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Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity. THE PHARMACOGENOMICS JOURNAL 2010; 10:524-36. [PMID: 20195289 DOI: 10.1038/tpj.2010.5] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Treatment of latent tuberculosis infection (LTBI) generally includes isoniazid (INH), a drug that can cause serious hepatotoxicity. Carboxylesterases (CES) are important in the metabolism of a variety of substrates, including xenobiotics. We hypothesized that genetic variation in CES genes expressed in the liver could affect INH-induced hepatotoxicity. Three CES genes are known to be expressed in human liver: CES1, CES2 and CES4. Our aim was to systematically characterize genetic variation in these novel candidate genes and test whether it is associated with this adverse drug reaction. As part of a pilot study, 170 subjects with LTBI who received only INH were recruited, including 23 cases with hepatotoxicity and 147 controls. All exons and the promoters of CES1, CES2 and CES4 were bidirectionally sequenced. A large polymorphic deletion was found to encompass exons 2 to 6 of CES4. No significant association was found. Eleven single-nucleotide polymorphisms (SNPs) in CES1 were in high linkage disequilibrium with each other. One of these SNPs, C(-2)G, alters the translation initiation sequence of CES1 and represents a candidate functional polymorphism. Replication of this possible association in a larger sample set and functional studies will be necessary to determine if this CES1 variant has a role in INH-induced hepatotoxicity.
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Yamada S, Tang M, Richardson K, Halaschek-Wiener J, Chan M, Cook VJ, Fitzgerald JM, Elwood RK, Brooks-Wilson A, Marra F. Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population. Pharmacogenomics 2009; 10:1433-45. [PMID: 19761367 DOI: 10.2217/pgs.09.66] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
AIMS TB is a serious global public health problem. Isoniazid, a key drug used to treat latent TB, can cause hepatotoxicity in some patients. This pilot study investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid-induced hepatotoxicity in TB contacts in British Columbia, Canada. MATERIALS & METHODS DNA re-sequencing was used to establish the spectrum of genetic variation in the exons, promoter and conserved regions of NAT2 in all subjects. For CYP2E1, the CYP2E1*1C polymorphism was genotyped by PCR-RFLP. Association tests of NAT2 variants and haplotypes, as well acetylator types were performed. RESULTS We enrolled 170 subjects on isoniazid treatment (23 cases and 147 controls). Systematic re-sequencing of NAT2 revealed 18 known and 10 novel variants. CONCLUSION No single genetic variant of NAT2 and CYP2E1 showed a significant association with isoniazid-induced hepatotoxicity in this highly heterogeneous population. There was evidence of a trend for increasing hepatotoxicity risk across the rapid, intermediate and slow acetylator groups (p = 0.08).
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Affiliation(s)
- So Yamada
- Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
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Rayhill SC, Kirby PA, Voigt MD, La Brecque DR, Lutz CT, Katz DA, Mitros FA, Kalil RS, Miller RA, Stolpen AH, Heisey D, Wu YM, Schmidt WN. Positive Serum Cryoglobulin Is Associated with Worse Outcome after Liver Transplantation for Chronic Hepatitis C. Transplantation 2005; 80:448-56. [PMID: 16123717 DOI: 10.1097/01.tp.0000164826.84041.f0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Recurrent hepatitis C virus (HCV) infection in patients after liver transplantation is an important clinical problem. Because serum cryoglobulins (CG) are known to be associated with an increased incidence of cirrhosis in nontransplant patients, the authors tested the hypothesis that CG would also predict aggressive recurrent HCV in patients after liver transplantation. METHODS Using a longitudinal database, the outcomes of 105 allografts transplanted into 97 HCV-positive patients from 1991 through 2002 were analyzed on the basis of CG status using a retrospective cohort design. Fifty-nine CG-negative and 38 CG-positive patients were identified. Histologic outcomes and graft survival were analyzed using Kaplan-Meier estimates and Cox univariate and multivariate analyses. Both overall survival and HCV-specific survival (non-HVC-related deaths and graft losses censored) were analyzed. RESULTS By Kaplan-Meier estimates, CG-positive patients showed earlier graft failure with decreased time to severe histologic activity and fibrosis as compared with CG-negative patients (P<0.05 for all outcomes). By univariate analysis, CG-positive patients had significantly higher risk ratios for shortened HCV-specific graft survival, severe activity-free survival, and severe fibrosis-free survival as compared with CG-negative patients (P<0.05 for all outcomes). In the multivariate model, CG was an independent predictor for severe activity-free, severe fibrosis-free, and HCV-specific graft survival (P<0.05 for all outcomes). CONCLUSIONS CG-positivity is associated with severe recurrent HCV disease in liver transplant recipients.
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Affiliation(s)
- Stephen C Rayhill
- Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
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Chen LK, Hwang SJ, Tsai ST, Luo JC, Lee SD, Chang FY. Glucose intolerance in Chinese patients with chronic hepatitis C. World J Gastroenterol 2003; 9:505-8. [PMID: 12632506 PMCID: PMC4621570 DOI: 10.3748/wjg.v9.i3.505] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence and the risk factors of glucose intolerance in Chinese patients with chronic hepatitis C and to evaluate the relationship between interferon (IFN) treatment and glucose intolerance in these patients.
METHODS: Prospective cross-sectional study was done to evaluate the prevalence of glucose intolerance in Chinese patients with chronic hepatitis C virus (HCV) infection from the outpatient clinic of Department of Family Medicine, Taipei Veterans General Hospital. Chronic hepatitis C was defined as persistent presence of anti-HCV and persistent elevation of liver transaminase for at least 1.5 folds for at least 6 months. Moreover, patients were further categorized into normal fasting glucose and glucose intolerance (diabetes mellitus (DM) and impaired fasting glucose) according to the diagnostic criteria of American Diabetic Association.
RESULTS: Totally, 359 Chinese patients with chronic hepatitis C were enrolled (212 males and 147 females, mean age = 58.1 ± 13.0 years). One hundred and twenty-three patients (34.3%) had received various forms of IFN treatment. One hundred and twenty-five patients (34.6%) had glucose intolerance, including 99 patients (27.6%) with DM and 26 patients (7.0%) with impaired fasting glucose. In comparison with those with normal fasting glucose levels, patients with chronic hepatitis C with glucose intolerance were significantly older, had a significantly higher body mass index, and they were more likely to suffer from obesity, to have family history of diabetes and to have had previous IFN treatment. Stepwise multivariate logistic regression revealed significantly that age 57 years, obesity, previous history of IFN treatment and the presence of family history of diabetes were independent risk factors associated with the presence of glucose intolerance in chronic hepatitis C patients.
CONCLUSION: In conclusion, 34.6% of Chinese patients with chronic hepatitis C had glucose intolerance. Chronic hepatitis C patients who were older in age, obese, had previous IFN treatment history and had family history of diabetes were prone to develop glucose intolerance. To our knowledge, this is the first population-based report to confirm that interferon treatment to be an independent risk factor to develop glucose intolerance.
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Affiliation(s)
- Liang-Kung Chen
- Department of Family Medicine, Taipei Veterans General Hospital, No. 201, Shih-Pai Road Sec 2, Taipei, 11217, Taiwan, China.
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Abstract
Approximately 40% of patients with chronic hepatitis C virus (HCV) infection develop detectable serum cryoglobulins or cryoprecipitates (CP), although most do not show clinical or physical signs of syndromic cryoglobulinemia. Although association of HCV with the extrahepatic complications of cryoglobulinemia is widely recognized, the relationship of cryoglobulinemia with liver disease is unclear. We wished to study the relationship between CP and cirrhosis and to determine whether the development of CP is a true covariate for progressive liver disease or a confounding variable that impacts cirrhosis because of patient age, duration of disease, or differences in gender. We undertook a meta-analysis of 19 studies published between 1994 and 2001. The incidence of cirrhosis was compared in patients with and without CP after logistic regression adjustments for accepted risk factors for progressive liver disease, including age, gender, and estimated duration of disease (EDD). A total of 2,323 patients with chronic hepatitis C were identified, with 1,022 (44%) having detectable CP. Cirrhosis was present in 40% of patients with CP but only 17% of patients without CP (total Chi;(2) = 141.69, P <.001). After adjusting for age, gender, and estimated duration of disease by logistic regression, the combined odds ratio for incidence of cirrhosis in patients CP positive versus CP negative was 4.87, (95% CI: 3.32, 7.15), indicating a highly significant association between cirrhosis and cryoglobulinemia. In conclusion, cryoglobulins may be a useful prognostic indicator for increased risk of cirrhosis with chronic hepatitis C.
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Affiliation(s)
- Zeid Kayali
- Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA
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Abstract
BACKGROUND Hepatitis C viral (HCV) infection is common in the general population and can cause disease in the nervous system. This article reviews the neurologic complications associated with this virus. REVIEW SUMMARY A vasculitic neuropathy is the most firmly linked neurologic illness associated with HCV infection. This type of neuropathy occurs frequently in the presence of cryoglobulinemia. HCV is considered the most common cause of cryoglobulinemia. Other types of neuropathy have been rarely reported with HCV infection and this association is less firm. In the central nervous system, vasculitis causing stroke appears to complicate HCV infection, usually in the setting of cryoglobulinemia. Several reports of myelitis, encephalitis,lymphoma are reviewed. HCV may be the etiologic virus of progressive encephalomyelitis with rigidity; a rare disorder similar to stiff-man syndrome although different because it is progressive and fatal. Treatment of the neurologic complications associated with HCV infection is summarized. CONCLUSIONS HCV infection is being increasingly recognized as a probable cause of a variety of neurologic disorders. Systematic study of the various therapeutic options remains unexplored.
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Affiliation(s)
- Sami L Khella
- Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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Hwang SJ, Chu CW, Huang DF, Lan KH, Chang FY, Lee SD. Genetic predispositions for the presence of cryoglobulinemia and serum autoantibodies in Chinese patients with chronic hepatitis C. TISSUE ANTIGENS 2002; 59:31-7. [PMID: 11972876 DOI: 10.1034/j.1399-0039.2002.590106.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Chronic hepatitis C virus (HCV) infection may induce immunological disorders in the host such as the presence of cryoglobulinemia or serum autoantibodies. The pathogenesis of these phenomena remains unclear but may reflect the host's genetic predispositions. The aim of this study was to evaluate the association between these immunological manifestations and human leukocyte antigen (HLA) expression in Chinese patients with chronic hepatitis C. The presence of serum cryoglobulin and autoantibodies (antinuclear antibody, antismooth muscle antibody, antimitochondrial antibody, antiliver-kidney-microsomal antibody) was determined in 122 Chinese patients with chronic hepatitis C. HLA class I and class II antigens were measured by microlymphocytotoxicity assay or by DNA typing in 122 chronic hepatitis C patients and 228 healthy controls. Of the 122 patients with chronic hepatitis C, 52 (43%) had cryoglobulinemia and 48 (39%) had serum autoantibodies. A significant difference in HLA frequency was noted for DR3, which was found in 36.5% of patients with cryoglobulinemia compared with 8.6% of patients without cryoglobulinemia and 11.3% of healthy controls. A significant difference in HLA frequency was also noted for DR4, which was found in 45.8% of patients with serum autoantibodies compared with 17.6% of patients without serum autoantibodies and 19% of healthy controls. Our results suggest the existence of HLA-linked susceptibility genes (DR3 or DR4) for the development of cryoglobulinemia or serum autoantibodies in Chinese patients with chronic hepatitis C.
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Affiliation(s)
- S-J Hwang
- Department of Family Medicine, Veterans General Hospital-Taipei, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China.
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Peng YC, Hsieh SC, Yang DY, Tung CF, Hu WH, Huang WN, Chen GH. Expression and clinical significance of antinuclear antibody in hepatitis C virus infection. J Clin Gastroenterol 2001; 33:402-6. [PMID: 11606858 DOI: 10.1097/00004836-200111000-00012] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. We attempted to determine the titer and to characterize the patterns and clinical significance of ANA in HCV infection. STUDY Forty-eight consecutive patients with positive anti-HCV antibody and positive HCV RNA were included in this study. Sera from patients were tested for ANA and anti-smooth muscle antibody by indirect immunofluorescence. Serum aminotransferase, alkaline phosphatase, alpha-fetoprotein, and cryoglobulin levels also were determined. RESULTS Eleven (23%) of 48 HCV-infected patients were positive for ANA. Antinuclear antibody revealed speckled pattern in 10 (91%) of the 11 ANA-positive HCV-infected patients. Twenty (54%) of 37 ANA-negative HCV-infected patients had detectable pattern with equivocal titer (titer <1.5). The ANA pattern was speckled in all 20 patients. Hepatitis C virus-infected patients with positive ANA were older than the HCV-infected patients with negative ANA (62.90 +/- 11.05 years vs. 56.46 +/- 14.94 years, respectively; p < 0.1). Serum levels of aspartate aminotransferase (39.36 +/- 14.98 IU/L vs. 30.70 +/- 23.15 IU/L, p < 0.05), alkaline phosphatase (189.00 +/- 75.63 IU/L vs. 122.41 +/- 40.88 IU/L, p < 0.01), and alpha-fetoprotein (47.72 +/- 80.47 pg/dL vs. 7.00 +/- 8.28 pg/dL, p < 0.01) were higher in ANA-positive HCV-infected patients than in ANA-negative HCV-infected patients, respectively. There were no significant differences in gender, alanine aminotransferase, anti-smooth muscle antibody, or cryoglobulin between the two groups. CONCLUSIONS Antinuclear antibody was present in 11 (23%) of 48 patients with HCV infection in our study. Speckled pattern is the major expression pattern of ANA in HCV infection. Antinuclear antibody-positive HCV-infected patients have significantly higher serum aspartate aminotransferase, alkaline phosphatase, and alpha-fetoprotein levels than ANA-negative HCV-infected patients.
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Affiliation(s)
- Y C Peng
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
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Bíró L, Varga L, Pár A, Nemesánszky E, Csepregi A, Telegdy L, Ibrányi E, Dávid K, Horváth G, Szentgyörgyi L, Nagy I, Dalmi L, Abonyi M, Füst G, Horányi M. Changes in the acute phase complement component and IL-6 levels in patients with chronic hepatitis C receiving interferon alpha-2b. Immunol Lett 2000; 72:69-74. [PMID: 10841940 DOI: 10.1016/s0165-2478(00)00183-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In order to study the effect of interferon alpha on the levels of acute phase complement proteins in vivo, serum concentrations of C9 and C1-inhibitor (C1-INH) were measured in patients with chronic hepatitis C before and 3 months after the beginning of interferon alpha2b therapy. Serum levels of the activation product of terminal complement pathway, C5b-9, HCV RNA and IL-6 were also determined. IFN alpha treatment significantly (P<0.0001) increased the serum concentrations of both complement proteins. C5b-9 levels were found to significantly decrease during the same period of time. When the patients were divided into responders or non-responders (more or less than 50% decrease in plasma HCV RNA concentrations) C9 and C1-INH levels were elevated only in the responder patients. There was no correlation between the changes of IL-6 levels or the amounts of IFN alpha administrated on one hand, and the changes in the complement protein levels on the other. These findings suggest that the marked increase in the serum concentrations of the acute phase complement proteins is a secondary phenomenon due to the IFN alpha-caused diminution of the viral load and the resulting immune complex-induced complement activation.
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Affiliation(s)
- L Bíró
- National Institute of Haematology and Immunology, Budapest, Hungary
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Luo JC, Hwang SJ, Lai CR, Lu CL, Li CP, Tsay SH, Wu JC, Chang FY, Lee SD. Clinical significance of portal lymphoid aggregates/follicles in Chinese patients with chronic hepatitis C. Am J Gastroenterol 1999; 94:1006-11. [PMID: 10201474 DOI: 10.1111/j.1572-0241.1999.01004.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Portal lymphoid aggregates/follicles (lymphoid A/F) is a characteristically histological finding in patients with chronic hepatitis C. We assessed the prevalence of lymphoid A/F in Chinese patients with chronic hepatitis C and evaluated the correlation of this phenomenon with clinical, biochemical, immunological, virological, and other histological features of these patients. METHODS Eighty-nine Chinese patients with chronic hepatitis C were enrolled and portal lymphoid A/F was evaluated in liver biopsy. Clinical, biochemical, immunological, histological, and virological data, including serum HCV RNA titer and HCV genotype and the response to interferon therapy, were compared between patients with and without portal lymphoid A/F. RESULTS Twenty-nine (33%) of 89 patients with chronic hepatitis C had portal lymphoid A/F. Patients with lymphoid A/F had a significantly higher frequency of HCV genotype 1b infection (p = 0.039) and had a significantly higher mean score of bile duct damage, periportal necroinflammation, and portal inflammation in liver histologies when compared with patients without lymphoid A/F. No significant difference in sex distribution, mean age, history of blood transfusion, serum liver biochemistry, presence of serum autoantibodies/cryoglobulinemia, serum viral titer, and response to interferon therapy was noted between the two groups. Multivariate logistic regression analysis showed HCV genotype 1b infection and periportal necroinflammation were significant independent predictors associated with portal lymphoid A/F. CONCLUSIONS The presence of portal lymphoid A/F in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection and periportal necroinflammation.
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Affiliation(s)
- J C Luo
- Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taiwan, Republic of China
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Luo JC, Hwang SJ, Li CP, Lu RH, Chan CY, Wu JC, Chang FY, Lee SD. Clinical significance of serum auto-antibodies in Chinese patients with chronic hepatitis C: negative role of serum viral titre and genotype. J Gastroenterol Hepatol 1998; 13:475-9. [PMID: 9641643 DOI: 10.1111/j.1440-1746.1998.tb00671.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) have been reported in 10-66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto-antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and HCV genotype) were compared between patients with and without serum auto-antibodies. Fifty-eight (48%) patients were associated with positive serum auto-antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto-antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not correlated to the presence of serum auto-antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.
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Affiliation(s)
- J C Luo
- Department of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University, School of Medicine, Taiwan, Republic of China
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Okuda K, Yokosuka O, Otake Y, Hayashi H, Yokozeki K, Kashima T, Kobayashi S, Sakuma K, Ohni T, Irie Y. Cryoglobulinaemia among maintenance haemodialysis patients and its relation to hepatitis C infection. J Gastroenterol Hepatol 1998; 13:248-52. [PMID: 9570236 DOI: 10.1111/j.1440-1746.1998.01551.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.
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Affiliation(s)
- K Okuda
- Department of Medicine, Chiba University Hospital, Japan
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