Correspondence
Discordant Manifestations of Hepatitis C in Monozygotic Twins
N Engl J Med 1995; 333:1224-1225November 2, 1995
- Article
To the Editor:
The clinical manifestations and evolution of hepatitis C virus (HCV) infection are thought to be influenced by the viral genotype and by the immunoreactivity of the infected person.1 These factors sometimes also determine the appearance of liver–kidney–microsomal autoantibodies type 1 (LKM-1).2 We report discordant manifestations and evolution of HCV infection in a pair of monozygotic twins (with a probability of monozygosity greater than 99 percent).3 One had acute hepatitis and recovered fully. The other had chronic hepatitis associated with the appearance of LKM-1 autoantibodies.
The two men, both 20 years of age, share the HLA haplotype A2,11;B8,44;DR3,4;DQ2,3. They were intravenous drug users from February through October 1992. In October 1992, both were negative for anti-HCV antibody by enzyme immunoassay and recombinant immunoblot assay. In January 1993, one presented with acute hepatitis (serum aspartate aminotransferase level, 1610 IU per liter; serum alanine aminotransferase level, 2042 IU per liter). His serum was positive for HCV RNA by the polymerase chain reaction; the viral genotype was 2a.4 A recombinant immunoblot assay (Ortho Diagnostics Systems, Raritan, N.J.) initially showed antibodies to c33 only. He was negative for anti–human immunodeficiency virus (HIV) antibodies, markers of hepatitis B virus (HBV) infection, and LKM-1 antibodies. This patient's aspartate aminotransferase and alanine aminotransferase values returned to normal within two months. HCV RNA was no longer detectable in his serum after six months. At one year, a liver-biopsy specimen had normal histologic features. The patient continued to be seronegative for HCV RNA and had normal aminotransferase levels in January 1995.
His identical twin was also tested for anti-HCV antibodies in January 1993. A recombinant immunoblot assay showed positivity for anti-c33 antibodies only; his serum was positive for HCV RNA, and the viral genotype was 2a. The aspartate aminotransferase and alanine aminotransferase levels were, however, only slightly abnormal (112 and 158 IU per liter, respectively). The patient's serum was negative for markers of HBV infection and anti-HIV antibodies; LKM-1 autoantibodies were detectable by immunofluorescence at a titer of 1:40; the titer increased to 1:320 by April 1993. This patient continued to have moderately elevated aminotransferase levels (two to five times higher than normal), and a recombinant immunoblot assay showed reactivity to all four antigens tested (c33, c22, c100, and 5-1-1). In September 1993, a liver-biopsy specimen showed moderately active chronic hepatitis. Treatment with recombinant interferon alfa-2b (Intron-A, Schering, Kenilworth, N.J.; 6 million units three times a week for six months, then 3 million units three times a week for six months) had no effect. In January 1995 the patient still had elevated levels of aspartate aminotransferase and alanine aminotransferase (140 and 218 IU per liter, respectively) and was seropositive for HCV RNA. The viral genotype was still 2a, and he was seropositive for LKM-1 autoantibodies at a titer of 1:320.
This experience suggests that HCV infections involving the same genotype can run different courses in monozygotic twins. The appearance of LKM-1 antibodies in only one brother suggests the importance of factors other than HCV5 or the “autoimmune” HLA haplotype B8,DR3 in the course of HCV infection.
5 ReferencesSandro Vento, M.D.
Lorenza Guella, M.D.
Ercole Concia, M.D.
University of Verona, 37124 Verona, Italy1
Genetic diversity of hepatitis C virus: implications for pathogenesis, treatment, and prevention. Lancet 1995;345:562-566
CrossRef | Web of Science | Medline2
Lenzi M ,Ballardini G ,Fusconi M , et al. Type 2 autoimmune hepatitis and hepatitis C virus infection. Lancet 1990;335:258-259
CrossRef | Web of Science | Medline3
Das Chaudhuri AB . Efficient sequential search of genetic systems for diagnosis of twin zygosity. Acta Genet Med Gemellol (Roma) 1991;40:159-164
Web of Science | Medline4
Simmonds P ,Holmes EC ,Cha TA , et al. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993;74:2391-2399
CrossRef | Web of Science | Medline5
Mackie FD ,Peakman M ,Yun M , et al. Primary and secondary liver/kidney microsomal autoantibody response following infection with hepatitis C virus. Gastroenterology 1994;106:1672-1675
Web of Science | Medline
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