Objective. To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).Methods. Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months.Results. Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ؎ SD of 11.9 ؎ 5.4 at baseline to 7.1 ؎ 5.7 at month 2; P < 0.001) up to month 24 (4.4 ؎ 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated.Conclusion. RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.Mixed cryoglobulinemia, which is also known as cryoglobulinemic syndrome or cryoglobulinemic vasculitis (CV), is a systemic vasculitis that is primarily mediated by immune complexes and is associated with hepatitis C virus (HCV) infection and B cell lymphoproliferation (1-5). HCV infection might be crucial for

Levels of tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-10 and transforming growth factor (TGF)-beta in cerebrospinal fluid (CSF) and serum of 29 patients with multiple sclerosis (MS) of the relapsing-remitting type and of 20 controls with other non inflammatory neurological diseases were studied. Sixteen patients were in the active phase of disease and 13 in remission. In CSF, higher IL-10 and TGF-beta concentrations were found in patients with a stable phase of MS, while in the active phase there were elevated levels of TNF-alpha and GM-CSF. These results suggest that a different cytokine pattern could be probably involved in the pathogenesis of relapsing-remitting MS.

To determine the association among the clinical, biochemical, and histological features of cholestasis, we analyzed all the relevant data of the patients recorded in our non-alcoholic fatty liver disease (NAFLD) database. We selected 20 NAFLD patients with abnormal transaminase levels, with both alkaline phosphatase >500 U/L and gamma-glutamyl transpeptidase >250 U/L. Their histological features were compared with those of a group of patients with NAFLD matched for sex, age, and body mass index and of a group of patients matched for sex, body mass index and histological NAFLD grading/staging. Cases and controls satisfied, on histology, the criteria for NASH. The presence of cholestasis in our patients was correlated with injury of the bile duct epithelium, characterized by cholangitis, swelling, variable bile duct loss, and bile stasis. Compared to NAFLD patients of similar age, sex, and body mass index, the cholestatic group had total and severe histological liver impairment. When we analyzed the group of patients histologically identified on the basis of identical stage and grade severity, we could not find any evidence of significant bile damage, compared to cases, despite the control group's significantly older age. NAFLD patients with biochemical cholestasis have a histological picture of bile damage; they have more advanced histological impairment than patients matched for age, sex and body mass index.

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Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites.