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


A total of 31 studies of acute hepatitis C with a total of 675 study subjects met the inclusion criteria for this systematic review.[7,12,13,16–19,23–46] Four studies resulted in more than one publication.[7,17,19,26,47–50] In these cases, the most recent or complete was included in the review.[7,17,19,26] Study populations were made up of 19 series of acute clinical hepatitis C, nine of post-transfusion hepatitis C and three of sero-incident cases. The mean study population was 22 (range 4–67) and follow-up ranged from 6 to 157 months ( Table 1 ). All studies enrolled subjects prospectively, although seven of these carried out virological assessments on stored specimens.[13,25,28,30,31,33,44]

Criteria for inclusion of acute HCV infection cases varied between the studies. Twenty-one studies included elevated ALT levels within their acute HCV infection definition. Identification of a rise in ALT level ranged between two[27] and 20[17,32] times the upper limit of normal. Virtually all (29) studies required seroconversion to anti-HCV antibody and/or HCV RNA for inclusion. The remaining two studies[26,35] required HCV RNA detection in the presence of elevated ALT levels 10 times the upper limit of normal.

The time at which clearance was measured differed across studies, with seven using 6 months of follow-up,[13,17,24,26,28,44,45] a further six studies using 12 months,[12,27,30,33,37,42] and the remainder using longer time periods ranging from 18[29] to 48 months[38,40] after their baseline assessment.

The proportion with viral clearance ranged from 0.0 to 0.8, with an unweighted mean of 0.27 (95% CI 0.20–0.33) and a weighted mean of 0.26 (95% CI 0.22–0.29). Examination of the funnel plot shows symmetry on either side of the weighted mean proportion of viral clearance (Fig. 1). The proportion with viral clearance was not significantly associated with the duration of follow-up (P = 0.6).

Funnel plot of the proportion of people with viral clearance against the study size of all studies included in the analysis. The pooled mean (—) and 95% CI (- - -) is shown. Visual examination of the plot reveals symmetry of the individual studies to the overall mean proportion for the 31 studies.

Viral clearance was less common among males (0.20 vs 0.42, RR 0.43, 95% 0.36–0.53) ( Table 2 ). However, viral clearance was not associated with age at infection (P-test for trend, P = 0.36) and HCV genotype (RR 0.96, 95% CI 0.76–1.21).

Studies based on acute clinical hepatitis C had a higher proportion of viral clearance (0.31, 95% CI 0.26–0.36) than both post-transfusion (0.18, 95% CI 0.13–0.24) and sero-incident studies (0.18, 95% CI 0.09–0.32) (P = 0.001) ( Table 3 ).

Taiwan, Japan and Italy were highly represented, with six studies performed in each country. The US had four studies included in the analysis. There was no association between country of study and viral clearance (P = 0.08) ( Table 3 ). Other countries represented in this review include Austria, Brazil, Egypt, Germany, Spain, Sweden and Turkey.


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