Hepatitis B Virus Reactivation Research Articles

HBV/HDV management after liver transplantation: Review

Chronic hepatitis B is a worldwide health problem. Hepatitis D virus (HDV) is a dependent virus that relies on hepatitis B virus (HBV) to synthesize the pathogenic genomes. This may lead to HDV and HBV coinfection or superinfection that results in rapid liver damage that may lead to various serious complications, such as acute liver failure, cirrhosis, and hepatocellular cancer requiring liver transplantation. However, post-transplant HBV reactivation is always a concern as it can be detrimental to allograft function, leading to poor survival. The mainstay strategy to prevent this has been prophylaxis with hepatitis B immunoglobulin (HBIG) and potent anti-viral drugs. This treatment option has been investigated over the years in terms of appropriate dosing, duration and combination. Furthermore, with the advent of more potent antivirals there have been suggestions to use them as a monotherapy. Although, currently there is no effective therapy available for HDV, but the success of the liver transplantation in these patients is dependent on preventing HBV recurrence. Therefore, there has been a continuous effort to come up with an effective treatment plan that is effective and economical. In this review, we discuss the available treatment options for HBV/HDV after liver transplantation.

Clinical Course of Hepatitis B Viral Infection in Patients Undergoing Anti-Tumor Necrosis Factor α Therapy for Inflammatory Bowel Disease.

Background/AimsLittle is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy.MethodsThis retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients’ medical records were reviewed, and data were collected using a web-based case report form.ResultsOverall, 191 patients (77 ulcerative colitis and 114 Crohn’s disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis.ConclusionsLiver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation.

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.

Ibrutinib in Advanced Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Lower Risk of Hepatitis B Virus Reactivation

Introduction: Therapy of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with drugs such as ibrutinib and rituximab is often associated with immune suppression, opportunistic infections, and reactivation of virus infections such as hepatitis B virus (HBV). This risk is especially important in geographical regions like Asia where many potential therapy recipients have HBV infection. Also, whether safety and efficacy of ibrutinib in Asians and Europeans with advanced CLL/SLL are similar is unknown. We determined the safety and efficacy of ibrutinib compared with rituximab in advanced CLL/SLL including persons with HBV infection. We compared outcomes with data published from trials in persons of European descent. Methods: This is a post hoc analysis of a multicenter, phase-3 trial (NCT01973387). Subjects with advanced CLL/SLL were randomized 2:1 to receive ibrutinib, 420 mg/day, or rituximab, 500 mg/mE + 2, for 6 cycles. Subjects with resolved HBV infection were included. Endpoints were progression-free survival (PFS), overall response rate (ORR), survival, and adverse events including resolved HBV reactivation. Results: 131 subjects received ibrutinib (N = 87) or rituximab (N = 44) including 53 with resolved HBV infection. Median follow-up was 31 months (95% confidence interval: 28, 32 months). ORR was 61% (50, 71%) versus 7% (2, 18%; p < 0.001). Median PFS was not reached in the ibrutinib cohort but must be >40 months versus 8 months (7, 9 months; p < 0.0001) in the rituximab cohort. Median survival was not reached but must be >40 months versus 27 months (17 months, NE; p = 0.0006). In multivariable analyses, receiving ibrutinib increased PFS (hazard rate [HR] for failure = 0.12 [0.06, 0.23]; p < 0.001) and decreased risk of death (HR = 0.31 [0.15, 0.63]; p < 0.001). Median duration of exposure to ibrutinib was significantly longer than exposure to rituximab (28 vs. 5 months). The safety profile of ibrutinib was consistent with that observed in previous studies with no new safety signal. No subject receiving ibrutinib had HBV reactivation versus 2 receiving rituximab, despite much greater use of drugs to prevent HBV reactivation in the rituximab cohort. Outcomes were like those reported in persons of European descent, except ORR which, was unreliably correlated with PFS in Asians. Conclusion: Ibrutinib is safe and effective in persons with advanced CLL/SLL and better than rituximab in all therapy outcomes including risk of HBV reactivation. Outcomes with ibrutinib in Chinese were like those reported in persons of predominately European descent.

Kinetics of quantitative hepatitis B surface antigen in patients with rheumatic disease and chronic hepatitis B receiving biologic agents.

The effect of biologic treatment on quantitative Hepatitis B surface Antigen (qHBsAg) levels and HBsAg clearance in rheumatic patients with chronic HBV infection has not been well studied. We prospectively followed rheumatic patients with HBeAg-negative chronic HBV infection (n=28) treated with biologics and oral antivirals, categorized into patients with chronic hepatitis B (CHB, group A n=13) and chronic HBV infection (group B n=15) and matched them to appropriate non-rheumatic controls. qHBsAg kinetics were serially measured and compared between groups. No HBV reactivation (HBVr) was recorded during the 108.25 patient-year follow-up. Among patients with CHB, the annual rapid qHBsAg decline (i.e. decline >0.5log10 IU/mL/year) as well as HBsAg clearance did not differ between rheumatic patients [n=4 (32.7%), n=1 (7.7%)] and controls [n=6 (28.4%), p=.726 and n=2 (7.7%), p=.818, respectively]. In contrast, there was a slower annual qHBsAg decline in rheumatic patients with chronic HBV compared to non-rheumatic controls (-0.04 vs -0.13log10 IU/mL at year 1, p=.019) with no cases of rapid qHBsAg decline or HBsAg clearance in rheumatic patients (0%) compared to a cumulative incidence of 24% and a rate of 20%, respectively in controls. In biologic-treated rheumatic patients with HBeAg-negative HBV receiving antiviral prophylaxis, there was slower qHBsAg decline, lower cumulative rates of rapid qHBsAg decline and HBsAg clearance compared to non-rheumatic controls.

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.

Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib.

The aim of this study was to investigate hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving tofacitinib. This was a retrospective study performed in a regional teaching hospital in southern Taiwan. During January 2017 and December 2020, patients with a clinician-confirmed diagnosis of RA using tofacitinib for at least 3months were enrolled. Serum HBV DNA levels and serum alanine aminotransferase were followed up around every 3 to 6months to assess HBV reactivation. A total of 98 patients with RA were enrolled, and eight were hepatitis B surface antigen positive (HBsAg+) (8.1%), 64 were HBsAg-negative (HBsAg-)/hepatitis B core antibody positive (HBcAb+) (65.3%). In the HBsAg+ patients, two patients received antiviral prophylaxis, and none of them had HBV reactivation or hepatitis flare-up. The HBV reactivation rate was 33.3% (2/6) in the HBsAg+ RA patient without antiviral prophylaxis. Among the HBsAg-/HBcAb+ patients, the HBV reactivation rate was 3.1% (2/64). The incidence rate of HBV reactivation was 153.8 per 1000 person-years for overall HBsAg+ patients and 250 per 1000 person-years after excluding patients receiving antiviral prophylaxis. The incidence rate was 11.2 per 1000 person-years for HBsAg-/HBcAb+ patients with RA receiving tofacitinib. Tofacitinib could induce HBV reactivation in both HBsAg+ and HBsAg-/HBcAb+ RA patients. HBsAg+ patients receiving tofacitinib have a high incidence rate of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, closely monitoring HBV DNA and alanine aminotransferase should be suggested.

Rates and characteristics for hepatitis B reactivation of inactive hepatitis B carriers in rural communities

Objective: To analyze the intensity and epidemiological characteristics of hepatitis B virus (HBV) reactivation among inactive HBsAg carriers (IHC) of rural areas in Ji'nan. Methods: In 2018 and 2020, follow-up investigations were conducted on IHC identified in the population physical examination in Zhangqiu district of Ji'nan. The results of the two follow-up visits were compared to analyze the incidence and distribution characteristics of HBV reactivation in IHC at the community level. Results: A total of 424 IHC completed two follow-up visits, and 47 cases of HBV reactivation were found, the cumulative reactivation rate was 11.08%, and the incidence density was 5.46/100 person-years. Multivariate analysis showed that gender, age, smoking, drinking , family history of liver disease and chronic diseases were not associated with HBV reactivation (P>0.05), and baseline HBV DNA load was associated with reactivation (P<0.05), in the HBV DNA level ≥1 000 IU/ml group, the reactivation rate could reach 18.92%. After reactivation, the mean level of ALT increased from baseline and the abnormal rate increased, liver function tended to be abnormal in reactivated patients. 4 (8.51%) reactivators had hepatitis, and 1 (2.13%) had jaundice hepatitis. Conclusions: The incidence of HBV reactivation was higher among IHC in rural communities in Ji'nan. Most of the reactivators were asymptomatic or mildly reactivated. Follow-up of inactive HBsAg patients should be strengthened and changes in ALT and HBV DNA levels should be closely monitored.

Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2

AimsTo evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients. MethodTransversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection. ResultsIn this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0–104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19). ConclusionScreening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.

Acute-on-Chronic Liver Failure Precipitated by Severe Acute Respiratory Syndrome Coronavirus 2 Infection in a Patient with Hepatitis B Virus-Related Cirrhosis: A Case Report

Abstract We present a case of acute-on-chronic liver failure (ACLF) in a patient with hepatitis B virus (HBV)-related decompensated cirrhosis and coronavirus disease 2019 (COVID-19). A 58-year-old woman with HBV-related and decompensated cirrhosis without any anti-viral treatment previously was admitted to the hospital due to a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On admission, she was in stable condition. Thoracic computed tomography (CT) and laboratory findings showed no significant abnormalities. Entecavir was initiated promptly for HBV, while antiviral therapy and supportive treatment were initiated for COVID-19. Her lung infection exacerbated after 10 days of recurrent fever despite treatments, and there were signs of HBV reactivation. ACLF and multiple organ dysfunction syndrome developed rapidly from day 10 to day 19. The patient's clinical deterioration was also consistent with pneumonia progression and elevated interleukin 6 levels. SARS-CoV-2 likely precipitated ACLF in cirrhotic patients, either by inducing HBV flare or serving as an acute insult directly. This study discussed the underlying mechanisms of this process and management details. Monitoring HBV status is necessary, and inflammatory parameters might be valuable. HBV suppression should be initiated early, and variceal hemorrhage primary prevention might be beneficial in COVID-19 patients with cirrhosis.

Long-term safety of rituximab in rheumatic patients with previously resolved hepatitis B virus infection

Conflicting results can be found in the literature on the frequency of hepatitis B virus (HBV) reactivation (HBVr) on rituximab (RTX) in rheumatic patients with previously resolved HBV (prHBV) infection. Here, we report the frequency of HBVr in a large historical cohort of caucasian rheumatic patients with prHBV receiving RTX. Registry data of rheumatic patients treated with RTX were retrospectively analysed. Demographic and clinical characteristics including evaluation of anti-HCV and HBV markers, annual HBV-DNA determination and aminotransferase levels assessed every three months, were recorded. Kaplan-Meier estimate was used to compare the risk of being still under therapy at different time points in patients with or without prHBV infection. Cox regression analysis was used to determine the association between recorded variables and treatment discontinuation. A total of 311 patients treated with RTX, 44 (14.1%) with and 267 (85.9%) without prHBV were analysed. No significant difference between the two groups regarding demographic and clinical characteristics was observed. During RTX treatment, detectable HBV-DNA and reappearance of HBsAg in patients with prHBV (seroreversion) were never observed. Kaplan-Meier functions were similar in patients with or without prHBV infection which was not associated with RTX discontinuation neither at univariate nor at multivariate analysis. These data are in favor of the concept that patients with rheumatologic diseases have a very low risk of reactivation of the HBV infection under RTX treatment. However, future prospective studies, including a larger number of patients, are still necessary to draw definitive conclusions.

Interaction between hepatitis B virus infection and the efficacy of camrelizumab in combination with apatinib therapy in patients with hepatocellular carcinoma: a multicenter retrospective cohort study.

BackgroundThe interaction between hepatitis B virus (HBV) load and anti-programmed cell death (PD)-1 in combination with (+) antiangiogenic therapy remains controversial, especially for hepatocellular carcinoma (HCC) patients. This study sought to explore the effects of HBV load and antiviral therapy on anti-PD-1+ antiangiogenic therapy, and the rate of HBV reactivation during anti-PD-1+ antiangiogenic treatment.MethodsWe performed a multicenter retrospective cohort study of camrelizumab combined with apatinib (C+A) therapy between January 1, 2019 and January 1, 2021 in patients with unresectable HCC who were seropositive for hepatitis B surface antigen (HBsAg) and received antiviral therapy before C+A involvement. The effects of HBV load and antiviral therapy on C+A and the rate of HBV reactivation during C+A treatment were examined.ResultsEighty-six patients were included in the analysis. The patients had a mean age of 55 years, and 72 (83.7%) were male. The objective response rates (ORRs) in patients with low (<2,000 IU/mL) and high (≥2,000 IU/mL) baseline HBV deoxyribonucleic acid (DNA) levels were 34.5% and 32.2%, respectively (χ2=0.046; P=0.829), while the disease control rates (DCRs) were 67.3% and 80.6%, respectively (χ2=1.762; P=0.184). The results of the univariate and multivariate analyses showed that the baseline HBV DNA level did not affect PD. Additionally, none of the 86 patients suffered from HBV reactivation or HBV-related hepatic impairment with continuous antiviral treatment, regardless of nucleos(t)ide analogue (NA) type (F=1.473; P=0.228).ConclusionsBaseline HBV loads did not affect the tumor responses of HCC patients receiving anti-PD-1+ antiangiogenic therapy. Thus, HBV reactivation should not be a contradiction for anti-PD-1+ antiangiogenic therapy among patients undergoing continuous and effective antiviral treatment.

Frequency of Hepatitis B Virus infection among Patients before Chemotherapy Treatment

Background:Hepatitis B virus (HBV) is an important public health problem worldwide. Chronic HBV in patients undergoing chemotherapy and immunosuppressive treatment are at risk of HBV reactivation. The consequence of HBV reactivation in immunosuppressed patients may lead to liver failure and death. Therefore, this study was conducted to investigate the frequency of HBV markers in cancer patients before chemotherapy. Materials and Methods:In this study cross-sectional, blood samples were collected from 90 cancer patients before chemotherapy. The patient’s sera were tested for the presence of HBsAg and anti-HBc using enzyme-linked immunosorbent assay (ELISA). The HBVDNA was tested for patient’s sera using nested polymerase chain reaction (nested-PCR). Results:Among 90 patients, 42(46.7%) were males and 48 (53.3%) females, with a mean age of 52.52 ± 11.71 years (range, 25–83 years). Of the 6/90 (6.66%) patients, including 4/42 (9.5%) males and 2/48 (4.1%) females cases were positive for HBsAg, anti-HBc and HBV DNA, (P=0.31). The frequency of HBV infection in cancer patients was rectal 3(3.33%), breast cancer 2 (2.22%) and prostate 1(1.11%) cases. The sera of 8/84 (9.52%) patients including 5/39 (12.82%) males and 3/45 (6.66%) females tested positive for anti-HBc, but negative for HBsAg and HBV DNA. (P=0.55). The results of phylogenetic tree revealed that four isolated HBV DNA in cancer patients were cluster with genotype D. Conclusions:High frequency of 6.66% HBV infection have been observed in cancer patients before chemotherapy. The sera of 9.52% patients were only positive for anti-HBc IgG which may indicate the past HBV infection or presence of OBI but requires further investigation. To prevent HBV or OBI reactivation, the screening of HBV DNA and anti HBc should be implemented for cancers patients before chemotherapy.

P-23 SEROLOGICAL PROFILE OF HEPATITIS B AND C IN REUMATHOLOGIC PATIENTS IN USE OF IMMUNOSSUPRESSIVE THERAPY

Autoimmune rheumatologic diseases are treated with immunosuppressive therapy to decrease inflammatory response reducing symptomatology and inducing the diseases remission. This therapy interferes in innate and/or adaptive immune response, elevating the risk of hepatitis B (HBV) reactivation and increasing viremia in patients infected by hepatitis C (HCV). To evaluate HBV and HCV`s serologic profile in patients that use immunosuppressive therapy in the rheumatology department in a tertiary hospital. Descriptive transversal clinical study, based in data collected from patients` medical records using a form elaborated by the authors. Two hundred-eight medical records were analyzed and of these fifty-two patients (25%) had an investigation for HBV and/or HCV (Figure), with a case of HBV reactivation and a diagnosis of HCV. Of those tested, 75% were women, with a mean aged 48.2 years and the most prevalent diagnoses being systemic lupus erythematosus and rheumatoid arthritis. The most used therapies are methotrexate, hydroxychloroquine and prednisone. There were low rates of HBV reactivation and of exacerbation of HCV, however few patients were adequately tested for these diseases. Therefore, the authors infer that HBV and HCV evaluation in patients in use of immunosuppressive therapy is a measure still to be consolidated amongst rheumatologists. Serological profile of HBV and HCV in patients from the rheumatology department.

Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma

Simple SummaryHepatocellular carcinoma pathogenesis is dependent on a chronic inflammation caused by several factors, including hepatotropic viruses, such as HCV and HBV. This chronic inflammation is established in the context of the immunotolerogenic environment peculiar of the liver, in which the immune system can be stimulated by HCV and HBV viral antigens. This complex interaction can be influenced by direct-acting antiviral drug treatments, capable of (almost totally) rapidly eradicating HCV infection. The influence of anti-viral treatments on HCC pathogenesis and progression remains to be fully clarified.Hepatocellular carcinoma (HCC) can be classified as a prototypical inflammation-driven cancer that generally arises from a background of liver cirrhosis, but that in the presence of nonalcoholic steatohepatitis (NASH), could develop in the absence of fibrosis or cirrhosis. Tumor-promoting inflammation characterizes HCC pathogenesis, with an epidemiology of the chronic liver disease frequently encompassing hepatitis virus B (HBV) or C (HCV). HCC tumor onset and progression is a serial and heterogeneous process in which intrinsic factors, such as genetic mutations and chromosomal instability, are closely associated with an immunosuppressive tumor microenvironment (TME), which may have features associated with the etiopathogenesis and expression of the viral antigens, which favor the evasion of tumor neoantigens to immune surveillance. With the introduction of direct-acting antiviral (DAA) therapies for HCV infection, sustained virological response (SVR) has become very high, although occurrence of HCC and reactivation of HBV in patients with co-infection, who achieved SVR in short term, have been observed in a significant proportion of treated cases. In this review, we discuss the main molecular and TME features that are responsible for HCC pathogenesis and progression. Peculiar functional aspects that could be related to the presence and treatment of HCV/HBV viral infections are also dealt with.

AML-184: Administration of Cyclophosphamide for GVHD Prophylaxis After Stem Cell Transplantation From Unrelated Donors And Infections: A Multi-Center Experience

<h3>Context:</h3> There is still no clear information about the incidence and consequences of infections with cyclophosphamide (PTCy) administration as prophylaxis against graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). <h3>Objectives:</h3> Revealing the incidence of pre-vaccination bacterial and viral infections (cytomegalovirus [CMV], herpes virus, and BK-polyomavirus hemorrhagic-cystitis), infection-related mortality, and predictive factors associated with PTCy application after allo-HSCT was the study aim. <h3>Design:</h3> Patients who underwent allo-HSCT from 9/10–10/10 HLA tissue-matched, unrelated donors and received cyclophosphamide for post-transplant GVHD prophylaxis from 3 centers between 2015 and 2020 were retrospectively reviewed. Infections that developed in the first 100 days after transplantation were recorded. <h3>Patients:</h3> Forty-one patients, M/F: 25/16, were included in the study. The mean age was 40.8 years (21–67), with 23 AML, 11 ALL, 3 NHL, 2 MDS, one biphenotypic leukemia, and 1 HL diagnosis. HLA tissue compatibility was 9/10 in 32 patients and 10/10 in 9 patients. All patients received one myeloablative priming regimen [TBI (800–1200 cGy)+Flu (30 mg/m²×5), Cy (60 mg/kg×2) + TBI (1200 cGy), treosulfan (10 g/m²×3) + Flu (40 mg/m²×4)]. In GVHD prophylaxis, PTCy was administered 72 and 96 hours following transplantation in combination with calcineurin inhibitors ± methotrexate ± mycophenolate mofetil. Levofloxacin, valacyclovir, fluconazole, and trimethoprim-sulfamethoxazole were empirically given to all patients along with the transplant preparation regimen. <h3>Results:</h3> At least one episode of febrile neutropenia (FEN) developed in all patients during the transplantation process. More than one episode of FEN developed in 22% of the patients. One patient died due to septic shock on post-transplant day 9. The incidence of CMV infection requiring treatment was 36.6% in the first 100 days and 41.5% at 1 year. All patients except 1 were CMV IgG-positive before transplantation. CMV reactivation was observed in 50% (15/15) of donor/patient CMV IgG (+/+). CMV reactivation was found in 30% (3/7) of the donor/patient CMVIgG (–/+) patients. Only one of these patients received antiviral therapy due to multiple reactivations. In 4 patients, CMV pneumonia developed, and 3 of them died. The rate of polyomavirus-associated cystitis was 7.3% (3/41). In the first year after transplantation, invasive fungal infection occurred in only 4 patients (9.8%), herpes virus infection occurred in 1 patient. Three patients received tenofovir–entecavir treatment because of anti-HBcIg positivity, and HBV reactivation was not detected in any of the patients. <h3>Conclusion:</h3> GVHD prophylaxis containing PTCy after allo-HSCT from an unrelated donor does not have an increased risk in terms of bacterial, viral, or fungal infections and can be used safely.

High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus.

HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.

Tenofovir alafenamide for prevention and treatment of hepatitis B virus reactivation and de novo hepatitis

Background and AimAdministration of tenofovir alafenamide (TAF) as prevention or treatment of hepatitis B virus (HBV) reactivation is not well known. The aim of this study is to reveal the efficacy and safety of TAF against HBV reactivation.MethodsEntecavir (ETV) and TAF were given to 66 and 11 patients, respectively, as prophylaxis against or treatment of HBV reactivation during chemotherapy or immune suppression therapy from January 2010 to June 2020. The antiviral effects and safety were assessed.ResultsAt week 24, the antiviral effects on patients receiving ETV and TAF were similar in terms of reduction of HBV DNA (−2.83 ± 1.45log IU/mL vs −3.05 ± 2.47log IU/mL; P = 0.857) and achieving undetectable levels of HBV DNA (78.8 vs 90.9%; P = 0.681). There was no significant difference in the decrease in the estimated glomerular filtration rate (eGFR) between the two groups (−0.62 ± 11.2 mL/min/1.73 m2 vs −3.67 ± 13.2 mL/min/1.73 m2; P = 0.291).ConclusionTAF is safe and effective against HBV reactivation.

Evaluation of Hepatitis B screening and reactivation in patients receiving rituximab containing chemotherapy: A single‐centre study

Hepatitis B virus (HBV) infection is a worldwide distributing viral disease. Hepatitis caused by HBV reactivation may progress to chronic illness and associated with increased risk of hepatic failure and hepatocellular cancer. Rituximab (RTX) is an immunosuppressive agent, is particularly used in the treatment of non-Hodgkin's Lymphoma. Patients have significant risk for HBV reactivation following chemotherapy with a RTX-containing regimen. This study aimed to determine the HBV screening manner and reactivation rates in patients with haematological neoplasm following chemotherapy including Rituximab. This is a single-centered retrospective cohort study. A total of 331 adults with haematological disorders who received chemotherapy regimen including RTX between years of 2006 and 2016 were enrolled. Patients who experienced reactivation were evaluated. Only 130 of 331 patients were screened appropriately for HBV infection for 10-year period. We found 18 patients were Hepatitis B surface antigen (HBsAg) (+) and 16 (88.8%) of them received antiviral prophylaxis. Among screened patients, 27 were HBsAg (-)/AntiHBc (+) and only 10 (37%) of them received HBV prophylaxis. In total, nine patients experienced reactivation, six were from screened and three were from unscreened group. Incomplete screening and inappropriate prophylaxis may result in HBV reactivation in patients under RTX-based chemotherapy and related complications such as death.

26163 Risankizumab to treat psoriasis in a patient with hepatitis B and hepatitis C

Recent advances in biologic therapy have revolutionized the treatment of psoriasis. Risankizumab, a humanized monoclonal antibody targeting interleukin 23A, is the newest Food and Drug Administration (FDA)-approved biologic agent for the treatment of moderate-to-severe plaque psoriasis. Due to its potential immunomodulating effect, considerations for serious infections such as hepatitis B (HBV) and hepatitis C (HCV) are important when initiating biologic therapy; in particular, the serious complications of HBV and HCV reactivation.