Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C

The relationship between cryoglobulin and severity of liver lesions is debated. No study has focused on the relationship between cryoglobulin, liver steatosis, and fibrosis. The aim of this study was to determine the relationship between cryoglobulins and liver lesions (necroinflammation, fibrosis, and steatosis) in patients with hepatitis C virus (HCV) infection. Four hundred and thirty‐seven consecutive patients with untreated chronic hepatitis C who had been admitted for liver biopsy were included in the study. Risk factors for fibrosis and steatosis were assessed. The mean age was 50.9 ± 13.8 years, and 49% were male. Cryoglobulin was present in 286 patients, 103 of whom had vasculitis. One hundred and eighty‐six patients (43%) had steatosis greater than 10%, and 110 (25%) had advanced fibrosis (Metavir score F3‐F4). On multivariate analysis, cryoglobulin increased by nearly threefold the risk of having advanced fibrosis and steatosis greater than 10%. Steatosis greater than 10% was associated with a higher body mass index (P < .001), HCV genotype 3 (P < .001), cryoglobulin (P = .002), and advanced liver fibrosis (P = .009). Advanced fibrosis (F3‐F4) was associated with a higher level of γ‐glutamyltransferase (P = .04), cryoglobulin (P < .001), a high grade of necroinflammation (Metavir score A2‐A3) (P < .001), and steatosis higher than 10% (P = .04). In conclusion, our study shows an independent association between cryoglobulin and steatosis as well as advanced fibrosis. (HEPATOLOGY 2006;43:1337–1345.)

[1]  T. Asselah,et al.  STEATOSIS IN CHRONIC HEPATITIS C: WHY DOES IT REALLY MATTER? , 2005, Gut.

[2]  M. Shlomchik,et al.  Attenuated liver fibrosis in the absence of B cells. , 2005, The Journal of clinical investigation.

[3]  D. Brenner,et al.  Erratum: Liver fibrosis (Journal of Clinical Investigation (2005) 115 (209-218) DOI:10.1172/JCI200524282) , 2005 .

[4]  J. Piette,et al.  Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis. , 2004, Journal of hepatology.

[5]  J. Piette,et al.  CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. , 2004, Blood.

[6]  J. McHutchison,et al.  The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. , 2004, Journal of hepatology.

[7]  L. Rubbia‐Brandt,et al.  Steatosis affects chronic hepatitis C progression in a genotype specific way , 2004, Gut.

[8]  Felicia A Tucci,et al.  Intrahepatic B cell clonal expansions and extrahepatic manifestations of chronic HCV infection , 2004, European journal of immunology.

[9]  F. Tubach,et al.  Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C , 2003, Gut.

[10]  M. Manns,et al.  Effect of treatment with peginterferon or interferon alfa‐2b and ribavirin on steatosis in patients infected with hepatitis C , 2003, Hepatology.

[11]  J. Pawlotsky,et al.  Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies , 2003, Gut.

[12]  G. Norkrans,et al.  Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. , 2002, Journal of hepatology.

[13]  T. Asselah,et al.  Fibrosis and disease progression in hepatitis C , 2002, Hepatology.

[14]  B. Zimmerman,et al.  Hepatitis C, cryoglobulinemia, and cirrhosis: A meta‐analysis , 2002, Hepatology.

[15]  C. Grunfeld,et al.  Steatosis in chronic hepatitis C: Relative contributions of obesity, diabetes mellitus, and alcohol , 2002, Hepatology.

[16]  J. Kench,et al.  Genotype‐specific mechanisms for hepatic steatosis in chronic hepatitis C infection , 2002, Journal of gastroenterology and hepatology.

[17]  A. Diehl,et al.  Hepatic steatosis and type 2 diabetes mellitus , 2002, Current diabetes reports.

[18]  M. Gambardella,et al.  Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity , 2001, Hepatology.

[19]  M. Lenzi,et al.  Enhanced monocyte Th1 cytokine production in HCV-infected cryoglobulinemic patients. , 2001, Journal of hepatology.

[20]  K. Abid,et al.  Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. , 2000, Journal of hepatology.

[21]  J. Piette,et al.  Extrahepatic manifestations of chronic hepatitis C , 1999, Arthritis &amp; Rheumatism.

[22]  A. Clouston,et al.  Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis , 1999, Hepatology.

[23]  T. Berg,et al.  A clinical and virological study of hepatitis C virus-related cryoglobulinemia in Germany. , 1998, Journal of hepatology.

[24]  A. Czaja,et al.  Host- and disease-specific factors affecting steatosis in chronic hepatitis C. , 1998, Journal of hepatology.

[25]  V. Agnello,et al.  Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia. , 1997, Arthritis and rheumatism.

[26]  A. Fayyazi,et al.  Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype , 1997, Hepatology.

[27]  P. Bedossa,et al.  An algorithm for the grading of activity in chronic hepatitis C , 1996, Hepatology.

[28]  M. Urdea,et al.  Accurate quantification of hepatitis C virus (HCV) RNA from all HCV genotypes by using branched-DNA technology , 1996, Journal of clinical microbiology.

[29]  C. Chu,et al.  T‐cell–mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection , 1995, Hepatology.

[30]  P. Bedossa,et al.  Intraobserver and Interobserver Variations in Liver Biopsy Interpretation in Patients with Chronic Hepatitis C , 1994 .

[31]  D. Valla,et al.  Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. , 1994, Gastroenterology.

[32]  L. Stuyver,et al.  Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. , 1993, The Journal of general virology.

[33]  L. Du,et al.  Characterization of cryoglobulins by immunoblotting. , 1992, Clinical chemistry.

[34]  Y. Levo,et al.  Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. , 1980, The American journal of medicine.

[35]  J. Clauvel,et al.  Biologic and clinical significance of cryoglobulins. A report of 86 cases. , 1974, The American journal of medicine.

[36]  M. Meltzer,et al.  Cryoglobulinemia--a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. , 1966, The American journal of medicine.

[37]  V. Agnello The etiology and pathophysiology of mixed cryoglobulinemia secondary to hepatitis C virus infection , 2004, Springer Seminars in Immunopathology.

[38]  O. Chazouilleres,et al.  Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. , 2001, Journal of hepatology.

[39]  M. Alter,et al.  Epidemiology of Hepatitis C: Geographic Differences and Temporal Trends , 2000, Seminars in liver disease.

[40]  P. Cacoub,et al.  Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. , 1999, Arthritis and rheumatism.

[41]  S. Bombardieri,et al.  Hepatitis C Virus Genotype Analysis in Patients with Type II Mixed Cryoglobulinemia , 1996, Annals of Internal Medicine.

[42]  L. Adinolfi,et al.  Epidemiology, clinical spectrum and prognostic value of mixed cryoglobulinaemia in hepatitis C virus patients: a prospective study. , 1996, The Italian journal of gastroenterology.

[43]  Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. , 1994, Hepatology.

[44]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.