Reemergence of hepatitis C virus after 8.5 years in a patient with hypogammaglobulinemia: evidence for an occult viral reservoir.
The question of whether viruses persist after apparent clearance of infection remains unanswered. Here, we describe a patient with hypogammaglobulinemia whose acute hepatitis C virus (HCV) infection appeared to resolve after receipt of interferon therapy, relapse immediately, and then clear spontaneously--only to relapse after receipt of corticosteroid therapy, and clear again, 8.5 years later. Sequencing indicated that the viruses detected during each relapse were virtually identical, with the hypervariable region 1 of E2 appearing to be monoclonal, which is typical of patients with hypogammaglobulinemia. Nonstructural 5A sequences exhibited quasispecies diversity initially but, after 8.5 years, had become monoclonal. The prolonged period of negativity for HCV RNA followed by relapse suggests that HCV may persist in apparent sustained viral responders.
Lee
William M
WM
Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas 75390-9151, USA. william.lee@utsouthwestern.edu
Polson
Julie E
JE
Carney
D Spencer
DS
Sahin
Bogachan
B
Gale
Michael
M
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications* / Q000821:virology; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D009154:Mutation; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D012008:Recurrence; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000305:Adrenal Cortex Hormones; D000410:Alanine Transaminase; D000998:Antiviral Agents; D007372:Interferons; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase