New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study.

INTRODUCTION: Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. OBJECTIVES: The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. METHODS: A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). RESULTS: APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. CONCLUSIONS: This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

New insights into systemic sclerosis related microcirculatory dysfunction by assessment of sublingual micr\ocirculation and vascular glycocalyx layer. Results from a preliminary study.

BACKGROUND: Initial morphological and functional markers of systemic sclerosis (SSc) are evidenced in microvascular structural damage. However, nailfold videocapillaroscopy (NVC) explores only morphological abnormalities. Sidestream Dark Field (SDF) imaging of sublingual microcirculation enables assessment of both morphological and functional capillary impairment and allows measurement of the glycocalyx layer, which is an indicator of endothelial dysfunction. OBJECTIVE: To describe and validate sublingual abnormalities assessed by SDF device in comparison with NVC findings and to measure the thickness of the glycocalyx layer. METHODS: From February to May 2014, 26 subjects (16 SSc patients and 10 healthy controls) underwent standardised NVC and SDF imaging of sublingual microcirculation. Glycocalyx thickness was also measured. RESULTS: Capillary density and percentage of perfused vessels were significantly reduced in patients with SSc (n = 13) compared to controls. Correlation between nailfold capillary density assessed by NVC and sublingual capillary density assessed by SDF was observed (r(2) = 0.59; P = 0.023). According to the NVC pattern, patients with "active" disease experienced greater reduction in capillary density than patients with "late" disease as suggested by the de Backer score (9.17 ± 0.81 vs 10.86 ± 1.19; P = 0.03). Additionally, the decrease in glycocalyx thickness was measured in SSc patients (n = 13) compared to controls (n = 10) (0.41 ± 0.03 versus 0.76 ± 0.29 P = 0.003). CONCLUSION: Our results suggest for the first time in SSc, that sublingual microcirculation and glycocalyx are impaired and that SDF imaging findings correlate with those of NVC. Nevertheless, further studies are required for the validation of our preliminary results.

[Translation into French and republication of: "Anticoagulant treatment of cancer-associated thromboembolism"]. / Traduction et republication de : « Traitement anticoagulant de la maladie veineuse thromboembolique associée au cancer ¼.

Venous thromboembolism (VTE) is a frequent and potentially fatal complication in patients with cancer. During the initial period after the thromboembolic event, a patient receiving anticoagulant treatment is exposed both to a risk of VTE recurrence and also to an elevated bleeding risk conferred by the treatment. For this reason, the choice of anticoagulant is critical. The choice should take into account patient-related factors (such as functional status, age, body mass index, platelet count and renal function), VTE-related factors (such as severity or site), cancer-related factors (such as activity and progression) and treatment related factors (such as drug-drug interactions), which all potentially influence bleeding risk, and patient preference. These should be evaluated carefully for each patient during a multidisciplinary team meeting. For most patients, apixaban or a low molecular-weight heparin is the most appropriate initial choice for anticoagulant treatment. Such treatment should be offered to all patients with active cancer for at least 6months. The patient and treatment should be re-evaluated regularly, and anticoagulant treatment changed when necessary. Continued anticoagulant treatment beyond 6months is justified if the cancer remains active or if the patient experienced recurrence of VTE in the first 6months. In other cases, the interest of continued anticoagulant treatment may be considered on an individual patient basis in collaboration with oncologists.

[Translation into French and republication of: "Management of cancer-associated thromboembolism in vulnerable population"]. / Traduction et republication de : « Prise en charge de la maladie thromboembolique veineuse associée au cancer chez les populations vulnérables ¼.

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with TAC on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR less than 30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (less than 50,000platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.

Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.

[Acquired hemophilia and pregnancy: A necessarily multidisciplinary approach]. / Hémophilie acquise et grossesse : une approche forcément multidisciplinaire.

The occurrence of acquired hemophilia during pregnancy or postpartum is rare (2 to 10 % in series). It is generally suspected in the presence of haemorrhagic manifestations (especially subcutataneous or mucosal bleeding) associated with an isolated prolongation of the activated partial thromboplastin time (APTT). The diagnosis is confirmed by the association of a low level of factor VIII (FVIII) and the presence of an anti-FVIII inhibitor. Postpartum management is similar to that of other acquired haemophilias: correction of a severe haemorrhagic syndrome by "bypassing" agents, eradication of the inhibitor by corticosteroids alone or in combination with another immunosuppressive agent depending on the residual level of FVIII and the titer of the inhibitor. Management of the forms occurring during pregnancy is based on rare experiences or expert opinions. The management of childbirth is particularly delicate in terms of haemorrhage, especially if the anti-FVIII inhibitor is still present, and must be prepared in a multidisciplinary manner. Finally, as with any acquired hemophilia, a relapse is possible, especially in the year following remission. During a subsequent pregnancy, the risk of recurrence is possible but should not be a contraindication to a new pregnancy.

[Identification of factors associated with performance in objective structured clinical examination in Rouen medical school]. / Identification des facteurs associés à la réussite aux examens cliniques objectifs et structurés dans la faculté de médecine de Rouen.

CONTEXT: Objective structured clinical examination (OSCE) became a national exam at the end of medical studies in France. The aim of this study was to identify the predictive factors for success at OSCEs. METHODS: Aurvey query after the OSCEs was completed by fifth-year medicine students at Rouen Uuniversity.. Data on continuous variables were compared using the Mann-Whitney test. Data on quantitative variables were compared using the Spearman's correlation. RESULTS: Two hundred and thirty-nine students, i.e., 98.7 % of the students, responded to the query. The median (IQR 25-75) OSCE score was 13.6/20 (12.5-14.2). Students' personal factors significantly associated with a higher OSCE performance were female sex (median score of 13.7 versus 13.4; P=0.03) and good health during the clerkship (median score of 13.6 versus 12.6; P=0.02). A higher OSCE performance was associated with an increased number (≥6)  of medicine clerkships (median score of 13.8 versus 13.3; P=0.02) and a decreased number (<3) of surgery clerkships (median score of 13.7 versus 12.9; P=0.009). There was no correlation between the OSCE score and medical school performance (Spearman's correlation, r=0.24). CONCLUSION: Homogenization of student's clerkships, assistance to students with health problems seem to be teaching approaches to promote success at OSCEs.

[Thrombin generation assay in autoimmune disease]. / Place du test de génération de thrombine dans les maladies auto-immunes.

Thrombin generation assay (TGA) is a useful tool to evaluate the initiation, propagation and inhibition of coagulation. TGA is a global test that is used to assess hemorrhagic risk in hemophilia patients, but it can also be used to study hypercoagulable states. The interest of TGA is to screen for cardiovascular risk, which is regularly associated with autoimmune disease (AID) such as antiphospholipid syndrome. Indeed, TGA has been used to evaluate hypercoagulability in patients with antiphospholipid syndrome treated with rivaroxaban versus warfarin. In other AIDs without thrombotic events, TGA measurement is elevated, mainly in rheumatoid arthritis (RA), systemic lupus erythematosus and Behçet's disease. These findings in RA are correlated with the inflammatory activity of the disease. In systemic lupus erythematosus and Behçet's disease, TGA appears to reflect disease activity. In conclusion, TGA remains relatively under used in the clinical evaluation of AID, but it could play a greater role in the evaluation of certain potentially thrombogenic treatments in AID. Finally, TGA helps measuring AID activity, due to the clearlink between coagulation and inflammation, despite some limitations of interpretation mainly due to a lack of standardization.

[Endothelial dysfunction in thrombotic thrombocytopenic purpura: therapeutic perspectives]. / Dysfonction endothéliale au cours du Purpura Thrombotique Thrombocytopénique : un nouvel axe de prise en charge ?

Immune Thrombotic Thrombocytopenic Purpura (iTTP) is a rare but severe disease with a mortality rate of almost 100 % in the absence of adequate treatment. iTTP is caused by a severe deficiency in ADAMTS13 activity due to the production of inhibitory antibodies. Age has been shown to be a major prognostic factor. iTTP patients in the elderly (60yo and over) have more frequent organ involvement, especially heart and kidney failures compared with younger patients. They also have non-specific neurologic symptoms leading to a delayed diagnosis. Factors influencing this impaired survival among older patients remain unknown so far. Alteration of the functional capacity of involved organs could be part of the explanation as could be the consequences of vascular aging. In fact, severe ADAMTS13 deficiency is necessary but likely not sufficient for iTTP physiopathology. A second hit leading to endothelial activation is thought to play a central role in iTTP. Interestingly, the mechanisms involved in endothelial activation may share common features with those involved in vascular aging, potentially leading to endothelial dysfunction. It could thus be interesting to better investigate the causes of mid- and long-term mortality among older iTTP patients to confirm whether inflammation and endothelial activation really impact vascular aging and long-term mortality in those patients, in addition to their presumed role at iTTP acute phase. If so, further insights into the mechanisms involved could lead to new therapeutic targets.

Systematic screening for a proximal DVT in COVID-19 hospitalized patients: Results of a comparative study.

INTRODUCTION: The COVID-19 pandemic is associated with a high incidence of venous thromboembolism questioning the utility of a systematic screening for deep venous thrombosis (DVT) in hospitalised patients. METHODS: In this prospective bicentric controlled study, 4-point ultrasound using a pocket device was used to screen for DVT, in patients with SARS-CoV-2 infection and controls admitted for acute medical illness not related to COVID-19 hospitalised in general ward, in order to assess the utility of a routine screening and to estimate the prevalence of VTE among those patients. RESULTS: Between April and May 2020, 135 patients were screened, 69 in the COVID+ group and 66 in the control one. There was no significant difference in the rate of proximal DVT between the two groups (2.2% vs. 1.5%; P=0.52), despite the high rate of PE diagnosed among COVID-19 infected patients (10.1% vs. 1.5%, P=0.063). No isolated DVT was detected, 37.5% of PE was associated with DVT. Mortality (7.2% vs. 1.5%) was not different (P=0.21) between COVID-19 patients and controls. CONCLUSION: The systematic screening for proximal DVT was not found to be relevant among COVID-19 patients hospitalized in general ward despite the increase of VTE among this population. Further studies are needed to confirm the hypothesis of a local pulmonary thrombosis which may lead to new therapeutic targets.

[Characteristics of patients admitted from emergency units in 18 internal medicine departments and organisation of these departments: A cross sectional study from SNFMI (SiFMI study group) in 2015]. / Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d'étude SiFMI) en 2015.

INTRODUCTION: Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments. METHODS: Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days. RESULTS: Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine. CONCLUSION: This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

A survey of chronic hepatitis B patient management practices in the European Union.

The current study sought to evaluate the characteristics of chronic hepatitis B virus (HBV) infection and current management practices in the European Union by surveying physician and patient records. A detailed survey of physician practices and management of patients with CHB was conducted between July and October 2006 in France, Germany, Italy and Spain. A total of 200 physicians participated in the survey, and data were collected from 2023 patients with chronic HBV infection. Most patients were men (69%), who had hepatitis B e antigen (HBeAg)-negative disease (64%), and demonstrated evidence of significant disease [53%; moderate fibrosis (35%), compensated cirrhosis (14%), or decompensated cirrhosis (4%)]. Among the 1665 HBV-monoinfected patients surveyed, 1184 (71%) were currently receiving treatment for chronic HBV infection. At treatment initiation, 70% of HBeAg-positive patients had both pretreatment serum HBV DNA levels or=2 x the upper limit of normal (ULN), and 81% of HBeAg-negative patients had HBV DNA levels of or=2 x ULN, while the HBeAg-negative patients had HBV DNA levels

[Long-term therapy for chronic hepatitis B in HIV co-infected patients]. / Traitements à long terme de l'hépatite chronique B chez le patient co-infecté par le VIH.

As human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are acquired through the same routes of contamination, the prevalence of HBV serological markers found in the HIV-infected population is approximately 7%. Liver-related mortality and morbidity is higher in HIV/HBV co-infected patients than in HBV mono-infected patients. Both viruses must be considered before a treatment decision is made. According to the European consensus conference on the treatment of chronic hepatitis B and C in HIV coinfected patients, treatment is based on whether there is an existing indication of anti- HIV therapy or not. In patients with no indication of anti-HIV therapy, drugs with dual anti-viral activity (lamivudine, entecavir, tenofovir disoproxil fumarate) should not be used due to the risk of developing HIV-resistance. Interferon or adefovir in combination with telbivudine are recommended. In patients with an indication of anti-HIV therapy, a backbone of highly active anti-retroviral therapy should include tenofovir in combination with lamivudine or emtricitabine. The same regimen is recommended in patients who develop lamivudine resistance.

Spatial distribution of contaminants in sediments of two rivers crossing Tangier (northern Morocco).

The distribution and accumulation of heavy metals in the sediments of two rivers which cross various agglomerations of Tangier city, Morocco, were investigated. Surficial sediment samples were collected during 2005 and characterized for metal content (Zn, Pb, Cd, Cu, Cr and Ni), organic matter, total nitrogen, and n-hexane extractable material (HEM). The organic components (organic carbon, total nitrogen and HEM) show a slightly increasing enrichment from the upstream to the downstream of the emissary. An evaluation of the heavy metal pollution status of both tributaries was carried out using the metal pollution index (MPI). The results revealed the importance of anthropic pressure and the zones influenced by industrial discharges, which keep the metals Pb, Cr and Ni at high levels. Comparison with international regulatory guidelines for sediments revealed serious contamination of Cr, Zn and Ni.

[Venous thrombo-embolism during immune-mediated thrombotic thrombocytopenic purpura is prevalent in patients with a prolonged treatment with therapeutic plasma exchange]. / La maladie thrombo-embolique veineuse au cours du purpura thrombotique thrombocytopénique autoimmun est associée à un traitement prolongé par échanges plasmatiques.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a devastating disease characterized by disseminated microvascular thrombosis. Despite pro-thrombotic predisposing conditions, the prevalence of macrovascular venous thrombosis event (VTE) in immune-mediated TTP (iTTP) has rarely been assessed. METHODS: We reviewed data of all iTTP patients of the French reference Center for thrombotic microangiopathies registry prospectively enrolled through a 10-year period, between 2008 and 2018. Venous thrombosis included either thrombosis of central venous catheter, symptomatic deep venous thrombosis of the limbs or pulmonary embolism. RESULTS: Forty-eight (12.7%) VTE were diagnosed. VTE was diagnosed after a median time of 7 [IQR, 3-16] days following the first therapeutic plasma exchange (TPE) and consisted mainly in catheter-related thrombosis (73%), and to a lesser extend symptomatic deep venous thrombosis (16%), proximal pulmonary embolism (8%) and splanchnic vein thrombosis (2%). Cases with VTE (VTE+ cases), required more TPE to achieve remission (P < 0.01), and the total volume of plasma required to achieve remission was larger (P < 0.01) than for VTE- cases. There was also a trend for more rituximab use in the VTE+ cases as compared to the VTE- cases (47% vs 33%; respectively; P = 0.07). Curative anticoagulation was started in 38 cases (79%), while 6 VTE cases did not receive any antithrombotic agents, and catheter was systematically removed when catheter-related thrombosis was diagnosed. VTE+ cases had a higher number of inserted central venous catheters than VTE- cases (P < 0.05). CONCLUSION: VTE is a frequent condition occurring during iTTP management and is observed when patients require a prolonged treatment with daily TPE and multiple catheter insertions. Therapeutic strategies aimed at reducing the duration of TPE treatment in iTTP should substantially reduce this complication.

[Giant cell arteritis: Role of color-duplex ultrasound]. / Artérite gigantocellulaire : apport de l'écho-doppler.

Giant cell arteritis is the most common primary vasculitis of large-vessel occurring in subjects over 50 years of age. Many imaging techniques has been evaluated to improve the diagnosis of giant cell arteritis. Among these imaging techniques, ultrasound has shown good performances to detect inflammatory involvement of the temporal arteries as well as branches of the aorta. Several publications and recent EULAR recommendations have emhasized the place of this tool in the diagnosis of giant cell arteritis.

Impact of adefovir dipivoxil on liver fibrosis and activity assessed with biochemical markers (FibroTest-ActiTest) in patients infected by hepatitis B virus.

SUMMARY: The aim was to assess the utility of FibroTest-ActiTest (FT-AT) as noninvasive markers of histological changes in patients with chronic hepatitis. Patients with chronic hepatitis B (HBeAg+ and HBeAg-) randomized in two trials of adefovir (ADV) vs placebo, with available paired liver biopsies and FT-AT at baseline and after 48 weeks of treatment were included. The predictive value of FT-AT was assessed using the area under the receiver operating characteristics curves (AUROCs) for the diagnosis of bridging fibrosis, cirrhosis and moderate-severe necroinflammatory activity. The impact of treatment with ADV vs placebo was assessed on liver injury according to baseline stage and virological response at 48 weeks. The analysis of 924 estimates for the diagnosis of bridging fibrosis, cirrhosis and moderate or severe necroinflammatory activity yielded FT-AT AUROCs: 0.76 +/- 0.02 (standardized 0.81 +/- 0.02), 0.81 +/- 0.02 and 0.80 +/- 0.01, respectively. Similar impacts of ADV on liver fibrosis and activity were observed both with paired biopsy (fibrosis stage from 1.6 to 1.4, activity grade from 2.5 to 1.3) and paired biomarkers (FT from 0.44 to 0.40, AT from 0.62 to 0.25) (P < 0.0001). FibroTest-ActiTest provides a quantitative estimate of liver fibrosis and necroinflammatory activity in patients with chronic hepatitis B and may be an alternative to reduce the need for liver biopsy.

An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa-2b combination therapy for chronic hepatitis C.

SUMMARY: Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE and FIBROSpect II) during interferon-based therapy. Ninety-five interferon-naïve patients with genotype 1 CHC were enrolled in a phase 2b, active-controlled study of albinterferon alfa-2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 +/- 8.0 mm. For detecting fibrosis stages 2-4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31-40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (-20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (-6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate-severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.

Impact of interferon-alpha treatment on liver fibrosis in patients with chronic hepatitis B: an overview of published trials.

BACKGROUND: The impact of interferon treatment in patients with hepatitis B virus (HBV) infection on fibrosis progression in comparison with its natural history has yet to be assessed in any large-scale randomized studies. The present report is a review of the evidence-based data published so far. METHODS: Studies were included if they had at least two repeated estimates of liver fibrosis per patient treated with interferon-alpha (whether pegylated or not). Meta-analysis was performed using a random-effects model. RESULTS: Altogether, 13 studies were included in the review, involving a total of 707 HBV patients treated with interferon-alpha-2a or -2b for 12-83 months. Only one study included pegylated interferon as monotherapy. A total of 787 untreated patients were also followed. Only one study used a non-invasive biomarker. There was a significant reduction in the fibrosis progression rate, with a risk reduction of 0.49 (95% CI: -0.64--0.34; chi(2)=119; degrees of freedom [DF]=6; P<0.0001), and significant heterogeneity (Cochran Q=81; P<0.0001). This significant impact was similar for both randomized (reduction of risk: -0.45; 95% CI: -0.64--0.26; P<0.0001) and not-randomized (controlled) studies (reduction of risk: -0.53; 95% CI: -0.79--0.28; P<0.0001). CONCLUSION: According to these findings, the benefit of interferon treatment on fibrosis progression is clinically significant in patients with advanced fibrosis by the reduction of fibrosis progression to cirrhosis. Pegylated interferon now needs to be compared, in terms of benefit-risk factors, with the new generation of HBV treatments (such as entecavir and tenofovir), using non-invasive biomarkers.