Non-organ specific autoantibodies associated with chronic C virus hepatitis

doi:10.1016/S0168-8278(05)80281-8

Journal of Hepatology

Volume 18, Issue 3, 1993, Pages 359-364

https://doi.org/10.1016/S0168-8278(05)80281-8 Get rights and content

Recently antibodies to hepatitis C virus were detected in sera of chronic active hepatitis patients, with anti-smooth muscle autoantibodies or with anti-liver/kidney microsomal type 1 autoantibodies. As the latter were used to differentiate autoimmune chronic active hepatitis from chronic non-A, non-B virus hepatitis, it was mainly important to discover if autoantibodies were associated with chronic hepatitis C virus infection. The sera of 272 chronic hepatitis C patients were screened by indirect immunofluorescence for non-organ specific autoantibodies. Antinuclear anti-bodies and anti-smooth muscle autoantibodies were more frequent in chronic hepatitis C patients than in blood donors (n = 100). Anti-liver/kidney microsomal type 1 autoantibodies were not detected in the sera of the blood donors, in the 74 hepatitis B patients or in the 30 alcoholic hepatitis or cirrhotic patients' sera tested as controls. They were detected in 14 chronic hepatitis C patients. These antibodies were compared in immunodiffusion to anti-liver/kidney microsomal type 1 autoantibodies sera obtained from type-2 autoimmune chronic active hepatitis patients and an identity reaction was observed. Chronic hepatitis C patients without or with anti-liver/kidney microsomal type 1 autoantibodies, did not differ in age, sex ratio, transaminases and gammaglobulin level, risk factors for hepatitis C virus infection, association with other autoimmune diseases. These patients differed significantly from type-2 autoimmune chronic active hepatitis patients. We conclude that: (i) in some chronic hepatitis C patients the pattern and the titer of autoantibodies may create confusion with an autoimmune chronic active hepatitis; (ii) There is no serological evidence for a hepatitis C virus infection in true type-2 autoimmune chronic active hepatitis.

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Anti-rods/rings are recognized as an example of a drug-induced autoantibody in hepatitis C patients treated with interferon and ribavirin, although new studies suggest anti-rods/rings may be detected in other contexts and may depend on unknown environmental or genetic factors in different populations. Recent data suggest that the assembly of IMPDH into rod and ring structures, the targets of anti-rods/rings autoantibody, is a mechanism for hyperproliferating cells, like activated T cells, to maintain increased guanine nucleotide levels to support rapid cell division.
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Citation Excerpt :
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Patients within the Swiss Hepatitis C Cohort Study who underwent successful (SVR 12) HCV treatment with DAA were tested for autoimmune liver serology according to dedicated guidelines before and at least 6 months after end of treatment.
A total of 235 patients were included; 62% males; median age 56 years; 27% with cirrhosis. Median time between end of DAA treatment and post-treatment serum sampling was 17 months. At least one autoantibody before treatment was found in 175 (74%) patients ; 32 (14%) were positive for 2 autoantibodies; no patient was positive for anti-SLA, anti-LC1 or typical AMA before or after DAA. ANA disappeared in 34%, SMA in 52% and anti-LKM1 in one of two patients after successful treatment, but, unexpectedly, one or more autoantibodies appeared in 27% of pre-treatment negative subjects.
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Extrahepatic Manifestations in Patients With Chronic Hepatitis C Virus Infection
2017, Handbook of Systemic Autoimmune Diseases
Citation Excerpt :
Circulating autoantibodies are often detected in patients with chronic HCV infection. Antinuclear antibodies (ANA), rheumatoid factor (RF), and anti–smooth muscle antibodies are the most frequently found, while other autoantibodies (such as anti-dsDNA, antiextractable nuclear antigens, antimitochondrial antibodies, or anti–liver/kidney microsomes antibodies) are infrequent [6–21] (Table 9.1). ANA have been detected in 589 (18.6%) out of 3169 unselected HCV patients included in 16 studies (Table 9.1), although the geographic prevalence varied significantly [21].
Autoimmunity and viral infections are closely related fields, and viruses have been proposed as possible etiologic or triggering agents of systemic autoimmune diseases (SAD). The hepatitis C virus (HCV), a linear, single-stranded RNA virus identified in 1989 (Choo et al., 1989 [1]), is recognized as one of the viruses most often associated with autoimmune features. A decade ago, various authors described the association of HCV infection with a heterogeneous group of extrahepatic conditions, such as pulmonary fibrosis, cutaneous vasculitis, glomerulonephritis, Mooren ulcers, porphyria cutanea tarda, or lichen planus (Gumber and Chopra, 1995 [2]), although it is currently accepted that a weak degree of association exists in some of them (Campisi et al., 2004 [3]). More recently, there has been a growing interest in the relationship between HCV and SAD (Ramos-Casals et al., 2001 [4]). The clinical association of the different SAD with chronic HCV infection may be analyzed from two different, but complementary, points of view. Firstly, a review of the literature found nearly 500 patients with coexisting SAD and chronic HCV infection (Ramos-Casals et al., 2005 [5]), with Sjögren syndrome (SS; 182 cases), rheumatoid arthritis (RA; 94 cases), systemic lupus erythematosus (SLE; 67 cases), and polyarteritis nodosa (PAN; 41 cases) being the most frequent SAD described. Secondly, analysis of all references to a series of patients with SAD tested for HCV shows the highest prevalence rates of HCV infection in patients with SS (17.6%), PAN (14.4%), SLE (9.6%), and RA (5.9%) (Ramos-Casals et al., 2005 [6]). Other recent studies have focused on the association between chronic HCV infection and circulating autoantibodies, organ-specific autoimmune diseases, and lymphoproliferative processes.
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Non-organ-specific autoantibodies (NOSA) are well-recognized diagnostic markers of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but can also be observed in patients with viral hepatitis as well as in healthy subjects. The aim of this study was to evaluate the prevalence of NOSA in subjects living in a rural community in Brazil and to correlate their occurrence with the presence of liver disease. Seven hundred twenty-five apparently healthy subjects were randomly selected for assessment of antinuclear (ANA), anti-smooth muscle (SMA), antimitochondrial (AMA), anti-liver/kidney microsome type 1, and anti-liver cytosol type 1 antibodies. Subjects with those NOSA were evaluated for the presence of AIH, PBC, and viral hepatitis. Reactivities for all NOSA, SMA, ANA, and AMA were detected, respectively, in 14, 10, 4, and 0.1% of subjects, with a mean titer of 1:40. NOSA-positive subjects were significantly older and more frequently females. No correlation was observed between the occurrence of NOSA and PBC, AIH, or viral hepatitis. The prevalence of NOSA in Brazilians was 14%. They were usually low titer. NOSA were more frequently observed in females and older subjects and their presence was not correlated with the presence of AIH, PBC, or viral hepatitis.
Chapter 16 Extrahepatic Manifestations in Patients with Chronic Hepatitis C Virus Infection
2008, Handbook of Systemic Autoimmune Diseases
Citation Excerpt :
Circulating autoantibodies are often detected in patients with chronic HCV infection. Anti-nuclear antibodies, rheumatoid factor, and anti-smooth muscle antibodies are the most frequently found, while other autoantibodies (such as anti-dsDNA, anti-ENA, AMA, or anti-LKM-1) are infrequent (Fried et al., 1993; Abuaf et al., 1993; Rolachon et al., 1994; Pawlotsky et al., 1994; McFarlane et al., 1994; Richardet et al., 1994; Borotto et al., 1994;Clifford et al., 1995; Czaja et al., 1995; Cassani et al., 1997; Buskila et al., 1998; Rivera et al., 1999b; Cacoub et al., 2000; Drygiannakis et al., 2001; Stroffolini et al., 2004; Yee et al., 2004) (Table 1). ANA have been detected in 589 (18.6%) out of 3169 unselected HCV patients included in 16 studies (Table 1), although the geographic prevalence varied significantly (Yee et al., 2004).
This chapter reviews the extrahepatic manifestations in patients with chronic hepatitis C virus (HCV) infection. HCV is a linear, single-stranded RNA virus identified and recognized as one of the viruses most often associated with autoimmune features. Autoimmunity and viral infections are closely related, and viruses are proposed as possible etiologic or triggering agents of Systemic Autoimmune Diseases (SAD). The clinical association of the different SAD with chronic HCV infection is also analyzed. The association between chronic HCV infection and circulating autoantibodies, organ-specific autoimmune diseases, and lymphoproliferative processes, such as thyroiditis or Diabetes Mellitus (DM) are focused. Circulating autoantibodies are often detected in patients with chronic HCV infection. The specific tropism of HCV for many extrahepatic cell types, especially for circulating blood cells is also emphasized. The therapeutic management of HCV-related autoimmune features is a clinical challenge in HCV patients, in whom chronic liver disease associated with severe autoimmune features contributes to a very poor prognosis. The treatment of HCV infection involves Anti-viral therapy, Mycophenolate Mofetil (MMF), Rituximab, and Anti-tumor Necrosis Factor (TNF) agents.
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2020, Annals of Hepatology
Chronic hepatitis C virus (HCV) infection and autoimmune disorders show a complex interplay, with HCV often being identified as the trigger of autoimmune phenomena or diseases. While there is evidence of successful HCV treatment with direct-acting antivirals (DAA) in patients with concomitant HCV and autoimmune hepatitis (AIH), there are also sparse reports of AIH developing during, or following, DAA treatment.
Here we report a case of a patient with suspected concomitant HCV and AIH who underwent liver biopsy but showed no histological hallmarks of autoimmunity. The patient later developed a hepatitic flare following DAA-induced viral clearance, and a second liver biopsy showed features compatible with AIH. Response to corticosteroid and azathioprine treatment was seen. This reports demonstrates that patients with features of auto-reactivity and HCV after DAA-induced viral clearance require careful follow-up.

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Regular PaperNon-organ specific autoantibodies associated with chronic C virus hepatitis

Lancet

Lancet

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Lancet

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J Hepatol

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Gastroenterology

Lancet

Lancet

Gastroenterology

Biochem Biophys Res Commun

Hepatitis C viraemia in adults with type 2 autoimmune hepatitis

J Med Virol

Type 2 autoimmune hepatitis and hepatitis C virus: a study group of 83 patients

J Hepatol

Anti-liver/kidney microsome antibody type 1 and hepatitis C virus infection

Hepatology

Absence of autoimmune serological reactions in chronic non A, non B viral hepatitis

Clin Exp Immunol

Regular Paper
Non-organ specific autoantibodies associated with chronic C virus hepatitis