Download PDF
Z Gastroenterol 2009; 47(5): 446-456
DOI: 10.1055/s-0028-1109296
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Extrahepatische Manifestationen der chronischen Hepatitis-C-Virus-Infektion

Extrahepatic Manifestations of Chronic Hepatitis C Virus InfectionK. P. Puchner1 , T. Berg1
  • 1Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin
Further Information

Publication History

Manuskript eingetroffen: 21.12.2008

Manuskript akzeptiert: 19.2.2009

Publication Date:
05 May 2009 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die chronische HCV-Infektion wird heute als eine infektiöse Systemerkrankung verstanden. Mehr als die Hälfte der Patienten mit chronischer Hepatitis-C-Infektion entwickelt im Verlauf ihrer Erkrankung eine extrahepatische Manifestation. Nicht selten stellen extrahepatische Manifestationen den einzigen klinischen Hinweis auf eine chronische HCV-Infektion dar. Bei unklaren Symptomen bzw. Kranheitsbildern des rheumatischen, hämatologischen, endokrinen und dermatologischen Formenkreises sowie bei chronischer Müdigkeit und Abgeschlagenheit sollte immer eine HCV-Infektion ausgeschlossen werden. Der HCV-Lymphotropismus und die Bildung von Kryoglobulinen spielen in der Pathogenese der extrahepatischen Manifestationen eine besondere Rolle. Für zahlreiche der mit der HCV-Infektion beschriebene extrahepatische Manifestationen sind jedoch die pathogenetischen Mechanismen unklar. Die Eradikation der chronischen Virusinfektion mittels antiviraler Kombinationstherapie stellt die Behandlung der Wahl bei extrahepatischen Manifestationen dar. Meist besteht eine enge Korrelation zwischen virologischer und klinischer Response. In seltenen Fällen, insbesondere bei HCV-assoziierten Zytopenien und Neuropathien, kann es durch die antivirale Therapie zu einer Aggravation der extrahepatischen Manifestation kommen. Bei der Therapieentscheidung müssen deshalb die Form der Organbeteiligung sowie der Schweregrad und Verlauf der Erkrankung berücksichtigt werden. Immusuppressiva, Plasmapherese und in jüngster Zeit insbesondere auch Rituximab stellen wichtige weitere Therapieoptionen dar, die entweder alternativ oder komplementär eingesetzt werden können.

Abstract

Current data suggest that HCV infection should be regarded as a systemic infectious disease with multiorgan involvement. More than 50 % of HCV-positive patients develop during the course of the disease at least one extrahepatic manifestation (EHM). The EHMs are often the first and only clinical signs of a chronic hepatitis C. Evidence of HCV infection should always be sought out in cases of unspecific chronic fatigue and/or rheumatic, haematological, endocrine or dermatological disorders. Key pathogenetic factors for the development of EHM are undisputably the HCV lymphotropism and cryoglobulinaemia. Nevertheless, the exact pathogenesis of many EHM still remains unclear. The therapeutic approach to EHM should concentrate on the eradication of HCV. Antiviral therapy in the form of peg-interferon and ribavirin should be regarded as the first-line therapy. Viral response leads mostly to a consecutive clinical response. However, in the case of HCV-related cytopaenias or neuropathies, antiviral therapy may trigger an aggravation of these conditions. Thus, organ-involvement, severity and course of the EHM should be always taken into account when choosing the appropriate therapeutic strategy. Immunosuppressive drugs, plasmapheresis and lately rituximab are counted among therapies that can be applied complementarly or alternatively to the antiviral therapy.

Schlüsselwörter

Virushepatitis - Leber - Hepatitis C

Key words

viral hepatitis - liver - hepatitis C

Literatur

  • 1 Cacoub P, Renou C, Rosenthal E. et al . Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. Groupe d’ Etude et de Recherche en Medicine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C.  Medicine. 2000;  79 47-56
    Google Scholar
  • 2 Cacoub P, Poynard T, Ghillani P. et al . Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC group. Multidepartment Virus C.  Athritis Rheum. 1999;  42 2204-2212
    Google Scholar
  • 3 Ferri C, Antonelli A, Mascia M T. et al . B cells and mixed cryoglobulinemia.  Autoimmun Rev. 2007;  7 114-120
    Google Scholar
  • 4 Zignego A L, Ferri C, Pileri S A. et al . Extrahepatic manifestations of the Hepatitis C Virus infection: a general overview and guidelines for clinical approach.  Dig Liver Dis. 2007;  39 2-17
    Google Scholar
  • 5 Wintrobe M, Buell M. Hyperproteinemia associated with multiple myeloma. With report of a case in which extraordinary hyperproteinemia was associated with thrombosis of the retinal veins and symptoms suggesting Raynoud’s disease.  Bull Johns Hopkins Hosp. 1933;  52 156-165
    Google Scholar
  • 6 Lunel F, Musset L, Cacoub P. et al . Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage.  Gastroenterology. 1994;  106 1291-1300
    Google Scholar
  • 7 Wong V S, Egner W, Elsey T. et al . Incidence, character and clinical relevance of mixed cryoglobulinaemia in patients with chronic hepatitis C virus infection.  Clin Exp Immunol. 1996;  104 25-31
    Google Scholar
  • 8 Weiner S M, Berg T, Berthold C. et al . A clinical and virological study of hepatitis C virus-related cryoglobulinemia in Germany.  J Hepatol. 1998;  29 375-384
    Google Scholar
  • 9 Saadoun D, Asselah T, Resche-Rigon M. et al . Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C.  Hepatology. 2006;  43 1337-1345
    Google Scholar
  • 10 Colantoni A, De Maria N, Idilman R. et al . Polymerase chain reaction for the detection of HCV-RNA: cryoglobulinaemia as a cause for false negative results.  Ital J Gastroenterol Hepatol. 1997;  29 273-274
    Google Scholar
  • 11 Ferri C, Sebastiani M, Guiggiolo D. et al . Mixed cryoglobulinaemia: demographic, clinical, and serologic features and survival in 231 patients.  Semin Arthritis Rheum. 2004;  33 355-374
    Google Scholar
  • 12 Agnello V, Ábel G. Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia.  Arthritis Rheumatism. 1997;  40 2007-2015
    Google Scholar
  • 13 Tarantino A, Campise M, Banfi G. et al . Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis.  Kidney Int. 1995;  47 618-23
    Google Scholar
  • 14 Tembl J I, Ferrer J M, Sevilla M T. et al . Neurologic complications associated with hepatitis C virus infection.  Neurology. 1999;  19 889-895
    Google Scholar
  • 15 Lidove O, Cacoub P, Maisonobe T. et al . Hepatitis C virus infection with peripheral neuropathy is not always associated with cryoglobulinaemia.  Ann Rheum Dis. 2001;  60 290-292
    Google Scholar
  • 16 Vigano M, Lampertico P, Rumi M G. et al . Natural history and clinical impact of cryoglobulins in chronic Hepatitis C: 10-year prospective study of 343 patients.  Gastroenterology. 2007;  133 835-842
    Google Scholar
  • 17 Mele A, Pulsoni A, Bianco E. et al . Hepatitis C virus and B-cell non-Hodgkin lymphomas: an Italian multicenter case-control study.  Blood. 2003;  102 996-999
    Google Scholar
  • 18 Duberg A S, Nordström M, Törner A. et al . Non-Hodgkin’s lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection.  Hepatology. 2005;  41 652-659
    Google Scholar
  • 19 Giordano T P, Henderson L, Landgren O. et al . Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus.  JAMA. 2007;  297 2010-2017
    Google Scholar
  • 20 Silvestri F, Barillari G, Fanin R. et al . Hepatitis C virus infection among cryoglobulinemic and non-cryoglobulinemic B-cell non-Hodgkin’s lymphomas.  Haematologica. 1997;  82 314-317
    Google Scholar
  • 21 Matsuo K, Kusano A, Sugumar A. et al . Effect of hepatitis C virus infection on the risk of non-Hodgkin’s lymphoma: a meta-analysis of epidemiological studies.  Cancer Sci. 2004;  95 745-752
    Google Scholar
  • 22 Cormier E G, Tsamis F, Kajumo F. et al . CD81 is an entry coreceptor for hepatitis C virus.  Proc Natl Acad Sci U S A. 2004;  101 7270-7274
    Google Scholar
  • 23 Zignego A L, Giannelli F, Marrocchi M E. et al . T(14;18) translocation in chronic hepatitis C virus infection.  Hepatology. 2000;  31 474-479
    Google Scholar
  • 24 Zignego A L, Giannini C, Ferri C. Hepatitis C virus-related lymphoproliferative disorders: an overview.  World J Gastroenterol. 2007;  13 2467-2478
    Google Scholar
  • 25 Zignego A L, Macchia D, Monti M. et al . Infection of peripheral mononuclear blood cells by hepatitis C virus.  J Hepatol. 1992;  3 382-386
    Google Scholar
  • 26 Roque Afonso A M, Jiang J, Penin F. et al . Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets.  J Virol. 1999;  73 9213-9221
    Google Scholar
  • 27 Sakamuro D, Furukawa T, Takegami T. Hepatitis C virus nonstructural protein NS 3 transforms NIH 3T3 cells.  J Virol. 1995;  69 (6) 3893-3896
    Google Scholar
  • 28 Ray R B, Meyer K, Ray R. Suppression of apoptotic cell death by hepatitis C virus core protein.  Virology. 1996;  226 (2) 176-182
    Google Scholar
  • 29 Machida K, Cheng K T, Sung V M. et al . Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes.  Proc Natl Acad Sci USA. 2004;  101 4262-4267
    Google Scholar
  • 30 Calleja J L, Albillos A, Moreno-Otero R. et al . Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.  Aliment Pharmacol Ther. 1999;  13 1179-1186
    Google Scholar
  • 31 Levine J W, Gota C, Fessler B J. et al . Persistent cryoglobulinemic vasculitis following successful treatment of hepatitis C virus.  J Rheumatol. 2005;  32 1164-1167
    Google Scholar
  • 32 Craxì A, Laffi G, Zignego A L. Hepatitis C virus (HCV) infection: a systemic disease.  Mol Aspects Med. 2008;  29 85-95
    Google Scholar
  • 33 Sansonno D, De Re V, Lauletta G. et al . Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20.  Blood. 2003;  101 3818-3826
    Google Scholar
  • 34 Saadoun D, Resche-Rigon M, Sene D. et al . Rituximab combined with Peg-Interferon-Ribavirin in refractory HCV-associated cryoglobulinemia vasculitis.  Ann Rheum Dis. 2008;  67 1431-1436
    Google Scholar
  • 35 Koskinas J, Kilidireas C, Karandreas N. et al . Severe hepatitis C virus-related cryoglobulinaemic sensory-motor polyneuropathy treated with pegylated interferon-a2b and ribavirin: clinical, laboratory and neurophysiological study.  Liver Int. 2007;  27 414-420
    Google Scholar
  • 36 Boonyapisit K, Katirji B. Severe exacerbation of hepatitis C-associated vasculitic neuropathy following treatment with interferon alpha: a case report and literature review.  Muscle Nerve. 2002;  25 909-913
    Google Scholar
  • 37 Khiani V, Kelly T, Adeel S. et al . Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon a 2a therapy for chronic hepatitis C virus infection.  World J Gastroenterol. 2008;  14 318-321
    Google Scholar
  • 38 Giannelli F, Moscarella S, Giannini C. et al . Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.  Blood. 2003;  102 1196-1201
    Google Scholar
  • 39 Vallisa D, Bernuzzi P, Arcaini L. et al . Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin’s lymphoma: a multicenter Italian experience.  J Clin Oncol. 2005;  23 468-473
    Google Scholar
  • 40 Besson C, Canioni D, Lepage E. et al . Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs.  J Clin Oncol. 2006;  24 953-960
    Google Scholar
  • 41 Wang C S, Yao W J, Wang S T. et al . Strong association of Hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection.  Clin Infect Dis. 2004;  39 790-796
    Google Scholar
  • 42 Afdhal N, McHutchison J, Brown R. et al . Thrombocytopenia associated with chronic liver disease.  J Hepatol. 2008;  48 1000-1007
    Google Scholar
  • 43 Takehara K, Otsuka T, Arai T. et al . Detection of hepatitis C virus (HCV) in platelets of type C chronic liver diseases by polymerase chain reaction (PCR).  Gastroenterology. 1994;  106 A995
    Google Scholar
  • 44 Bordin G, Ballare M, Zigrossi P. et al . A laboratory and thrombokinetic study of HCV-associated thrombocytopenia: a direct role of HCV in bone marrow exhaustion?.  Clin Exp Rheumatol. 1995;  Suppl 13 S39-S43
    Google Scholar
  • 45 De Almeida A J, Campos-de-Magalhaes M, Okawa M Y. et al . Hepatitis C virus-associated thrombocytopenia: a controlled prospective, virological study.  Ann Hematol. 2004;  83 434-440
    Google Scholar
  • 46 García-Suárez J, Burgaleta C, Hernanz N. et al . HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy.  Br J Haematol. 2000;  110 98-103
    Google Scholar
  • 47 Rajan S K, Espina B M, Liebman H A. Hepatitis C virus-related thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura.  Br J Haematol. 2005;  129 818-824
    Google Scholar
  • 48 Iga D, Tomimatsu M, Endo H. et al . Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-α therapy: possible etiology of HCV-associated immune thrombocytopenia.  Eur J Haematol. 2005;  75 417-423
    Google Scholar
  • 49 Fattovich G, Giustina G, Favarato S. et al . A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon.  J Hepatol. 1996;  24 38-47
    Google Scholar
  • 50 Bussel J B, Cheng G, Saleh M N. et al . Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.  N Engl J Med. 2007;  29 (357) 2237-2247
    Google Scholar
  • 51 McHutchison J G, Dusheiko G, Shiffman M L. et al . Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C.  N Engl J Med. 2007;  357 2227-2236
    Google Scholar
  • 52 Weitz I C. Treatment of immune thrombocytopenia associated with interferon therapy of hepatitis C with the anti-CD20 monoclonal antibody, rituximab.  Am J Hematol. 2005;  78 138-141
    Google Scholar
  • 53 Chao T C, Chen C Y, Yang Y H. et al . Chronic hepatitis C virus infection associated with primary warm-type autoimmune hemolytic anemia.  J Clin Gastroenterol. 2001;  33 232-233
    Google Scholar
  • 54 Fernandéz A. An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection.  Hematology. 2006;  11 385-387
    Google Scholar
  • 55 Srinivasan R. Autoimmune hemolytic anemia in treatment naive chronic hepatitis C infection.  J Clin Gastroenterol. 2001;  32 245-247
    Google Scholar
  • 56 De la Serna-Higuera C, Bárcena-Marugán R, Sanz-Villalobos de E. Hemolytic anemia secondary to alpha-interferon treatment in a patient with chronic C hepatitis.  J Clin Gastroenterol. 1999;  28 358-359
    Google Scholar
  • 57 Nomura H, Tanimoto H, Kajiwara E. et al . Factors contributing to ribavirin-induced anemia.  J Gastroenterol Hepatol. 2004;  19 (11) 1312-1317
    Google Scholar
  • 58 Arase Y, Ikeda K, Murashima N. et al . Glomerulonephritis in autopsy cases with hepatitis C virus infection.  Intern Med. 1998;  37 836-840
    Google Scholar
  • 59 Daghestani L, Pomeroy C. Renal manifestations of hepatitis C infection.  Am J Med. 1999;  106 347-354
    Google Scholar
  • 60 Doutrelepont J M, Adler M, Willems M. et al . Hepatitis C virus infection and membranoproliferative glomerulonephritis.  Lancet. 1993;  341 (8840) 317
    Google Scholar
  • 61 Rollino C, Roccatello D, Giachino O. et al . Hepatitis C virus Infection and membranous glomerulonephritis.  Nephron. 1991;  59 319-320
    Google Scholar
  • 62 McGuire B M, Julian B A, Bynon J S. et al . Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation.  Ann Intern Med. 2006;  144 (10) 735-741
    Google Scholar
  • 63 Sansonno Jr D, Gesualdo L, Manno C. et al . Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis.  Hepatology. 1997;  25 1237-1244
    Google Scholar
  • 64 Paydas S, Seyrek N, Gonlusen G. et al . The frequencies of hepatitis B virus markers and hepatitis C virus antibody in patients with glomerulonephritis.  Nephron. 1996;  74 617-619
    Google Scholar
  • 65 Sabry A A, Sobh M A, Sheaashaa H A. et al . Effect of combination therapy (ribavirin and interferon) in HCV-related glomerulopathy.  Nephrol Dial Transplant. 2002;  17 1924-1930
    Google Scholar
  • 66 Alric L, Plaisier E, Thébault S. et al . Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN.  Am J Kidney Dis. 2004;  43 617-623
    Google Scholar
  • 67 Fabrizi F, Lunghi G, Messa P. et al . Therapy of hepatitis C virus-associated glomerulonephritis: current approaches.  J Nephrol. 2008;  21 813-825
    Google Scholar
  • 68 Bruchfeld A, Lindahl K, Stahle L. et al . Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency.  Nephrol Dial Transplant. 2003;  18 (8) 1573-1580
    Google Scholar
  • 69 Baid-Agrawal S, Pascual M, Moradpour D. et al . Hepatitis C virus infection in haemodialysis and kidney transplant patients.  Rev Med Virol. 2008;  18 97-115
    Google Scholar
  • 70 Leusen van R, Adang R P, Vries R A. et al . Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with chronic hepatitis C.  Nephrol Dial Transplant. 2008;  23 721-725
    Google Scholar
  • 71 Garini de G, Allegri L, Lannuzzella F. et al . HCV-related cryoglobulinemic glomerulonephritis: implications of antiviral and immunosuppressive therapies.  Acta Biomed. 2007;  78 51-59
    Google Scholar
  • 72 Margin S, Craxi A, Fabiano C. et al . Hepatitis C viraemia in chronic liver disease: relationship to interferon alpha or corticosteroid treatment.  Hepatology. 1994;  19 273-279
    Google Scholar
  • 73 Roccatello D, Baldovino S, Rossi D. et al . Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis.  Nephrol Dial Transplant. 2004;  19 3054-3061
    Google Scholar
  • 74 Roccatello D, Baldovino S, Rossi D. et al . Rituximab as a Therapeutic Tool in Severe Mixed Cryoglobulinemia.  Clin Rev Allergy Immunol. 2008;  34 111-117
    Google Scholar
  • 75 Kamar N, Rostaing L, Alric L. Treatment of hepatitis C-virus-related glomerulonephritis.  Kidney Int. 2006;  69 436-439
    Google Scholar
  • 76 Antonelli A, Ferri C, Pampana A. et al . Thyroid disorders in chronic hepatitis C.  Am J Med. 2004;  117 10-13
    Google Scholar
  • 77 Prummel M F, Laurberg P. Interferon-alpha and autoimmune thyroid disease.  Thyroid. 2003;  13 547-551
    Google Scholar
  • 78 Marazuela M, Garcia-Buey L, Gonzalez-Fernandez B. et al . Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha therapy.  Clinical Endocrinology. 1996;  44 635-642
    Google Scholar
  • 79 Knobler H, Schihmanter R, Zifroni A. et al . Increased risk of diabetes in noncirrhotic patients with chronic hepatitis C virus infection.  Mayo Clin Proc. 2000;  75 355-359
    Google Scholar
  • 80 Mason A L, Lau J Y, Hoang N. et al . Association of diabetes mellitus and chronic hepatitis C virus infection.  Hepatology. 1999;  29 328-333
    Google Scholar
  • 81 Hui J M, Sud A, Farrell G C. et al . Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression.  Gastroenterology. 2003;  125 1695-1617
    Google Scholar
  • 82 Mehta S H, Brancati F L, Strathdee S A. et al . Hepatitis C virus infection and incident type 2 diabetes.  Hepatology. 2003;  38 50-56
    Google Scholar
  • 83 Kawaguchi T, Ide T, Taniguchi E. et al . Clearance of HCV improves insulin resistance, ß-cell function, and hepatic expression of insulin receptor substrates 1 and 2.  Am J Gastroenterol. 2007;  102 1-7
    Google Scholar
  • 84 White D L, Ratziu V, El-Serag H B. Hepatitis C infection and risk of diabetes: A systematic review and meta-analysis.  J Hepatol. 2008;  49 831-844
    Google Scholar
  • 85 Imazeki F, Yokosuka O, Fukai K. et al . Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients.  Liver international. 2008;  28 355-362
    Google Scholar
  • 86 Moucari R, Asselah T, Cazals-Hatem D. et al . Insulin resistance in chronic hepatitis C: Association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis.  Gastroenterology. 2008;  134 416-423
    Google Scholar
  • 87 Kawaguchi T, Yoshida T, Harada M. et al . Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3.  Am J Pathol. 2004;  165 1499-1508
    Google Scholar
  • 88 Plöckinger U, Krüger D, Bergk A. et al . Hepatitis-C patients have a reduced growth hormone (GH) secretion which improves during long-term therapy with pegylated interferon-a.  Am J Gastroenterol. 2007;  102 2724-2731
    Google Scholar
  • 89 Hadziyannis S J. Skin diseases associated with hepatitis C virus infection.  J Eur Acad Dermatol Venereol. 1998;  10 12-21
    Google Scholar
  • 90 Fargion S, Piperno A, Cappellini M D. et al . Hepatitis C virus and porphyria cutanea tarda: evidence of a strong association.  Hepatology. 1992;  16 1322-1326
    Google Scholar
  • 91 Stölzel U, Köstler E, Koszka C. et al . Low prevalence of hepatitis C virus infection in porphyria cutanea tarda in Germany.  Hepatology. 1995;  21 1500-1503
    Google Scholar
  • 92 Nagao Y, Sata M, Tanikawa K. et al . Lichen planus and hepatitis C virus in the northern Kyushu region of Japan.  Eur J Clin Invest. 1995;  25 910-914
    Google Scholar
  • 93 Carrozzo M, Gandolfo S, Carbone M. et al . Hepatitis C virus infection in Italian patients with oral lichen planus: a prospective case-control study.  J Oral Pathol Med. 1996;  25 527-533
    Google Scholar
  • 94 Ingafou M, Porter S R, Scully C. et al . No evidence of HCV infection or liver disease in British patients with oral lichen planus.  Int J Oral Maxillofac Surg. 1998;  27 65-66
    Google Scholar
  • 95 Gandolfo S, Carrozzo M. Lichen planus and hepatitis C virus infection.  Minerva Gastroenterol Dietol. 2002;  48 89
    Google Scholar
  • 96 Ueda T, Ohta K, Suzuki N. et al . Idiopathic pulmonary fibrosis and high prevalence of serum antibodies to hepatitis C virus.  Am Rev respire Dis. 1992;  146 266-268
    Google Scholar
  • 97 Yamaguchi S, Kubo K, Fujimoto K. et al . Bronchoalveolar lavage fluid findings in patients with chronic hepatitis C before and after treatment with interferon alpha.  Thorax. 1997;  52 33-37
    Google Scholar
  • 98 Ferri C, La Civita L, Fazzi P. et al . Intestinal lung fibrosis and rheumatic disorders in patients with hepatitis C virus infection.  Br J Rheumatol. 1997;  36 360-365
    Google Scholar
  • 99 Cacoub P, Sbai A, Hausfater P. et al . Central nervous system involvement in hepatitis C virus infection.  Gastroenterol Clin Biol. 1998;  22 631-633
    Google Scholar
  • 100 Aktipi K M, Ravaglia S, Ceroni M. et al . Severe recurrent myelitis in patients with hepatitis C virus infection.  Neurology. 2007;  68 468-469
    Google Scholar
  • 101 Perry W, Hilsabeck R C, Hassanein T I. Cognitive dysfunction in chronic hepatitis C: a review.  Dig Dis Sci. 2008;  53 307-321
    Google Scholar
  • 102 Forton D M, Taylor-Robinson S D, Thomas H C. Cerebral dysfunction in chronic hepatitis C infection.  J Viral Hepat. 2003;  10 81-86
    Google Scholar
  • 103 Carta M G, Hardoy M C, Garofalo A. et al . Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy.  Clin Pract Epidemol Ment Health. 2007;  3 22
    Google Scholar
  • 104 Weissenborn K, Ennen J C, Bokemeyer M. et al . Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment.  Gut. 2006;  55 1624-1630
    Google Scholar
  • 105 Forton D M, Allsop J M, Main J. et al . Evidence for a cerebral effect of the hepatitis C virus.  Lancet. 2001;  358 38-39
    Google Scholar
  • 106 Zignego A L, Cozzi A, Carpenedo R. et al . HCV patients, psychopathology and tryptophan metabolism: analysis of the effects of pegylated interferon plus ribavirin treatment.  Dig Liver Dis. 2007;  39 (Suppl 1) S107-S111
    Google Scholar
  • 107 Matsumori A, Yutani C, Ikeda Y. et al . Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy.  Lab Invest. 2000;  80 1137-1142
    Google Scholar

Prof. Dr. Thomas Berg

Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin

Augustenburger Platz 1

13353 Berlin

Phone: + + 49/30/4 50 55 30 71

Fax: + + 49/30/4 50 55 39 03

Email: thomas.berg@charite.de

      >