M. van der Valk

HIV-associated adipose redistribution syndrome as a selective autonomic neuropathy.

Abnormal body-fat distribution in HIV-1-associated adipose redistribution syndrome (HARS) remains unexplained at present. White adipose tissue is controlled by humoral factors and by neural regulation. Sympathetic innervation stimulates lipolysis, whereas parasympathetic innervation has an anabolic influence on white adipose tissue. Results of neuroanatomical studies showed a clear somatotopy with respect to autonomic control of white adipose tissue by both the sympathetic and parasympathetic branch, with separate sets of autonomic neurons innervating either the subcutaneous or the visceral fat compartment. Thus, the CNS is likely to be a key player in regulation of body-fat distribution. We propose that HARS is mediated by effects of antiretroviral treatment on the CNS and could indicate a change in autonomic balance resulting in redistribution of adipose tissue.

Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study

Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0–52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63–15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04–12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02–6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27–192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39–8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19–2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60–14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.

Risk factors and outcome of HIV‐associated idiopathic noncirrhotic portal hypertension

Idiopathic noncirrhotic portal hypertension (INCPH) has been reported increasingly in patients with HIV infection.

Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life

Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver‐related death. Recently, multiple regimens of different direct‐acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real‐life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon‐based treatment, and one was treatment naive. In this real‐life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment‐experienced patients as recommended in guidelines.

Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe

[Marshall, A. D.; Cunningham, E. B.; Dore, G. J.; Grebely, J.] UNSW Sydney, Kirby Inst, Sydney, NSW, Australia. [Nielsen, S.] Freelance Epidemiologist, Madrid, Spain. [Aghemo, A.] Univ Milan, Fdn IRCCS CA Granda Osped Maggiore Policlin, Div Gastroenterol & Hepatol, Milan, Italy. [Alho, H.] Helsinki Univ Hosp, Abdominal Ctr, Helsinki, Finland. [Alho, H.] Univ Helsinki, Helsinki, Finland. [Backmund, M.] Univ Hosp Munich, Dept Med 2, Munich, Germany. [Bruggmann, P.] Arud Ctr Addict Med, Zurich, Switzerland. [Dalgard, O.] Univ Oslo, Akershus Univ Hosp, Dept Infect Dis, Oslo, Norway. [Dalgard, O.] Univ Oslo, Fac Med, Oslo, Norway. [Flisiak, R.] Med Univ Bialystok, Dept Infect Dis & Hepatol, Bialystok, Poland. [Foster, G.] Queen Mary Univ London, London, England. [Gheorghe, L.] Fundeni Clin Inst, Gastroenterol & Hepatol, Bucharest, Romania. [Goldberg, D.] Hlth Protect Scotland, Glasgow, Lanark, Scotland. [Goulis, I.] Dept Internal Med, Thessaloniki, Greece. [Hickman, M.] Univ Bristol, Social Med, Bristol, Avon, England. [Hoffmann, P.] Minist Hlth Luxembourg, Luxembourg, Luxembourg. [Jancoriene, L.] Vilnius Univ Hosp, Santariskiu Klin, Ctr Infect Dis, Vilnius, Lithuania. [Jarcuska, P.] Univ Hosp, Dept Internal Med 1, Kosice, Slovakia. [Jarcuska, P.] Univ Pavol Jozef Safarik, Kosice, Slovakia. [Kaberg, M.] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. [Makara, M.] St Istvan & St Laszlo Hosp, Hepatol Ctr, Budapest, Hungary. [Maimets, M.] Univ Tartu, Dept Internal Med, Tartu, Estonia. [Marinho, R.] Hosp Santa Maria, Med Sch Lisbon, Dept Gastroenterol & Hepatol, Lisbon, Portugal. [Maticic, M.] Univ Med Ctr, Clin Infect Dis & Febrile Illnesses, Ljubljana, Slovenia. [Norris, S.; Tait, M.] Dr Steevens Hosp, Natl Hepatitis Treatment Programme C, Hlth Serv Execut, Dublin, Ireland. [Olafsson, S.] Landspitali Univ Hosp, Dept Med, Div Gastroenterol, Reykjavik, Iceland. [Ovrehus, A.] Univ Southern Denmark, Odense Univ Hosp, Dept Infect Dis, Odense, Denmark. [Pawlotsky, J. -M.] Univ Paris Est, Hop Henri Mondor, Creteil, France. [Pocock, J.] Mater Hosp, Gastroenterol Dept, Msida, Malta. [Robaeys, G.] Ziekenhuis Oost Limburg, Dept Gastroenterol & Hepatol, Genk, Belgium. [Robaeys, G.] UHasselt, Dept Med & Life Sci, Hasselt, Belgium. [Robaeys, G.] UZLeuven, Dept Hepatol, Leuven, Belgium. [Roncero, C.] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Psychiat Serv, Addict & Dual Diag Unit, Barcelona, Spain. [Simonova, M.] Mil Med Acad, Dept Gastroenterol HPB Surg & Transplantol, Sofia, Bulgaria. [Sperl, J.] Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic. [Tolmane, I.] Infectol Ctr Latvia, Dept Hepatol, Riga, Latvia. [Tomaselli, S.] Off Publ Hlth, Vaduz, Liechtenstein. [van der Valk, M.] Acad Med Ctr, Dept Infect Dis, Amsterdam, Netherlands. [Vince, A.] Univ Zagreb, Sch Med, Univ Hosp Infect Dis, Zagreb, Croatia. [Lazarus, J. V.] Univ Copenhagen, Rigshosp, CHIP, Copenhagen, Denmark. [Lazarus, J. V.] Hosp Clin Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain.

LO7 : A single subcutaneous dose of 2mg/kg or 4mg/kg of RG-101, a GalNAc-conjugated oligonucleotide with antagonist activity against MIR-122, results in significant viral load reductions in chronic hepatitis C patients

GWAS hits were validated in independent cohorts from Germany (529 cases vs. 761 controls) and Belgium (619 cases vs. 161 controls) and the results of the joint analyses combined. Genotyping was undertaken using Illumina BeadChips (Illumina Inc., San Diego, CA, USA); SNP replication was undertaken using Taqman chemistry (Applied Biosystems, Foster City, Ca, USA) on an automated platform. Results: The strongest association signal in the initial metaanalysis was observed between the rs738409 variant in PNPLA3 (Pmeta =1.17×10−28, OR=2.38 [2.08–2.69]); 102 separate variants at the PNPLA3 locus associated with genome-wide significance (Pthreshold <5×10−8). In addition, nine other independent loci provided borderline association signals (Pthreshold ≤1.1×10−5). Validation genotyping for rs738409 in PNPLA3 and lead markers for the top 10 associated regions confirmed disease association for rs738409 in PNPLA3, and for (MBOAT7: rs641738 Preplication = 1.35×10−4; Pcombined = 9.25×10−10; OR=1.63 [1.46–1.80] and TM6SF2: rs10401969 Preplication = 3.29×10−5; Pcombined = 1.73×10−8; OR=1.35 [1.25–1.44]).

High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

Abstract Background Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF.

LBP-505 – Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe

[Marshall, A. D.; Cunningham, E. B.; Dore, G. J.; Grebely, J.] UNSW Sydney, Kirby Inst, Sydney, NSW, Australia. [Nielsen, S.] Freelance Epidemiologist, Madrid, Spain. [Aghemo, A.] Univ Milan, Fdn IRCCS CA Granda Osped Maggiore Policlin, Div Gastroenterol & Hepatol, Milan, Italy. [Alho, H.] Helsinki Univ Hosp, Abdominal Ctr, Helsinki, Finland. [Alho, H.] Univ Helsinki, Helsinki, Finland. [Backmund, M.] Univ Hosp Munich, Dept Med 2, Munich, Germany. [Bruggmann, P.] Arud Ctr Addict Med, Zurich, Switzerland. [Dalgard, O.] Univ Oslo, Akershus Univ Hosp, Dept Infect Dis, Oslo, Norway. [Dalgard, O.] Univ Oslo, Fac Med, Oslo, Norway. [Flisiak, R.] Med Univ Bialystok, Dept Infect Dis & Hepatol, Bialystok, Poland. [Foster, G.] Queen Mary Univ London, London, England. [Gheorghe, L.] Fundeni Clin Inst, Gastroenterol & Hepatol, Bucharest, Romania. [Goldberg, D.] Hlth Protect Scotland, Glasgow, Lanark, Scotland. [Goulis, I.] Dept Internal Med, Thessaloniki, Greece. [Hickman, M.] Univ Bristol, Social Med, Bristol, Avon, England. [Hoffmann, P.] Minist Hlth Luxembourg, Luxembourg, Luxembourg. [Jancoriene, L.] Vilnius Univ Hosp, Santariskiu Klin, Ctr Infect Dis, Vilnius, Lithuania. [Jarcuska, P.] Univ Hosp, Dept Internal Med 1, Kosice, Slovakia. [Jarcuska, P.] Univ Pavol Jozef Safarik, Kosice, Slovakia. [Kaberg, M.] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. [Makara, M.] St Istvan & St Laszlo Hosp, Hepatol Ctr, Budapest, Hungary. [Maimets, M.] Univ Tartu, Dept Internal Med, Tartu, Estonia. [Marinho, R.] Hosp Santa Maria, Med Sch Lisbon, Dept Gastroenterol & Hepatol, Lisbon, Portugal. [Maticic, M.] Univ Med Ctr, Clin Infect Dis & Febrile Illnesses, Ljubljana, Slovenia. [Norris, S.; Tait, M.] Dr Steevens Hosp, Natl Hepatitis Treatment Programme C, Hlth Serv Execut, Dublin, Ireland. [Olafsson, S.] Landspitali Univ Hosp, Dept Med, Div Gastroenterol, Reykjavik, Iceland. [Ovrehus, A.] Univ Southern Denmark, Odense Univ Hosp, Dept Infect Dis, Odense, Denmark. [Pawlotsky, J. -M.] Univ Paris Est, Hop Henri Mondor, Creteil, France. [Pocock, J.] Mater Hosp, Gastroenterol Dept, Msida, Malta. [Robaeys, G.] Ziekenhuis Oost Limburg, Dept Gastroenterol & Hepatol, Genk, Belgium. [Robaeys, G.] UHasselt, Dept Med & Life Sci, Hasselt, Belgium. [Robaeys, G.] UZLeuven, Dept Hepatol, Leuven, Belgium. [Roncero, C.] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Psychiat Serv, Addict & Dual Diag Unit, Barcelona, Spain. [Simonova, M.] Mil Med Acad, Dept Gastroenterol HPB Surg & Transplantol, Sofia, Bulgaria. [Sperl, J.] Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic. [Tolmane, I.] Infectol Ctr Latvia, Dept Hepatol, Riga, Latvia. [Tomaselli, S.] Off Publ Hlth, Vaduz, Liechtenstein. [van der Valk, M.] Acad Med Ctr, Dept Infect Dis, Amsterdam, Netherlands. [Vince, A.] Univ Zagreb, Sch Med, Univ Hosp Infect Dis, Zagreb, Croatia. [Lazarus, J. V.] Univ Copenhagen, Rigshosp, CHIP, Copenhagen, Denmark. [Lazarus, J. V.] Hosp Clin Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain.

The effect of cryoprecipitate on the seroprevalence of Varicella-Zoster virus in patients with severe hemophilia

Cilostazol, a platelet inhibitor, in treating intermittent claudication : A systematic reviewIntroduction: Patients with mild/moderate hemophilia A (MHA) usually have a milder phenotype and far less bleeding episodes than severely affected patients and the use of Factor VIII (FVIII) concentrates is limited. Data on treatment and complications in MHA patients are scarce. The aim of this study is to describe treatment and its complications in an unselected large cohort of MHA patients. Methods: The INSIGHT study is an international cohort study collecting data on all MHA patients that were treated between 1980 and 2010 in 34 participating centers across 10 European countries and Australia. Figures are median (interquartile range), or number (percentage). Results: On February 1st 2011, 2627 MHA patients with a median age of 36 years (18-54) and a median FVIII baseline level of 11 IU/ dL (6-18) were included. First treatment took place at a median age of 10 years (3-25), mostly for bleeding/trauma (62%) or surgery (35%). The median number of cumulative exposure days (ED) to FVIII concentrates was 19 (8-75). Inhibitors developed in 113 patients (4%) at a median age of 37 years (15-60) years and after a median of 25 ED (15-57) to FVIII concentrates. Infection with hepatitis or HIV was present in 940 patients (38%), 99% of them were born before 1990. The prevalence among moderate patients was slightly higher than in mild patients (42% and 37% respectively). One third (32%) of all patients was infected with hepatitis C, 11% with hepatitis β and 2% with HIV. One hundred and twenty patients (5%) died during the observation period at a median age of 61 years (42-75). Cause of death is presently known in half of the patients (n = 66, 49%) and was associated with HIV or hepatitis infection in one-quarter (n = 16; 24%) of the patients. Conclusion: Viral infections are present in 38% of MHA patients. They are the cause of death in 24% of the patients that died during the study period.Background: Recombinant activated factor VII (rFVIIa) is used for the treatment of hemophilia A patients with inhibitors. However, in clinical practice, the response to rFVIIa is variable and the mechanism for this variability is unclear. Aim: To investigate the anti-fibrinolytic effects of rFVIIa in relation to thrombin generation (TG) and hemostatic parameters. Patients and Methods: Nineteen hemophilia A patients with current inhibitors (median: 26 BU/mL; range: 0.8-750) from three centres were included. A clot-lysis assay was performed in plasma with the addition of rFVIIa. TG was assessed with two methods: tissue factor (TF)-independent (addition of phospholipids) and TF-dependent (addition of phospholipids plus TF 1 pM). Several pro- and anticoagulant factors, as well as fibrinolytic parameters were assessed. Results: The clot-lysis test distinguished two groups of patients, one with normal (n = 8) and one with impaired (n = 11) anti-fibrinolytic response to rFVIIa. The addition of rFVIIa showed a dose-dependent increase in TF-dependent and -independent TG in all cases. The TF-independent TG parameters were significantly lower in the impaired anti-fibrinolytic response group. In addition, there was a significant difference between the normal and impaired anti-fibrinolytic response group in prothrombin time (11.6 vs. 12.5 s, P <0.05), which correlated with significantly higher levels of factors V, VII, IX and X in the normal response group. Soluble thrombomodulin was decreased in the impaired response group (19.1 vs. 26.3 ng/mL, P <0.01). Conclusions: We established an in vitro test that identified different anti-fibrinolytic responses upon rFVIIa addition in plasma of hemophilia A patients with inhibitors. The different responses could be attributed to different levels of pro-coagulant proteins and soluble thrombomodulin. Further analyses are underway to determine a correlation between laboratory findings and the clinical efficacy of rFVIIa treatment in these patients.