Analysis of the hepatitis C virus genome in patients with anti-LKM-1 autoantibodies

doi:10.1016/S0168-8278(05)80408-8

Journal of Hepatology

Volume 21, Issue 2, 1994, Pages 273-276

https://doi.org/10.1016/S0168-8278(05)80408-8 Get rights and content

Hepatitis C virus genotypes have been characterized in 22 patients with anti-LKM-1 positive chronic hepatitis C. Following the Simmonds classification, 77% of patients were infected by hepatitis C virus genotype 1, 18% by genotype 2 and 5% by genotype 3, thus excluding the association of the autoimmune reaction with a particular viral type. Prevalences of genotype 1 and 2 were significantly different from those obtained in 79 patients with chronic hepatitis C who were negative for anti-LKM-1, as these were more rarely infected by genotype 1 and more frequently by genotype 2. Clinical findings of anti-LKM-1 positive patients were similar in all three groups. Sequence analysis of the amplified 5'UTR provided identification of peculiar and identical nucleotide substitutions in two out of four patients with genotype 2. The analysis of the secondary structure of this region showed that the observed nucleotide mutations increased the stability of the stem formed in this position.

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Cited by (32)

Autoantibodies in Autoimmune Liver Disease
2005, Advances in Clinical Chemistry
Citation Excerpt :
Antibodies to LKM1 are extremely rare in North American patients with chronic hepatitis C [13, 88] and this rarity may reflect differences in the indigenous virus or the genetic susceptibility of the host [87]. Studies in Germany [89] and Italy [90] have not found an association between structural changes within the viral genome and the presence of anti‐LKM1 and a host factor for anti‐LKM1 expression has been implicated. Patients with autoimmune hepatitis and anti‐LKM1 from Germany have DRB1*07 more frequently than seronegative white North American patients with autoimmune hepatitis and normal subjects [91].
Diagnosis and treatment of autoimmune hepatitis
2002, Hepatology
Current concepts in the diagnosis, pathogenesis, and treatment of autoimmune hepatitis
2001, Mayo Clinic Proceedings
Citation Excerpt :
This molecular mimicry may result in cross-reacting antibodies in some patients. Analyses of the viral genomic sequences in patients with and without anti-LKM1 have not indicated a virus-specific basis for the autoantibodies, and a host-specific genetic predisposition for autoantibody expression is likely.71,72 Antibodies to liver cytosol type 1 (anti-LC1) were originally described in uninfected patients with anti-LKM1, and they were considered adjunctive markers of the disease that reinforced the diagnosis of type 2 autoimmune hepatitis.73
Autoimmune hepatitis has a global distribution and affects all ages. Genetic factors strongly influence susceptibility, clinical expression, and treatment response. The diagnosis of autoimmune hepatitis has been codified by an international panel. An acute or fulminant presentation is recognized but not a cholestatic form. Subclassifications by predominant autoantibody profile have been proposed, but they lack etiologic and prognostic differences. Autoanti-bodies continue to be characterized to improve diagnostic specificity, predict outcome, and identify pertinent antigenic targets. Cytosolic enzymes are prime candidates as autoantigens. DRB1*0301 and DRB1*0401 are the susceptibility alleles in Caucasoid Northern Europeans and North Americans, and they also affect clinical expression and treatment outcome. Other autoimmune promoters affecting cytokine production and immunocyte activation may act in synergy with the susceptibility alleles to affect disease behavior. Cell-mediated and antibody-dependent forms of cytotoxicity are probably interactive pathogenic mechanisms, and novel site-specific therapies are feasible because these mechanisms are defined. Potent new immunosuppressive agents are emerging from the transplantation arena, but prednisone alone or in combination with azathioprine remains the mainstay of treatment. Cortico-steroid therapy is effective but not ideal.
Autoantibodies in liver disease
2001, Gastroenterology
Citation Excerpt :
Homologies exist between P450 IID6 and the genomes of the hepatitis C virus and herpes simplex type 1 virus.63 Consequently, anti-LKM1 can be found in these infections.107-111 Reactivities associated with chronic hepatitis C infection are usually against diverse epitopes, and epitope screening can distinguish the antibody subtypes.102,110,112,113
Viral genotypes as determinants of autoimmune expression in chronic hepatitis C
1999, Mayo Clinic Proceedings
To correlate viral genotypes with the immune manifestations of chronic hepatitis C and evaluate the effect of immune features on disease expression and response to antiviral treatment.
We undertook a retrospective analysis of 67 patients with chronic hepatitis C.
Patients were selected for study if they had been screened for autoantibodies and concurrent immune diseases and if viral genotyping had been performed or was possible. Concurrent immune manifestations and responses to interferon therapy were determined.
Of the 67 patients, 18 (27 % ) had one or more immune features. Immune manifestations occurred as commonly in patients with genotype 1 as in those with other genotypes (30% versus 14%; P = 0.3). Concurrent immune features did not distinguish patients, and responses to interferon therapy were similar between patients with and those without immune manifestations. None of the 14 patients with concurrent immune diseases or high-titer autoantibodies (serum titers, 1:320 or more) entered remission during interferon treatment. In contrast, 6 of 53 patients without concurrent immune diseases and no or low-titer autoantibodies had treatment-related remission. These differences, however, were not statistically significant (0% versus 11 %; P = 0.3).
Autoantibodies and concurrent immune diseases are not associated with a particular viral genotype, clinical profile, or treatment outcome. Larger studies are necessary for complete assessment of the influence of prominent immune manifestations on treatment response.
Biology of the hepatitis C virus: Clinical implications
1997, Revue de Medecine Interne
Les infections par le virus de l'hépatite C sont caractérisées par le risque élevé de passage à la chronicité et une virémie faible. Le virus n'a été identifié que récemment, et on ne dispose pas actuellement de système efficace de culture. Il s'agit d'un virus à ARN à polarité positive qui présente des homologies avec la famille des Pestivirus et Flavivirus. Plusieurs études montrent que la variabilité génétique du virus pourrait avoir des implications cliniques importantes; en particulier l'infection par le génotype Ib répond moins bien au traitement par interféron.
Infection by hepatitis C virus is characterized by a high rate of chronicity and low viremia. The virus has only been recently identified; it is a positively stranded RNA virus which shows homology in its genetic organisation with the pestiviruses andflaviviruses. There is not yet an efficient culture system available. Evidence indicates that the genetic variability of the HCV genome might have important clinical implications.

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Rapid PublicationAnalysis of the hepatitis C virus genome in patients with anti-LKM-1 autoantibodies

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Analysis of the hepatitis C virus genome in patients with anti-LKM-1 autoantibodies