• Glomerular disease
• Kidney biopsy
• Proteinuria
• Small vascular disease
• Tubulointerstitial disease

• Humans
• Female
• Male
• Middle Aged
• Adult
• Retrospective Studies
• China/epidemiology
• Kidney/pathology
• Proteinuria
• Glomerular Filtration Rate
• Acute Kidney Injury/pathology
• Acute Kidney Injury/etiology
• Aged

• chronic kidney disease
• dialysis
• glomerulonephritis
• hepatitis C virus
• kidney transplantation
• nephrotoxicity
• renal manifestations
• vasculitis

• Amyloidosis
• Cryoglobulinemia
• Glomerular disease
• Immunotactoid glomerulopathy
• Light chain deposition disease
• Monoclonal gammopathy
• Nephrotic syndrome
• Paraproteinemia

• Humans
• Paraproteinemias/pathology
• Paraproteinemias/diagnosis
• Paraproteinemias/metabolism
• Glomerulonephritis/pathology
• Glomerulonephritis/metabolism
• Glomerulonephritis/diagnosis
• Kidney Glomerulus/pathology
• Kidney Glomerulus/metabolism
• Paraproteins/metabolism
• Kidney Diseases/pathology
• Kidney Diseases/metabolism
• Biopsy
• Amyloidosis/pathology
• Amyloidosis/metabolism
• Amyloidosis/diagnosis

• Cryoglobulinemia
• Glomerular diseases
• Hepatitis B
• Hepatitis C
• Membranous nephropathy
• Secondary IgA nephropathy

• Humans
• Glomerulonephritis/epidemiology
• Glomerulonephritis/pathology
• Glomerulonephritis/immunology
• Glomerulonephritis/etiology
• Cryoglobulinemia/etiology
• Cryoglobulinemia/epidemiology
• Hepatitis C/complications
• Hepatitis C/epidemiology
• Hepatitis C/drug therapy
• Antiviral Agents/therapeutic use
• Hepatitis B/complications
• Hepatitis B/epidemiology
• Glomerulonephritis, IGA/epidemiology
• Glomerulonephritis, IGA/pathology

• Cryofiltration
• Cryoglobulinemic vasculitis
• Plasma exchange
• Plasmapheresis
• Renal outcome

• Adult
• Female
• Humans
• Male
• Middle Aged
• Blood Component Removal/methods
• Cryoglobulinemia/therapy
• Immunosuppressive Agents/therapeutic use
• Plasma Exchange/adverse effects
• Plasmapheresis/adverse effects
• Vasculitis/complications
• Vasculitis/therapy

• Cryoglobulinemia/diagnosis
• Cryoglobulins
• Female
• Glomerulonephritis/complications
• Hepatitis C/complications
• Humans
• Middle Aged
• Rheumatoid Factor
• Vasculitis/complications

Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection.

The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits.

Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes.

Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.

• Cryofibrinogen
• Cryoglobulin
• Systemic sclerosis

• MGRS
• MPGN
• cryoglobulinemic glomerulonephritis
• kidney biopsy
• serum cryoglobulin

• Hepatitis
• Kidney
• Liver disease
• Nephropathy

• Clinicopathological spectrum
• Cryoglobulinemic glomerulonephritis
• Monoclonal gammopathy
• Renal prognosis

Culture-negative infective endocarditis (IE) constitutes approximately 10% of all cases of IE. Bartonella endocarditis is a common cause of culture-negative endocarditis and is associated with a high mortality rate. To date, no cases of Bartonella IE has been reported in association with cryoglobulinemia in the UK. We present a unique case of Bartonella IE causing secondary cryoglobulinemia in a young female.

A 17-year-old female with a background of pulmonary atresia and ventricular septal defect repaired with a cardiac conduit at the age of 4, presented with a one-year history of weight loss (from 53 to 39 kg) and poor appetite. She subsequently developed a vasculitic rash and haematoproteinuria with decline in renal function, requiring urgent hospital admission. Initial blood tests showed a near normal creatinine, but a raised cystatin C. Renal biopsy showed focal necrotizing glomerulonephritis with no acute tubular necrosis or chronic change. Subsequent blood tests supported a diagnosis of cryoglobulinaemic vasculitis (high rheumatoid factor, low complement, polyclonal gammopathy, Type 3 cryoglobulin). A weak positive PR3 meant there was some uncertainty about whether this could be a primary ANCA-associated vasculitis (AAV). Initial workup for an infectious cause, including multiple blood cultures, were negative. However, an echocardiogram showed definite vegetations on her surgical conduit. The patient did not respond to empirical antimicrobials and so was referred for surgical revision of her conduit. Tissue samples obtained intra-operatively demonstrated Bartonella species. With targeted antimicrobials post-operatively, she improved with resolution of immunologic abnormalities and at last review had a normal renal profile. On reviewing her social history, she had adopted several stray cats in the preceding year; and thus, the cause of the Bartonella infection was identified.

This is the first reported case of Bartonella endocarditis causing secondary cryoglobulinemia reported in the UK. The key learning points from this case include that Bartonella endocarditis can present as a cryoglobulinaemic vasculitis and should be considered in any differential when the cause of cryoglobulinaemia is not clear and to enquire about relevant exposures especially when culture-negative endocarditis is suspected.

• Aspergillus
• Bartonella endocarditis
• Case report
• Cryoglobulinemia
• Culture-negative endocarditis

• DAA therapy
• cryoglobulinemia
• cryoglobulinemic vasculitis
• hepatitis C

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.

• arthralgia
• cryoglobulinemia
• direct-acting antivirals (DAAs)
• hepatitis C virus
• purpura

• Cryoglobulinemia
• Hepatitis C virus
• Pathophysiology
• Treatment
• Vasculitis

• Cryoglobulinemic vasculitis
• Hepatitis C virus
• Mixed cryoglobulinemia
• Outcome
• Predictor
• Severity index

• Arthritis
• Autoimmunity
• Cryoglobulinemia
• HCV
• Sjogren's Syndrome

• cryoglobulinemia
• rituximab
• systemic vasculitis

Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90–100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.

• cryoglobulinemia
• entecavir
• hepatitis B virus
• tenofovir
• vasculitis

• Aged
• Combined Modality Therapy
• Cryoglobulinemia/diagnosis
• Cryoglobulinemia/etiology
• Cryoglobulinemia/therapy
• Disease Management
• Disease Susceptibility
• Female
• Follow-Up Studies
• Hepatitis B/complications
• Hepatitis B/virology
• Hepatitis B virus
• Humans
• Italy
• Male
• Middle Aged
• Nucleosides/analogs & derivatives
• Nucleosides/therapeutic use
• Phenotype
• Treatment Outcome
• Vasculitis/diagnosis
• Vasculitis/etiology
• Vasculitis/therapy

• Electron microscopy
• Glomerulonephritis
• Hepatitis C
• Structured deposits

• HBV
• diabetic foot
• extremity gangrene
• type III cryoglobulinemia vasculitis

• Hong Kong
• chronic kidney disease
• cryoglobulinemia
• epidemiology and outcomes
• glomerulonephritis
• kidney disease

• Antiviral therapy
• Cryogo-bulinemic vasculitis
• Hepatitis B virus
• Hepatitis C virus
• Human hepatitis viruses
• Polyarteritis nodosa

• Cryoglobulinemia
• Endothelial Cells
• Hepacivirus
• Hepatitis B virus
• Hepatitis C
• Humans

Therapy with direct-acting antivirals (DAA) for HCV is safe and effective in the liver (LT) and kidney transplant (KT) recipients; however, data on the quality of life (QoL) of patients are scanty. This pilot study is aimed at prospectively evaluating the QoL in LT and KT recipients before and after DAA treatment.

We prospectively enrolled 17 LT and 11 KT recipients with HCV infection starting a sofosbuvir-based antiviral therapy for 12 weeks. All participants before (T0), 12 (T12), and 24 (T24) weeks after the end of the therapy completed the Short Form Health Survey (SF-36) questionnaire, the Zung Self-rating Depression Scale, and State-Trait Anxiety Inventory (STAI—Y1–Y2).

At T0, LT and KT patients were similar for gender, age, BMI, smoking habits, marital status, mean liver stiffness values at Fibroscan, and HCV genotype distribution (p > 0.05). There were no significant differences between the 2 groups in STAI-Y1, STAI-Y2, Zung, and SF-36 scores (p > 0.05). At T12, all the participants showed a sustained virological response (SVR). All items of the SF-36 questionnaire improved from the pretreatment to posttreatment period within the LT group, and the 4 domains role-physical, bodily pain, social function, role-emotional, and mental health reached statistical significance (p < 0.05 in all cases). On the contrary, in KT patients, there was no significant improvement in SF-36 mean scores compared to at baseline at T12 and T24.

This pilot study suggested that DAA therapy is associated with a significant improvement of the QoL only in LT recipients. Probably, KT recipients did not consider HCV a “central player” in the course of their disease, and HCV eradication did not significantly impact on their QoL.

• CKD
• DAA
• HCV
• Sofosbuvir
• hemodialysis
• renal transplant

Systemic vasculitides represent uncommon conditions characterized by the inflammation of blood vessels that can lead to different complex disorders limited to one organ or potentially involving multiple organs and systems. Systemic vasculitides are classified according to the diameter of the vessel that they mainly affect (small, medium, large, or variable). The pathogenetic mechanisms of systemic vasculitides are still partly unknown, as well as their genetic basis. For most of the primary systemic vasculitides, a single gold standard test is not available, and diagnosis is often made after having ruled out other mimicking conditions. Current research has focused on new management protocol and therapeutic strategies aimed at improving long-term patient outcomes and avoiding progression to multiorgan failure with irreversible damage. In this narrative review, authors describe different forms of systemic vasculitides through a review of the literature, with the aim of highlighting the current knowledge and recent findings on etiopathogenesis, diagnosis and therapy.

• Behcet's disease
• Giant cell arteritis
• Kawasaki disease
• Polyarteritis nodosa
• Systemic vasculitides
• Takayasu arteritis

• Direct-acting antivirals
• HCV
• Mixed Cryoglobulinemia
• Rituximab
• Type I Cryoglobulinemia
• gC1qR

• Antiviral therapy
• Cryoglobulinemia
• Hematological disease
• Hepatitis C virus
• Immunoglobulins
• Rituximab
• Vasculitis

• Glucocorticoids
• Hepatitis C virus
• Life-threatening manifestations
• Mixed cryoglobulinemia syndrome
• Rituximab
• Severe cryoglobulinemia
• Therapeutic plasma exchange

• Cryoglobulinemia
• Direct-acting antiviral agents
• Glomerulonephritis
• Hepatitis C virus
• Immunosuppression

• Neuropatía vasculítica
• Review
• Revisión
• Rituximab
• Vasculitic neuropathy
• Vasculitis

• Cryoglobulinemia
• Cryoglobulinemic vasculitis
• Direct-acting antiviral agents
• Hepatitis C virus
• Non-Hodgkin lymphoma
• Rheumatoid factor

The course of cryoglobulinaemia varies widely, from asymptomatic patients to severe vasculitis syndrome. Renal involvement (RI) is the major prognostic factor, and frequently occurs several years after diagnosis. However, predictive factors for RI are not well known. The aim of our study was to identify RI predictive factors during cryoglobulinaemia.

We retrospectively reviewed the clinical charts of a consecutive series of 153 patients positive for cryoglobulinaemia in the University Hospital of Lyon (France). RI was defined either histologically or biologically if cryoglobulinaemia was the only possible cause of nephropathy.

Among the 153 positive patients (mean age 55 years, 37% male), cryoglobulinaemia was associated with RI in 45 (29%) patients. Sixty-five percent of patients had Type II cryoglobulinaemia, 28% had Type III and 7% had Type I. Autoimmune diseases were the most common aetiology (48%), followed by infectious diseases (18%) and lymphoproliferative disorders (13%). Membranoproliferative glomerulonephritis was the main histological pattern (93% of the 14 histological analyses). A multivariable logistic regression showed that Type II cryoglobulinaemia, a high serum cryoglobulin concentration, the presence of an IgG kappa monoclonal component and diabetes were independently associated with the risk for developing RI.

We identified several factors predictive of RI in patients with cryoglobulinaemia, which were different from the diagnostic criteria for cryoglobulinaemic vasculitis. This could suggest a specific pathophysiology for RI. We suggest performing an extensive renal monitoring and ensure nephroprotection when a diagnosis of cryoglobulinaemia is made in patients with these predictive factors.

• cryoglobulinaemia
• kidney failure
• predictive factors
• proteinuria
• renal involvement

• Kidney failure
• glomerulonephritis
• hepatitis
• hepatitis B
• hepatitis C
• kidney transplantation

• HCV
• cardiovascular
• dermatologic
• extrahepatic
• hematologic
• neuropsychiatric manifestations
• ophthalmologic
• pulmonary
• renal
• rheumatologic

We aim to describe the persistence of symptoms associated with HCV-associated cryoglobulinemic vasculitis following achievement of (SVR) with IFN- free direct acting antiviral (DAA) therapy. In particular, we describe the persistence of C4 hypocomplementemia and positive Rheumatoid Factor (RF).

We analyzed a case series of four patients enrolled from the Cleveland VA and known to have chronic HCV infection complicated by mixed cryoglobulinemia. The study included patients treated with interferon (IFN) based treatment and IFN free direct acting antiviral (DAA) therapy.

Of the four patients, patients 1 and 2 experienced decline of RF without resolution following DAA therapy. Patient 1 continues to have evidence of disease following treatment. Patient 3 did not have resolution of RF during IFN-based treatment and experienced stabilization of kidney function while on treatment. Patient 4, previously a non-responder to IFN based treatment, experienced significant decline in RF titers along with resolution of cryoglobulin-associated rash with DAA therapy. C4 remained low following treatment in patients 1 and 3. Of the four patients, only patient 1 had prolonged persistence of cryoglobulinemia, measured at 3%, 17 months following achievement of SVR.

We highlight the complexity of the viral-mediated immunologic mechanism that causes cryoglobulinemic vasculitis. Our cases also emphasize the need to consider cryoglobulinemic vasculitis as part of the differential diagnosis even with treated HCV infection. Recognizing these findings are important in our understanding of the pathophysiology of the disease and management in the era of IFN-free DAA therapy.

• Cryoglobulinemic vasculitis
• HCV infection
• Tumor

• Direct-acting agents
• Kidney transplantation
• Renal insufficiency, chronic
• Hepatitis C virus

• Antiviral Agents/therapeutic use
• Drug Therapy, Combination
• Hepacivirus/drug effects
• Hepatitis C
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/therapy
• Hepatitis C, Chronic/virology
• Humans
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/therapy
• Ribavirin

• HCV associated membranoproliferative glomerulonephritis
• HCV-associated cryoglobulinemic vasculitis
• mixed cryoglobulinemia
• necrotizing skin ulcers
• polyneuropathies

• Antiviral agents
• cryoglobulinemia
• glomerulonephritis
• hepatitis C
• immunosuppression