Increase In HBV DNA Research Articles

Similar Hepatitis B virus reactivation risk for patients with inflammatory arthritis or connective tissue diseases: a multicenter retrospective study.

Hepatitis B reactivation and administration of prophylactic antiviral treatment are considered in patients with autoimmune inflammatory rheumatic diseases (AIIRD) undergoing immunosuppressive/immunomodulatory treatment. Data are more robust for rheumatoid arthritis patients receiving bDMARDs but are limited for other AIIRD and drug categories. Adult patients with AIIRD (inflammatory arthritis [IA] or connective tissue diseases [CTD]) and documented chronic or resolved HBV infection (defined as serum HBsAg positivity or anti-HBcAb positivity in the case of HBsAg non-detection respectively), followed-up in six rheumatology centers in Greece and Italy, were included. Data collected included demographic characteristics, AIIRD medications prior and after HBV screening [cs-DMARDs, (b-ts)- DMARDs, other immunosuppressants initiated and mean glucocorticoid dose], HBV prophylactic treatment, and possible HBV-reactivation (defined as increase in HBV-DNA or HBsAg seroconversion) within one year of HBV screening. Frequency of HBV reactivation and possible association with recorded parameters were examined. During one year of follow-up, HBV reactivation occurred in 5.6% and 7.9% of IA and CTD patients, respectively. In patients with chronic hepatitis B, reactivation rates were 14.8% for IA and 22.2% for CTD, while in patients with resolved hepatitis B were 3.7% and 6%, respectively. In patients with resolved hepatitis B no association was found between HBV reactivation and antiviral prophylactic treatment, or the use of csDMARDs, bDMARDS, or other immunosuppressants. The risk of HBV reactivation was similar between IA and CTD patients and was significantly higher in chronic compared to resolved hepatitis B infection. For the latter, prophylactic treatment was not associated with lower reactivation risk.

Association between Hepatitis B virus infection and COVID-19: outcomes from clinical analysis and online survey from Beijing, China

ObjectiveWe aim to investigate whether Coronavirus disease 2019 (COVID-19) worsens chronic hepatitis B virus(HBV)infection and explore the incidence of long COVID symptoms in patients with chronic hepatitis B virus infection.MethodsPatients with chronic HBV infection and COVID-19 patients attending the hepatitis clinic or fever clinic were included in the study. Clinical manifestations of COVID-19 and information about long COVID were collected for all patients. For patients with chronic hepatitis B virus infection, laboratory test results such as HBV-DNA, liver function, and kidney function were collected three months before and after COVID-19.ResultsA total of 940 patients with COVID-19 were included in this study. These patients were divided into two groups: the hepatitis B virus infection group with 189 patients and the non-hepatitis B group with 751 patients. Further matching analysis was conducted, selecting 156 patients from each group. Within the hepatitis B group, patients were further divided into two subgroups based on whether they received antiviral therapy: 90 patients in the antiviral therapy group and 99 patients in the non-antiviral therapy group. Neither group experienced a significant increase in HBV-DNA after COVID-19. There were significant differences between the two groups regarding BMI and symptoms of sore throat, loss of smell, and nasal congestion during COVID-19. The incidence of long COVID symptoms was higher in the hepatitis B group compared to the non-hepatitis B group (64.1% vs. 48.7%, p < 0.001), with the top five symptoms being cough, fatigue, palpitations, insomnia, and memory impairment.ConclusionPatients with chronic HBV infection did not show a significant rise in HBV DNA after COVID-19 in this study. They had a lower incidence of COVID-19 symptoms but experienced a higher incidence of long COVID symptoms.

Abstract CT211: Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B

Abstract Background: Chronic hepatitis B is an etiology of HCC. Clinical trials using immune checkpoint inhibitors (ICIs) as HCC treatment typically exclude patients with chronic active hepatitis B (serum hepatitis B virus [HBV] viral load &amp;gt; 2000 IU/mL) or require the HBV viral load to be below a certain level using anti-HBV medications. In the phase 3 HIMALAYA study, the STRIDE regimen was superior to sorafenib and durvalumab was noninferior to sorafenib in overall survival benefits. This study explored the safety of concurrent administration of STRIDE or durvalumab with anti-HBV mediations for patients with chronic, active hepatitis B infection. Methods: We enrolled patients with advanced HCC, Child-Pugh A liver function reserve, and chronic active hepatitis B not under anti-HBV treatment. Initially, only patients naïve to ICIs were eligible, and patients received durvalumab 1500mg iv every 4 weeks until disease progression, occurrence of unacceptable toxicities, or the maximum treatment duration of 2 years. After the positive results of the HIMALAYA study, we added tremelimumab 300mg iv on D1 following the STRIDE regimen and allowed enrollment of patients who had received prior programmed cell death-1 blockade therapy. Patients initiated entecavir as HBV treatment within 7 days of starting ICI therapy. The plan was to enroll 30 patients, with the primary outcome of HBV reactivation (a ≥2 log increase in serum HBV DNA compared to the baseline level). Results: The study is still ongoing and as of 31 Aug 2023, 19 patients were enrolled. Two patients were female, and the median age was 65.5 years. Ten patients received durvalumab alone, and 9 received the STRIDE regimen. The ALBI grade was 1 and 2 in 3 (16%) and 16 (84%) patients, respectively. Macrovascular invasion and extrahepatic spread were present in 11 (58%) and 11 (58%) patients, respectively; 12 (63%) patients had alpha-fetoprotein level ≥ 400 ng/mL. Eleven (58%) patients had received prior systemic therapy for HCC, such as sorafenib (n = 9), lenvatinib (n = 5), and regorafenib (n = 4). The mean±standard deviation baseline HBV viral load was 1.18±0.44 mIU/mL. With the median follow-up on 6.1 months, no patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare (ALT increase to ≥3 times the baseline level) was noted in 4 (21%) patients, but none were considered HBV-associated. The best objective tumor response was complete and partial response in 0 and 5 (26.3%) patients, respectively, and the disease control rate was 63.2%. Conclusion: In the preliminary results, simultaneous initiation of immunotherapy and anti-HBV medications in patients with HCC and chronic active hepatitis B did not increase HBV reactivation rate. This study was supported by AstraZeneca (NCT04294498). Citation Format: Yu-Yun Shao, Ching-Tso Chen, Tsung-Che Wu, Tsung-Hao Liu, Chien-Huai Chuang, Ann-Lii Cheng, Chih-Hung Hsu. Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT211.

Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study

IntroductionProspective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis.MethodsHEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+).ResultsFrom August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0–609). Median follow-up was 3.1 years (2.1–4.0). Median number of cycles of anti-CD20 antibodies was 6 (3–7), with a cumulative dose of 8.5 g (5.8–11.2) of rituximab and 3 g (1.8–3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies.ConclusionsIn this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis.

A Prospective Study of Preemptive Tenofovir Disoproxil Fumarate Therapy in HBsAg-Positive Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).

Serum cytokine/chemokine profiles predict hepatitis B reactivation in HBV/HCV co-infected subjects receiving direct-acting antiviral agents

Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting. From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by>1.5-fold elevated ALT level than nadir and >100U/L; or>2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation). There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85pg/mL, P=0.015), lower week-4 IFN-gamma (1.07 versus 8.74pg/mL, P=0.020) levels and significant declines of CCL2 and TNF-alpha (P<0.05). Single or combination of these cytokines helped predict clinical reactivation (all P<0.05). Higher serum TNF-alpha at baseline and lower IFN-gamma at week 4 were associated with mild clinical reactivation of HBV in patients with HBV/HCV co-infection receiving DAAs. Combination of these cytokines reliably predicted HBV reactivation early.

Risk of HCC With Hepatitis B Viremia Among HIV/HBV-Coinfected Persons in North America.

Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV. We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]). Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.

A transient early HBV-DNA increase during PEG-IFNα therapy of hepatitis D indicates loss of infected cells and is associated with HDV-RNA and HBsAg reduction.

HBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFNα on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFNα-2a plus tenofovir-disoproxil-fumarate (PEG-IFNα/TDF, n=59) or placebo (PEG-IFNα/PBO; n=61) for 96weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFNα/PBO-treated patients but also in 76% of PEG-IFNα/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFNα/TDF-treated and 12 PEG-IFNα/PBO-treated patients. This increase was positively associated with HBsAg loss [(P=0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P=0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFNα-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFNα-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.

Effect of pembrolizumab (pembro) on hepatitis B viral (HBV) load and aminotransferase (ALT) levels in patients (pts) with advanced hepatocellular carcinoma (aHCC) in KEYNOTE-224 and KEYNOTE-240.

4587 Background: The effect of PD-1 inhibition on HBV infection is unclear, and pts with HBV are often excluded from trials. This analysis evaluated HBV viral load and liver function (ALT levels) in pts with HBV infection in 2 trials of pembro: KEYNOTE-224 and KEYNOTE-240. Methods: Eligible pts with aHCC post first-line sorafenib and controlled HBV received pembro 200 mg IV Q3W until progression. Pts with active HBV (HBsAg positive and/or HBV DNA detectable) and inactive HBV (anti-HBc positive, HBsAg negative, and HBV DNA not detectable) at baseline (BL) were included. Results: Of 104 pts in KEYNOTE-224 and 413 pts in KEYNOTE-240, 8 (7.7%) and 101 (24.5%) had active HBV and 13 (12.5%) and 102 (24.7%) had inactive HBV, respectively. All pts with HBV received nucleos(t)ide analogs. In KEYNOTE-240, 2 (2.8%) pts with active HBV in the pembro arm and 1 (3.4%) in placebo (pbo) had a &gt; 1 log increase (incr) of HBV DNA and 1000 IU/mL over BL; none in the pembro arm were associated with ALT elevation. No pts with inactive HBV in KEYNOTE-240 and no pts in KEYNOTE-224 had a &gt; 1 log incr and 1000 IU/mL over BL. No pts in KEYNOTE-224 and 28 (38.9%) with active HBV and 1 (1.4%) with inactive HBV in the pembro arm, and 8 (27.6%) with active HBV and 0 with inactive HBV in the pbo arm in KEYNOTE-240 had a &gt; 1 log decrease (decr) in HBV DNA. Conclusions: Few pts with aHCC and HBV had viral load incr with pembro. In KEYNOTE-240 no clinically meaningful differences between pembro and pbo were observed. ALT elevation was not associated with viral load incr with pembro. These data suggest that pembro is unlikely to significantly affect underlying HBV infection in pts with aHCC receiving HBV antiviral therapy. Clinical trial information: KEYNOTE-224, NCT02702414; KEYNOTE-240, NCT02702401 . [Table: see text]

Risk of Hepatitis B Reactivation in Patients with Psoriasis on Ustekinumab.

Ustekinumab is used to treat moderate-to-severe psoriasis by blocking the interleukin-12/23 pathway, which is also essential against intracellular pathogens. Because there is a high prevalence of hepatitis B viral infection in Taiwan, the expected risk of reactivation is higher among ustekinumab-treated patients. We performed this study to investigate the risk of hepatitis reactivation. Patients with psoriasis treated with ustekinumab from October 2011 to June 2016 were enrolled in a prospective cohort study. All patients were tested for hepatitis B serology and serum viral DNA at baseline. For those positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibodies (anti-HBc) testing for HBV DNA was conducted at least annually. An increase of HBV DNA > 2 log scale or emergence of HBV DNA were defined as reactivation. The primary outcome of this study was HBV reactivation. Ninety-three psoriasis patients receiving ustekinumab were included. The average duration of treatment and follow-up was 24 ± 12months. There were 39 patients classified as naïve to HBV or vaccinated, and none of these patients had HBV reactivation. Among the remaining 54 patients classified as inactive HBV carriers, resolved HBV infection, or isolated anti-HBc positivity, only 3 patients experienced virologic reactivation, and none had liver failure. The study outcomes indicate that ustekinumab could be safe for psoriasis patients since none developed persistent hepatitis or acute liver failure during therapy. However, the re-appearance of plasma HBV DNA requires appropriate monitoring of HBV viral load during ustekinumab treatment.

Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection

Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation. We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation. HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (≥6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio [HR] 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92-76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15-5.05; p = 0.02). Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients. In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources. Clinical trial number: NCT 00931229.

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes.

Hepatitis B surface antigen reduction by switching from long-term nucleoside/nucleotide analogue administration to pegylated interferon.

Hepatitis B surface antigen (HBsAg) reduction during nucleoside/nucleotide analogue (NA) therapy is slow and an alternative strategy for patients receiving ongoing NA to facilitate HBsAg reduction is required. We investigated whether switching to pegylated interferon (PEG-IFN) after long-term NA administration enhances HBsAg reduction. Forty-nine patients who switched from long-term NA to 48weeks of PEG-IFN alfa-2a were studied. The mean duration of previous NA was 48months (sequential group). A total of 147 patients who continued NA and matched for baseline characteristics were analysed for comparison (NA continuation group). The treatment response was defined as HBsAg reduction ≥1.0 logIU/mL at the end of PEG-IFN. HBsAg reduction at week 48 was 0.81±1.1 logIU/mL in the sequential group, which was significantly higher than that in the NA continuation group (0.11±0.3 logIU/mL, P<.001). The treatment response was achieved in 29% and 2% of the sequential group and NA continuation group (P<.001), and the odds ratio of sequential therapy for the treatment response was 19 compared with the NA continuation (P<.001). In patients tested positive for hepatitis B e antigen (HBeAg), HBeAg seroconversion was higher in the sequential group (44% vs 8%, P<.001). In HBeAg-negative patients, only patients in the sequential group achieved HBsAg loss. No patient needed to resume NA administration because of HBV DNA increase accompanied by alanine aminotransferase flares. In summary, sequential therapy with PEG-IFN after long-term NA enhances the reduction of HBsAg and may represent a treatment option to promote HBsAg loss.

Is DAA Treatment Associated with HBV Reactivation? Results from ERCHIVES

Background Reactivation of HBV infection has been reported in patients with HCV treated with newer directly acting antiviral agents (DAAs). Magnitude of this problem and its consequences are not fully understood.Methods Using ERCHIVES, a well-established national database of HCV infected Veterans, we identified all persons who received DAA treatment for >28 days. We determined the proportion of patients who had HBV viral reactivation (≥1 log10 increase in HBV DNA from baseline), seroconversion (from HBsAg or HBeAg seronegative to seropositive), or flare of hepatitis (HBV viral reactivation plus ALT increase ≥10 times baseline value) at anytime after initiating DAA treatment. We also determined factors associated with HBVr using Cox regression analysis.ResultsWe identified 43,137 persons on DAA therapy. Among those with available follow-up data, overall HBV reactivation was observed in 795 persons. HBV viral reactivation was observed in 4.8% (17/352), clinical hepatitis in 0.3% (1/350), seroconversion in 16.0% (695/4339) and ALT flare in 0.2% (85/41652). In a Cox proportional hazards model, factors associated with increased risk of HBV reactivation were black race, male sex, alcohol use or dependence, and detectable HBV DNA at baseline (table). Treatment with any regimen was associated with a significantly lower risk (number of persons on sofosbuvir/daclatasvir and elbasvir/grazoprevir were small to make meaningful inferences) of HBV reactivation.Conclusion Among HCV infected persons treated with a DAA regimen, HBV viral reactivation and HBV seroconversion are common, but clinical hepatitis or ALT flares are rare. DAA regimens are not associated with HBV reactivation.Disclosures A. Butt, Merck: Investigator, Grant recipient

Flares during long-term entecavir therapy in chronic hepatitis B.

The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of alanine aminotransferase (ALT) flares during long-term entecavir (ETV) in chronic hepatitis B (CHB). CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as > 3× increase in ALT compared with baseline or lowest on-treatment level and an absolute ALT > 3× ULN. Flares were designated as host-induced (preceded by hepatitis B virus (HBV)-DNA decline), virus-induced (HBV-DNA increase), or indeterminate (stable HBV-DNA). Seven hundred and twenty-nine patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline hepatitis B e antigen (HBeAg)-positivity (HR 2.84; P = 0.005) and high HBV-DNA (Hazard ratio (HR) 1.30; P = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs 83 weeks; P = 0.027) or indeterminate flares (15 vs 109 weeks; P = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and hepatitis B surface antigen (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1). The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares.

Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B

The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9±2.6 vs. 13.2±12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (≥18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.

Risk of Severe Acute Exacerbation of Chronic HBV Infection Cancer Patients Who Underwent Chemotherapy and Did Not Receive Anti-Viral Prophylaxis.

BackgroundReactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 20–50% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences.AimTo investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis.MethodsA retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies.ResultsA total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] vs 4.3% [6/140]); P = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% vs 4.1%, P = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively.ConclusionSevere acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and rituximab-based chemotherapy are the risk factors related to severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients undergoing chemotherapy.

Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy

ObjectiveTo explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. ResultsSeveral findings were demonstrated with the increase of serum HBV DNA: 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly (P<0.05), while the plasma level of albumin decreased significantly (P<0.05); The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group (P<0.01). ConclusionWith the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Treatment cessation in noncirrhotic, e-antigen negative chronic hepatitis B is safe and effective following prolonged anti-viral suppression with nucleosides/nucleotides.

The treatment of HBeAg-negative chronic hepatitis B (CHB) is considered to be open-ended, with no guidelines for treatment cessation. To evaluate biochemical and virological relapse requiring retreatment in noncirrhotic HBeAg-negative CHB in patients who stopped treatment following a period of prolonged viral suppression with nucleotides/nucleosides. We performed a single-centre retrospective chart review of patients with HBeAg-negative CHB who maintained viral suppression for 4-5 years on anti-viral treatment, and thus subsequently stopped treatment. The primary end point of composite relapse was defined by an increase in HBV DNA >2000 IU/mL, ALT elevation above 1.25 × normal or doubling of ALT from cessation, and re-initiation of anti-viral therapy. We identified 33 patients with HBeAg-negative CHB who stopped treatment following viral suppression. Mean treatment duration was 5.28 ± 2.73 years. Patients were treated with lamivudine (3), adefovir (14), entecavir (4), and tenofovir (12). Eleven (33%) patients met the primary end point of composite relapse. For individual end points, 21 (63%) patients had a viral relapse, 16 (48%) had a biochemical relapse, and 16 (48%) restarted treatment, leaving 17 (52%) patients who remained treatment-free over a median 36 months of follow-up. Lower pre-treatment ALT and detectable HBV DNA within the first month after treatment discontinuation were associated with increased rates of composite relapse (HR 1.01; P = 0.022 for ALT and HR 1.01; P = 0.038 for HBV DNA). Patients with noncirrhotic HBeAg-negative CHB can stop treatment after greater than 4-5 years of suppressive therapy with nucleosides/nucleotides with more than 50% remaining treatment-free.

SAT0258 Low Risk of Hepatitis B Virus Surface Antigen Seroreversion in Hbsag Negative, Anti-Hbc Positive Carriers Undergoing Rituximab for Rheumatoid Arthritis

BackgroundRituximab (RTX), an anti-CD20 monoclonal antibody, is an effective treatment for Rheumatoid arthritis (RA), targeting B cells. However, the safety of this drug in hepatitis B surface antigen (HBsAg) negative/anti-hepatitis...