Retningslinjer for screening og profylakse før behandling med biologiske lægemidler (2023)
Omhandler biologiske og målrettede syntetiske lægemidler (BMSL) til patienter i forhold til risiko for tuberkulose (TB), Humant Papillom Virus (HPV), Hepatitis B og C (HBV og HCV), Varicella Zoster Virus (VZV), Herpes Simplex Virus (HSV), Cytomegalovirus (CMV), Epstein Barr Virus (EBV) og Humant Immundefekt Virus (HIV) og øvrige infektioner.
Vejledningen er udarbejdet af repræsentanter fra Dansk Selskab for Gastroenterologi og Hepatologi (DSGH), Dansk Reumatologisk Selskab (DRS), Dansk Dermatologisk Selskab (DDS) og Dansk Selskab for Infektionsmedicin (DSI).
961 KB, uploadet 9.01.2024
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Hepatitis B (2018)
National guideline udarbejdet af en arbejdsgruppe nedsat af medlemmer fra Dansk Selskab for Infektionsmedicin og medlemmer fra Dansk Selskab for Gastroenterologi og Hepatologi.
172 KB, uploadet 6.02.2023
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Hepatitis C (2022)
National guideline udarbejdet af en arbejdsgruppe nedsat af medlemmer fra Dansk Selskab for Infektionsmedicin og medlemmer fra Dansk Selskab for Gastroenterologi og Hepatologi.
293 KB, uploadet 6.02.2023
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Stikuheld og anden blodeksposition (2020)
Revideret september 2020. Arbejdsgruppen bestod af Suzanne Lunding (formand), Peer Brehm Christensen, Christian Erikstrup, Terese L. Katzenstein, Henrik Krarup, Alex Lund Laursen, Birgitte Mørn og Nina Weis
158 KB, uploadet 5.02.2023
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Fertilitetsbehandling ved HIV og hepatitis B og C (2018)
Forfattere: Jan Gerstoft, Nina Weis, Terese L. Katzenstein (Dansk Selskab for Infektionsmedicin), Anders Nyboe Andersen og Jens Fedder (Dansk Fertilitetsselskab).
Prevalence of vaccine-derived hepatitis B surface antibodies in children and adolescents in Germany: results from a population-based survey, 2014–2017
BMC Infectious Diseases, 15.03.2024
Tilføjet 15.03.2024
Abstract Introduction Childhood vaccination against hepatitis B has been recommended in Germany since 1995. WHO defines a primary vaccination series as successful if the initial hepatitis B surface antibody (anti-HBs) level is ≥ 10 IU/L directly after vaccination. Anti-HBs levels vary depending on the number of doses, type of vaccine, and time interval between the last two doses. In 2021, Germany began to recommend three instead of four doses of polyvalent hepatitis-B-containing vaccines. Our aim was to estimate the proportion of vaccinated children in Germany with anti-HBs levels
Hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia
Elena Cama, Loren Brener, Timothy Broady, Robyn Horwitz, Defeng Jin, Hoang Minh Khoi Vu, K. O. E. Wu, Carla Treloar
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by Elena Cama, Loren Brener, Timothy Broady, Robyn Horwitz, Defeng Jin, Hoang Minh Khoi Vu, K. O. E. Wu, Carla Treloar Research has shown that there are significant gaps in hepatitis B knowledge among migrant communities who are at risk of hepatitis B, such as Chinese and Vietnamese communities. Many students studying within Australia come from countries with high prevalence of hepatitis B. However, there is very little research examining hepatitis B knowledge, screening, or vaccination among university students in Australia or worldwide. The aim of this paper was to measure both levels of and demographic differences in hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia. Online surveys were completed by 112 Chinese- and 95 Vietnamese-identifying students in Australia, measuring knowledge of hepatitis B, engagement in screening and vaccination, and demographic characteristics. Results show that although engagement in screening and vaccination for hepatitis B was high, there were significant gaps in knowledge around transmission of hepatitis B. There were also some key demographic differences in screening and knowledge. For instance, those born in Australia were more likely to have been screened compared to those born Mainland China, Hong Kong, or Vietnam. Chinese students born in Australia had lower levels of knowledge compared to those born in Mainland China or Hong Kong. Among both samples, knowing someone living with hepatitis B was associated with higher levels of knowledge. Findings underscore the need for education-based interventions to address the significant gaps that exist in knowledge around hepatitis B, with a specific need for culturally appropriate resources in a range of languages to cater to the diverse communities who may be at risk of hepatitis B.
Inhibition of cellular factor TM6SF2 suppresses secretion pathways of Hepatitis B, Hepatitis C and Hepatitis D viruses
Journal of Infectious Diseases, 28.02.2024
Tilføjet 28.02.2024
Abstract Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all these viruses rely on secretion through the host endoplasmic reticulum-Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions and HBV subviral particles. Moreover, in a cohort of people with hepatitis B a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.
Prevalence of hepatitis B and C infection and linkage to care among patients with Non-Communicable Diseases in three rural Rwandan districts: a retrospective cross-sectional study
BMC Infectious Diseases, 24.02.2024
Tilføjet 24.02.2024
Abstract Introduction Rwanda’s Hepatitis C elimination campaign has relied on mass screening campaigns. An alternative “micro-elimination” strategy focused on specific populations, such as non-communicable disease (NCD) patients, could be a more efficient approach to identifying patients and linking them to care. Methods This retrospective cross-sectional study used routine data collected during a targeted screening campaign among NCD patients in Kirehe, Kayonza, and Burera districts of Rwanda and patients receiving oncology services from the Butaro District Hospital. The campaign used rapid diagnostic tests to screen for Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (anti-HCV). We reported prevalences and 95% confidence intervals for HBsAg and anti-HCV, assessed for associations between patients’ clinical programs and hepatitis B and C, and reported cascade of care for the two diseases. Results Out of 7,603 NCD patients, 3398 (45.9%) self-reported a prior hepatitis screening. Prevalence of HBsAg was 2.0% (95% CI: 1.7%-2.3%) and anti-HCV was 6.7% (95% CI: 6.2%-7.3%). The prevalence of HBsAg was significantly higher among patients
A case-control study of risk factors for incident hepatitis B virus infection in South African blood donors
Ute Jentsch, Marion Vermeulen, Karin van den Berg, Ronel Swanevelder, Darryl Creel, Genevieve Jacobs, Jennifer Jay Hemingway-Foday, Cynthia Nyoni, Edward L. Murphy, Brian Custer
International Journal of Infectious Diseases, 17.02.2024
Tilføjet 17.02.2024
Hepatitis B virus (HBV) infection remains a serious health problem globally with 3.5% (296 million) of the adult population estimated to have chronic infection. Of 1.5 million new infections in 2019, most have been acquired in Africa [1]. Furthermore, HBV continues to be endemic in Africa and the Western Pacific countries which carry the highest global burden with an HBsAg prevalence of 6% each [2-4].
The prevalence of hepatitis B in Chinese general population from 2018 to 2022: a systematic review and meta-analysis
BMC Infectious Diseases, 17.02.2024
Tilføjet 17.02.2024
Abstract Background Within China, Hepatitis B virus (HBV) infection remains widely prevalent and one of the major public health problems. There have been only two previous estimates of its prevalence at the population level in China, with the latest survey conducted in 2006. A meta-analysis estimated the prevalence of HBV within China between 2013 and 2017 as 7%. This review provides an updated estimate of HBV prevalence in China from 2018 to 2022. Methods Systematic searches of literature from January 1, 2018 to December 25, 2022 were conducted in four international databases (Medline, Web of Science, Embase, Cochrane Database of Systematic Reviews) and three Chinese databases (CNKI, CBM, and WanFang data). Random-effects meta-analyses were conducted to calculate the pooled HBV prevalence with 95% confidence intervals in the overall population and subgroups. Publication bias, heterogeneity between studies, and study quality were assessed. Results Twenty-five articles were included in the meta-analysis. The pooled prevalence of HBV infection in the Chinese general population from 2018 to 2022 was 3% (95%CI: 2–4%). The prevalence of HBV infection was similar between males and females (both 3%), while rural areas had a higher prevalence than urban areas (3% vs 2%). The highest prevalence of HBV was reported in the eastern provinces (4, 95%CI: 2–6%). The HBV prevalence of people aged ≥18 years old (6, 95%CI: 4–8%) was higher than people aged
The prevalence of hepatitis B in Chinese general population from 2018 to 2022: a systematic review and meta-analysis
BMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
Abstract Background Within China, Hepatitis B virus (HBV) infection remains widely prevalent and one of the major public health problems. There have been only two previous estimates of its prevalence at the population level in China, with the latest survey conducted in 2006. A meta-analysis estimated the prevalence of HBV within China between 2013 and 2017 as 7%. This review provides an updated estimate of HBV prevalence in China from 2018 to 2022. Methods Systematic searches of literature from January 1, 2018 to December 25, 2022 were conducted in four international databases (Medline, Web of Science, Embase, Cochrane Database of Systematic Reviews) and three Chinese databases (CNKI, CBM, and WanFang data). Random-effects meta-analyses were conducted to calculate the pooled HBV prevalence with 95% confidence intervals in the overall population and subgroups. Publication bias, heterogeneity between studies, and study quality were assessed. Results Twenty-five articles were included in the meta-analysis. The pooled prevalence of HBV infection in the Chinese general population from 2018 to 2022 was 3% (95%CI: 2–4%). The prevalence of HBV infection was similar between males and females (both 3%), while rural areas had a higher prevalence than urban areas (3% vs 2%). The highest prevalence of HBV was reported in the eastern provinces (4, 95%CI: 2–6%). The HBV prevalence of people aged ≥18 years old (6, 95%CI: 4–8%) was higher than people aged
New window into hepatitis B in Africa: Liver sampling combined with single cell omics enables deep and longitudinal assessment of intrahepatic immunity in Zambia
Journal of Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
Abstract In Lusaka, Zambia, we introduced liver fine needle aspiration (FNA) into a research cohort of adults with treatment-naïve chronic hepatitis B virus (HBV) infection, with and without HIV coinfection, as well as with acute HBV infection. Over 117 enrollment and 47 longitudinal FNAs (at 1 year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.
Prevalence of hepatitis B virus infection among general population of Armenia in 2021 and factors associated with it: a cross-sectional study
Demirchyan, A., Dudareva, S., Sahakyan, S., Aslanyan, L., Muradyan, D., Musheghyan, L., Mozalevskis, A., Sargsyants, N., Ghukasyan, G., Petrosyan, V.
BMJ Open, 8.02.2024
Tilføjet 8.02.2024
ObjectivesThis study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia. DesignA population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals. SettingAll administrative units of Armenia including 10 provinces and capital city Yerevan. ParticipantsThe study frame was the general adult population of Armenia aged ≥18 years. Primary and secondary outcome measuresThe participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models. ResultsThe seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93). ConclusionThis study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.
High‐speed centrifugation rather than Lipoclear reagent can be used for removing the interference of lipemia on serological tests of infectious diseases: AIDS, hepatitis B, hepatitis C, and syphilis by chemiluminescent microparticle immunoassay
Weiping Liu, Lin Li, Minggang Yin, Chengjian Cao, Yaohui Song, Xia Long
Journal of Medical Virology, 7.02.2024
Tilføjet 7.02.2024
Journal of Medical Virology, Volume 96, Issue 2, February 2024.
Enrichment reveals extensive integration of hepatitis B virus DNA in hepatitis delta-infected patients
Journal of Infectious Diseases, 29.01.2024
Tilføjet 29.01.2024
Abstract Introduction Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited.Methods We investigated 50 pieces of liver explant tissue from five patients with hepatitis D-induced cirrhosis, using a deep sequencing strategy targeting HBV RNA.Results We found that integrations were abundant and highly expressed, however with large variation in number of integration derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of both HBsAg. Still, most of the HBV reads represented a few predominant integrations.Conclusions The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small part of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV co-infected patients with liver cirrhosis.
Information seeking behavior on hepatitis B virus, and its associated factors among pregnant women at teaching and specialized hospitals, Northwest Ethiopia: A cross-sectional study
by Adamu Ambachew Shibabaw, Masresha Derese Tegegne, Agmasie Damtew Walle, Sisay Maru Wubante, Nebebe Demis Baykemagn, Melaku Molla Sisay, Adane Nigusie Weldeab Introduction Hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. Health information-seeking behavior is critical to obtain information about health, diseases such as the Hepatitis B virus, health risks, and health promotion and it has become a major concern of health policymakers. However, there is little evidence of information-seeking behavior on the Hepatitis B virus in Ethiopia. So, this study aimed to assess Hepatitis B virus information-seeking behavior and its associated factors among pregnant women at teaching and Specialized Hospitals, in Northwest Ethiopia. Methods An institution-based cross-sectional study was conducted among pregnant women at teaching and specialized hospitals, in Northwest Ethiopia from May 01 to June 01, 2022. A total of 423 participants were selected using a systematic random sampling method. The data was collected through an interview-administered questionnaire by kobo-collect software. Then export into SPSS version 20 for analysis. Descriptive statistics, bi-variable, and multivariable logistic regression analyses were done to identify factors associated with Hepatitis B virus information-seeking behavior. Results The proportion of information-seeking behavior on the Hepatitis B virus among pregnant women was 40.5% (CI = 35.7, 45.6). Education(diploma and above) [AOR = 3.3, 95% CI (1.31, 8.16)], more than one ANC visit [AOR = 5.99, 95% CI (3.20, 12.31)], smart-phone ownership [AOR = 4.1, 95%CI (1.35, 12.31)], internet access [AOR = 5.1, 95%CI (1.35, 15.60)], perceived susceptibility [AOR = 2.7, 95%CI (1.38, 5.31)], perceived severity [AOR = 3.7, 95%CI (2.06, 6.55)], and self-efficacy [AOR = 1.9, 95%CI (1.03, 3.73)] were factors influencing information seeking on Hepatitis B virus. Conclusion The overall proportion of information-seeking behavior on HBV among pregnant women was low. To improve information-seeking behavior on HBV among pregnant women we should connect the women to the internet and technology. Creating women’s awareness about the Hepatitis B virus severity and their venerability and increasing their antenatal care (ANC) visits, self-efficacy, internet access, and women’s education can improve information seeking about the Hepatitis B virus.
Virological, serological and clinical outcomes in chronic hepatitis B virus infection: development and validation of the HEPA-B simulation model
Mohareb, A. M., Kim, A. Y., Boyd, A., Noubary, F., Kouame, M. G., Anglaret, X., Coffie, P. A., Eholie, S. P., Freedberg, K. A., Hyle, E. P.
BMJ Open, 13.01.2024
Tilføjet 13.01.2024
ObjectivesDetailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes. MethodsWe developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC). ResultsModel-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies. ConclusionsWe simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.
Structural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core
Ruoyu Yang, Ying-Hui Ko, Fenglin Li, Ravi K. Lokareddy, Chun-Feng David Hou, Christine Kim, Shelby Klein, Santiago Antolínez, Juan F. Marín, Carolina Pérez-Segura, Martin F. Jarrold, Adam Zlotnick, Jodi A. Hadden-Perilla, Gino Cingolani
Science Advances, 11.01.2024
Tilføjet 11.01.2024
Science Advances, Volume 10, Issue 2, January 2024.
No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment.
J Viral Hepat 2017; 24(1):68-74
Liu Y, Corsa AC, Buti M, Cathcart AL, Flaherty JF, Miller MD, Kitrinos KM, Marcellin P, Gane EJ
A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes.
Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection.
N Engl J Med 2015; 373(27):2608-17
Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourlière M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M
In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.
Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection.
N Engl J Med 2015; 373(27):2599-607
Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S
A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.
Extrahepatic morbidity and mortality of chronic hepatitis C.
Gastroenterology 2015; 149(6):1345-60
Negro F, Forton D, Craxì A, Sulkowski MS, Feld JJ, Manns MP
Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.
Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study.
Lancet Infect Dis 2015; 15(9):1049-1054
Kohli A, Kapoor R, Sims Z, Nelson A, Sidharthan S, Lam B, Silk R, Kotb C, Gross C, Teferi G, Sugarman K, Pang PS, Osinusi A, Polis MA, Rustgi V, Masur H, Kottilil S
Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections.
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Ann Intern Med 2015; 163(1):1-13
Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR
Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection.
Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent.
J Hepatol 2015; 63(3):564-72
Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M
The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy.
Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial.
Lancet 2015; 385(9986):2502-9
Hézode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, Marcellin P, Hall C, Schnell G, Pilot-Matias T, Mobashery N, Redman R, Vilchez RA, Pol S
Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin.
Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS).
Lancet Infect Dis 2015; 15(4):397-404
Bourlière M, Bronowicki JP, de Ledinghen V, Hézode C, Zoulim F, Mathurin P, Tran A, Larrey DG, Ratziu V, Alric L, Hyland RH, Jiang D, Doehle B, Pang PS, Symonds WT, Subramanian GM, McHutchison JG, Marcellin P, Habersetzer F, Guyader D, Grangé JD, Loustaud-Ratti V, Serfaty L, Metivier S, Leroy V, Abergel A, Pol S
Patients with cirrhosis resulting from chronic hepatitis C virus (HCV) infection are at risk of life-threatening complications, but consistently achieve lower sustained virological response (SVR) than patients without cirrhosis, especially if treatment has previously failed. We assessed the efficacy and safety of the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir, with and without ribavirin.
Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.
Lancet 2014; 384(9956):1756-65
Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, DeJesus E, Pearlman B, Rabinovitz M, Gitlin N, Lim JK, Pockros PJ, Scott JD, Fevery B, Lambrecht T, Ouwerkerk-Mahadevan S, Callewaert K, Symonds WT, Picchio G, Lindsay KL, Beumont M, Jacobson IM
Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.
Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.
N Engl J Med 2014; 370(16):1483-93
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P
Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.
Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.
N Engl J Med 2014; 370(17):1604-14
Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, Bourlière M, Sulkowski MS, Wedemeyer H, Tam E, Desmond P, Jensen DM, Di Bisceglie AM, Varunok P, Hassanein T, Xiong J, Pilot-Matias T, DaSilva-Tillmann B, Larsen L, Podsadecki T, Bernstein B
In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin.
No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis.
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection.
N Engl J Med 2014; 370(3):211-21
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM
All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3.
Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial.
Lancet Infect Dis 2013; 13(6):497-506
Deterding K, Grüner N, Buggisch P, Wiegand J, Galle PR, Spengler U, Hinrichsen H, Berg T, Potthoff A, Malek N, Großhennig A, Koch A, Diepolder H, Lüth S, Feyerabend S, Jung MC, Rogalska-Taranta M, Schlaphoff V, Cornberg M, Manns MP, Wedemeyer H
Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.
Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C.
Hepatology 2013; 58(2):497-504
Kraus MR, Schäfer A, Teuber G, Porst H, Sprinzl K, Wollschläger S, Keicher C, Scheurlen M
Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders.
Hepatitis C prevalence in Denmark -an estimate based on multiple national registers.
BMC Infect Dis 2012; 12:178
Christensen PB, Hay G, Jepsen P, Omland LH, Just SA, Krarup HB, Weis N, Obel N, Cowan S
A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare.
Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection.
AIDS 2010; 24(12):1799-812
van de Laar TJ, Matthews GV, Prins M, Danta M
Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.
Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.
N Engl J Med 2008; 359(23):2442-55
Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F
Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase.
Diagnosis and treatment of hepatocellular carcinoma.
Gastroenterology 2008; 134(6):1752-63
El-Serag HB, Marrero JA, Rudolph L, Reddy KR
The diagnosis and treatment of hepatocellular carcinoma (HCC) have witnessed major changes over the past decade. Until the early 1990s, HCC was a relatively rare malignancy, typically diagnosed at an advanced stage in a symptomatic patient, and there were no known effective palliative or therapeutic options. However, the rising incidence of HCC in several regions around the world coupled with emerging evidence for efficacy of screening in high-risk patients, liver transplantation as a curative option in select patients, ability to make definitive diagnosis using high-resolution imaging of the liver, less dependency on obtaining tissue diagnosis, and proven efficacy of transarterial chemoembolization and sorafenib as palliative therapy have improved the outlook for HCC patients. In this article, we present a summary of the most recent information on screening, diagnosis, staging, and different treatment modalities of HCC, as well as our recommended management approach.
The HBV drug entecavir - effects on HIV-1 replication and resistance.
N Engl J Med 2007; 356(25):2614-21
McMahon MA, Jilek BL, Brennan TP, Shen L, Zhou Y, Wind-Rotolo M, Xing S, Bhat S, Hale B, Hegarty R, Chong CR, Liu JO, Siliciano RF, Thio CL
Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.
Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group.
Hepatology 1999; 30(4):1054-8
Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, Vidaud M, Bricaire F, Opolon P, Katlama C, Poynard T
The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count =200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.
Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.
Gastroenterology 1997; 112(2):463-72
Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, Nevens F, Solinas A, Mura D, Brouwer JT, Thomas H, Njapoum C, Casarin C, Bonetti P, Fuschi P, Basho J, Tocco A, Bhalla A, Galassini R, Noventa F, Schalm SW, Realdi G
Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C.
Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis.
N Engl J Med 1989; 321(22):1494-500
Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, Kuo G
We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified.