Anne Claire Desbois

Systemic sclerosis: An update in 2016.

Systemic sclerosis (SSc) is a chronic immune disorder of unknown origin, dominated by excessive fibrosis responsible for cutaneous and pulmonary fibrosis, and by vascular endothelial dysfunction at the origin of skin ischemia, renal and pulmonary artery lesions. Renal and pulmonary complications are mainly responsible for the severity of the disease. Recent advances led to a better understanding of pathological mechanisms and a more accurate classification of patients according to clinical and biological (auto-antibodies) phenotype. Recent trials provided interesting data on different therapeutic strategies, depending on organ involvement. These data are of particular importance in such disease, still characterized by increased mortality and morbidity rates. In this review, we aim to synthetize recent advances in diagnosis and prognosis leading to better classification of SSc patients, and in therapeutic management.

Extrahepatic manifestations of chronic hepatitis C virus infection

During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined.

International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement

Hepatitis C virus (HCV) infection is responsible for both hepatic and extra-hepatic disorders (HCV-EHDs); these latter are correlated on one hand clearly with HCV lymphotropism causing immune-system dysregulation as well as with viral oncogenic potential, and on the other hand probably with chronic inflammatory status causing cardio-metabolic complications as well as neurocognitive disturbances. The spectrum of HCV-EHDs ranges from mild or moderate manifestations, such as arthralgia, sicca syndrome, peripheral neuropathy, to severe, life-threatening complications, mainly vasculitis and neoplastic conditions. Given the clinical heterogeneity of HCV-EHDs, HCV-infected individuals are inevitably referred to different specialists according to the presenting/prevalent symptom(s); therefore, the availability of comprehensive diagnostic guidelines is necessary for a patients whole assessment that is decisive for early diagnosis and correct therapeutic approach of various hepatic and HCV-EHDs, regardless of the specific competencies of different physicians or referral centers. In this respect, a multidisciplinary network of experts, the International Study Group of Extrahepatic Manifestations Related to Hepatitis C Virus Infection (ISG-EHCV), was organized with the intention to formulate diagnostic guidelines for the work-up of possible HCV-EHDs. There was a broad consensus among ISG-EHCV members on the proposed guidelines, which essentially are based on two main levels of patients assessment. At the referral stage, it is proposed that all patients with HCV infection should be invariably examined by means of first-line diagnostic procedures including virological and hepatic parameter evaluation, as well as the detection of clinical findings that may suggest one or more HCV-EHDs. This preliminary assessment should reveal specific HCV-EHDs, which will be deeper analyzed by means of second-line, targeted investigations. The proposed multidisciplinary expert statement represents the first attempt to draw comprehensive diagnostic guidelines for HCV-infected individuals encompassing the entire spectrum of HCV-related disorders, namely typical hepatic manifestations along with less common, often unpredictable HCV-EHDs. The HCV-EHDs may compromise to a substantial degree the overall disease outcome in a significant number of HCV-infected individuals that renders their timely identification and treatment an imperative. In conclusion, the application of standardized but thorough diagnostic guidelines of HCV-EHDs is advisable at the referral stage as well as during the follow-up period of HCV infected patients. It is envisioned that the proposed strategy will result in improvement of clinical outcomes in such patients.

Cannabis-Associated Arterial Disease

BACKGROUNDnThe aim of this study was to describe the different arterial complications reported in cannabis smokers.nnnMETHODSnThis study was a literature review.nnnRESULTSnCannabis use was found to be associated with stroke, myocardial infarction, and lower limb arteritis. Arterial disease involved especially young men. There was a very strong temporal link between arterial complications and cannabis use for stroke and myocardial infarction episodes. Patient outcome was closely correlated with cannabis withdrawal and relapses associated with cannabis rechallenge. Cannabis use was associated with particular characteristics of arterial disease. The increased risk of myocardial infarction onset occurred within 1 hour of smoking marijuana compared with periods of non-use. Strokes occurred mainly in the posterior cerebral circulation. Compared with cohorts of thromboangiitis obliterans patients, those with cannabis-associated limb arteritis were younger, more often male, and had more frequent unilateral involvement of the lower limbs at clinical presentation.nnnCONCLUSIONnCannabis use is associated with arterial disease such as stroke, myocardial infarction, and limbs arteritis. It appears essential to investigate cannabis use in young patients presenting with such arterial manifestations, as outcome is closely correlated with cannabis withdrawal.

Hepatitis C virus infection and chronic kidney disease: Time for reappraisal

Hepatitis C virus (HCV) infection is associated with tremendous morbidity and mortality due to liver complications. HCV infection is also associated with many extrahepatic manifestations including cardiovascular diseases, glucose metabolism impairment, cryoglobulinemia vasculitis, B cell non-Hodgkin lymphoma and chronic kidney disease (CKD). Many studies have shown a strong association between HCV and CKD, by reporting (i) an increased prevalence of HCV infection in patients on haemodialysis, (ii) an increased incidence of CKD and proteinuria in HCV-infected patients, and (iii) the development of membranoproliferative glomerulonephritis secondary to HCV-induced cryoglobulinemia vasculitis. HCV seropositivity is found to be associated with an increased relative risk for all-cause and cardiovascular mortality in the dialysis population. HCV seropositivity is linked to lower patient and graft survival after kidney transplantation. Such poor HCV-associated prognosis should have encouraged clinicians to treat HCV in CKD patients. However, due to frequent side effects and the poor efficacy of interferon-based treatments, very few HCV dialysis patients have received HCV medications until now. The emergence of new direct acting, interferon-free antiviral treatment, leading to HCV cure in most cases with a satisfactory safety profile, will shortly modify the management of HCV infection in CKD patients. In patients with a glomerular filtration rate (GFR) >30ml/min, the choice of DAA is not restricted. In those with a GFR <30 and >15ml/min, only paritaprevir/ritonavir/ombitasvir/dasabuvir or a grazoprevir plus elbasvir regimen are approved. In patients with end stage renal disease (GFR <15ml/min or dialysis), current data only allows for the use of a grazoprevir plus elbasvir combination. No doubt these data will be modified in the future with the advent of new studies including larger cohorts of HCV patients with renal impairment.

International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement

Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.

Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease: An Observational Study.

AbstractTo report the safety and efficacy of anti-tumor necrosis factor &agr; (TNF&agr;) therapy in severe and refractory neuro-Behçet disease (NBD) patients.Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24–60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNF&agr; (infliximab 5u200amg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months.Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1–6). The median Rankin score was 2 (1–4) at the initiation of anti-TNF&agr; versus 1 (0–4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases.TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population.

Effectiveness and cost of hepatitis C virus cryoglobulinemia vasculitis treatment: from interferon-based to direct acting antivirals era

The net benefits of new hepatitis C virus (HCV) direct‐acting antiviral drugs (DAA) in patients with cryoglobulinaemia vasculitis (CryoVas) are unknown.

Hepatitis C Virus Infection and Rheumatic Diseases: The Impact of Direct-Acting Antiviral Agents

Chronic hepatitis C virus (HCV) infection is associated with liver and extrahepatic complications, including B-cell lymphoma, cardiovascular and kidney diseases, glucose metabolism impairment and rheumatic conditions ie, arthralgia, myalgia, cryoglobulinemia vasculitis, sicca syndrome and the production of autoantibodies. The treatment has long been based on interferon alpha (IFN) that was found poorly effective, and contraindicated in many autoimmune/inflammatory disorders because of possible exacerbation of rheumatic disorders. The recent emergence of new oral IFN-free combinations offers an opportunity for HCV infected patients with autoimmune/inflammatory disorders to be cured with a short treatment duration and low risk of side effects.

Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis

Background and aims Extrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected patients, call for a better understanding of the benefits of treating non-cirrhotic chronically infected individuals. Methods A systematic review was conducted. Identified studies from targeted database searches on Embase and Medline were screened. The methodological quality of the included publications was evaluated. Random-effect model meta-analyses were performed. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Results Data were extracted from a total of 48 identified studies. Achieving sustained virological response (SVR) was associated with reduced extrahepatic mortality (vs no SVR, OR 0.44 (95%u2009CI 0.28 to 0.67)). SVR was associated with higher complete remissions in patients with cryoglobulinemia vasculitis (OR 20.76 (6.73 to 64.05)) and a higher objective response in those with malignant B-cell lymphoproliferative diseases (OR 6.49 (2.02 to 20.85)). Achieving SVR was also associated with reduced insulin resistance at follow-up (OR 0.42 (0.33 to 0.53)) and a significant protective effect on the incidence of diabetes (OR 0.34 (0.21 to 0.56)). Lack of randomised data comparing SVR versus non-SVR patients for the relevant extrahepatic indications attenuated these analyses. Conclusion Antiviral therapy can reduce extrahepatic manifestations related to HCV when SVR is achieved. Higher quality data, and reporting over longer follow-up periods, will be required to thoroughly explore comprehensive HCV treatment strategies.