have the potential for ADAPVEM to emerge during treatment. It was concluded that after determination of antiviral drug resistance and ADAPVEMs replanning of treatment should be done in the NA treatment of patients with CHB.

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.

Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with Standard Chemoimmunotherapy

IntroductionHepatitis B virus (HBV) is one of the most common viral infections in humans. Global prevalence of chronic HBV infection is heterogeneous, with 2-20% of a given population being infected with HBV. In some parts of Africa, Asia and South America, HBV infection is endemic and remains to be a significant public health issue.Previous studies have shown a positive association between hepatitis B surface antigen (HBsAg)-positive HBV infection and B-cell non-Hodgkin lymphoma (NHL), such as diffuse large B-cell lymphoma (DLBCL), the most common subtype of B-cell NHL. Nevertheless, the clinical characteristics of HBsAg positivity and negativity, as well as their prognostic implications in DLBCL patients treated with frontline standard chemoimmunotherapy remain to be clarified.MethodsWe conducted a single-institution retrospective study in a tertiary referral hospital in Taiwan, an HBV prevalent country in Asia. From January 2001 to December 2015, patients aged ≥20 years with newly diagnosed DLBCL treated with standard rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were selected. Retrospective chart review was performed to collect data on clinical features, laboratory profiles, serum markers for HBV infection such as HBsAg and HBV-DNA loads before chemotherapy, as well as data on treatment response and outcome. The cohort was followed up until the cutoff date of June 30, 2018.ResultsA total of 393 DLBCL patients were analyzed in this study, with a median age of 60.5 years (range, 23.5 years to 90.9 years) and the sex ratio of 1.38 to 1.The 5-year overall survival (OS) rates were 65.2% after a median follow-up time of 68.8 months. In this cohort, 100 patients (25.4%) were found to have HBsAg positivity before treatment.Eighty-two of them had received prophylactic antiviral therapy, including 28 with lamivudine, 44 with entecavir and 10 with others. Besides, forty-five of HBsAg-positive patients had data of serum HBV-DNA loads before treatment, and 44 of them had received prophylactic anti-HBV therapy. Compared to HBsAg-negative patients, HBsAg-positive patients had a younger median onset age (55.9 years vs. 61.4 years, P=0.004), a trend of more advanced stage (stage III/IV: 62% vs. 51.2%, P=0.064), higher serum LDH levels at diagnosis (62% vs. 50.2%, P=0.048), and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (high-intermediate/high: 50% vs. 41.6%, P=0.162).Regarding to treatment response and outcome, HBsAg-positive patients, compared to HBsAg-negative patients, had a trend of lower overall response rates (78% vs. 84.3%, P=0.169) and complete remission rates (73% vs. 79.9%, P=0.163). Furthermore, compared to HBsAg-negative patients, HBsAg-positive patientshad a poorer median OS (median OS, not reached vs. 95.8 months, P=0.001, Figure 1) and a shorter median progression-free survival (PFS) (median PFS, not reached vs. 34.3 months, P=0.031), respectively. By multivariate analysis, HBsAg positivity is an independent poor prognostic factor for OS irrespective of NCCN-IPI score, serum albumin levels and B symptoms.No significant difference was found in outcome between patients with high HBV-DNA loads (> 2000 IU/mL, n=21) and those with low HBV-DNA loads (≤2000 IU/mL, n=24). With respect to prophylactic anti-HBV treatment, patients without prophylactic therapy (n=18), compared to those with prophylactic therapy (n=82), had a trend of shorter median OS (27.9 months vs. 96.2 months, P=0.346). Moreover, no significant difference was found in median OS between HBsAg-positive patients when administrated with anti-HBV lamivudine and those when administrated with anti-HBV entecavir.ConclusionsThis study demonstrated that HBsAg positivity has unique clinical relevance to patients with DLBCL, as well as its impact in the efficacy of treatment. HBsAg positivity may serve as a relevant biomarker to predict clinical outcome in DLBCL patients treated with R-CHOP. Prophylactic anti-HBV therapy may be of great importance in HBsAg-positive DLBCL patients. Further studies to explore the etiopathogenesis of HBV infection in DLBCL may help to discovery new treatment targets to improve the outcome of this group of patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

High CONUT score predicts poor survival and postoperative HBV reactivation in HBV-related hepatocellular carcinoma patients with low HBV-DNA levels

BackgroundPostoperative hepatitis B virus (HBV) reactivation (PHR) is associated with resection-induced immunosuppression in patients with HBV-related hepatocellular carcinoma (HCC). Controlling Nutritional Status (CONUT) score is an effective index for evaluating immune-nutrition function. However, the value of COUNT in predicting PHR in HBV-HCC patients remains unknown. MethodsTotally, 209 HCC patients were enrolled. ResultsPreoperative immune function (CD3+CD4+, CD3+CD8+, IgG and IgM) in patients with high CONUT score was significantly worse than that in patients with low CONUT score (P<0.05). Blood test results on postoperative day 7 showed the same trend. In addition, patients with high CONUT score experienced a significantly larger decrease in the proportions of CD3+CD4+ and CD3+CD8+ than those with low CONUT score (P < 0.05). In patients with high CONUT score, the incidence of overall complications was also significantly higher (P = 0.029) and hospital-stay was significantly longer (P = 0.020). Besides, overall survival and recurrence free survival in patients with high CONUT score were significantly worse than those in patients with low CONUT score (48.32 vs. 38.12 months, P<0.001; 36.08 vs. 27.03 months, P = 0.001). The incidence of PHR was significantly higher in patients with high COUNT score (P<0.001), and CONUT score was strongly associated with PHR (P<0.001). Additionally, the fellow subgroup results also demonstrated that COUNT score was more effective in predicting PHR in patients with HBV-DNA level <500 copies/ml than patients with HBV-DNA 500–1000 copies/ml. ConclusionCONUT score is an effective indicator predicting survival and PHR in HBV-HCC patients, especially in those with HBV-DNA levels <500 copies/ml.

Genotype Matters in Patients with Acute-on-chronic Liver Failure Due to Reactivation of Chronic Hepatitis B.

BackgroundAcute-on-chronic liver failure (ACLF) can be caused by reactivation of chronic hepatitis B virus (HBV) infection (HBV-ACLF). It’s unclear whether HBV genotypes affect the clinical and therapeutical outcomes of patients with HBV-ACLF. This study was to investigate the short-term antiviral response and overall survival in HBV-ACLF patients treated by tenofovir or entecavir.MethodsSeventy-three consecutive patients with HBV-ACLF were stratified into genotype B group (n = 33) and C group (n = 40). They were prospectively followed-up.ResultsAt 2 weeks, the genotype B group had significantly lower HBV-DNA load (P = 0.005), greater HBV-DNA decline (P = 0.026), higher proportion of patients with HBV-DNA < 500 IU/ml (P = 0.007), improved Child-Turcotte-Pugh (CTP; P = 0.032) and model for end-stage liver disease (MELD; P = 0.039) scores compared to the genotype C group. At three months, survivors in both groups had undetectable HBV-DNA loads, comparable CTP (P = 0.850) and MELD (P = 0.861) scores; the genotype C group had markedly lower overall survival rate than the B group (P = 0.013). The genotype (hazard ratio [HR]: 2.138; 95% confidence interval [CI]: 1.034–4.143; P = 0.041), MELD score (HR:1.664, 95%CI: 1.077–2.571; P = 0.022) and HBV-DNA decline (HR: 0.225, 95% CI: 0.067–0.758; P = 0.016) at 2 weeks were significantly associated with mortality at 3 months. No severe adverse event was noted.ConclusionsGenotype B was associated with better short-term antiviral response and clinical outcome compared to genotype C in patients with HBV-ACLF.

Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa.

Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.

Analysis of clinical characteristics and S gene sequences in chronic asymptomatic HBV carriers with low-level HBsAg

During the natural hepatitis B virus (HBV) infection process, some infected subjects are characterized by a sustained low serum HBV surface antigen (HBsAg) expression level. Most members in this population are chronic asymptomatic HBV carriers (ASCs). To elucidate the mechanism underlying low-level HBsAg expression in ASCs, we sequenced the HBV S gene in these patients to reveal specific sequence characteristics. Overall, 1308 cases of chronic ASCs were grouped according to their HBsAg serum expression levels (10 IU/mL). The clinical characteristics of the population were analysed in detail. The HBV S gene was sequenced from 276 ASC cases with low-level HBsAg expression. Additionally, 100 of 1032 ASC cases with high-level HBsAg expression were randomly selected for HBV S gene sequencing based on age matching according to the low-level HBsAg group. A comparative analysis was conducted with the HBV S gene sequences from ASCs with low HBsAg expression and the HBV reference S gene sequences from ASCs with high HBsAg expression. The population with low-level HBsAg expression displayed the following primary clinical characteristics: mostly chronic asymptomatic HBV carriers, older age (mean age 55.09 years), HBsAg/anti-HBe/anti-HBc (core) positivity as the main serological pattern (97.1%), low HBV DNA replication (1.32 ± 1.60 log10 IU/mL), a low HBV-DNA positive rate (45.65%) and primarily genotype B (82.54%) and serotype adw (84.13%). The comparative analysis of the HBV S gene sequences from ASCs with low-level HBsAg showed significant mutations (including co-mutations) on both sides of the main hydrophilic region (MHR). Significant mutations in multiple regions and at multiple sites (including co-mutations) on both sides of the MHR may be one cause of the low HBsAg expression level in this population.

A Challenging Case of Triple Hepatitis Virus Infection: An Accurate Diagnostic Test for Hepatitis D Virus Is Urgently Needed

Hepatitis D virus (HDV) has 8 genotypes and has common routes of transmission as HBV, HCV and HIV. HDV is an incomplete RNA virus that can only be acquired as a coinfection or superinfection with HBV. Patients with both HBV and HDV infection usually have severe, progressive liver disease. HDV serological assays are available for screening but false negative rates are high due to the lack of sensitivity for the various genotypes. This case illustrates the critical need for an accurate HDV diagnostic test. The patient is a 49-year-old Chinese male who initially presented in 2013 with HBeAg positive chronic hepatitis B with HBV DNA <1,000 IU/ml, ALT 66U/L, AST 48U/L and normal hepatic synthetic function. His risk factor was nasal cocaine use between 1992 and 1993. He denied history of acute hepatitis and alcohol use. Initial screening was positive for anti-HCV and negative for anti-HDV by ELISA assay. He had documented HCV genotype 6 but HCV RNA was later repeatedly undetectable without antiviral therapy. Liver biopsy in 2014 reported advanced stage 3 bridging fibrosis and mild predominantly mononuclear inflammation without steatosis. EGD in 2015 was normal. Tenofovir was initiated in 2014 with optimal HBV DNA suppression but serum aminotransferases elevated further (ALT 166 U/L, AST 94 U/L). Fibroscan score (10.5 kpa) from 2017 was consistent with stage 3-4 fibrosis. Repeat EGD in 2017 showed 3 cords of grade 1 varices in the lower third of esophagus. Patient remained asymptomatic. He had regular HCC surveillance and abdominal ultrasound was normal in 2018 without focal lesion. HDV coinfection remained a concern, especially with his liver disease progression. His serial stored serum samples from 2013 to 2017 were tested by the new pan-genotypic Quantitative Microarray Antibody Capture Assay (QMAC). The low limit of detection of anti-HDV IgG for QMAC is only 10 pg/ml compared to 1 μg/ml with ELISA. All the samples, including those tested negative previously, were tested anti-HDV positive with high 2.0 intensity units (>1.659 IU is predictive of replicative HDV RNA). HDV RNA levels >5 log10IU/ml were confirmed in the serial samples. This case underscores the importance to pursue hepatitis D diagnosis especially if the patient has low HBV DNA level but progressive liver disease. A standardized HDV diagnostic test is essential for the management of this important disease especially as promising new therapy for hepatitis D is becoming available.

1786P - Antiviral prophylaxis cannot reduce the risk of hepatitis B reactivation during chemotherapy for non-HCC solid tumor patients with lower HBV DNA titer: A retrospective cohort study

1786P - Antiviral prophylaxis cannot reduce the risk of hepatitis B reactivation during chemotherapy for non-HCC solid tumor patients with lower HBV DNA titer: A retrospective cohort study

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

O‐044: Low serum HBsAg and HBV DNA levels identify strongest responders of pegylated interferon addition to entecavir in HBeAg positive chronic hepatitis B

Journal of Viral HepatitisVolume 25, Issue S2 p. 27-28 Abstracts O-044: Low serum HBsAg and HBV DNA levels identify strongest responders of pegylated interferon addition to entecavir in HBeAg positive chronic hepatitis B First published: 12 June 2018 https://doi.org/10.1111/jvh.38_12922Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume25, IssueS2Special Issue: 16th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) held from June 14th to 17th, 2018, in Toronto, CanadaJune 2018Pages 27-28 RelatedInformation

FRI-346 - Low serum HBsAg and HBV DNA predict response of peg-interferon addition to entecavir in HBeAg positive chronic hepatitis B

FRI-346 - Low serum HBsAg and HBV DNA predict response of peg-interferon addition to entecavir in HBeAg positive chronic hepatitis B

Characterization of hepatitis B and delta coinfection in Israel

BackgroundCharacteristics of hepatitis B (HBV) and delta (HDV) coinfection in various geographical regions, including Israel, remain unclear. Here we studied HDV seroprevalence in Israel, assessed HDV/HBV viral loads, circulating genotypes and hepatitis delta antigen (HDAg) conservation.MethodsSerological anti HDV IgG results from 8969 HBsAg positive individuals tested in 2010-2015 were retrospectively analyzed to determine HDV seroprevalence. In a cohort of HBV/HDV coinfected (n=58) and HBV monoinfected (n=27) patients, quantitative real-time PCR (qRT-PCR) and sequencing were performed to determine viral loads, genotypes and hepatitis delta antigen (HDAg) protein sequence.Results6.5% (587/8969) of the HBsAg positive patients were positive for anti HDV antibodies. HDV viral load was >2 log copies/ml higher than HBV viral load in most of the coinfected patients with detectable HDV RNA (86%, 50/58). HDV genotype 1 was identified in all patients, most of whom did not express HBV. While 66.6% (4/6) of the HBV/HDV co-expressing patients carried HBV-D2 only 18.5% (5/27) of the HBV monoinfections had HBV-D2 (p=0.03). Higher genetic variability in the HDAg protein sequence was associated with higher HDV viral load.ConclusionsThe overall significant prevalence of HDV (6.5%) mandates HDV RNA testing for all coinfected patients. Patients positive for HDV RNA (characterized by low HBV DNA blood levels) carried HDV genotype 1. Taken together, the significant HDV seroprevalence and the lack of effective anti-HDV therapy, necessitates strict clinical surveillance especially in patients with higher HDV viral loads and increased viral evolution.

CD4+ T Cell Recovery and Hepatitis B Virus Coinfection in HIV-Infected Patients from Côte d'Ivoire Initiating Antiretroviral Therapy.

Immunorecovery could be attenuated in HIV-hepatitis B virus (HBV) coinfection versus HIV monoinfection during antiretroviral therapy (ART), yet, whether it also occurs in individuals from sub-Saharan Africa without severe comorbidities is unknown. In this study, 808 HIV-infected patients in Côte d'Ivoire initiating continuous ART were included. Six-month CD4+ count trajectories and the proportion reaching CD4+ T cell counts >350/mm3, HIV-RNA <300 copies/mL, still alive and not lost to follow-up within 18 months ("optimal immunorecovery") were compared between coinfected groups. At inclusion, 80 (9.9%) patients were HIV-HBV coinfected, 40 (50.0%) of whom had high HBV-DNA viral load (VL) (>104 copies/mL). Coinfected patients with high HBV-DNA replication initiated ART with significantly lower median CD4+ T cell counts [216/mm3, interquartile range (IQR) = 150-286] compared to coinfection with low HBV-DNA replication (268/mm3, IQR = 178-375) or HIV monoinfection (257/mm3, IQR = 194-329) (p = .003). These patients had significantly faster rates of CD4+ cell count increase from baseline after adjusting for baseline age, World Health Organization stage III/IV, and CD4+ cell counts (p = .04), yet, were not more likely to exhibit optimal immunorecovery (82.5% vs. 80.0% and 77.9%, respectively) (p = .8). In conclusion, change in CD4+ cell counts after ART-initiation was accelerated in coinfected patients with high HBV DNA VLs, but this did not lead to increased rates of optimal immunorecovery.