Spontaneous Viral Clearance Following Acute Hepatitis C Infection: A Systematic Review of Longitudinal Studies

J. M. Micallef; J. M. Kaldor; G. J. Dore


J Viral Hepat. 2006;13(1):34-41. 

In This Article


English literature was searched using the MEDLINE database (January 1990 to April 2003) for studies that examined the natural history of acute HCV infection. The search strategies used were: (hepatitis C OR HCV) AND (acute OR incident OR natural history). The computerized search was supplemented with manual searches of reference lists for additional studies.

Studies were included if they satisfied the following criteria: (i) longitudinal assessment of individual cases from time of acute HCV infection; (ii) at least one follow-up assessment within 24 months of initial diagnosis; (iii) HCV RNA measured and reported for all study subjects; and (iv) individuals untreated for acute HCV infection during follow-up. In studies that included both treated and untreated individuals, only untreated individuals were included in the analyses, provided information was available specific to the untreated group.

We accepted the definition of acute HCV infection used by the authors. Clearance of infection was redefined on the basis of HCV RNA assessment, even if study authors had used other criteria such as elevated serum alanine aminotransferase (ALT) levels. Studies were excluded if they presented either a subgroup or reanalysis of data from another included study. Studies only reported in abstract form were not included.

The following study variables were abstracted for each study: country, method of recruitment, mode of HCV acquisition, number of study subjects, demographic characteristics (age and gender distribution), duration of follow-up, and proportion with clearance of HCV infection. In addition and where available, individual characteristics were abstracted for study subjects.

The primary outcome measure was spontaneous clearance of HCV infection (viral clearance) at the time point reported by the authors. The proportion of subjects who cleared was presented for each study with 95% confidence intervals (95% CI). An unweighted mean was determined by calculating the average of the proportions from all studies. The pooled mean of proportions from all included studies was calculated, weighing the overall proportion by sample size. To identify publication bias, heterogeneity was investigated in a funnel plot of proportions of clearance against the study size.

To examine predictors of viral clearance, age at infection was grouped into three categories (≤30, 31–50, >50 years) and genotype into two categories (genotype 1 and nongenotype 1). Subjects that had a 'nondetermined' genotype were excluded from the analysis.

Study population, country of study, and timing of assessment of clearance were also investigated as study predictors associated with viral clearance. Study population was grouped into three categories: post-transfusion, acute clinical hepatitis and sero-incident.

Univariate data comparisons among groups were performed using Stata version 7.0 (StataCorp, College Station, TX, USA). Tests for trend and chi-squared tests were performed for ordinal and nominal categories, respectively, using Epi Info version 6.04 (Centers for Disease Control and Prevention, Atlanta, GA, USA). Regression analyses were performed using SPSS version 10.0 (SPSS Inc., Chicago, IL, USA). A P < 0.05 was considered significant.


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