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Background & Aims: The impact of chronic liver disease on outcomes in patients with COVID-19 is uncertain. Hence, we aimed to explore this association., Methods: We explored the outcomes of all adult inpatients with COVID-19 in France, in 2020. We computed adjusted odds ratios to measure the associations between chronic liver disease, alcohol use disorders, mechanical ventilation and day-30 in-hospital mortality., Results: The sample comprised 259,110 patients (median [IQR] age 70 (54-83) years; 52% men), including 15,476 (6.0%) and 10,006 (3.9%) patients with chronic liver disease and alcohol use disorders, respectively. Death occurred in 38,203 (15%) patients, including 7,475 (28%) after mechanical ventilation, and 2,941 (19%) with chronic liver disease. The adjusted odds ratios for mechanical ventilation and day-30 mortality were 1.54 (95% CI 1.44-1.64, p <0.001) and 1.79 (1.71-1.87, p <0.001) for chronic liver disease; 0.55 (0.47-0.64, p <0.001) and 0.54 (0.48-0.61, p <0.001) for mild liver disease; 0.64 (0.53-0.76; p <0.001) and 0.71 (0.63-0.80, p <0.001) for compensated cirrhosis; 0.65 (0.52-0.81, p <0.001) and 2.21 (1.94-2.51, p <0.001) for decompensated cirrhosis; 0.34 (0.24-0.50; p <0.001) and 1.38 (1.17-1.62, p <0.001) for primary liver cancer; and 0.82 (0.76-0.89; p <0.001) and 1.11 (1.05-1.17; p <0.001) for alcohol use disorders. Chronic viral hepatitis; non-viral, non-alcoholic chronic hepatitis; organ, including liver, transplantation, and acquired immunodeficiency syndrome were not associated with COVID-19-related death., Conclusion: Chronic liver disease increased the risk of COVID-19-related death in France in 2020. Therapeutic effort limitation may have contributed to COVID-19-related death in French residents with a liver-related complication or an alcohol use disorder., Lay Summary: We studied the outcomes, including mechanical ventilation and day-30 mortality, of all adults with COVID-19 who were discharged from acute and post-acute care in France in 2020 (N = 259,110). Patients with mild liver disease; compensated cirrhosis; organ, including liver, transplantation; or acquired immunodepression syndrome were not at increased risk of COVID-19-related mortality. Patients with alcohol use disorders, decompensated cirrhosis, or primary liver cancer were at increased risk of COVID-19-related mortality but were less likely to receive mechanical ventilation. Our results suggest that therapeutic effort limitation may have contributed to the excess mortality in French residents with a liver-related complication or an alcohol use disorder., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: HIV, HBV and HCV infections continue to represent major health concerns, especially among key at-risk populations such as men who have sex with men (MSM), people who inject drugs (PWIDs), transgender women (TGW) and sex workers (SW). The objective of the ANRS-CUBE study was to evaluate the acceptability of a healthcare, community-based strategy offering a triple rapid HIV-HBV-HCV testing, and HBV vaccination, targeted at three priority groups (MSM, PWIDs and TGW/SWs), in three community centers, in the Paris area., Methods: This longitudinal multicentric non-randomized study included all adult volunteers attending one of the three specialized community centers in Paris, between July 2014 and December 2015. HIV, HBV and HCV status and acceptability of HBV vaccination were evaluated., Results: A total of 3662, MSM, 80 PWIDs and 72 TGW/SW were recruited in the three centers respectively. Acceptability of rapid tests was 98.5% in MSM and 14.9% in TGW/SWs, but could not be estimated in PWIDs since the number of users attending and the number of proposals were not recorded. User acceptability of HBV vaccination was weak, only 17.9% of the eligible MSM (neither vaccinated, nor infected) agreed to receive the first dose, 12.2% two doses, 5.9% had a complete vaccination. User acceptability of HBV vaccination was greater in PWIDs and TGW/SWs, but decreased for the last doses (66.7 and 53.3% respectively received a first dose, 24.4 and 26.7% a second dose and 6.7 and 0% a third dose). Fifty-three participants (49 MSM and 4 PWIDs) were discovered HIV positive, more than half with a recent infection. All but two HIV positive participants were linked to appropriate care in less than one month., Conclusions: Rapid HIV-HCV-HBV screening showed a very high level of acceptability among MSM. Efforts need to be made to improve immediate acceptability for HBV vaccination, especially among MSM, and follow-up doses compliance. Our results show the important role of community centers in reaching targets, often fragile, populations, while also suggesting the need to reinforce on-site human support in terms of testing and vaccination, especially when addressing PWIDs.

Rare individuals can naturally clear chronic hepatitis B virus (HBV) infection and acquire protection from reinfection as conferred by vaccination. To examine the protective humoral response against HBV, we cloned and characterized human antibodies specific to the viral surface glycoproteins (HBsAg) from memory B cells of HBV vaccinees and controllers. We found that human HBV antibodies are encoded by a diverse set of immunoglobulin genes and recognize various conformational HBsAg epitopes. Strikingly, HBsAg-specific memory B cells from natural controllers mainly produced neutralizing antibodies able to cross-react with several viral genotypes. Furthermore, monotherapy with the potent broadly neutralizing antibody Bc1.187 suppressed viremia in vivo in HBV mouse models and led to post-therapy control of the infection in a fraction of animals. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving HBV functional cure in chronically infected humans., Competing Interests: Disclosures: V. Hehle reported a patent to anti-HBV antibodies and methods of use, pending. M. Beretta reported a patent to anti-HBV antibodies and methods of use, pending. M. Bourgine reported a patent to anti-HBV antibodies and methods of use, pending. M. Ait-Goughoulte reported a patent planned on the antibodies pending, "Roche." S. Pol reported personal fees from Gilead, Abbvie, BMS, Janssen, and Roche outside the submitted work. H. Strick-Marchand reported a patent to human neutralizing HBV antibodies and their use thereof, pending. N. Pelletier reported personal fees from Hoffmann-La Roche outside the submitted work; in addition, N. Pelletier had a patent planned to be submitted, pending "Roche Innovation Center Basel." H. Mouquet reported grants from Institut Roche during the conduct of the study; in addition, H. Mouquet had a patent to anti-HBV antibodies and methods of use, pending. No other disclosures were reported., (© 2020 Hehle et al.)

Direct-acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg-positive and HBsAg-negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA-associated sustained virological response in 3 kidney-transplant recipients initially HBsAg-negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti-HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin., Methods: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group)., Results: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log 10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29)., Conclusions: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

Objective: Immunosuppressive therapy may trigger hepatitis B virus (HBV) reactivation for increased morbidity and mortality. We aimed to describe HBV reactivation in patients receiving treatment for immune-mediated inflammatory diseases (IMIDs) and to evaluate a predefined algorithm for its prevention., Methods: Physicians submitted data for patients receiving treatment for IMIDs and exhibiting HBV reactivation, defined as an increase of >1 log10 IU/ml of HBV DNA levels or DNA reappearance. We systematically reviewed cases in the literature., Results: The 35 physician-collected patients had rheumatoid arthritis (n = 14), connective tissue disease (n = 7), vasculitis (n = 5), and other diseases (n = 9). At baseline, 65.7% of patients were positive for hepatitis B surface antigen (HBsAg), 31.4% had a history of HBV infection, and 2.9% had occult HBV infection. Reactivation occurred a median of 35 weeks (range 2-397 weeks) after the start of corticosteroid and/or immunosuppressive therapy. In all, 88.6% of patients were clinically asymptomatic, but 25.7% had severe hepatitis; none had fulminant hepatitis. Management was antiviral therapy for 91.4%, with discontinuation or decrease of immunosuppressive therapy for 45.7%. In pooling these 35 cases and 103 patients from the literature, 73.9% of patients were clinically asymptomatic, 33.3% had severe hepatitis, and 12.3% died and/or had fulminant hepatitis. Reactivation occurred early with rituximab or cyclophosphamide therapy and in HBsAg-positive/HBV DNA-positive patients. Using the predefined algorithm, 78% of patients with reactivation would have received preemptive antiviral therapy., Conclusion: We provide new insights into HBV reactivation in patients receiving treatment for IMIDs. A predefined algorithm may be effective in reducing the risk of HBV reactivation in this population., (Copyright © 2013 by the American College of Rheumatology.)

Hepatitis B virus (HBV) infection is more frequent in immune deficient populations than in the general population with lower rates of spontaneous recovery in acute cases, thus explaining the high rate of chronic infection and the increased risk of cirrhosis and hepatocellular carcinoma, resulting in increased morbidity-mortality in these patients. The negative impact of immune deficiency on chronic HBV infection is related to two non-exclusive factors: (i) high viral load enhances the progression of fibrosis and may result in a rare severe liver disease called fibrosing cholestatic hepatitis, which reflects the direct toxicity of high levels of HBV proteins; (ii) The pathobiology of HBV infection is mainly immune-mediated via HBV-specific T lymphocytotoxicity. The reduction or discontinuation of immune deficiency may result in severe liver disease including fulminant hepatitis from immune restoration. Thus, immune deficiency enhances the hepatitis B viral load, which results in the progression of fibrosis and/or acute exacerbation of underlying liver disease (HBV reactivation) on one hand, whereas reduction in immune deficiency may also be harmful because of immune restoration on the other hand. This double-edged sword explains why the diagnosis and evaluation of the impact of HBV infection on the liver must be especially rigorous in cases of immune deficiency whatever the cause: transplantation, oncology, haematology, internal medicine (rheumatology, gastroenterology …) or HIV infection, and why pre-emptive therapy by HBV nucleos(t)ide analogues should be considered for all HBV-infected patients., (© 2012 John Wiley & Sons A/S.)

Defective hepatitis B virus (dHBV) generated from spliced RNA is detected in the sera of HBV-chronic carriers. Our study was designed to determine whether the proportion of dHBV changed during the course of infection, and to investigate whether dHBV might interfere with HBV replication. To achieve this, HBV wild-type and dHBV levels were determined by Q-PCR in sera from 56 untreated chronic patients and 23 acute patients, in sequential samples from 4 treated-patients and from liver-humanized mice after HBV infection. The proportion of dHBV was higher in patients with severe compared to null/moderate liver disease or with acute infection. Follow-up showed that the proportion of dHBV increased during disease progression. By contrast, a low and stable proportion of dHBV was observed in the humanized-mouse model of HBV infection. Our results highlight a regulation of the proportion of dHBV during liver disease progression that is independent of interference with viral replication., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Defective hepatitis B virus (HBV) particles, generated from singly spliced HBV RNA, have been detected in chronic carriers of HBV. The present study was designed to quantify the expression of defective HBV (dHBV) and wild-type HBV (wtHBV) genomes in the serum of patients with HBV infection and its relation to the severity of liver disease., Methods: HBV and dHBV loads were determined by quantitative polymerase chain reaction in the serum of 89 untreated HBV-infected patients (31 coinfected with human immunodeficiency virus [HIV] type 1) with liver disease of different stages. The ratio of dHBV DNA to total (wtHBV plus dHBV) HBV DNA (dHBV/HBV ratio) was used to express data independently of the level of viral replication., Results: Despite a global correlation between dHBV and wtHBV load, the dHBV/HBV ratio ranged from 0.001% to 69%. The variation in dHBV/HBV ratio was independent of HIV coinfection, HBV genotype, and precore mutations. The mean dHBV/HBV ratio was higher in patients with severe liver necrosis and fibrosis., Conclusions: Our data indicate that an elevated dHBV/HBV ratio is associated with liver necroinflammation and fibrosis disease, suggesting a regulation of dHBV expression according to the severity of the liver disease. The dHBV/HBV ratio may help to better define liver disease stage during HBV infection.

Background/aims: This study aimed at correlating the presence of extrahepatic manifestations with hepatitis B virus (HBV) genotypes in patients with chronic HBV infection., Methods: This was a national (France), multicenter, retrospective, cross-sectional study. HBV genotypes were determined in 190 patients HBsAg-positive for at least 6 months and documented before any treatment., Results: Patients were aged 42+/-15 years and mainly male (77%). Alcohol intake was high in 6% of them, ALT elevated in 73%; 27% were cirrhotic. All HBV genotypes were found, mainly A (24%), D (29%), C (11%), and E (10%). Thirty (16%) patients had clinical extrahepatic manifestations, mainly sensory-motor deficiency, sicca syndrome, myalgia, glomerulonephritis, and arthralgia-arthritis. Their presence was not related to any epidemiologic, viral (including genotypes) or hepatic factor, but to a higher platelet count (P=0.004). Twenty-nine (15%) patients had biological extrahepatic manifestations, mainly anti-smooth muscle, antinuclear, and anti-nucleosome antibodies. Their presence was related only to anti-HBe antibodies positivity (P=0.007) or elevated platelet count (P=0.003). Carrying precore mutant HBV increased by 2.8 folds the risk to have at least one extrahepatic biological manifestation., Conclusions: No relationships between HBV genotypes and the presence of extrahepatic manifestations were evidenced in patients with chronic HBV infection.

Background/aims: We have previously demonstrated the in vivo expression of a new spliced hepatitis B virus (HBV) protein (HBSP) encoded by a singly spliced pregenomic RNA. The present study was designed to evaluate the impact of HBSP expression on the clinical status and liver pathology of HBV infection., Methods: Sera from 125 chronic HBV carriers were tested for the presence of HBSP antibodies by an indirect enzyme-linked immunosorbent assay test. The severity of liver damage was evaluated using the Knodell score., Results: Anti-HBSP antibody prevalence in HBV chronic carriers was 46%. We highlighted the concomitant expression of HBSP protein and anti-HBSP antibody. An association between anti-HBSP antibody detection and serum markers of HBV replication was demonstrated. With respect to HBV-related liver disease, an association was only observed with the severity of fibrosis. Furthermore, an elevation of secreted tumor necrosis factor alpha (TNFalpha), but not of soluble TNFalpha receptor 75, was observed in anti-HBSP-antibody-positive patients. Multivariate analysis showed that anti-HBSP antibody detection was independently associated with viral replication, severity of fibrosis and elevated TNFalpha secretion., Conclusions: Our data suggest the hypothesis that HBSP might play a role in the natural history of HBV infection and may be involved in the pathogenesis and/or persistence of HBV infection.

PreS2/S vaccination of chronic hepatitis B virus (HBV) carriers led to a reduction in HBV replication or clearance of virus in 30% of treated patients. This study assessed whether vaccinotherapy of chronic HBV carriers induced the selection of escape mutants in the envelope 'a' determinant and whether envelope genetic variability might affect the response to vaccination. No amino acid differences were observed in the 'a' determinant between sequences obtained before and after treatment (five responders and seven non-responders). However, alignment with HBV prototype sequences revealed seven amino acid changes. Two mutations (T140S and P127L) diverged from subtype variations. In the complete envelope sequence (five non-responders and five responders), ten amino acid modifications were detected between sequences obtained before and after treatment. The absence of any common mutations did not enable the definition of a hot spot of mutations implicated in the response to vaccination. Moreover, vaccinotherapy does not induce the selection of escape mutants in the 'a' determinant.

Novel treatments for hepatitis Delta virus (HDV) infection provide promising opportunities to treat patients with hepatitis B virus (HBV) and HDV co‐infection. However, current clinical trials on HDV treatment rarely explore patients' barriers to treatments. In Europe, HDV infection mostly affects young migrants from HDV‐endemic areas who experience early liver‐related mortality. Migrants are more likely to face multiple situations of statutory and socioeconomic insecurity and structural barriers than non‐migrants. These obstacles may impact their quality of life and can (i) lead them to give secondary importance to certain HDV care options, (ii) delay treatment initiation and (iii) affect their adherence and commitment to care. Preliminary results from the ANRS CO22 HEPATHER cohort show that the majority (61.6%) of HBV‐HDV co‐infected migrants live in poverty. Moreover, half were diagnosed and a quarter of those who initiated HBV treatment had been in France for no more than two years, a period when language skills are often still poor and when knowledge of the health and administrative system may be lacking. We advocate for increased social science research, in particular qualitative studies, to investigate the effects that multiple forms of precarity (weak access to social rights, language barriers, housing insecurity, unexpected expenditures and other difficulties) may have on HDV screening opportunities, follow‐up, and treatment pathways in migrants. This will help adapt communication and care around viral hepatitis, as well as inform and orient medical services and public health actors about the difficulties that migrants encounter. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications: cirrhosis decompensation, hepatocellular carcinoma (HCC, the fourth most common cause of cancer‐related mortality worldwide), liver transplantation and death. It is now 40 years since development of the first plasmatic vaccine which has been proven to prevent (liver) cancer. Aims: To update firstly the molecular and epidemiological aspects of HBV‐related HCC and its natural history together with the benefits associated with viral suppression and secondly the safety, immunogenicity and efficacy of HBV vaccination. Methods: Analysis of recent published data regarding HBV replication, anti‐viral treatments and vaccination. Results: The nuclear HBV replication cycle in the hepatocyte combines two limiting steps to achievement of HBV cure during chronic infection: the formation of a minichromosome, the supercoiled cccDNA, and host‐genome integration of HBV DNA which triggers direct viral hepatocarcinogenesis. Even if specific anti‐viral treatments significantly reduce viral replication, they decrease but do not cancel the risk of liver‐related events in contrast with the prevention of HBV through HBV vaccination. Conclusions: To achieve the 2030 viral hepatitis elimination plan, the HBV vaccine is a priority tool for achieving the sustainable development goals of the World Health Organization. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has proposed a plan for the elimination of viral hepatitis with a goal of reducing new hepatitis infections by 30% and 90% in 2020 and 2030, and associated mortality by 10% and 65% respectively. Actions and targets to reach these goals include improving hepatitis B virus (HBV) vaccination programs, the prevention of mother‐to‐child transmission of HBV, improving the safety of blood products and injections, risk reduction policies and optimizing the diagnosis and treatment of hepatitis. The goal of eliminating hepatitis C virus (HCV) by 2030 is based on three main actions: increased screening, strengthening access to care and the prevention of infections and re‐infections. But, can this goal be reached? The answer to this question is yes in some countries, perhaps in others and no in most countries. Success will be limited by a "diagnosis burn‐out" with 5 times more new viral infections than diagnoses in 2016 and a "treatment burn‐out" with cure rates that are 5 times lower than the number of new infections. Nevertheless, France, like 10 other countries, is on track to achieve the WHO elimination plan by 2030. In France, the prioritization of oral antivirals in 2013‐2014 which was extended to high‐risk populations in 2015 (HIV‐infected patients) and 2016 (men who have sex with men, dialyzed or kidney transplant recipients), then in 2017 to universal treatment with full coverage by French national healthcare (10 to 15 000 treatments per year) has resulted in half of the 120 000 patients needed to be treated by 2022 have been treated. Renewed efforts should make it possible to reach the target announced by the French Minister of Health in May 2018 by 2025. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications, cirrhosis decompensation (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), death or any of these outcomes (composite endpoint [CE]). Nucleos(t)ide analogues (NUCs) such as tenofovir or entecavir are associated with a reduction in these complications. Aim: To compare the impact of tenofovir and entecavir on these outcomes in patients treated for HBV infection and included in the prospective Hepather cohort. Methods: All patients with HBV infection who had received tenofovir or entecavir for more than 6 months at or after entry in the ANRS CO22 cohort were selected. Patients with HDV and HCV co‐infection or prior liver event were excluded. Incidence rates of events were compared using inverse probability of treatment weighting (IPW). Results: The cohort included 1800 patients (986 tenofovir and 814 entecavir). Median follow‐up was 4.2 years. The incidences of HCC, DC, LT, ACD, LRD and CE were not different between tenofovir‐ (1.8 (0.9; 3.2), 0.6 (0.2; 1.6), 0.2 (0.0; 0.8), 1.7 (0.8; 3.0), 0.8 (0.2, 1.8) and 4.1 (3.0; 5.4) per 1000 person‐years) and entecavir‐treated patients (1.6 (0.7; 3.0), 0.7 (0.2; 1.8), 0.2 (0.0; 1.0), 3.0 (1.7, 4.8), 0.5 (0.1; 1.5) and 5.0 (3.3; 7.2)) per 1000 person‐years, respectively. Conclusion: The risk of liver‐related events or death was not different between tenofovir‐ and entecavir‐treated patients in this large prospective cohort of predominantly non‐cirrhotic French patients. Trial registration number: NCT019553458. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg‐negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). Methods: HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg‐positive non‐CHD non‐KTx patients (positive controls) and 40 HBsAg‐negative healthy subjects (negative controls). Results: Chronic haemodialysis group: two of 376 patients were HBsAg‐positive. The 374 HBsAg‐negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg‐positive. One of 403 HBsAg‐negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti‐HBc‐negative and HBV DNA‐negative in both serum and PBMCs. In the long term, the only case of anti‐HBc‐negative OBI lost anti‐HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re‐seroconversion. Conclusions: We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value. [ABSTRACT FROM AUTHOR]

Patients treated with chemotherapy for haematological disease have a known risk of reactivation of hepatitis B virus (HBV) with an estimated incidence of 14-72%. Conversely, very little data exist on viral B reactivation in patients receiving chemotherapy for a digestive malignancy. In this review, a search of the literature data was carried out in an attempt to evaluate the risk of reactivation of HBV during treatment for a digestive malignancy. Based on these data, a ranking of the risk of HBV reactivation and recommendations for the most commonly used anticancer drugs in solid tumors was performed. The majority of anti-cancer drugs can in patients with HBs-positive antigen induce reactivation of HBV. Screening for HBs antigen should be recommended before chemotherapy. Thus, preventive antiviral therapy can therefore reduce the risk of reactivation of HBV. [ABSTRACT FROM AUTHOR]

Résumé Les infections chroniques par les virus des hépatites B et C (VHB et VHC) posent des problèmes diagnostiques et thérapeutiques, chez les patients dialysés et chez les transplantés rénaux. L’exposition de ces malades aux risques transfusionnel et nosocomial explique la haute prévalence des infections à VHB et à VHC dans cette population. Une infection chronique par le VHB et/ou le VHC réduit la survie du patient hémodialysé et du transplanté rénal, ainsi que celle du greffon rénal, notamment par le biais d’une glomérulopathie de novo. La cirrhose est une contre-indication à la transplantation rénale en raison d’un risque de décompensation et d’évolution fatale à court terme après la greffe et il faut, en cas de cirrhose prouvée, envisager une double transplantation foie-rein. Il est donc indispensable de dépister précocement les hépatites virales chez les hémodialysés, qu’ils soient, ou non, candidats à la transplantation rénale. La biopsie (les tests non invasifs de fibrose biochimique ou élastométrique méritent encore une validation dans cette population) apprécie le retentissement histologique et l’évolutivité des hépatopathies virales pour au mieux préciser les indications thérapeutiques. Le traitement des hépatites C repose sur l’interféron-α pégylé qui est contre-indiqué chez les patients transplantés, en partie en raison du risque de rejet induit. Il doit donc être proposé au moment de la dialyse, éventuellement en association à la ribavirine. Le VHB ne pose plus de problème thérapeutique depuis l’avènement des analogues nucléos(t)idiques de deuxième génération (entécavir et ténofovir), qui doivent être proposés chez les patients hémodialysés qui ont une maladie modérée ou sévère (supérieure ou égale à A2 ou F2 selon le score Métavir) et chez tous les patients juste avant ou au moment de la transplantation rénale, quelle que soit l’évaluation histologique initiale. Le meilleur traitement des hépatites virales est avant tout préventif par une vaccination pour le VHB et, pour le VHC, par un respect des règles d’hygiène universelles. Chronic infections by hepatitis B (HBV) and C virus (HCV) result in diagnosis and therapeutic issues in dialysis and kidney recipients patients. The exposure to nosocomial, including blood transfusion, risk explains the high prevalence of HBV and HCV infection in this setting. Chronic infection reduces the survival of both patients and allografts, including a specific risk of de novo glomerulonephritis. Cirrhosis was considered as a contra-indication to renal transplantation given the high risk of decompensation and death, questionning the indication of a combined liver and kidney transplantation. Thus, it is mandatory to screen HBV and HCV markers in all dialysis patients, whether or not they are candidates to transplantation. Liver biopsy allows evaluating the severity of the liver disease since the noninvasive markers of fibrosis appear to be less accurate in “renal” patients than in the general population and to better define antiviral therapeutic indications. HCV treatment was mainly based on pegylated interferon α (and low doses of ribavirin), which is contra-indicated in kidney recipients given the risk of graft rejection; HCV treatment is now based on the use of oral direct acting antivirals, which are very potent and well tolerated. HBV replication is now easily suppressed by second-generation nucleos(t)tidic analogues (entecavir and tenofovir), which will be indicated in all the dialysis patients with significant fibrosis (F2,3 or 4 according to the Metavir scoring system) and in any candidate to renal transplantation and to any HBsAg-positive kidney recipients. The best treatment remains preventive by anti-HBV vaccination for HBV and by the respect of universal hygiene rules for HCV. [ABSTRACT FROM AUTHOR]

Background & Aims Few data are available on the prevalence of renal abnormalities in chronic hepatitis B virus ( HBV)-infected patients. The multicentric cross-sectional HARPE study evaluated the prevalence of kidney disease indicators, in chronic HBV surface antigen carriers patients ( HBsAg+) with active or inactive infection. Patients and methods Two hundred and sixty-eight HBsAg+ adult patients, naïve of any oral antihepatitis B virus treatment were prospectively included over 2 years. Data for renal assessment were collected once from patient files. Univariate tests and multiple linear regressions were performed with the SAS software, version 8.02 ( SAS, Inc., Cary, NC, USA). Results Among the 260 patients analysed, 58% were men, the mean age was 42 ± 14 years, 59.6% were inactive carriers whereas 47 patients, mostly active, were about to start an antiviral therapy. Prevalence of proteinuria, haematuria, glycosuria, uninfectious leukocyturia was 38.1%, 20.6%, 3.9% and 9% respectively. According to the international definition, a total of 64.6% of patients were found to have kidney disease. Diabetes, hypertension and dyslipidaemia were observed, respectively, in 4.6%, 9.2% and 38.8% patients. There were no significant differences in these results within the three subgroups. Conclusion Renal abnormalities are highly prevalent in our population and pre-exist before the initiation of any antihepatitis B virus treatment. This emphasizes the need for: (i) a baseline renal evaluation in all HBs antigen-positive patients; (ii) a regular renal monitoring before and during antihepatitis B virus treatment to diagnose and manage renal impairment and adjust antihepatitis B virus treatment doses to renal function when necessary. [ABSTRACT FROM AUTHOR]

The goal of chronic hepatitis B (CHB) treatment is to improve survival by preventing disease progression to decompensated cirrhosis and hepatocellular carcinoma which is the cause of over 1 million deaths annually. The risk of disease progression is reduced when a sustained reduction of hepatitis B virus (HBV) DNA to undetectable levels and suppression of HBV replication are obtained which can result in regression of liver fibrosis and may even reverse cirrhosis. However, even if HBsAg loss occurs, HBV is not completely eradicated by treatment, and long-term therapy is required in patients who are HBeAg– and HBeAg+ who do not maintain off-treatment virological suppression and in those with advanced liver disease. The recently updated European Association of the Study of the Liver (EASL) clinical practical guidelines for HBV have clarified, first, how to treat HBV (interferon or the most potent oral drugs with optimal resistance profiles, i.e. entecavir and tenofovir disoproxil fumarate, should be used as first-line monotherapies); second, who should be treated (CHB in patients with significant liver disease but also patients who are HBsAg+ and are receiving immunosuppressive treatment, patients coinfected with HBV and human immunodeficiency virus, mothers who are HBsAg+ with high viral load in late pregnancy associated with sero vaccination to reduce the risk of vertical transmission of HBV; and third, when to stop antiviral therapies. The aim of this review was to clarify how to treat HBV and who should be treated, as well as when to stop treatment. Although the answer to these questions is clear for pegylated interferon, it is more debatable for nucleos(t)ide analogues (anti-HBe seroconversion, HBsAg loss or anti-HBs seroconversion with undetectable HBV DNA are clear indications to discontinue treatment but sustained undetectable HBV DNA in patients who are anti-HBe+ without significant fibrosis might be another indication). [ABSTRACT FROM PUBLISHER]

Background & Aims: To compare the management and the virological and serological efficacy of treatments for chronic hepatitis B (CHB) in HIV positive and negative patients. Methods: Two hundred and forty-six HIV positive and 205 HIV negative consecutive patients with past or present CHB, seen in October 2008 in participating departments, were included in a multicenter study. All the data were retrospectively collected from the first visit to October 2008 through a standardized questionnaire. Results: Compared to HIV negative patients, HIV positive patients more often presented positive HBeAg (46.4% vs. 32.8%, p =0.01), HBV genotype A (54.8% vs. 17.1%, p <0.0001), co-infection with HCV (12.4% vs. 5.9%, p =0.0002) or HDV (12.6% vs. 2.9%, p =0.04). HIV positive patients were more often on HBV therapy (92.7% vs. 57.1%, p <0.0001), leading to undetectable serum HBV DNA levels (71.0% vs. 44.1%, p <0.0001). In HIV positive patients, multivariate analysis showed that older age, lower initial HBV DNA levels, and longer time on HBV therapy significantly correlated with undetectable HBV DNA. No difference in efficacy was observed between tenofovir used alone or in combination. HBsAg (but not HBe) loss was more often observed in HIV positive patients, sometimes followed by HBsAg re-appearance after withdrawal of HBV treatment. Excluding the 37 HBV–HCV-co-infected patients, the last clinical presentation and liver fibrosis scores were similar in HIV positive and negative patients. Conclusions: The assessment of CHB and the efficacy of HBV therapy have improved in HIV positive patients. HIV infection did not have a negative impact on the likelihood of HBV therapeutic success. [ABSTRACT FROM AUTHOR]

Abstract: Patients with cirrhosis are immunocompromised and have an increased risk of infection, with a worse outcome. Some of those infections may be prevented by vaccination. Immunization can reduce the morbidity and mortality associated with cirrhosis. Immunizations against hepatitis A and B viruses, influenza and pneumococcus are recommended by the French Haute Autorité de Santé since 2007. Vaccination against hepatitis A is recommended in non-immunized cirrhotic patients. Vaccination against hepatitis B is recommended in every cirrhotic patient with no serological markers, and post-vaccinal antibodies titer should be checked. Annual influenza immunization can be done in cirrhotic patients, and pneumococcal polysaccharide vaccine should be repeated after 3–5 years. Few data regarding vaccination coverage are available, but studies suggest that immunization rates are too low in this population. [Copyright &y& Elsevier]

People living with chronic hepatitis B virus (HBV) infection are at high risk of liver disease progression, which is positively associated with metabolic disorders, but inversely associated with dyslipidemia. Diet, including dietary antioxidants, is a lever of metabolic disorder management. In particular, elevated coffee consumption is associated with different metabolic outcomes in the general population. We aimed to test whether such associations occur in HBV-infected people. Based on cross-sectional data from the ANRS CO22 Hepather cohort, we performed logistic regression models with (i) dyslipidemia, (ii) hypertension, and (iii) diabetes as outcomes, and with demographic, clinical, and socio-behavioral (including coffee consumption) data as explanatory variables. Among 4746 HBV-infected patients, drinking ≥3 cups of coffee per day was associated with a higher risk of dyslipidemia (adjusted odds ratio [95% confidence interval] 1.49 [1.10–2.00], p = 0.009) and a lower risk of hypertension (0.64 [0.50–0.82], p = 0.001). It was not associated with diabetes. Elevated coffee consumption was associated with a higher risk of dyslipidemia and a lower risk of hypertension in HBV-infected patients, two effects expected to be associated with favorable clinical outcomes. Further studies should test whether such metabolic benefits translate into reduced mortality risk in this population. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Chronic HBV infection no longer influences 10-year patient or graft survival in kidney transplant recipients. • Chronic HCV infection still negatively impacts 10-year patient and graft survival. • The negative effect of chronic HCV infection is removed by sustained viral suppression. • Antiviral therapy should be systematically proposed for HBV- and/or HCV-infected kidney transplant recipients/candidates. Background & Aims Before antiviral therapy, kidney transplant recipients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) had poor outcomes. Since the 90s, nucleos(t)ide analogues have been widely used in HBV-infected patients, while interferon-based therapy was rarely used in HCV-infected patients. The aim of this study was to assess the impact of HBV and HCV on patient and graft survival, according to viral replication status. Methods Data from January 1993 to December 2010 were extracted from the French national database CRISTAL. A total of 31,433 kidney transplant recipients were included, of whom 575, 1,060 and 29,798 had chronic hepatitis B, C, or were not infected, respectively. Results Ten-year survival was lower in HCV-infected (71.3%) than in HBV-infected (81.2%, p = 0.0004) or non-infected kidney transplant recipients (82.7%, p <0.0001). Ten-year kidney graft survival was lower in HCV-infected (50.6%) than in HBV-infected (62.3%, p <0.0001) or non-infected kidney transplant recipients (64.7%, p <0.0001). A random analysis of the medical records of 184 patients with HBV and 504 patients with HCV showed a control of viral replication in 94% and 35% of cases, respectively. Ten-year patient and graft survival in patients with detectable HCV RNA was lower than in their matching controls. Conversely, patients with HCV and undetectable HCV RNA had higher 10-year survival than their matched controls without significant differences in graft survival. Conclusions Chronic HBV infection does not impact 10-year patient and kidney graft survival thanks to control of viral replication with nucleos(t)ide analogues. In kidney transplant recipients infected with HCV, patients with detectable RNA had worse outcomes, whereas the outcomes of those with undetectable RNA were at least as good as non-infected patients. Thus, direct-acting antivirals should be systematically offered to HCV-infected patients. Lay summary Previously, infections with hepatitis B or hepatitis C virus led to poor outcomes in kidney transplant recipients. However, the outcomes of kidney transplants in patients with viral suppression are as good as those for kidney transplants in non-infected patients. Antiviral therapy should be systematically proposed to hepatitis B and/or hepatitis C-infected kidney transplant recipients or candidates to prevent the deleterious hepatic and extrahepatic impact of chronic viral replication. Recent access to direct-acting antivirals in patients with hepatitis C virus and renal dysfunction provides exciting new opportunities. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis B virus (HBV) infection is more frequent in kidney recipients than in the general population with a higher rate of liver-related morbidity and mortality. We evaluated the benefit associated with HBV viral suppression by nucleos(t)ide analogues treatment in HBV-infected kidney recipients. Methods: This retrospective study included 42 HBsAg-positive kidney recipients, 33 males, 9 females, median age 54years, followed up during a mean of 15.4±11.8years after kidney transplantation. Mean treatment duration by single or combined nucleos(t)ide analogues was 6.8±4.3years. Fibrosis, before treatment, according to Metavir score was: F4 for 6 patients, F3 for 10, F2 for 6, and F0–F1 for 20 patients. The primary end point, the patient survival, was defined as patient death or liver transplantation, the secondary end point was graft survival. Results: HBV DNA at the last evaluation was undetectable (<12IU/ml) in 92.8% of patients. During the follow-up, 8 patients died (17.7%), death being related to hepatocellular carcinoma in 4 (9.5%), including 1 patient with baseline mild fibrosis, and to extrahepatic causes in 4. This mortality rate is strikingly lower than that previously reported in HBV-infected kidney recipients before oral antiviral therapies. Graft survival seems to be improved when compared to the former series. Conclusions: Suppression of HBV replication associated with nucleo(s)tide analogues treatment improves the survival of HBV-infected kidney recipients. Viral suppression does not exclude regular follow-up given the risk of occurrence of hepatocellular carcinoma even in non-cirrhotic patients. [Copyright &y& Elsevier]

Transplantation is the best treatment for end-stage organ failure. Hepatitis virus infections, mainly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections still constitute a major problem because they are common in allograft recipients and are a significant cause of morbidity and mortality after transplantation. Recently, hepatitis E virus infection has been added as an emergent cause of chronic hepatitis in organ transplantation. The prevalence of HBV and HCV infections has markedly decreased in patients who are candidates for transplantation since the introduction of screening, hygiene and prevention measures, including systematic screening of blood and organ donations, use of erythropoietin, compliance with universal hygiene rules, segregation of HBV-infected patients from non-infected patients and systematic vaccination against HBV. A liver biopsy is preferable to non-invasive biochemical and/or morphological tests of fibrosis to evaluate liver fibrosis before and even after transplantation. Treatment with entecavir or tenofovir is indicated in HBV-infected dialyzed patients who have moderate or severe disease (⩾A2 or F2 on the Metavir scale) in preparation for renal transplantation. Due to the risks of severe reactivation, fibrosing cholestatic hepatitis or histological deterioration after transplantation, systematic use of nucleoside or nucleotide analogues shortly before or at the time of transplantation is recommended (tenofovir or entecavir are preferable to lamivudine) in all patients, whatever the baseline histological evaluation. In HCV-infected dialyzed patients who are not candidates for renal transplantation, the indication for antiviral therapy is limited to significant fibrosis (fibrosis ⩾2 on the Metavir scale). Treatment must be proposed to all candidates for renal transplantation, whatever their baseline histopathology, and interferon-α should be used as monotherapy. After transplantation, interferon-α is contraindicated but may be used in patients for whom the benefits of antiviral treatment clearly outweigh the risks, especially that of allograft rejection. All cirrhotic patients, notably after solid organ transplantation, should be screened for hepatocellular carcinoma. Sustained suppression of necro-inflammation may result in regression of cirrhosis, which in turn may lead to decreased disease-related morbidity and improved survival. Finally, due to the high mortality after renal transplantation, active (namely without sustained viral suppression) cirrhosis should be considered a contraindication to kidney transplantation, but an indication to combined liver-kidney transplantation; on the contrary, inactive (namely with sustained viral suppression) compensated cirrhosis may permit renal transplantation alone. Organ transplantations other than kidney (cardiac or pulmonary transplantations) involve the same diagnosis and therapeutic issues. [Copyright &y& Elsevier]

• In Europe, HDV patients comprise many migrants and people living in poverty. • The linkage and retention in care of this vulnerable population must be documented. • Additional prevalence data are needed for this severe form of chronic hepatitis. [ABSTRACT FROM AUTHOR]