Inflammatory cytokines and S-100b protein in patients with hepatitis C infection and cryoglobulinemias

Objective: To investigate a predictive role for the protein S-100b and serum circulating levels of Th1/Th2 cytokines in patients with chronic hepatitis C virus (HCV) infection with and without mixed cryoglobulinemia (MC). Methods: Sixty chronically HCV-infected patients were divided into two groups: 30 with and 30 without MC. Patients with MC presented detectable mixed cryoglobulins and clinical weakness, purpura and arthralgias. HCV-RNA and genotype, serum levels of cryoglobulins, principal hepatic indexes and levels of IL-6, IL-18 and S-100b protein were evaluated. Twenty uninfected healthy subjects were a control group to evaluate serum levels of S-100b protein. Results: IL-6 and IL-18 serum levels were higher in the MC+ group than the MC- group (8.7 ± 4.5 pg/mL versus 4.6 ± 2.3 pg/mL P < 0.0001 and 743.5 ± 128.2 pg/mL versus 578.5 ± 296.5 pg/mL P < 0.001 respectively). S-100b serum levels were higher in HCV+ with MC (0.23 ± 0.07 microg/L) respect to HCV+ patients without MC (0.17 ± 0.05 microg/L, P < 0.0001) and were statistically higher than in the control group (0.08 ± 0.03 microg/L, P < 0.0001 and P < 0.0001, respectively). A positive correlation was shown between serum levels of S-100b protein and levels of cryoglobulins in the group of HCV+ patients MC+ (r=0.72 and P < 0.0001). Conclusion: HCV patients with MC have a worse inflammatory condition than those without MC. Moreover, S-100b protein seems to be a sensitive marker of endothelial and tissue damage in chronic HCV hepatitis with cryoglobulinemia.

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Spontaneous Clearance of Chronic HCV: The Key Ending Left in the Dark

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.134 ◽

2019 ◽

Vol 7 (10) ◽

pp. 1657-1659

Author(s):

Nikola Hristov Mumdzhiev ◽

Daniela Valerieva Radicheva ◽

Mariana Penkova Radicheva ◽

Rumen Valchev Tenev ◽

Zlatina Dimitrova Vasileva

Keyword(s):

Hepatitis C ◽

Hcv Rna ◽

Spontaneous Clearance ◽

Hepatitis C Infection ◽

Positive Serology ◽

Mild Disease ◽

Spontaneous Hcv Clearance ◽

Chronic Hcv ◽

Direct Acting ◽

Special Circumstances

BACKGROUND: Hepatitis C is the second leading cause of liver cirrhosis and hepatocellular carcinoma. Although the discovery of direct-acting agents made the disease curable, HCV elimination can be achieved solely by the host’s immunologic arsenal. CASE REPORT: We report the case of a 29-year-old woman with chronic hepatitis C infection - elevated transaminases, positive serology. HCV was detectable on two occasions, and histology showed mild disease - A1F1. Upon follow up and without any treatment, the patient achieved spontaneous clearance confirmed by two consecutive undetectable HCV RNA tests. Spontaneous HCV clearance rarely occurs – 0.5% per person-year. This is sometimes accompanied by special circumstances like additional disease or medical interventions. Host factors like gender and interleukin-28B polymorphisms have been known to contribute to clearance. Viral factors like HCV RNA levels are also a factor. The characteristics of host-viral interplay – age of acquisition and fibrosis stage – cannot be overlooked. CONCLUSION: All of the abovementioned factors contribute to the complex immunological interaction between virus and host and the result, although rarely can be spontaneous clearance.

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Interferon treatment for chronic hepatitis C infection in hemophiliacs-- influence of virus load, genotype, and liver pathology on response

Blood ◽

10.1182/blood.v87.5.1704.bloodjournal8751704 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1704-1709 ◽

Cited By ~ 1

Author(s):

JP Hanley ◽

LM Jarvis ◽

J Andrew ◽

R Dennis ◽

PC Hayes ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Early Stage ◽

Hcv Infection ◽

Hcv Rna ◽

Interferon Treatment ◽

Hepatitis C Infection ◽

Virus Load ◽

Chronic Hcv

In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

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Haplotype HLA-B8-DR3 Confers Susceptibility to Hepatitis C Virus-Related Mixed Cryoglobulinemia

Blood ◽

10.1182/blood.v91.6.2062 ◽

1998 ◽

Vol 91 (6) ◽

pp. 2062-2066 ◽

Cited By ~ 68

Author(s):

Marco Lenzi ◽

Magda Frisoni ◽

Vilma Mantovani ◽

Paolo Ricci ◽

Luigi Muratori ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Blood Chemistry ◽

Mixed Cryoglobulinemia ◽

Hcv Rna ◽

Hla Polymorphism ◽

Number Of Patients ◽

Host Genetic ◽

Chronic Hcv ◽

Normal Controls

Abstract Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10.1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected= .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.

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Interferon treatment for chronic hepatitis C infection in hemophiliacs-- influence of virus load, genotype, and liver pathology on response

Blood ◽

10.1182/blood.v87.5.1704.1704 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1704-1709 ◽

Cited By ~ 28

Author(s):

JP Hanley ◽

LM Jarvis ◽

J Andrew ◽

R Dennis ◽

PC Hayes ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Early Stage ◽

Hcv Infection ◽

Hcv Rna ◽

Interferon Treatment ◽

Hepatitis C Infection ◽

Virus Load ◽

Chronic Hcv

Abstract In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

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High interleukin-6 and tumor necrosis factor-alpha serum levels in hepatitis C infection associated or not with mixed cryoglobulinemia

Clinical Rheumatology ◽

10.1007/s10067-009-1218-8 ◽

2009 ◽

Vol 28 (10) ◽

pp. 1179-1185 ◽

Cited By ~ 17

Author(s):

Alessandro Antonelli ◽

Clodoveo Ferri ◽

Silvia Martina Ferrari ◽

Emiliano Ghiri ◽

Santino Marchi ◽

...

Keyword(s):

Hepatitis C ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Serum Levels ◽

Mixed Cryoglobulinemia ◽

Hepatitis C Infection ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

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Haplotype HLA-B8-DR3 Confers Susceptibility to Hepatitis C Virus-Related Mixed Cryoglobulinemia

Blood ◽

10.1182/blood.v91.6.2062.2062_2062_2066 ◽

1998 ◽

Vol 91 (6) ◽

pp. 2062-2066 ◽

Cited By ~ 1

Author(s):

Marco Lenzi ◽

Magda Frisoni ◽

Vilma Mantovani ◽

Paolo Ricci ◽

Luigi Muratori ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Blood Chemistry ◽

Mixed Cryoglobulinemia ◽

Hcv Rna ◽

Hla Polymorphism ◽

Number Of Patients ◽

Host Genetic ◽

Chronic Hcv ◽

Normal Controls

Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10.1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected= .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.

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

The American Journal of Gastroenterology ◽

10.1111/j.1572-0241.2008.02040.x ◽

2008 ◽

Vol 103 (10) ◽

pp. 2488-2494 ◽

Cited By ~ 48

Author(s):

Alessandro Antonelli ◽

Clodoveo Ferri ◽

Poupak Fallahi ◽

Silvia Martina Ferrari ◽

Marco Sebastiani ◽

...

Keyword(s):

Hepatitis C ◽

Serum Levels ◽

Mixed Cryoglobulinemia ◽

Hepatitis C Infection

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Serum Concentrations of Interleukin 1ß, CXCL10, and Interferon-γ in Mixed Cryoglobulinemia Associated with Hepatitis C Infection

The Journal of Rheumatology ◽

10.3899/jrheum.090246 ◽

2009 ◽

Vol 37 (1) ◽

pp. 91-97 ◽

Cited By ~ 17

Author(s):

ALESSANDRO ANTONELLI ◽

CLODOVEO FERRI ◽

SILVIA MARTINA FERRARI ◽

EMILIANO GHIRI ◽

SANTINO MARCHI ◽

...

Keyword(s):

Hepatitis C ◽

Systemic Vasculitis ◽

Interleukin 1 ◽

Serum Levels ◽

Mixed Cryoglobulinemia ◽

Interferon Γ ◽

Medium Size ◽

Hepatitis C Infection ◽

Skin Ulcers ◽

Ifn Γ

Objective.Mixed cryoglobulinemia (MC) is a systemic vasculitis of small and medium-size vessels, often associated with the hepatitis C virus. Research has shown an emerging role for chemokines and type 1 cytokines in the pathophysiology of this vasculitis. Interleukin 1 (IL-1) plays a role in initiating the cascade of immunoinflammatory responses, and levels of the interferon-γ (IFN-γ) inducible chemokine CXCL10 have been shown to be significantly associated with the presence of active vasculitis in patients with MC. We evaluated serum levels of IL-1ß, IFN-γ, and CXCL10 in a series of patients with hepatitis C-related MC (MC+HCV), and correlated these measurements with clinical disease features.Methods.Serum IL-1ß, IFN-γ, and CXCL10 were assayed in 54 patients with MC+HCV, in 54 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 54 controls.Results.MC+HCV patients showed significantly higher mean IL-1ß and CXCL10 serum levels than controls (p < 0.01) or HCV+ patients (p < 0.01). CXCL10 was significantly increased in 14 cryoglobulinemic patients with active vasculitis (necrotizing vasculitis or vasculitic skin ulcers) compared to those without (p < 0.001); IL-1ß was increased in cryoglobulinemic patients with active vasculitis (p = 0.06). No differences were observed for serum IFN-γ levels.Conclusion.Serum levels of IL-1ß and CXCL10 were high in patients with MC+HCV. Increased CXCL10 and IL-1ß levels were associated with the presence of active vasculitis in MC+HCV patients.

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Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection

PeerJ ◽

10.7717/peerj.10723 ◽

2021 ◽

Vol 9 ◽

pp. e10723

Author(s):

Mirela Pavicic Ivelja ◽

Kresimir Dolic ◽

Leida Tandara ◽

Nikola Perkovic ◽

Antonio Mestrovic ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Endothelial Dysfunction ◽

Chronic Hepatitis C ◽

Cerebrovascular Reactivity ◽

Control Group ◽

Hepatitis C Infection ◽

Endothelial Markers ◽

Chronic Hcv Infection ◽

Chronic Hcv

Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.

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Relationship between Duffy Antigen Receptor for Chemokines and Clinical Characteristics in Han People with Chronic Hepatitis C Infection in Dalian, China

10.32592/ircmj.2020.22.10.146 ◽

2020 ◽

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Hepatic Fibrosis ◽

Protective Factor ◽

Hcv Infection ◽

Hcv Rna ◽

Hepatitis C Infection ◽

Duffy Antigen ◽

Chronic Hcv

Background and Objectives: Most patients with untreated chronic hepatitis C virus (HCV) infection develop hepatic fibrosis. Hepatic disease progression is monitored with hematological markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin and platelet [PLT] count, AST/ALT ratio, AST/PLT ratio index [APRI], and fibrosis 4 score [FIB-4]) and FibroScan. The present study aimed to investigate the association between Duffy antigen/chemokines receptor (DARC) polymorphisms and clinical parameters in the Han people with chronic hepatitis C infection in Dalian, China. Materials and Methods: This cohort study was performed on 245 Han people with chronic HCV at Dalian infectious hospital during April-December 2015. The participants of the research were selected using the consecutive sampling method. The DARC genotyping was performed using the TaqMan probe method and transient elastography was measured by FibroScan. Results: Based on the findings, DARC polymorphisms correlated with ALT concentrations (FY*A/FY*A vs. FY*A/FY*B, P=0.025). However, the DARC polymorphism did not have an association with HCV RNA titers (FY*A/FY*A vs. FY*A/FY*B, P=0.241) or hepatic fibrosis (FY*A/FY*A vs. FY*A/FY*B, P=0.325). Moreover, correlation analyses showed that APRI (P<0.001, rho=0.603) and FIB-4 (P<0.001, rho=0.698) were useful predictors of hepatic fibrosis in chronic HCV infection. Besides, HCV RNA titers (P=0.327) and hepatic injury markers (P=0.814, 0.198, 0.767, and 0.171 for ALT, AST, ALB, and AST/ALT, respectively) were not useful for the estimation of the fibrosis stage in patients with chronic hepatitis C. Conclusion: The FY*A allele is a potentially valuable protective factor against hepatocyte damage in chronic HCV-infected patients.

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