The Natural History of Acute Hepatitis C

Clinical Presentation, Laboratory Findings and Treatment Outcomes

R. Loomba; M. M. Rivera; R. McBurney; Y. Park; V. Haynes-Williams; B. Rehermann; H. J. Alter; S. K. Herrine; T. J. Liang; J. H. Hoofnagle; T. Heller


Aliment Pharmacol Ther. 2011;33(5):559-565. 

In This Article

Abstract and Introduction


Background Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined.
Aim To establish natural history and complications of treatment of acute hepatitis C.
Methods Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed.
Results Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4–8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%.
Conclusions Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects.


Chronic infection with the hepatitis C virus (HCV) is now the leading cause of liver-related morbidity and mortality in the US and accounts for an estimated 10 000 deaths yearly.[1] In contrast, acute HCV infection has become uncommon, new cases having decreased markedly over the last 15 years to a currently historic low level.[2] Nevertheless, cases of acute hepatitis C continue to occur and eventuate in chronic infection in 70–80% of cases. Among patients who develop chronic hepatitis C, between 20% and 30% develop cirrhosis over the subsequent two to three decades; and likely a higher proportion thereafter.[1–6]

Clearance of HCV during the acute phase of infection is typically associated with appearance of a vigorous T-cell response against multiple HCV epitopes; whereas evolution to chronicity is associated with poor T-cell responses that are limited in scope and depth.[7,8] Jaundice and young age are clinical factors associated with an increased likelihood of clearance of HCV.[9] In an individual case, however, there are no features that reliably predict recovery. Even serial testing for HCV RNA can be unreliable as levels of virus may fluctuate widely during the acute course and become transiently undetectable, only to be followed by its reappearance and persistence.

The high rate of chronicity of acute hepatitis C has led to studies of therapy. In a study from Germany, a 24-week course of standard alpha interferon monotherapy was reported to result in sustained viral clearance in 98% of persons treated during the acute phase of hepatitis C.[10] This response rate was higher than would be expected to occur spontaneously and far higher than a similar regimen would achieve in chronic hepatitis C. Subsequent studies, however, have reported somewhat lower rates of response (71–94%) even using similar cohorts.[9,11–15]

Acute hepatitis C has been a focus of natural history and immunological studies at the Clinical Center of the National Institutes of Health during the last 15 years. Because of publications on the success of therapy of acute hepatitis C in 2001, subsequent patients were offered therapy during the acute phase of disease using the combination of peginterferon α-2a and ribavirin for 24 weeks. This study describes the clinical course of 25 patients with acute hepatitis, some relevant virological features and responses to anti-viral therapy.


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