Viral clearance or persistence after acute hepatitis C infection: interim results from a prospective study.
OBJECTIVE
Hepatitis C virus infection (HCV) has a high rate of chronic evolution; however, the underlying mechanisms remain to be elucidated. We investigated natural clinical, virological, and immunological course of acute HCV infection in order to identify possible prognostic factors of spontaneous resolution and to gain more understanding of early characteristics responsible for viral clearance or persistence.


METHODS
Eight patients with acute symptomatic hepatitis C were prospectively followed up for more than 6 months (range, 8-14 months). None of the individuals received antiviral therapy during the study period. We analyzed biochemical, virological, and immunological parameters of these patients detected at different time-points of the follow-up. Plasma HCV RNA was quantitated using TaqMan real-time polymerase chain reaction. Virus-specific CD4(+) T cells were enumerated by interferon-gamma (IFN-gamma) ELISpot assay.


RESULTS
Two of eight individuals resolved HCV spontaneously, while the remaining patients developed chronic HCV infection. HCV RNA became undetectable within 14 days of the study, followed by a rapid alanine aminotransferase normalization in patients with resolved infection. On the contrary, chronically infected subjects demonstrated persistent viremia or intermittently undetectable HCV-RNA, accompanied by polyphasic alanine aminotransferase profile throughout the study. Patients with self-limited hepatitis C displayed the strongest virus-specific CD4(+) T (IFN-gamma) cell reactivity within the first weeks of the follow-up, while persistently infected subjects initially showed a weak antiviral CD4(+) T (IFN-gamma) cell response.


CONCLUSIONS
In most cases, acute hepatitis C progresses to chronic disease. Viral clearance within the first month after clinical presentation accompanied by monophasic alanine aminotransferase profile could predict recovery. Early and strong CD4(+)/Th1 immune response against HCV might play an important role in the disease resolution.
Guobuzaite
Ausra
A
Department of Infectious Diseases, Faculty of Medicine, Vilnius University,Vilnius, Lithuania. aguobuzaite@yahoo.com
Chokshi
Shilpa
S
Balciūniene
Ligita
L
Voinic
Alina
A
Stikleryte
Ausra
A
Zagminas
Kestutis
K
Ambrozaitis
Arvydas
A
Naoumov
Nikolai
N
D000208:Acute Disease; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000175:diagnosis; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D019562:Viral Load
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D000410:Alanine Transaminase