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Han HX, Su W, Zhou DB, Li J, Cao XX. Hepatitis B virus-related cryoglobulinemia: Clinical characteristics, virological features, and treatment. Virus Res 2023; 336:199212. [PMID: 37640269 PMCID: PMC10474225 DOI: 10.1016/j.virusres.2023.199212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/22/2023] [Accepted: 08/25/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a rare etiology of cryoglobulinemia, and its clinical characteristics, virological features and treatment are poorly understood. METHODS This retrospective study enrolled 23 patients with HBV-related cryoglobulinemia from 497 cryoglobulinemia patients at Peking Union Medical College Hospital between January 2015 and February 2023. We analyzed the clinical characteristics, virological features and management of patients with HBV-related cryoglobulinemia. RESULTS The 23 patients (13 males; median age 48 years) were all mixed cryoglobulinemia and serological HBsAg positive, while 15 patients exhibited HBV-DNA replication. The presence of HBsAg in cryoglobulins was evaluated in 7 patients, all of whom were positive. The most commonly involved organs were kidneys (69.6%), skin (65.2%), peripheral nerves (21.7%), joints (8.7%), gastrointestinal tract (4.3%), and cardiac (4.3%). Eight patients received antiviral therapy with nucleot (s)ide analogues (NAs) alone, 12 patients received NA- and corticosteroid-based regimens, and 3 patients received NA- and rituximab-based regimens based on the severity of clinical symptoms. After a median follow-up of 44 months, four patients died, and one patient was lost to follow-up. All remaining patients (n = 18) achieved clinical remission, and HBV-DNA replication was not detected in 16 out of 18 patients. There was no HBV reactivation in patients treated with rituximab. The three-year overall survival and progression-free survival were 87.0% and 80.3%, respectively. CONCLUSIONS HBV-related cryoglobulinemia patients should be treated with antiviral therapy. Corticosteroids and rituximab are effective for severe cases, but patients need to be closely monitored for therapy-related infection.
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Affiliation(s)
- Hong-Xiao Han
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Su
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China
| | - Dao-Bin Zhou
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China
| | - Jian Li
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China
| | - Xin-Xin Cao
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China.
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Retamozo S, Quartuccio L, Ramos-Casals M. Cryoglobulinemia. Med Clin (Barc) 2022; 158:478-487. [PMID: 35216803 DOI: 10.1016/j.medcli.2021.11.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 11/27/2021] [Accepted: 11/29/2021] [Indexed: 12/26/2022]
Abstract
Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures below 37 ̊C. Cryoglobulin-associated disease is heterogeneous, as not all patients present with it, includes various syndromic presentations (vasculitis is the most common, hyperviscosity syndrome is more exceptional), and can be associated with acute clinical pictures with high mortality. Until the appearance of specific antiviral treatments, the main aetiology has been chronic HCV infection, and currently it is mainly associated with systemic autoimmune diseases, malignant neoplasms and cases with no identified aetiology (essential cryoglobulinemia). Treatment should be modulated according to the predominant etiopathogenesis (vasculitis or hyperviscosity), the severity of internal organ involvement and, especially, the associated underlying disease. Due to the complex aetiological, clinical and pathological scenario of cryoglobulinaemia, early recognition of the most common clinical presentations, a comprehensive clinical assessment of the different organs that may be affected, and multidisciplinary work led by a unit specialised in systemic autoimmune diseases is essential.
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Affiliation(s)
- Soledad Retamozo
- Servicio de Reumatología, Hospital Universitari Parc Taulí, Sabadell, Barcelona, España; Servicio de Reumatología, Hospital Quirón Salud, Barcelona, España
| | - Luca Quartuccio
- Departamento de Medicina, Reumatología, Universidad de Udine, Udine, Italia
| | - Manuel Ramos-Casals
- Servicio de Enfermedades Autoinmunes, ICMiD, Hospital Clínic, Barcelona, España; Departamento de Medicina, Universitad de Barcelona, Barcelona, España.
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3
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Hepatitis B Virus Infection and Extra-Hepatic Manifestations: A Systemic Disease. Am J Gastroenterol 2022; 117:253-263. [PMID: 34913875 DOI: 10.14309/ajg.0000000000001575] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 11/11/2021] [Indexed: 12/11/2022]
Abstract
People living with hepatitis B virus (HBV) chronic infection are exposed to high rates of liver complications including end-stage liver disease and hepatocellular carcinoma. Extrahepatic manifestations of HBV infection have long been underestimated. Several of these extrahepatic syndromes have been well described, including systemic vasculitides, glomerulonephritis, and cutaneous manifestations. Other manifestations have been more recently described such as hematological malignancies and neurological diseases. These extrahepatic manifestations are associated with significant morbidity and mortality. Although not completely understood, underlying mechanisms include HBV-induced local and systemic inflammation. Suppression of HBV replication usually improves extrahepatic manifestations. This review will discuss how HBV induces inflammation and the extrahepatic manifestations of HBV infection to guide clinical management.
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Wang CR, Tsai HW. Human hepatitis viruses-associated cutaneous and systemic vasculitis. World J Gastroenterol 2021; 27:19-36. [PMID: 33505148 PMCID: PMC7789062 DOI: 10.3748/wjg.v27.i1.19] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/19/2020] [Accepted: 12/27/2020] [Indexed: 02/06/2023] Open
Abstract
Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause liver inflammation in their common human host. Usually, HHV is rapidly cleared by the immune system, following acute HHV invasion. The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion, in the acute stage. Nevertheless, the viral infectious process can persist for a long period of time, especially in HBV and HCV infection, leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer. HHV infection brings about complications in other organs, and both acute and chronic hepatitis have been associated with clinical presentations outside the liver. Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation; moreover, there is growing evidence for a possible causal relationship between viral pathogens and vasculitis. Except for hepatitis delta virus, other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms, including direct viral invasion of vascular endothelial cells, immune complex-mediated vessel wall damage, and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells. Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection. Although therapeutic guidelines for HHV-associated vasculitis have not yet been established, antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids. Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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5
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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:819-837.e6. [DOI: 10.1016/b978-0-323-67293-1.00075-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Li C, Li H, Su W, Wen YB, Ye W, Ye WL, Cai JF, Qin XZ, Li XM, Li XW. Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection. BMC Nephrol 2020; 21:395. [PMID: 32928133 PMCID: PMC7490876 DOI: 10.1186/s12882-020-02057-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 09/06/2020] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. METHODS This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. RESULTS Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. CONCLUSIONS The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients' renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.
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Affiliation(s)
- Chao Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Hang Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Wei Su
- Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Yu-Bing Wen
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Wei Ye
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Wen-Ling Ye
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Jian-Fang Cai
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xu-Zhen Qin
- Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xue-Mei Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xue-Wang Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
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Kolopp-Sarda MN, Miossec P. Contribution of Hepatitis C Infection to a Large Cohort of Cryoglobulin-Positive Patients: Detection and Characteristics. Front Immunol 2020; 11:1183. [PMID: 32695098 PMCID: PMC7338377 DOI: 10.3389/fimmu.2020.01183] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 05/13/2020] [Indexed: 01/29/2023] Open
Abstract
Cryoglobulins (CGs) are cold precipitating immunoglobulins, and hepatitis C virus (HCV) infection is its most common cause. The purpose of the study was to determine the contribution of HCV in a large cohort of CG. Biological characteristics and specificity of CGs in HCV patients were compared to non-HCV subjects. Cryoglobulin analysis included isotype, clonality, concentration, and rheumatoid factor (RF) in cryoprecipitate and serum complement and RF. This study is an extension of the study carried out on a cohort of 13,439 patients tested for CGs from all medical units, in which 1,675/13,439 (12.5%) patients had a CG, and 680/1,675 (40.6%) had HCV serology or viral load determination (HCV RNA). Among these 680 CG patients tested for HCV, 325 of 680 (47.8%) HCV patients (272 HCV RNA+ and 45 HCV RNA− patients) were compared to 355/680 (52.2%) non-HCV subjects. After a positive detection of CG, HCV status was determined only for 37.7% (256/680) of patients, allowing the diagnosis of a previously unknown HCV infection for 39.8% (102/256). Concentration of HCV RNA+ CGs (median = 80.5 mg/L) was significantly higher than that of HCV RNA− CG (median = 50.5 mg/L, p = 0.001) and HCV− CG (median = 32 mg/L, p < 0.0001). There was no difference of median CG concentration between HCV RNA− patients and non-HCV subjects. Rheumatoid factor titer was significantly higher in type II CG compared to type III CG in HCV RNA+ patients (254 ± 720 vs. 15 ± 21 IU/mL, p < 0.0001) and non-HCV subjects (333 ± 968 vs. 16.8 ± 26 IU/mL, p = 0.0004). Complement functional activity CH50 was lower in HCV RNA+ patients (36 ± 24 U/mL) and in HCV RNA− patients (32 ± 21 U/mL) than in non-HCV subjects (50 ± 25 U/mL, p = 0.001 and p = 0.004). In conclusion, HCV infection and treatment influence CG characteristics. It is essential, and far from always tested, to determine the HCV status of patients with mixed CG, and conversely to search for CG in patients with HCV infection.
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Affiliation(s)
- Marie N Kolopp-Sarda
- Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Lyon, France.,Immunology Laboratory, Hospices Civils de Lyon, Lyon, France
| | - Pierre Miossec
- Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Lyon, France.,Department of Immunology and Rheumatology, Clinical Immunology Unit, Hospices Civils de Lyon, Lyon, France
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8
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Cozzani E, Herzum A, Burlando M, Parodi A. Cutaneous manifestations of HAV, HBV, HCV. Ital J Dermatol Venerol 2019; 156:5-12. [PMID: 31804053 DOI: 10.23736/s2784-8671.19.06488-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Hepatotropic viral infections are a relevant global health problem and present multiple extrahepatic manifestations in addition to hepatic disease. Along with generic cutaneous symptoms correlated to the cholestatic liver disease that may arise during the infection, some cutaneous manifestations of hepatotropic viral infections are characteristic, enabling to suspect the underlying infection. This review will present the principal cutaneous manifestations of hepatotropic virus infection. Cutaneous manifestations are rare in HAV infections: these include urticaria, panniculitis, scarlatiniform eruption, evanescent skin rash, maculopapular prolonged rash, serum sickness-like illness rash, cutaneous vasculitis, cryoglobulinemia. The commonest cutaneous manifestation associated to HBV infection is serum sickness-like syndrome. Polyarteritis nodosa (PAN) is among the most common and serious cutaneous manifestations of HBV infection. In children, HBV infection may acutely manifest as papular acrodermatitis of childhood (Gianotti-Crosti Syndrome), with non-pruritic, non-coalescing, round papules. Patients with chronic HBV infection may also develop mixed cryoglobulinemia, that is, inter alia, the most documented extrahepatic manifestation of HCV infection. Cutaneous lichen planus has been associated to HBV and HCV infection. As for oral lichen planus, the association with HBV and HCV is more debated. Interestingly, patients with oral lichen planus with HCV have a higher risk of developing oral squamous cell carcinoma. Dermatologists should be aware of the possible cutaneous manifestations associated to viral hepatitis.
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Affiliation(s)
- Emanuele Cozzani
- Section of Dermatology, Department of Health Sciences (DISSAL), IRCCS San Martino University Hospital, Genoa, Italy -
| | - Astrid Herzum
- Section of Dermatology, Department of Health Sciences (DISSAL), IRCCS San Martino University Hospital, Genoa, Italy
| | - Martina Burlando
- Section of Dermatology, Department of Health Sciences (DISSAL), IRCCS San Martino University Hospital, Genoa, Italy
| | - Aurora Parodi
- Section of Dermatology, Department of Health Sciences (DISSAL), IRCCS San Martino University Hospital, Genoa, Italy
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9
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Malchesky PS. Aging, Disease, and Therapeutic Apheresis. Ther Apher Dial 2019; 22:312-316. [PMID: 30993875 DOI: 10.1111/1744-9987.12706] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 05/03/2018] [Indexed: 11/30/2022]
Affiliation(s)
- Paul S Malchesky
- International Center for Artificial Organs & Transplantation, Painesville, OH, USA
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10
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Kolkhir P, Pereverzina N, Olisova O, Maurer M. Comorbidity of viral hepatitis and chronic spontaneous urticaria: A systematic review. Allergy 2018; 73:1946-1953. [PMID: 29786879 DOI: 10.1111/all.13482] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/16/2018] [Indexed: 12/17/2022]
Abstract
Chronic viral infections including those by hepatitis B (CHB) virus and hepatitis C (CHC) virus have been reported to be comorbidities of chronic spontaneous urticaria (CSU). Here, we performed the first comprehensive review of the peer-reviewed literature (PubMed, Web of Science and Google Scholar) on the prevalence of CHB and CHC in patients with CSU and vice versa. The prevalence of CHB and CHC in CSU does not appear to be increased. Less than 5% and 2% of patients with CSU have markers of CHB and CHC, respectively, according to most of the 32 studies reviewed. Urticarial rash including CSU occurs in ≤3% of patients with CHC as reported by most of 20 studies analysed. Very few patients have been assessed for the effects of antiviral hepatitis treatment on their CSU, and two but not all reportedly showed improvement. Hepatitis B/C infections appear unlikely to be linked to CSU. We suggest that routine screening for these infections in patients with CSU is not relevant or cost-effective and should not be performed unless liver function tests are abnormal, risk factors or symptoms of viral hepatitis are present, or urticarial vasculitis is suspected.
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Affiliation(s)
- P. Kolkhir
- Division of Immune‐mediated Skin Diseases Department of Dermatology and Venereology I.M. Sechenov First Moscow State Medical University Moscow Russian Federation
- Department of Dermatology and Allergy Charité – Universitätsmedizin Berlin Berlin Germany
| | - N. Pereverzina
- Division of Immune‐mediated Skin Diseases Department of Dermatology and Venereology I.M. Sechenov First Moscow State Medical University Moscow Russian Federation
| | - O. Olisova
- Division of Immune‐mediated Skin Diseases Department of Dermatology and Venereology I.M. Sechenov First Moscow State Medical University Moscow Russian Federation
| | - M. Maurer
- Department of Dermatology and Allergy Charité – Universitätsmedizin Berlin Berlin Germany
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12
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Li SJ, Xu ST, Chen HP, Zhang MC, Xu F, Cheng SQ, Liu ZH. Clinical and morphologic spectrum of renal involvement in patients with HBV-associated cryoglobulinaemia. Nephrology (Carlton) 2018; 22:449-455. [PMID: 27062412 DOI: 10.1111/nep.12795] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 04/01/2016] [Accepted: 04/03/2016] [Indexed: 12/30/2022]
Abstract
AIM Cryoglobulinaemic glomerulonephritis related to hepatitis B virus (HBV) infection has been rarely reported. The aim of this study was to investigate the clinical features, renal biopsy findings in patients with HBV-associated cryoglobulinaemia. METHODS Twelve patients with HBV-associated cryoglobulinaemia were identified in this study. The demographic, clinical, pathological characteristics, treatment and follow-up data were analyzed. RESULTS Renal involvement was characterized by nephrotic range proteinuria with microscopic haematuria in all patients, and impaired renal function in nine patients (75%). Purpuric rash was the main extrarenal manifestation (58.3%). Type II cryoglobulinaemia was presented in three patients and type III in nine patients. Hypocomplementaemia and positive of rheumatoid factors were present in all patients. Membranoproliferative glomerulonephritis (MPGN) was observed in all kidney specimens. Seven patients also had evidence of prominent cryoglobulins thrombi on renal biopsy, but only three patients had HBV antigen deposits in renal tissues. Antiviral and steroids or immunosuppressive agents have been used in most of patients. During follow-up, two patients died, and four reaching end-stage renal disease; three patients had complete remission, and three patients had renal function improved after therapy. CONCLUSIONS Nephrotic syndrome with haematuria and renal insufficiency are the main clinical manifestation; cryoglobulinaemic glomerulonephritis are the main renal lesion in patients with HBV-Associated cryoglobulinaemia; half of patients have poor outcome even with antiviral and immunosuppressive therapy. The results of this study indicate that cryoglobulins should be detected in hepatitis B virus-Associated nephropathy in endemic area.
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Affiliation(s)
- Shi-Jun Li
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Shu-Tian Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Hui-Ping Chen
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Ming-Chao Zhang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Feng Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Shui-Qin Cheng
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Zhi-Hong Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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13
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Chowdhury R, Tsen A. Recurrent Mixed Cryoglobulinemia Despite Sustained Virologic Response to Treatment: A Case Report. Am J Kidney Dis 2017; 70:301-304. [PMID: 28343737 DOI: 10.1053/j.ajkd.2017.01.041] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 01/03/2017] [Indexed: 01/01/2023]
Abstract
Cryoglobulinemia is a manifestation of hepatitis C virus (HCV) infection. Treatment of HCV is the mainstay of therapy for mixed cryoglobulinemia syndrome, and newer HCV therapies with direct-acting antiviral agents have achieved great success in treating HCV infection compared with pegylated interferon alfa and ribavirin. Recurrence of mixed cryoglobulinemia syndrome following successful treatment with direct-acting antiviral agents is uncommon, and when it occurs, it is most often due to relapse of HCV viremia. We report a case of recurrent mixed cryoglobulinemia syndrome following HCV treatment with a new direct-acting antiviral agent (sofosbuvir) and ribavirin, in which HCV RNA was undetectable in serum, but detectable in the cryoprecipitate.
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Affiliation(s)
| | - Adrianne Tsen
- University of Texas Health Science Center at San Antonio, San Antonio, TX.
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Abstract
Chronic hepatitis B infection (CHB) is a known risk factor for malignancy. Unlike hepatocellular carcinoma (HCC), less is known about the risk of non-HCC malignancy. However, epidemiology and pathologic evidence suggests a strong association between non-Hodgkin lymphoma and CHB. Data regarding the risk of other malignancies, such as pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma, are mixed. Surveillance and appropriate treatment of infection and malignancy in these patients is essential. Further study of these associations is needed and may bring new insights in the pathogenesis and treatment of these diseases.
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Affiliation(s)
- Ryan M Kwok
- Gastroenterology Fellowship Program, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA.
| | - Tram T Tran
- Gastroenterology Fellowship Program, Cedars Sinai Medical Center, Geffen School of Medicine at University of California Los Angeles, 8900 Beverly Boulevard, Los Angeles, CA 90048, USA
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15
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Agnello V. The Kunkel legacy and hepatitis C virus infection. Clin Immunol 2016; 172:78-82. [PMID: 27503146 DOI: 10.1016/j.clim.2016.07.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 07/25/2016] [Indexed: 11/17/2022]
Abstract
In commemoration of Henry Kunkel's 100th birthday, the effect of his legacy on the investigation of hepatitis C virus is recounted. The delineation of a major cross-idiotype (WA) among patients with essential mixed cryoglobulinemia led to the discovery that HCV was the etiologic agent for this disease. Studies of the cryoglobulins led to the discovery that WA RF reacted specifically with HCV-VLDL like particles that on electronmicroscopy and binding studies appeared to be the virion within a lipid shell. This particle mediates cell entry via LDLr and may serve to avoid the immune response by masking the virion. In addition, the WA B cell may be a prognostic marker for cutaneous vasculitis and B cell malignancy in HCV-infected patients. In commemoration of Henry Kunkel's 100th birthday, this is an account of how his legacy had a role in the investigation of hepatitis C virus (HCV) infection. There is a bit of a historical basis for the legacy of this great immunologist having a role in virology. He began his research career studying hepatitis. Later he worked with HCV in his studies of mixed cryoglobulins although he didn't know it at the time. There may also have been a Kunkel historical basis for why he accepted me as fellow in his laboratory considering that my credentials paled in comparison with those of the fellows and PhD students in his laboratory. Like Henry I was drafted into the Navy following my internship, I had had minimal research experience in medical school and only one minor publication, and I had a passion for clinical investigation. It may have been fortuitous that while on active duty at the Bayonne NJ Naval Base I visited Henry Kunkel in my Navy uniform and told him I was interested in studying SLE. I did not know at the time the dramatic role the Navy had played in his career or that one of his major training goals was to teach MDs to use clinical observation as a focus for delineating disease mechanisms in the laboratory. When I started work in the laboratory on discharge from the Navy, the first thing he told me was that it took five years to make a clinical investigator so I might as well get a Rockefeller University PhD while working in his laboratory. I was sure I would leave the laboratory after two years so I declined his offer. I did not leave until six years later!
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Affiliation(s)
- Vincent Agnello
- Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA 01805, United States.
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Herrera GA, Ojemakinde KO, Turbat-Herrera EA, Gu X, Zeng X, Iskandar SS. Immunotactoid Glomerulopathy and Cryoglobulinemic Nephropathy: Two Entities with Many Similarities. A Unified Conceptual Approach. Ultrastruct Pathol 2016; 39:270-80. [PMID: 26270724 DOI: 10.3109/01913123.2015.1017070] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease.
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17
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1921] [Impact Index Per Article: 213.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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18
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Grigorescu I, Dumitrascu DL. Spontaneous and antiviral-induced cutaneous lesions in chronic hepatitis B virus infection. World J Gastroenterol 2014; 20:15860-15866. [PMID: 25400473 PMCID: PMC4229554 DOI: 10.3748/wjg.v20.i42.15860] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 03/03/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To describe spontaneous, or interferon (IFN)- or immunization-induced skin lesions in hepatitis B virus (HBV) infection. METHODS A comprehensive literature search of all the papers presenting case reports of dermatological lesions in patients with chronic HBV infection was carried out. We included only patients with histologically proven skin lesions that appeared in the normal course of hepatitis B infection, or after immunization for hepatitis B or antiviral treatment. RESULTS We found 44 papers on this topic, reporting 151 cases. About 2% of patients with hepatitis B infection, mainly men, presented with skin lesions. Among patients with chronic hepatitis B, vasculitis and essential mixed cryoglobulinemia seemed to be the most frequent skin lesion (53.3%), followed by papular changes, rashes and Gianotti-Crosti syndrome, skin carcinoma and Henoch-Schönlein purpura were rare. IFN treatment seemed to be effective against HBV-associated and immunoglobulin-complex-mediated disease (vasculitis). Two cutaneous lesions (lichen planus and granuloma annulare) were described after hepatitis B vaccination. Systemic lupus and lupus-like lesions were the most frequently encountered lesions after antiviral treatment. Immunosuppressive and steroid therapy ameliorates lichen planus lesions in 50% of cases. CONCLUSION Vasculitis was the most frequent spontaneous skin lesion found in chronic hepatitis B. Lichen planus was most frequent after immunization and lupus/lupus-like lesions after IFN.
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Nishida N, Kudo M. Clinical features of vascular disorders associated with chronic hepatitis virus infection. Dig Dis 2014; 32:786-90. [PMID: 25376297 DOI: 10.1159/000368023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Hepatitis virus infections can be accompanied by extrahepatic manifestations that may be caused by the host's immune reaction to the viral infection. Vascular involvement is one of these manifestations and is occasionally associated with life-threatening conditions due to systemic organ failure. The unique profile of hepatitis-related vascular involvement is associated with infection by different types of hepatitis viruses. For example, polyarteritis nodosa is more frequently reported in patients with chronic hepatitis B than those with chronic hepatitis C. Similarly, membranous nephropathy is a notable manifestation among hepatitis B virus-positive patients. In contrast, patients infected with hepatitis C virus are at risk for cryoglobulinemia and membranoproliferative glomerulonephritis. Antiviral therapy is necessary to control these kinds of vasculitis related to hepatitis virus infections; however, immunosuppressive agents may be required to treat severe cases. New antiviral drugs for viral hepatitis could improve the prognosis of vascular and renal involvement.
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Affiliation(s)
- Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan
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20
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Ojemakinde K, Turbat-Herrera EA, Zeng X, Gu X, Herrera GA. The many faces of cryoglobulinemic nephropathy: a clinico-pathologic study of 47 cases with emphasis on the value of electron microscopy. Ultrastruct Pathol 2014; 38:367-76. [PMID: 25191813 DOI: 10.3109/01913123.2014.952803] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The clinical and pathologic manifestations of cryoglobulinemic nephropathy (CN) are heterogeneous. The role that electron microscopy plays in the diagnosis of CN has not been properly evaluated. The main objective of this study was to define the value of ultrastructural evaluation in the diagnosis of CN. Although most of the CN cases in this series exhibited glomerular pathology with a membranoproliferative pattern, a significant number of the cases showed less well-defined morphologic patterns on light microscopic examination (i.e. mesangial proliferation, hyaline thrombi in glomerular capillaries without significant cellular proliferation, exudative glomerulonephritis, etc). Immunofluorescence microscopy also revealed variable immunoglobulin and complement component patterns, some with "full-house" expression of immunoreactants. A subset of these CN cases was associated with light chain restriction. Thus, differential diagnosis can be a challenge as many other glomerulonephritis overlap in immunomorphologic characteristics. Because the immunomorphologic manifestations of CN are so varied, confirmation of a suspected diagnosis of CN or making a diagnosis in a less than a typical immunomorphologic setting required careful ultrastructural evaluation to find unequivocal diagnostic findings or at least supportive evidence in the form of detection of substructure in the electron dense glomerular deposits consistent with cryoglobulins. Even in cases where the light and immunofluorescence findings in suspicious clinical situations were quite consistent with CN, electron microscopy provided the final proof to substantiate the diagnosis in the great majority of the cases.
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Affiliation(s)
- Kunle Ojemakinde
- Department of Pathology, Louisiana State University Health Sciences Center , Shreveport , USA
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21
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Viganò M, Martin P, Cappelletti M, Fabrizi F. HBV-Associated Cryoglobulinemic Vasculitis: Remission after Antiviral Therapy with Entecavir. Kidney Blood Press Res 2014; 39:65-73. [DOI: 10.1159/000355778] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2014] [Indexed: 11/19/2022] Open
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22
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Yamazaki T, Akimoto T, Okuda K, Sugase T, Takeshima E, Numata A, Morishita Y, Iwazu Y, Yoshizawa H, Komada T, Iwazu K, Saito O, Takemoto F, Muto S, Kusano E. Purpura with ulcerative skin lesions and mixed cryoglobulinemia in a quiescent hepatitis B virus carrier. Intern Med 2014; 53:115-9. [PMID: 24429450 DOI: 10.2169/internalmedicine.53.1203] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Mixed cryoglobulinemia is occasionally seen in patients with hepatitis B virus (HBV) infection. This report presents the case of a quiescent HBV carrier who had type II mixed cryoglobulinemia, protracted purpura, ulcerative skin lesions and advanced chronic kidney disease. The cutaneous manifestations of the patient improved along with a decrease in the serum cryoglobulin and HBV-deoxyribonucleic acid levels following the initiation of oral entecavir in combination with plasmapheresis. However, the patient ultimately required prednisolone due to the limited benefits of these treatments. We also discuss various concerns regarding steroid treatment in patients with mixed cryoglobulinemia complicated by HBV infection.
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Affiliation(s)
- Tomoyuki Yamazaki
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Japan
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23
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Sellner J, Steiner I. Neurologic complications of hepatic viruses. HANDBOOK OF CLINICAL NEUROLOGY 2014; 123:647-61. [PMID: 25015509 DOI: 10.1016/b978-0-444-53488-0.00031-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Johann Sellner
- Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University, Salzburg, Austria; Department of Neurology, Klinikum rechts der Isar, Technische Universität Munich, Germany
| | - Israel Steiner
- Department of Neurology, Rabin Medical Center, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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24
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Naik P, Premsagar B, Mallikarjuna M. Acute renal failure in liver transplant patients: Indian study. Indian J Clin Biochem 2013; 30:94-8. [PMID: 25646048 DOI: 10.1007/s12291-013-0410-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 11/11/2013] [Indexed: 12/14/2022]
Abstract
The acute renal failure is the frequent medical complication observed in liver transplant patients. The objective of this study was to determine the cause of acute renal failure in post liver transplant patients. A total of 70 patients who underwent (cadaveric 52, live 18) liver transplantation were categorized based on clinical presentation into two groups, namely hepatorenal failure (HRF, n = 29), and Hepatic failure (HF, n = 41). All the patients after the liver transplant had received tacrolimus, mycophenolate and steroids. We analyzed the modification of diet in renal disease, (MDRD) serum urea, creatinine and albumin before and after 5th and 30th day of liver transplant and data was categorized into survivors and non-survivors group. In HRF survivor group, serum creatinine, and urea levels were high and, albumin, MDRD were low in pre- transplant and reached to normal levels on 30th day of post transplant, and 79.3 % of patients in this group showed resumption of normal kidney function. On the contrary in HRF nonsurvivor group, we did not observed any significant difference and 20.7 % of patients showed irreversible changes after the liver transplant. In HF survivor group, 82.9 % of liver failure patients did not show any deviation in serum creatinine, urea, albumin and MDRD, whereas in HF non survivor group, 17.1 % of liver failure patients who had HCV positive before the transplant developed acute renal failure. The levels of creatinine, urea, albumin and MDRD were normal before the transplant and on day 30th, the levels of albumin and MDRD were significantly low whereas serum urea, creatinine levels were high. In conclusion, based on these observations, an diagnosis and treatment of Acute renal failure is important among the liver transplantation cases in the early postoperative period.
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Affiliation(s)
- Pradeep Naik
- Department of Clinical Biochemistry, Global Hospitals, Lakdikapool, Hyderabad, 500004 India
| | - B Premsagar
- Department of Clinical Biochemistry, Global Hospitals, Lakdikapool, Hyderabad, 500004 India
| | - M Mallikarjuna
- Department of Clinical Biochemistry, Global Hospitals, Lakdikapool, Hyderabad, 500004 India
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25
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Abstract
Approximately 400 million worldwide are chronically infected with the hepatitis B virus (HBV). During the course of illness, approximately 20% of patients develop disease manifestations outside the liver. Neuropathy develops in approximately 5% of patients with chronic HBV infection and rarely during acute HBV infection. The pathogenesis of the various HBV-associated neuropathy syndromes possibly involves deposition of immune complexes in nerves or blood vessel walls. Direct viral infection of nerves has not been demonstrated. Management entailed supportive care with antiviral and immunomodulatory treatment as clinically indicated. Rare cases of muscle disease, mostly inflammatory myopathy, have been associated with HBV infection. Presumably, HBV-associated antigens trigger immune mechanisms directed against components of muscle tissue. There is no evidence of replicative virus infection of muscle fibers. Management entailed immunomodulatory treatment, occasionally with anti-HBV therapy. Physicians should be aware that HBV infection has the potential to trigger presumed immune-mediated neuromuscular syndromes.
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26
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27
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Otani M, Kuroki A, Kikuchi S, Kihara M, Nakata J, Ito K, Furukawa JI, Shinohara Y, Izui S. Sialylation determines the nephritogenicity of IgG3 cryoglobulins. J Am Soc Nephrol 2012; 23:1869-78. [PMID: 23024299 DOI: 10.1681/asn.2012050477] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Monoclonal 6-19 IgG3 anti-IgG2a rheumatoid factor derived from lupus-prone MRL-Fas(lpr) mice can induce GN and cryoglobulinemia, but the features that confer nephritogenic potential are not completely understood. Asparagine-linked oligosaccharide chains of 6-19 IgG3 mAb are poorly galactosylated and hardly sialylated, possibly contributing to the pathogenic potential of 6-19 IgG3 rheumatoid factors. Here, we used the 6-19 model of cryoglobulin-associated GN to define the relative contributions of galactosylation and sialylation, in relation to cryoglobulin activity, to the nephritogenic potential of IgG3 antibodies. We generated one highly sialylated and two distinct more galactosylated 6-19 IgG3 rheumatoid factor variants. Although the mere extent of galactosylation had no effect on either the cryogenic and nephritogenic activities of 6-19 IgG3 rheumatoid factor, terminal sialylation attenuated the nephritogenic potential of 6-19 IgG3 by limiting its cryoglobulin activity. These data suggest a protective role of IgG sialylation against the development of cryoglobulin-mediated GN, highlighting the anti-inflammatory activity of sialylated IgG antibodies.
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Affiliation(s)
- Masako Otani
- Department of Pathology and Immunology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland
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Extrahepatic manifestations of hepatitis B virus infection: Addison's disease and myelofibrosis in a patient with persistent hepatitis B surface antigenemia. Can J Infect Dis 2012; 4:139-44. [PMID: 22346436 DOI: 10.1155/1993/393861] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/1991] [Accepted: 03/31/1992] [Indexed: 11/18/2022] Open
Abstract
A 60-year-old white male patient was admitted to the hospital with acute abdominal pain, seemingly a self-limited ileus. He was found to be hepatitis B surface antigen (HBsAg)-positive. Previous dental treatment was suspected to be the initial source of the infection with hepatitis B virus. Five months later he was re-admitted with a diagnosis of adrenal insufficiency (Addison's disease) which responded well to steroids. Four years later he developed fever and leucocytosis. A bone marrow biopsy revealed myelofibrosis. He had several episodes of pyrexia during his lifetime. After a 12-year period the patient suffered a fatal myocardial infarction. At autopsy the adrenal glands were reduced to scarred remnants and HBsAg was found to be present in the residual adrenocortical cells by immunoflouresence methods. Bone marrow at autopsy revealed myelosclerosis as well HBsAg (via immunofluoresence). Hepatitis B virus was therefore closely correlated with the development of Addison's disease and myelofibrosis in this case.
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29
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Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia. Clin Rev Allergy Immunol 2012; 42:238-46. [PMID: 21633930 DOI: 10.1007/s12016-011-8275-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al. Semin Arthritis Rheum 33:19-28, 2003). MC is associated with infectious and systemic disorders, principally autoimmune and lymphoproliferative diseases. Since the 1990s, a striking association (>90%) between MC and hepatitis C virus (HCV) infection has been established (Ferri and Bombardieri 2004; Pascual et al. J Infect Dis 162:569-570, 1990). However, information regarding the etiopathogenesis of HCV-negative MC is scant (Mascia et al. Dig Liver Dis 39:61-64, 2007). We hereby present our findings, as well as previously published data, regarding the presence of antibodies against infectious agents and autoantibodies in patients with MC in an attempt to establish novel associations which may shed light on the etiopathogenesis of this disease.
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30
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Autoimmune manifestations in viral hepatitis. Semin Immunopathol 2012; 35:73-85. [PMID: 23010889 DOI: 10.1007/s00281-012-0328-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Accepted: 07/01/2012] [Indexed: 02/06/2023]
Abstract
Infections by the viruses responsible for hepatitis B, C and D are accompanied by a number of immunopathological manifestations. A link between infection and autoimmunity is particularly well documented for the hepatitis C virus. Immunopathological manifestations range from production of autoantibodies to overt autoimmune disease, including thyroiditis and autoimmune hepatitis, and to immune-complex-mediated disorders, including cryoglobulinaemia, glomerulonephritis and vasculitis. Several of these manifestations improve with successful antiviral treatment, directly incriminating the virus in their pathogenesis. Mechanisms considered responsible for hepatitis virus-related immunopathology, including molecular mimicry, impairment of regulatory T cells and activation of B lymphocytes, will be examined in this review.
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Hassan M, Selimovic D, El-Khattouti A, Ghozlan H, Haikel Y, Abdelkader O. Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies. World J Exp Med 2012; 2:7-25. [PMID: 24520529 PMCID: PMC3905577 DOI: 10.5493/wjem.v2.i2.7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2012] [Revised: 04/16/2012] [Accepted: 04/18/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon based therapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection (HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.
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Affiliation(s)
- Mohamed Hassan
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Denis Selimovic
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Abdelouahid El-Khattouti
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Hanan Ghozlan
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Youssef Haikel
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Ola Abdelkader
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
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32
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Lok ASF, Negro F. Hepatitis B and D. SCHIFF'S DISEASES OF THE LIVER 2011:537-581. [DOI: 10.1002/9781119950509.ch24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Stübgen JP. Immune-mediated myelitis associated with hepatitis virus infections. J Neuroimmunol 2011; 239:21-7. [PMID: 21945641 DOI: 10.1016/j.jneuroim.2011.09.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Revised: 07/24/2011] [Accepted: 09/02/2011] [Indexed: 12/14/2022]
Abstract
Virus-induced spinal cord damage results from a cytolytic effect on anterior horn cells or from predominantly cellular immune-mediated damage of long white matter tracts. Infection with the hepatitis virus group, most notably hepatitis C virus, has infrequently been associated with the occurrence of myelitis. The pathogenesis of hepatitis virus-associated myelitis has not been clarified: virus-induced autoimmunity (humoral or cell-mediated, possibly vasculitic) seems the most likely disease mechanism. Limited available information offers no evidence of direct hepatitis virus infection of the spinal cord. Virus neuropenetration may occur after virus-infected mononuclear cells penetrate the blood-brain barrier, but a true neurolytic effect has not been demonstrated. Attacks of acute myelitis usually respond favorably to immunomodulatory therapy. Antiviral therapy plays no confirmed role in the treatment of acute bouts of myelitis, but may limit the relapsing course of HCV-associated myelitis.
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Affiliation(s)
- Joerg-Patrick Stübgen
- Department of Neurology and Neuroscience, Cornell University Medical College/New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065-4885, USA.
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Abstract
Chronic liver disease is associated with several cutaneous manifestations. Although many of these changes are nonspecific, some are associated with distinct liver diseases and correlate with the severity of hepatic pathology. Often the first clue to a liver disease is manifested through skin. Although cirrhosis is associated with spider nevi and palmar erythema, disorders can result in noncirrhotic cutaneous manifestations. It is important for physicians to be familiar with the spectrum of these manifestations, to recognize, help detect, and treat the underlying hepatic disease. This article reviews the medical literature and discusses the spectrum of dermatologic manifestations of liver disorders and their pathogenesis, significance, and treatment.
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Affiliation(s)
- Sanjaya K Satapathy
- Long Island Jewish Medical Center at Albert Einstein College of Medicine, North Shore-Long Island Jewish Health system, 270-05 76th Avenue, New Hyde Park, NY 11040, USA
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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2011:811-828.e5. [DOI: 10.1016/b978-1-4377-0774-8.10075-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Enríquez R, Sirvent A, Andrada E, Escolano C, Rodríguez J, Millán I, Gutiérrez F, Amorós F. Cryoglobulinemic glomerulonephritis in chronic hepatitis B infection. Ren Fail 2010; 32:518-22. [DOI: 10.3109/08860221003675252] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Nakahara K, Takahashi H, Okuse C, Shigefuku R, Yamada N, Murao M, Matsunaga K, Koike J, Yotsuyanagi H, Suzuki M, Kimura K, Itoh F. Membranous nephropathy associated with chronic hepatitis B occurring in a short period after acute hepatitis B virus infection. Intern Med 2010; 49:383-8. [PMID: 20190469 DOI: 10.2169/internalmedicine.49.2812] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We herein present a case of membranous nephropathy associated with chronic hepatitis B following acute hepatitis B virus (HBV) infection. A 22-year-old man was admitted to our hospital for evaluation of proteinuria, pitting edema on both legs, and increased body weight in December 2002. At the age of 18, he had suffered from acute hepatitis A and syphilis, and was found to be negative for hepatitis B surface antigen (HBsAg). Furthermore, he suffered from acute hepatitis B (AH-B) at the age of 21; he was found to be positive for HBsAg and anti-IgM antibody to core antigen (IgM HBcAb). However, he discontinued outpatient treatment before confirmation of HBsAg clearance or the appearance of antibody to HBsAg (HBsAb). At the present admission, HBsAg, antibody to hepatitis B e antigen (HBeAg), and HBcAb were positive, while IgM HBcAb was negative. His genotype of HBV was type A (HBV/A). Histopathological findings of the renal biopsy specimen confirmed glomerulonephritis and glomerular deposition of HBsAg. Thus, he was diagnosed as having nephrotic syndrome caused by membranous nephropathy (MN) associated with chronic hepatitis B (CH-B) following AH-B. Although interferon-alpha (IFN-alpha) administration was started for the treatment and temporary improvement of proteinuria was observed, remission of MN was not achieved.
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Affiliation(s)
- Kazunari Nakahara
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University, School of Medicine, Kawasaki
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Shirato K, Reid C, Ibbetson JS, Hissaria P, Shireen S. Diagnosis of type I cryoglobulinaemia made through identifying crystals in the blood smear. Australas J Dermatol 2009; 50:281-4. [DOI: 10.1111/j.1440-0960.2009.00559.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
This article focuses on autoimmune manifestations related to the hepatitis B virus (HBV). Although the HBV vaccination has resulted in the decline of the virus, approximately 400 million individuals are infected worldwide. Up to twenty percent of the afflicted may develop extrahepatic manifestations ranging from the severe polyarteritis nodosa to the many, varied, and less severe clinical and biologic forms. Currently, control of the viral infection is mainly based on the use of antiviral drugs (with the current availability of potent agents). Discussion of two hypotheses of the pathophysiology of the virus is followed by descriptions of the general, renal, rheumatologic, neurologic, skin, ophthalmologic, and hematologic manifestations.
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Affiliation(s)
- Patrice Cacoub
- Service de Médecine Interne, AP, HP Pitié-Salpêtrière Hospital Group, 75651 Paris Cedex 13, France.
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HBV and HCV chronic infection: autoimmune manifestations and lymphoproliferation. Autoimmun Rev 2009; 8:107-11. [PMID: 18700171 DOI: 10.1016/j.autrev.2008.07.012] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis B (HBV) and C (HCV) viruses differ both in viral structure and in natural history of chronic infection. However, they seem to share, although to a different extent, some characteristics, like the possibility to infect not only hepatic but also lymphatic cells and to associate with some hepatic and/or extrahepatic disorders of an autoimmune and/or lymphoproliferative nature. These characteristics have been more widely studied in the case of chronic HCV infection, where they are more evident, but they have been described also in the case of HBV infection.
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Abstract
Vasculitis may be associated with infection, immunization or anti-microbial drugs. Infections are responsible for a number of different types of vasculitis. Conversely, patients with vasculitis may develop infections, which sometimes mimic relapse. The aim of this review is to summarize the various aspects of the inter-relationship between vasculitis and infection, and the physiopathological mechanisms involved, in light of our current knowledge from animal models. Currently, a causal relationship between infection and vasculitis has only been established in a few instances and many mechanisms remain hypothetical. This inter-relationship is further assessed from the point of view of clinical presentation and therapeutic options, based on case reports and prospective observational data.
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Abstract
Cryoglobulinemia are immune complexes that may induce systemic cryoglobulinemic vasculitis, a small-vessel vasculitis involving the skin, the joints, the peripheral nerve system, and the kidneys. During the last 15 years, progresses have been done after the discovery of the hepatitis C virus, the main cause of cryoglobulins. Main factors associated with cryoglobulin production are female gender, alcohol intake above 50 g/day, extensive liver fibrosis, and steatosis. Symptomatic cryoglobulins (i.e., vasculitis) are associated with older age, longer duration of infection, and main characteristics of cryoglobulin (type II, IgM kappa, high serum levels). The physiopathology is complex, and it involves humoral immunity, B- and T-cellular immunity but not the virus itself. Peg-Interféron alpha Ribavirine combination leads to a virological and clinical response of the vasculitis in about 70% of patients. In nonresponders, recent open series suggested the efficacy of Rituximab with a good response in up to 80% of patients but a relapse in 42% after 7 months after the last infusion. For future prospects and projects, new therapeutic strategies include a combination of best antiviral treatment with Peg-Interferon plus Ribavirin and Rituximab. Multicenter controlled trials are mandatory.
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Abstract
Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable organ involvement including skin lesions (orthostatic purpura, ulcers), chronic hepatitis, membranoproliferative glomerulonephritis, peripheral neuropathy, diffuse vasculitis, and, less frequently, interstitial lung involvement and endocrine disorders. Some patients may develop lymphatic and hepatic malignancies, usually as a late complication. MC may be associated with numerous infectious or immunological diseases. When isolated, MC may represent a distinct disease, the so-called 'essential' MC. The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. Moreover, MC may be associated with other infectious agents or immunological disorders, such as human immunodeficiency virus (HIV) infection or primary Sjögren's syndrome. Diagnosis is based on clinical and laboratory findings. Circulating mixed cryoglobulins, low C4 levels and orthostatic skin purpura are the hallmarks of the disease. Leukocytoclastic vasculitis involving medium- and, more often, small-sized blood vessels is the typical pathological finding, easily detectable by means of skin biopsy of recent vasculitic lesions. Differential diagnoses include a wide range of systemic, infectious and neoplastic disorders, mainly autoimmune hepatitis, Sjögren's syndrome, polyarthritis, and B-cell lymphomas. The first-line treatment of MC should focus on eradication of HCV by combined interferon-ribavirin treatment. Pathogenetic treatments (immunosuppressors, corticosteroids, and/or plasmapheresis) should be tailored to each patient according to the progression and severity of the clinical manifestations. Long-term monitoring is recommended in all MC patients to assure timely diagnosis and treatment of the life-threatening complications. The overall prognosis is poorer in patients with renal disease, liver failure, lymphoproliferative disease and malignancies.
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Affiliation(s)
- Clodoveo Ferri
- Dipartimento Medicine e Specialità Mediche, Cattedra ed U,O,C, di Reumatologia, Università di Modena & Reggio Emilia, Modena, Italy.
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Abstract
PURPOSE OF REVIEW Cryoglobulinemia occurs in a variety of clinical settings including lymphoproliferative disorders, infection and autoimmune disease. The worldwide pandemic of hepatitis C virus infection has resulted in a significant increase in its extrahepatic complications including cryoglobulinemia and renal disease. Here we review the types of cryoglobulins, mechanisms of cryoglobulin formation, links between hepatitis C virus and renal disease, and current approaches to therapy. RECENT FINDINGS The prevalence of cryoglobulinemia in hepatitis C virus-infected individuals is surprisingly large and may be found in more than 50% of some infected subpopulations. Most of these patients will not have overt renal disease, but there is a population of unknown size of patients with subclinical glomerular disease that has the potential to become clinically significant. In cases of hepatitis C virus-associated cryoglobulinemia, treatment remains focused on eradication of viremia, but interventions directed at B lymphocytes are increasingly utilized. The mechanisms of cryoglobulin formation and renal injury remain largely obscure, but recent evidence implicates the innate immune system in the initiation of disease. SUMMARY The most common renal injury associated with hepatitis C virus infection, in patients both with and without evidence of cryoglobulinemia, is membranoproliferative glomerulonephritis. There has been increasing focus on defining the mechanisms that link these processes and the evolution of renal injury in all clinical settings of cryoglobulinemia.
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Carella G, Digeon M, Feldmann G, Jungers P, Drouet J, Bach JF. Detection of hepatitis B antigen in circulating immune complexes in acute and chronic hepatitis. Scand J Immunol 2008; 6:1297-304. [PMID: 24265 DOI: 10.1111/j.1365-3083.1977.tb00369.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
By using polyethylene glycol precipitation at low concentration (PEG test) and the radiolabeled C1q binding test, immune complexes were detected sera from acute (23/28) and chronic (28/32) hepatitis patients, hemodialyzed patients with chronic hepatitis B surface (HBs) antigenemia (7/19), and asymptomatic HBs antigen carriers (2/11). After treatment of PEG precipitates with acidic pH, heating, or proteolytic enzyme (protease), electroimmunodiffusion or radioimmunoassay revealed the presence of HBs antigen or antibody in dissociated immune complexes in sera from several acute and chronic hepatitis patients. Electron microscopy showed immune complexes of HB virus in 9 of 12 PEG precipitates obtained from PEG-test-positive sera; these 9 precipitates were from patients with acute or chronic hepatitis and the other three from chronic HBs Ag carriers. Free HB virus particles were observed after protease digestion of PEG precipitates. Neither immune complexes nor virus particles were seen in precipitates from PEG-test-negative but HBs-Ag-positive sera from chronic carriers.
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ABE Y, TANAKA Y, TAKENAKA M, YOSHIDA H, YATSUHASHI H, YANO M. Leucocytoclastic vasculitis associated with mixed cryoglobulinaemia and hepatitis C virus infection. Br J Dermatol 2008. [DOI: 10.1046/j.1365-2133.1997.d01-1186.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Dore MP, Fattovich G, Sepulveda AR, Realdi G. Cryoglobulinemia related to hepatitis C virus infection. Dig Dis Sci 2007; 52:897-907. [PMID: 17380399 DOI: 10.1007/s10620-006-9510-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2006] [Accepted: 07/05/2006] [Indexed: 12/15/2022]
Abstract
A causal link among hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia, cryoglobulinemic glomerulonephritis, and vasculitis is strongly supported. HCV triggers autoimmune response in predisposed individuals that manifests as organ-specific and non-organ-specific autoantibodies and as polyclonal/monoclonal rheumatoid factor, which has a central role in causing damaging cryoglobulin and immune complex tissue levels. Immunologic events are mainly induced by HCV infection persistence, with excessive immune stimulation. Humoral immune dysfunction leads to autoantibodies and rheumatoid factor production with cryoglobulinemia, glomerulonephritis, vasculitis, neuropathy, and probably thyroiditis, and arthritis in rare cases. Cellular immune dysfunction leads to lymphocytic infiltration, proliferation, and cytokine production. Pegylated (or not) interferon-alpha in combination with ribavirin appears to be the treatment of choice for patients with symptomatic essential mixed cryoglobulinemia with or without glomerulonephritis. Novel treatment with rituximab is promising.
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Affiliation(s)
- Maria Pina Dore
- Istituto di Clinica Medica, University of Sassari, Sassari, Italy.
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Huang JF, Chuang WL, Dai CY, Ho CK, Hwang SJ, Chen SC, Lin ZY, Wang LY, Chang WY, Yu ML. Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link? J Intern Med 2006; 260:255-262. [PMID: 16918823 DOI: 10.1111/j.1365-2796.2006.01686.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND OBJECTIVES Virus hepatitis may lead to nephropathy as one of its multiple extrahepatic manifestations. Proteinuria by dipstick, a simple test in practice, is a useful and cardinal sign of underlying renal abnormalities. The aim of this study was to elucidate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections on the occurrence of proteinuria amongst adults. DESIGN AND SETTING A prospective, cross-sectional, community-based study was conducted in an HBV/HCV endemic area of southern Taiwan. Eligible subjects aged 40-65 years (n=9934) underwent testing of hepatitis B surface antigen (HBsAg), HCV antibody (anti-HCV) and other related biochemical profiles. Urinalysis with repeated dipstick for proteinuria detection was performed. RESULTS Anti-HCV-positive rate amongst proteinuria subjects was significantly higher than nonproteinuria subjects (9.6% vs. 6.2%, P<0.001). By contrast, HBsAg-positive rate did not differ between subjects with and without proteinuria (13.0% vs. 13.8%, P=0.57). Prevalence of proteinuria amongst anti-HCV-positive subjects (10.2%) was significantly higher than that in HBsAg-positive subjects (6.4%, P=0.004) and in HBsAg-negative or anti-HCV-negative subjects (7.0%, P=0.004). The difference persisted even after excluding diabetics. Multivariate logistic regression analyses showed that diabetes was the most important significant factor associated with proteinuria, followed by hypertension, anti-HCV seropositivity, body mass index, age and triglyceride levels. CONCLUSION We demonstrated the significant association between proteinuria and HCV, but not HBV, infection in this HBV/HCV-endemic area.
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Affiliation(s)
- J-F Huang
- Graduate Institute of Medicine, Kaohsiung Medical University, and Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan
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Abstract
PURPOSE OF REVIEW Cryoglobulinemic vasculitis is an immune-complex-mediated systemic vasculitis involving small-medium-sized vessels. A causative role of hepatitis C virus in over 80% patients has been definitively established, with heterogeneous geographical distribution. This review focuses on recent etiopathogenetic, clinico-diagnostic, and therapeutical studies. RECENT FINDINGS Hepatitis C virus cannot be integrated into the host genome; it may exert a chronic stimulus to the immune system. The interaction between hepatitis C virus envelope protein E2 with B-cell CD 81 receptor may increase the frequency of VDJ rearrangement in antigen-reactive B lymphocytes. One consequence is the activation of various protooncogenes, including anti-apoptotic Bcl-2. The extended B-cell survival is responsible for autoantibody and immune-complex production, including mixed cryoglobulins; some malignancies, mainly B-cell lymphomas, may complicate cryoglobulinemic vasculitis. Environmental or viral/host genetic cofactors should be relevant in the pathogenesis of hepatitis C virus-related diseases. Cryoglobulinemic vasculitis may overlap with other diseases (systemic vasculitides, Sjögren's syndrome, autoimmune hepatitis, lymphoma), which should be carefully considered for a correct diagnosis and treatment. Cumulative survival of cryoglobulinemic vasculitis is significantly lower compared with the general population. Therapeutic strategies for cryoglobulinemic vasculitis include etiologic (antiviral), pathogenetic (cyclophosfamide, rituximab), or symptomatic (steroids, plasmapheresis) treatments, which should be tailored to the individual patient according to the severity/activity of clinical symptoms. SUMMARY Cryoglobulinemic vasculitis represents a crossroads among autoimmune and lymphoproliferative disorders; as hepatitis C virus infection is the major causative factor, cryoglobulinemic vasculitis is an important model for etiopathogenetic studies of virus-related diseases.
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Affiliation(s)
- Clodoveo Ferri
- Chair and Rheumatology Unit, Department of Internal Medicine, University of Modena e Reggio Emilia, Medical School, Modena, Italy.
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