Cryoglobulinemia Research Articles

Reactive granulomatous dermatitis: A useful and encompassing term

Reactive granulomatous dermatitis: A useful and encompassing term

Non HCV-Related Mixed Cryoglobulinemic Vasculitis With Biopsy-Proven Renal Involvement: The Effects of Rituximab.

In the countries where HCV infection is still endemic, about 90% of subjects with mixed cryoglobulinemia had previously been infected with HCV and about 80% are RNA positive. Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking. This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome. The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p < 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p < 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively. In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.

Взаємозв’язки імунологічних та клініко-морфологічних показників у хворих на хронічний гепатит С залежно від наявності змішаної кріоглобулінемії

Актуальність. Змішана кріоглобулінемія є найчастішим позапечінковим проявом хронічної HCV-інфекції. Питання ролі цитокінів та особливостей ураження печінки при хронічній HCV-інфекції за наявності змішаної кріоглобулінемії дискусійні. Мета дослідження — визначити взаємозв’язок між змінами імунологічних параметрів (кріоглобуліни, інтерферон γ, інтерлейкін‑4) та клініко-морфологічними показниками хронічного гепатиту С у хворих зі змішаною кріоглобулінемією. Матеріали й методи. Обстежені 82 хворі на хронічний гепатит С. Стадію фіброзу печінки визначали при морфологічному дослідженні гепатобіоптатів. Вміст інтерферону γ та інтерлейкіну‑4 визначали методом імуноферментного аналізу. Вміст кріоглобулінів визначали спектрофотометричним методом. Результати. У хворих зі змішаною кріоглобулінемією виявлено нижчий вміст інтерферону γ та найвищий вміст інтерлейкіну‑4 у сироватці крові, зареєстровано кореляцію між концентрацією кріоглобулінів та вмістом інтерферону γ (r = –0,32; р &lt; 0,05) та інтерлейкіну‑4 (r = 0,36; р &lt; 0,05). Виявлено вищий вміст змішаних кріоглобулінів у хворих зі стадіями фіброзу F3–4 (р &lt; 0,05). Зареєстровано більшу частоту клінічних ознак кріоглобулінемічного синдрому в пацієнтів зі стадіями фіброзу печінки F3–4. Підвищення вмісту змішаних кріоглобулінів асоціюється з появою та кількістю ознак кріоглобулінемічного синдрому (виражена загальна слабкість, шкірна пурпура й синдром Рейно) і вираженістю фіброзу печінки. Підвищення вмісту інтерлейкіну‑4 асоціюється з появою загальної слабкості, шкірної пурпури та тяжким фіброзом печінки. Висновки. Підвищення вмісту змішаних кріоглобулінів асоціюється з появою та кількістю ознак кріоглобулінемічного синдрому та вираженістю фіброзу печінки. Підвищення вмісту інтерлейкіну‑4 корелює з концентрацією кріоглобулінів та асоціюється з клінічними проявами кріоглобулінемічного синдрому та фіброзом печінки F3–4. Для покращення діагностики перебігу хронічного гепатиту С доцільно визначати вміст кріоглобулінів та інтерлейкіну‑4.

Diagnosis and management of Waldenström macroglobulinaemia-A British Society for Haematology guideline.

The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Waldenström macroglobulinaemia. In individual patients, circumstances may dictate an alternative approach. This guideline was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. Recommendations are based on a review of the literature using Medline, Pubmed, Embase, Central, Web of Science searches from beginning of 2013 (since the publication of the previous guidelines) up to November 2021. The following search terms were used: Waldenström('s) macroglobulin(a)emia OR lymphoplasmacytic lymphoma, IgM(-related) neuropathy OR cold h(a)emagglutinin disease OR cold agglutinin disease OR cryoglobulin(a)emia AND (for group a only) cytogenetic OR molecular OR mutation OR MYD88 OR CXCR4, management OR treatment OR transfusion OR supportive care OR plasma exchange OR plasmapheresis OR chemotherapy OR bendamustine OR bortezomib OR ibrutinib OR fludarabine OR dexamethasone OR cyclophosphamide OR rituximab OR everolimus,bone marrow transplantation OR stem cell transplantation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by UK Charity WMUK; these organisations do not necessarily approve or endorse the contents.

Transforming mutations in the development of pathogenic B cell clones and autoantibodies.

Autoimmune diseases are characterized by serum autoantibodies, some of which are pathogenic, causing severe manifestations and organ injury. However, autoantibodies of the same antigenic reactivity are also present in the serum of asymptomatic people years before they develop any clinical signs of autoimmunity. Autoantibodies can arise during multiple stages of B cell development, and various genetic and environmental factors drive their production. However, what drives the development of pathogenic autoantibodies is poorly understood. Advances in single-cell technology have enabled the deep analysis of rare B cell clones producing pathogenic autoantibodies responsible for vasculitis in patients with primary Sjögren's syndrome complicated by mixed cryoglobulinaemia. These findings demonstrated a cascade of genetic events involving stereotypic immunoglobulin V(D)J recombination and transforming somatic mutations in lymphoma genes and V(D)J regions that disrupted antibody quality control mechanisms and decreased autoantibody solubility. Most studies consider V(D)J mutations that enhance autoantibody affinity to drive pathology; however, V(D)J mutations that increase autoantibody propensity to form insoluble complexes could be a major contributor to autoantibody pathogenicity. Defining the molecular characteristics of pathogenic autoantibodies and failed tolerance checkpoints driving their formation will improve prognostication, enabling early treatment to prevent escalating organ damage and B cell malignancy.

Синдром змішаної кріоглобулінемії: особливості клінічного перебігу та лікування. Огляд літератури та опис клінічного випадку, асоційованого з COVID-19

Abstract. The aim of the study was to analyze the literature rewiew regarding modern methods of diagnosis and treatment of mixed cryoglobulinemia. Mixed cryoglobulinemia syndrome (MCS) is a unique systemic inflammatory syndrome, which includes small- and medium-sized vessel vasculitis caused by cryoglobulin-containing immune complexes. MCS is potentially caused by hepatitis C virus infection. It may also be associated with autoimmune or lymphoproliferative disorders or, rarely, may be idiopathic. The diagnosis of MCS should be suspected in any patient who presents with one or more of the following clinical features: palpable purpura, skin ulcers, arthralgias and/or arthritis, peripheral neuropathy, and/or microscopic hematuria or proteinuria with or without chronic kidney disease. The general approach of management of moderate to severe mixed cryoglobulinemia should include targeted treatment of the underlying disease causing the cryoglobulinemia along or with additional immunosuppressive therapy. In some cases, immunosuppressive therapy is started first, and then, after stabilization of disease, therapy for the underlying disease is added. The main indication for immunosuppressive therapy is a progressive systemic disease of the kidneys, nervous system, gastrointestinal tract, skin, or vasculitis with necrosis. The prognosis is variable and depends on the severity of the disease and the response of the underlying disease to therapy. In this publication, we also describe a rare clinical case of mixed cryoglobulinemia associated with COVID-19. Thus, the syndrome of cryoglobulinemia is quite difficult both in diagnosis, taking into account the heterogeneity of clinical and laboratory data, and in treatment which makes it necessary to select effective immunosuppressive therapy in specific clinical cases.

Mixed Cryoglobulinaemia Vasculitis Treated with Obinutuzumab in a Patient Allergic to Rituximab.

Cryoglobulinaemia is defined as the presence of cryoglobulins in the serum, which are immunoglobulins that reversibly precipitate and form a gel when the temperature is <37ºC. Autoimmune diseases such as Sjogren’s syndrome, systemic lupus erythematosus and rheumatoid arthritis could be associated with mixed cryoglobulinaemia vasculitis (MCV). The treatment of MCV generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab. Here, we present a case of a 60-year-old woman who developed type II MCV in the context of overlap autoimmune disease and who has been treated with a new anti-CD20 agent, obinutuzumab.LEARNING POINTSMixed cryoglobulinaemia can occur in the context of autoimmune diseases such as Sjogren’s syndrome, systemic lupus erythematosus and rheumatoid arthritis.The treatment generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab.New generations of humanized anti-CD20 monoclonal antibodies such as obinutuzumab have been developed to increase complement-dependent cytotoxicity and/or antibody-dependent cellular cytotoxicity, while limiting immunogenicity. These new optimized B-cell depletion strategies could be very interesting and useful in autoimmune disease treatment.

A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy

Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.

IgM Paraprotein-Associated Type 1 Cryoglobulinaemia: Clinical Characteristics and Outcomes

IntroductionType 1 cryoglobulinaemia (CG) is characterised by monoclonal immunoglobulins which precipitate at temperatures below 37°C and redissolve on warming. They may be associated with lymphoproliferative disorders including Waldenström's macroglobulinemia (WM), other non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL) or monoclonal gammopathy of undetermined significance (MGUS). Due to their rarity and heterogeneous clinical manifestations, incidence and outcomes are not well characterised and they are likely underdiagnosed. We retrospectively reviewed our cohort of patients (pts) with IgM paraprotein-associated type 1 CG.MethodsData from consecutive pts during 2013 and 2021, aged >18 years were extracted from clinical databases at two specialist centres [UCLH, United Kingdom (UK) and AMC, Netherlands].ResultsA total of 62 pts (38 male, 24 female) were identified (Table 1); 59 from UK and 4 from Netherlands: 49 (79%) had WM, 7 (11%) IgM MGUS and 6 (10%) NHL (5 other lymphoma, 1 CLL). Median age at CG diagnosis was 66 (range 39-90) years; 32 (52%) were >65 years. MYD88 was mutated in 23/25 (92%) evaluable cases of WM. All cases were negative for hepatitis C.CG was detected after the monoclonal disorder in 46 (74%), with a median time to CG diagnosis of 8 (range 0-1390) months, concurrently in 11 (18%) pts and at a median of 1 month (range 0-4) in 5 (8%) pts prior to the monoclonal disorder. These patients were diagnosed due to CG symptoms. Eight pts (of which 50% had WM) also had active cold agglutinin disease (CAD).CG symptoms were present at time of testing in 25 (40%) pts; the others were diagnosed as a part of asymptomatic screening. CG symptoms were more common in those with MGUS / NHL compared to WM, most frequently in MGUS compared to WM (33% v 71%, p=0.05). Skin manifestations including acrocyanosis, purpura, ulcer and necrosis were noted in 14 (23%); 11 (18%) had peripheral neuropathy (6 sensory, 5 mixed) and 8 (13%) hyperviscosity. Median plasma viscosity was >7 (range 4.7 - >7) mPa of 5/8 pts measured with hyperviscosity and a median paraprotein of 29 (range 5-63) g/l. One patient with WM had cryoglobulinaemic glomerulopathy demonstrated by renal biopsy.In all, 53 (85%) pts received treatment, 10 (16%) for the CG and 43 for the monoclonal disorder, including plasma exchange (11/53). Thirty had Rituximab-based therapy (Table 1), and one received Ibrutinib. All achieved complete resolution of symptoms and 3/6 (50%) treated for CG had complete biochemical response with cryoglobulins undetectable after treatment. Two (20%) required further lines of therapy >4 years later. Overall at a follow up of 21 (range 0-94) months, median survival was not reached. Nine (14%) pts died, with 1 (2%) CG-related death due to relapse disease. Estimated 5-year overall survival (OS) was 67% (95% CI 40-84%) (figure 1).ConclusionsIn our cohort of 62 pts with type I IgM paraprotein-associated CG, the majority had WM compared to other NHL and MGUS, likely reflecting the clinical bias of the centres and our policy of screening for CG at first visit. A greater proportion of cases (40%) were symptomatic than previous reports (16%; Néel et al, 2014); when present, symptoms were dominated by skin manifestations, neuropathy and hyperviscosity. Patients tested for CG with IgM MGUS were more likely to be symptomatic compared to WM. CAD co-existed in a proportion. Those with CG symptoms treated had good clinical responses; treatment subgroups were too small to draw conclusions as to relative efficacy, but Rituximab-based therapy appeared effective in most cases. CG-related mortality was low with an estimated 5-year OS 67%. [Display omitted] DisclosuresVos: Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel reimbursement. D'Sa: Janssen Cilag: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Sanofi: Honoraria.

Direct-Acting Antiviral Therapy Effect on Extrahepatic Rheumatic Manifestations in Egyptian Chronic Hepatitis C (HCV) Patients

Background: Hepatitis C virus infection is an important cause of many rheumatic diseases, especially cryoglobulinemic vasculitis, fibromyalgia, arthralgia and Sicca Syndrome. Direct acting antivirals are found to be highly effective for the treatment of chronic Hepatitis C virus infection. Objective: The aim of this study was to evaluate the clinical and serological course of extrahepatic rheumatic manifestations in chronic hepatitis C Egyptian patients after treatment with new direct-acting antivirals. Patients and Methods: This study was carried out on 60 Egyptian patients with chronic hepatitis C with one or more of the HCV- related rheumatic manifestations treated with sofosbuvir (400 mg daily) plus daclatasvir (60 mg daily) as a direct-acting antivirals for 3 months. All patients were subjected to clinical and serological course of extrahepatic rheumatic manifestations evaluation. Results: show that among the 60 patients, 21 patients (35.0%) met the criteria of mixed cryoglobulinemia syndrome (MC), 19 patients (31.7%) were complaining of arthralgia, 17 patients (28.3%) were complaining of fibromyalgia and 3 patients (5.0%) were complaining of Purpura without other criteria of mixed cryoglobulinemia syndrome. Complete clinical response was achieved in a significant number of patients with mixed cryoglobulinemia syndrome (MCS), the results also show significant clinical improvement in patients with fibromyalgia, arthralgia and purpura. Significant reduction but not complete normalization in auto-antibodies at short term follow-up was observed. Conclusion: It could be concluded that sustained virologic response correlates with clinical and immunological improvement in most patients with extrahepatic rheumatic manifestations among the studied group of chronic hepatitis C Egyptian populations.

Clinico-biological characteristics and treatment of hepatitis B virus-related mixed cryoglobulinemia.

Clinico-biological characteristics and treatment of hepatitis B virus-related mixed cryoglobulinemia.

HCV-RELATED VASCULITIS

Up to 3% of people in the world are infected with HCV, and 75-80% of them have chronic currency of infection. In the clinical picture of HCV infection, a significant place is given to extrahepatic manifestations - more than half of patients suffer from lesions of the skin, kidneys, heart, blood vessels, autoimmune and lymphoproliferative syndromes associated with HCV. Usually, mortality from chronic hepatitis C is associated with liver cirrhosis and hepatocellular carcinoma, but in fact, more patients die from complications associated with the development of cryoglobulinemic vasculitis - chronic renal failure and cardiovascular catastrophes. 40-60% of patients with chronic HCV infection suffer from cryoglobulinemic vasculitis in a wide range of clinical manifestations: from minimal to life-threatening. The pathogenesis of mixed cryoglobulinemia syndrome is based on polyclonal activation of lymphocytes.The systemic nature of the lesion, which is observed in HCV infection, reflects its generalized nature with the involvement of many organs and tissues in the pathological process, which complicates timely diagnosis and treatment. A variety of systemic extrahepatic pathology, which often outstrips the clinical picture of hepatitis itself, masquerading as another disease means that a specialist of any profile can meet with chronic HCV infection and its consequences.

The enigma of complement activation in mixed cryoglobulinemia

Mixed Cryoglobulins are immune complexes which form when subsets of IgM Rheumatoid Factor complex with IgG in the cold. The IgM component of these complexes demonstrates a spectrum of clonality ranging from being polyclonal (Type III) to monoclonal (Type II), the latter almost always IgMκ defined in part by cross-reactive idiotypy. They are prevalent in patients infected with Hepatitis C Virus (HCV), as well as some patients with Primary Sjogren's syndrome (SS) or Systemic Lupus Erythematosus (SLE) with the clinical manifestations of vasculitis and/or glomerulonephritis [1].

Dynamics of serum α-fetoprotein in viral hepatitis C without hepatocellular carcinoma.

Viral hepatitis C represents a significant liver pathology worldwide, with a detrimental impact on national health systems. The present study aimed to correlate the levels of serum α-fetoprotein (AFP) with prognostic tools such as Fibroscan®, the presence of mixed cryoglobulinemia, and various demographic and standard biochemical markers, in patients with chronic hepatitis C, unrelated to hepatocellular carcinoma (HCC). A clinical study was designed considering three study groups: Hepatitis C virus (HCV) group including 35 patients with chronic hepatitis C and detectible viral load; sustained viral response (SVR) group including 20 HCV patients without detectable virus load 12 weeks after therapy cessation; a control group represented by 37 healthy volunteers. It was observed that serum AFP was moderately increased in the HCV and SVR groups and was positively correlated with aspartate transaminase (AST), alkaline phosphatase (AP), and γ-glutamyl transferase (GGT). The incidence of mixed cryoglobulinemia was increased in the HCV group, and the degree of fibrosis assessed by Fibroscan® was increased in both the HCV and SVR groups. In conclusion, the data revealed that a moderate increase in AFP levels could be present in patients with HCV even in the absence of HCC, unrelated to viral load or therapy response and that there was a linear positive correlation between serum levels of AFP and the degree of hepatic cytolysis and cholestasis. Additionally, mixed cryoglobulinemia was present in HCV patients with patent viral load, decreasing in those with SVR after therapy cessation unrelated to any renal impairment, while the degree of fibrosis was increased in HCV-infected patients, with no reversibility 12 weeks after successful therapy.

Polymorphism of mixed cryoglobulinemia manifestations in hepatitis C virus chronic infection

Objective: to analyze the characteristics of hepatitis C virus chronic infection with concurrent cryogobulinemia, to assess the prevalence of extrahepatic diseases in the population of Belarusian patients under study.Material and methods. An open, non-randomized observational study with the inclusion of patients with hepatitis C virus (HCV) chronic infection and cryoglobulinemia (CG) was conducted.Results. The study has determined the core characteristics of HCV infection in CG patients, incidence rates and a wide array of extrahepatic diseases (EHDs), as well as HCV infection distinctive features compared to those without extrahepatic diseases.Conclusion. The revealed variety of common EHDs in HCV infection indicates that many organs and systems are involved in the pathological process and this variety should be taken into account when considering prognosis and treatment tactics.

Dermatological manifestations of monoclonal gammopathies

Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.

Impact of direct acting antivirals on hepatitis C virus-related cryoglobulinemic syndrome.

Mixed cryoglobulinemia (MC) is a B-cell lymphoproliferative disorder largely attributable to Hepatitis C virus (HCV) infection. MC clinical manifestations are determined by systemic vasculitis of low/medium sized vessels (mixed cryoglobulinemia syndrome or cryoglobulinemic vasculitis [CV]) caused by the deposition of cryoglobulins in blood vessels. A systematic review was performed via the Medline and Scopus databases to evaluate studies concerning CV treatment with new direct antiviral agents (DAAs) and their effect on the syndrome. The introduction of interferon-free protocols has led to more evident positive effects than those observed in the treatment of hepatitis C. In fact, IFN-free, DAA-based therapy minimized side effects permitting the treatment of previously contraindicated patients and led to a particularly high SVR rate and to a clinical/immunological response in the majority of patients, even if at different levels in different patients, from restitutio ad integrum to partial response. In view of the clearly positive evolution in CV management, the persistence of CV manifestations, in partial or non-responders continues to pose problems in the clinical approach to patients who represent a new condition that is still not completely known. Results of DAA-based therapy strongly confirm the use of anti-HCV therapy as the first-line therapeutic option in CV patients. However, growing evidence of a possible persistence or late relapse of CV suggests the need for longer/more accurate post-DAA follow-ups as well as biomarkers that are capable of predicting the risk of clinical relapse/persistence to allow for the design of rational post-HCV eradication clinical flow-charts.

Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals

Genetic profiles of hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) in Asians remain elusive. A 10-year prospective cohort study was conducted with 1043 consecutive HCV Ab-positive Taiwanese surveyed with 13 single nucleotide polymorphisms (SNPs). Of 1043, 589 (56.5%) had baseline MC, 934 (89.5%) had positive HCV RNA, 796 completed anti-HCV therapy, and 715 had sustained virological responses (SVRs). SNP associations were surveyed withgenotypic, allelic, trend, permutation and multivariate analyses. At baseline, higher male sex and MC rates were noted in HCV RNA-positive than RNA-negative patients; higher female sex and positive HCV RNA rates but lower HCV RNA levels were noted in patients with than those without MC. Baseline associations were: HLA II-rs9461776 A allele, IFNL3-rs12979860 T allele, SERPINE1-rs6976053 C allele and MC with HCV RNA positivity; IFNL3-rs12979860 C allele, ARNTL-rs6486122 T allele and HCV RNA positivity with baseline MC. In SVR patients, RETN-rs1423096 C allele and SERPINE1-rs6976053 T allele were associated with 24-week and 10-year post-therapy MC, respectively. Conclusions: HCV RNA, IFNL3-rs12979860 and ARNTL-rs6486122 were associated with baseline MC; RETN-rs1423096 and SERPINE1-rs6976053 were associated with short- and long-term post-therapy MC in SVR patients, respectively. Links with HCV RNA and immune-associated SNPs suggest MC an immune reaction to expel HCV.

Glomerulonephritis in AKI: From Pathogenesis to Therapeutic Intervention.

Acute kidney injury (AKI) is increasingly emerging as a global emergency. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in hospitalized patients. However, glomerulonephritis accounts for about 10% of AKI episodes in adults, mainly related to rapidly progressive glomerulonephritis resulting from granulomatous polyangiitis (GPA, Wegener granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane (GBM) disease. Also, diffuse proliferative lupus nephritis, immunoglobulin A nephropathy, post-streptococcal glomerulonephritis, mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, membranous nephropathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and scleroderma can induce acute renal failure. Early diagnosis of AKI due to glomerulonephritis is crucial for prompt, effective management to improve short- and long-term outcomes. Kidney biopsy is the gold standard for the diagnosis of glomerular disease, but it is not frequently performed in critically ill patients because of their clinical conditions. In this setting, a growing number of diagnostic assays can support the working hypothesis, including antineutrophil cytoplasmic antibodies (ANCAs), anti-double-stranded DNA antibodies, anti-GBM antibodies, antistreptolysin O and anti-DNase B antibodies, cryoglobulins, antiphospholipid antibodies, and complement levels. Therapeutic strategies in AKI patients with glomerulonephritis include high-dose corticosteroids, cyclophosphamide, and plasma exchange. This article reviews the wide spectrum of glomerulopathies associated with AKI, describing the immunological mechanisms underlying glomerular diseases and presenting an overview of the therapeutic options.

Renal Involvement and HBV Infection Are Common in Chinese Patients With Cryoglobulinemia.

Objectives: This study aimed to describe the main characteristics of Chinese patients with cryoglobulinemia, especially the characteristics of patients with different causes of cryoglobulinemia.Methods: Eighty inpatients diagnosed with cryoglobulinemia from different wards in Peking Union Medical College Hospital were included in this study. Demographic, clinical, biological, and renal pathological data were collected. We analyzed the characteristics of 61 patients with different causes of cryoglobulinemia.Results: Most patients (36/80, 45%) were diagnosed between 40 and 60 years of age. The male: female ratio was 1:1.5. Mixed (II + III) cryoglobulinemia accounted for the majority (43.8%) of cases. Renal involvement (87.5%), cutaneous involvement (57.5%), and fever (27.5%) were the most common clinical manifestations, while other manifestations included serositis and pulmonary and gastrointestinal involvement. The most common renal histopathological pattern was membranoproliferative glomerulonephritis (25/42, 59.5%). The secondary causes of cryoglobulinemia included infectious diseases (26/61, 32.5%), such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and connective tissue diseases (22/61, 27.5%), such as lupus and hematologic tumors (13/61, 16.3%). Patients with hematologic tumors were diagnosed at an older age (P = 0.044) and mostly had type I cryoglobulinemia (P < 0.001). No significant difference in clinical or biological manifestations was found among patients with different causes of cryoglobulinemia.Conclusions: This is the largest cohort of Chinese patients with cryoglobulinemia. We found that renal involvement and HBV infection might be more common in Chinese patients with cryoglobulinemia.