abt-267 and Cryoglobulinemia

Mixed Cryoglobulinemia (MC) is the most frequent extrahepatic manifestation of Hepatitis C virus (HCV) infection. MC is an autoimmune /B-cell lymphoproliferative disorder characterized by circulating immune-complexes, named cryoglobulins. MC patients exhibit symptoms due to a systemic vasculitis of small/medium size vessels (mixed cryoglobulinemia syndrome, MCS) in a percentage going from 5 to 30%. The first-line therapeutic option in MCS patients is the etiologic treatment and, in the past fifteen years, antiviral therapy with Pegylated-Interferon (Peg-IFN) plus Ribavirin (RBV) represented the standard of care. Lately, the arrival of direct acting antivirals (DAAs) significantly modified the cure of HCV infection, consenting the use of IFN-free regimens. Here we report a review of the literature about the role of antiviral treatment, following its evolution, in treating HCVrelated MC. Furthermore, we report the results, after 8 weeks of treatment, of a preliminary pilot prospective study, counting 17 patients with HCV-related MC with or without MCS, treated with new generation DAAs in IFN-free regimens. After 8 weeks of DAA administration, all the subjects were HCV RNA negative. Moreover, in 6/17 (35%) patients cryoglobulins disappeared and, on the whole, in all patients a decrease of the cryocrit values was observed (p<0.05). Furthermore, three MCS-HCV patients (30%) resulted to be complete clinical responders and 5 subjects (50%) partial clinical responders. Therefore, IFN-free anti-HCV treatment appears to be safe and effective in MC patients from virological and clinical points of view, thus supporting the importance of HCV eradication in leading MC remission.

Topics: Aged; Anilides; Antiviral Agents; Carbamates; Cryoglobulinemia; Cyclopropanes; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Pilot Projects; Proline; Prospective Studies; Ritonavir; RNA, Viral; Sulfonamides; Treatment Outcome; Valine

This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment.. We conducted an observational prospective study, on 232 patients with chronic kidney disease, undergoing treatment with paritaprevir/ombitasvir/ritonavir and dasabuvir, for chronic hepatitis C infection - genotype 1b. Renal and liver function were assessed at the beginning of therapy, monthly during treatment and three months after therapy completion.. All patients achieved sustained virologic response. Common side effects were nausea, fatigue and headache. Close monitoring of tacrolimus blood levels and dose reduction was required in kidney transplant recipients.. HCV therapy in the setting of renal dysfunction has always been a challenging topic. Direct-acting antivirals have shown promising effects, demonstrating good tolerance and efficacy in patients with HCV infection and renal impairment. Sustained virologic response within our study population was 100%.

Topics: 2-Naphthylamine; Anilides; Antiviral Agents; Carbamates; Cryoglobulinemia; Cyclopropanes; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Lupus Erythematosus, Systemic; Male; Middle Aged; Proline; Prospective Studies; Renal Insufficiency, Chronic; Ritonavir; Sulfonamides; Sustained Virologic Response; Uracil; Valine

Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of chronic hepatitis C (CHC), with the presence of symptoms in 10-15% of cases. There have been encouraging data regarding immunological and clinical responses in patients treated with the novel combinations of direct-acting antivirals (DAAs), but the role of ribavirin (RBV) in the treatment of MC has not yet been demonstrated. We prospectively enrolled 132 patients affected by MC and CHC, and virological, immunological and clinical responses were evaluated at 12 weeks after completion of treatment. All subjects were treated with interferon (IFN)-free regimens according to clinical guidelines, with or without RBV. All patients achieved a virological response. A complete immunological response (CR) was observed in 71 subjects (53.8%), a partial response in 44 (33.3%), and no response in 17 (12.8%). Ten patients showed a complete resolution of symptoms (7.6%), and 31 showed a significant improvement (23.5%). CR was significantly higher in patients taking RBV (71.1 vs. 44.8%, p < 0.001) and in treatment-naïve patients (62.5 vs. 43.3%, p < 0.001). In logistic regression analysis, duration of HCV infection of less than 20 years (OR 2.448; 95% IC 1.335-6.202; p = 0.019), treatment-naïve status (OR 2.885; 95% IC 1.404-9.660; p = 0.025) and the use of RBV (OR 6.961; 95% IC 3.912-26.885; p < 0.001) were predictors of CR. In MC patients, IFN-free regimens are effective and well tolerated, and RBV seems to significantly increase the immunological response and promote a decline in cryocrit.

Topics: 2-Naphthylamine; Adult; Anilides; Antiviral Agents; Carbamates; Cryoglobulinemia; Cyclopropanes; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Interferons; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Prospective Studies; Pyrrolidines; Ribavirin; Ritonavir; Sofosbuvir; Sulfonamides; Treatment Outcome; Uracil; Valine

We report the case of a 75-year-old woman who was found to have hepatitis C virus (HCV) infection in 1987. Before treatment in 2016, she was found to have mixed cryoglobulinemia (MC). Direct-acting antiviral (DAA) treatment produced a sustained virological response 12 (SVR12). She noticed gradual muscle weakness in 2015 and the gradual development of dysarthria and dysphagia in 2017. We performed a muscle biopsy that showed inclusion body myositis (IBM). To the best of our knowledge, this is first case of a patient with HCV infection, MC, and IBM, in which MC and IBM did not improve after an SVR12 was obtained by DAA treatment.

Topics: Aged; Anilides; Antiviral Agents; Carbamates; Cryoglobulinemia; Cyclopropanes; Female; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Myositis, Inclusion Body; Proline; Ritonavir; Sulfonamides; Sustained Virologic Response; Valine