Hepatitis C-associated Cryoglobulinemia Research Articles

“Explosive” worsening of chronic hepatitis C-associated cryoglobulinemia vasculitis, as unmasking of lymphoma a case report.

“Explosive” worsening of chronic hepatitis C-associated cryoglobulinemia vasculitis, as unmasking of lymphoma a case report.

Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals.

Hepatitis C virus (HCV) infection is responsible for both hepatic and extrahepatic manifestations. Before the era of direct-acting antivirals (DAA), cryoglobulinemia was related to HCV infection in 70–90% of cases. Observed in 30% to 40% of patients with hepatitis C, mixed cryoglobulinemia is mainly asymptomatic. Conversely, symptomatic cryoglobulinemia vasculitis (CV) can occur in 5–10% of patients with HCV-associated cryoglobulinemia. CV is a small-vessel systemic vasculitis, and organ damage results from circulation and precipitation of cryoglobulins and complement activation. A wide range of clinical symptoms can be observed during CV, and manifestations are potentially life-threatening. The most frequent manifestations occurring in CV are cutaneous, with recurrent purpura, articular with joint pains, neurologic with peripheric neuropathy, and renal with membranoproliferative glomerulonephritis. DAA have drastically changed chronic HCV therapy. DAA induce sustained virological response (SVR) rates greater than 95%, and also improve extrahepatic manifestations such as CV. We review recent studies investigating the clinical and immune effects of DAA therapy on HCV-CV.

Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis

Objective No data are available about circulating levels of the CXCL11 chemokine in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with or without autoimmune thyroiditis (AT). The aim of the present study, therefore, was to evaluate serum CXCL11 levels in these patients.Design Serum CXCL11 (and for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex- and age-matched patients with AT without cryoglobulinemia (control 2), and in 45 sex- and age-matched patients with hepatitis C chronic infection without MC (HCV+).Results Serum CXCL11 and CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10 significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11 levels were not associated with any of the clinical features of cryoglobulinemia in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11 in HCV+ patients were significantly higher than in controls 1 and 2, but lower than in MC or MC+AT patients.Conclusion Our study first demonstrates higher serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and in particular in the presence of AT.

Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis

No data are available about circulating levels of the CXCL11 chemokine in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with or without autoimmune thyroiditis (AT). The aim of the present study, therefore, was to evaluate serum CXCL11 levels in these patients. Serum CXCL11 (and for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex- and age-matched patients with AT without cryoglobulinemia (control 2), and in 45 sex- and age-matched patients with hepatitis C chronic infection without MC (HCV+). Serum CXCL11 and CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10 significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11 levels were not associated with any of the clinical features of cryoglobulinemia in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11 in HCV+ patients were significantly higher than in controls 1 and 2, but lower than in MC or MC+AT patients. Our study first demonstrates higher serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and in particular in the presence of AT.

A rare presentation of pulmonary hemorrhage with hepatitis C-associated cryoglobulinemia and membranoproliferative glomerulonephritis

Cryoglobulinemia (CG)-associated pulmonary hemorrhage is an unusual entity. An even rarer occurrence is that of membranoproliferative glomerulonephritis (MPGN) in a patient with CG and alveolar hemorrhage. As far as we can tell, there has been no more than a total of four such cases that have been formally published, and this would be the fifth case [1,2]. A 46-year-old Caucasian woman presented to the emergency department with acute respiratory failure, petechiae, pulmonary hemorrhage, azotemia, proteinuria, and hematuria for 10 days. A ventilation/perfusion lung scan was read as low probability for a pulmonary embolism. Additional serologic examinations included negative ANA, anti-GBM, pANCA, cANCA, hepatitis B and HIV antibody. SPEP (serum protein electrophoresis) was also unremarkable. Hepatitis C antibody was positive, and quantitative testing for CG revealed type II (mixed CG, 0.2 g/dL). C3 and C4 complement levels were low. Renal biopsy revealed MPGN. Bronchoscopy did not demonstrate any endobronchial abnormality. The patient was treated with intravenous methylprednisolone, and both hemoptysis and renal function improved. She did not return for follow-up care. CG associated with HCV has been recognized to cause pulmonary complications which are usually mild and without any significant signs or symptoms. Alveolar hemorrhage in CG is rare; there have been only 10 case reports in English medical literature [1]. Patients with the cryoglobulinemic pulmonary hemorrhage have an extremely poor prognosis and high mortality at presentation and even a poorer prognosis in survivors having further hemorrhagic episodes [1]. Diagnosis of pulmonary hemorrhage associated with HCV-associated CG requires a high index of suspicion; in this case, the patient presented to the emergency services with severe respiratory insufficiency and bilateral alveolar infiltrates on chest radiograph. Her acute respiratory decompensation with diffuse alveolar infiltrates and hemoptysis is indicative of alveolar hemorrhage syndrome [3]. The diagnosis can also be confirmed with the demonstration of hemosiderophages in alveolar lavage obtained by bronchoscopy. It has been established that patients with CG with chronic infection by HCV are sometimes linked to membranoproliferative glomerulonephritis with a survival rate of 33–49% after a mean follow-up of 10 years. Managing an autoimmune manifestation of an infectious disease is complex. Although immunosuppressive agents may be needed to control potentially life-threatening autoimmune complications, there is a risk that the infection might get worse. A reasonable approach is first to control the acute autoimmune manifestations of disease with immunosuppressive therapy and then to deal with the underlying infection to prevent relapse [3]. We conclude that both alveolar hemorrhage and renal involvement associated with HCV-related type CG are exceptional entities. This poses problems regarding treatment as each patient may need a tailored treatment [1]. Conflict of interest statement. None declared.

Pseudoleukocytosis secondary to hepatitis C-associated cryoglobulinemia: a case report

IntroductionLaboratory tests play a central role in assessing a patient and orienting the diagnostic evaluation. We report a case where the discrepancy between the manual and automatic cell count gave a hint to the final diagnosis.Case presentationA 55-year-old Caucasian man, known to have hepatitis C, was admitted with acute respiratory failure secondary to acute pulmonary edema and diffuse petechial rash of the lower extremities for the previous 2 months. The initial laboratory tests showed acute renal failure (creatinine of 2.6 mg/dL). During his hospital stay, the patient had a fluctuating white blood cell count with a recorded value of 96,000 cells/mL. On a peripheral smear, the blood cell count was in the normal range. The acute renal failure was secondary to membranoproliferative glomerulonephritis secondary to essential mixed cryoglobulinemia diagnosed by biopsy. The complete blood count values, performed by Beckman/Coulter GenS, were falsely high due to precipitation of plasma cryoglobulins at room temperature. This spurious leukocytosis was previously described in several case reports, but values as high as 96,000 cells/mL were never reported.ConclusionThe presence of cryoglobulins in the blood creates a clinical challenge for the interpretation of several laboratory tests. Pseudoleukocytosis secondary to cryoglobulinemia has been observed in several reported cases with white blood cell counts up to 54,000 cells/mL at room temperature and 85,600 cells/mL at 4°C. If the cryoglobulin precipitates rapidly, aggregated cryoglobulin particles may be interpreted as blood cells. We report the first patient with pseudoleukocytosis secondary to hepatitis C cryoglobulinemia with a spurious leukocytosis of 96,000 cells/mL at room temperature. Other laboratory tests could also be affected: underestimation of true erythrocyte sedimentation rate, pseudothrombocytosis and pseudolymphocytosis. The precipitation can remove the hepatitis C virus and the antibody of cryoglobulins from serum leading to a false negative result. Any discrepancy between the automated and manual white blood cell count should lead to the suspicion of cryoglobulinemia in the clinical setting.

High Values of CXCL10 Serum Levels in Mixed Cryoglobulinemia Associated With Hepatitis C Infection

No study has evaluated circulating CXCL10 in patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) chronic infection. The aim of this study is to measure inteferon-inducible protein 10 (CXCL10/IP-10), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) (Th1 cytokines) in a series of cryoglobulinemic patients and to correlate this parameter to the clinical phenotype. Serum CXCL10, IFN-gamma, and TNF-alpha were assayed in 102 patients with hepatitis C-associated cryoglobulinemia (MC + HCV), in 102 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 102 sex- and age-matched controls. Cryoglobulinemic patients showed significantly higher mean CXCL10 serum levels than controls (P < 0.0001) or HCV+ patients (P < 0.0001) (397 +/- 132 pg/mL, 92 +/- 53 pg/mL, 280 +/- 149 pg/mL, respectively). Moreover, CXCL10 was significantly increased in 30 cryoglobulinemic patients with active vasculitis compared to those without it (460 +/- 104 pg/mL vs 369 +/- 139 pg/mL, respectively; P < 0.001). Both groups of MC + HCV patients with or without active vasculitis had serum CXCL10 significantly higher than HCV+ patients (P < 0.001, P= 0.02, respectively). IFN-gamma levels were not significantly different in MC + HCV than in HCV+ patients or controls. Serum TNF-alpha levels were significantly higher in MC + HCV than in HCV+ patients or controls (median [interquartile range]: 12.0 [9.8], 5.7 [5.4], 1.3 [2.1] pg/mL, respectively; P < 0.0001). The study demonstrates high CXCL10 and TNF-alpha serum levels in patients with hepatitis C-associated cryoglobulinemia. Moreover, in MC + HCV patients, increased CXCL10 levels were significantly associated with the presence of active vasculitis.

Acute exacerbation of vasculitis during interferon- α therapy for hepatitis C-associated cryoglobulinaemia

A significant, previously unreported, adverse reaction to interferon-alpha therapy is reported. Immediately after the commencement of low dose therapy a man with hepatitis-C associated cryoglobulinaemia developed a purpuric rash and a severe, reversible impairment of renal function. This observation may elucidate the immunopathogenesis of vasculitis.