Acute Hepatitis C Infection and Spontaneous Viral Clearance in Adults and Children

Studies of acute hepatitis C virus (HCV) infection can be challenging, since a majority of infected people do not experience symptoms, and thus do not present for care and HCV testing.

Past research, including a meta-analysis published last year*, indicates that approximately 25% of adults infected with HCV spontaneously clear the virus without treatment (though different studies have found rates ranging from about 10% to 50%). Spontaneous clearance rates tend to be higher among women than men (40% vs 19% in the recent meta-analysis) and among individuals who experience acute hepatitis C symptoms, which is thought to signal a more robust immune response. Clearance, if it occurs, usually happens within 4 months, but may take up to 18 months, or possibly even longer.

Two recent studies provide further data about acute hepatitis C and spontaneous HCV clearance in adults and children.
 

Acute HCV in Adults

In the first study, reported in the November 15, 2007 Journal of Infectious Diseases, C.C. Wang and colleagues assessed acute HCV infection in a cohort of 67 individuals enrolled at multiple U.S. clinics between 2003 and 2005. Acute infection was identified based on HCV seroconversion within 1 year of a previous test (n=45), new HCV antibody seropositivity plus clinical hepatitis symptoms (n=21), or HCV viral sequencing after an iatrogenic (medical) (n=1). Risk factors were assessed using a questionnaire and participants were followed prospectively with serial HCV RNA measurements.


Results

66% of subjects with acute HCV infection were injection drug users.

13 individuals (19%) had an unknown route of transmission.

Of these, 11 (85%) reported high-risk sexual behavior (which was defined broadly and included sex before age 15, more than 6 lifetime sexual partners, exchanging sex for money, sex with a prostitute, having a same-sex partner, and sex with an injection drug user or a person known to have HCV).

10 people developed acute infection within 3 months of exposure in a medical setting, and 3 had confirmed iatrogenic infection.

3 people had gotten a tattoo in the past year and 1 lived with an HCV positive household member.

Overall, 64% of study participants were asymptomatic.

After 6 months, 18% spontaneously cleared HCV without treatment.

The rate of spontaneous HCV clearance was 34% for women, compared with 3% for men (P < 0.001).

Conclusion

Based on these findings, the authors concluded that, “High-risk sexual or iatrogenic exposures may be important contemporary risk factors for HCV infection.”

They added that, “The spontaneous viral clearance rate (18%) in this contemporary study was similar to that reported for past studies of transfusion-associated HCV infection.”

University of Washington, Seattle, WA; Public Health-Seattle and King County, WA; Oregon Health Sciences University, Portland, OR; University of Colorado Health Sciences University, Denver, CO; Mid-South Regional Blood Center (Lifeblood), Memphis, TN; University of Pittsburgh, Pittsburgh, PA.

Spontaneous Clearance in Children

Fewer studies to date have assessed acute HCV infection and rates of spontaneous viral clearance in children. This is an interesting question, since in the case of acute hepatitis B, about 95% of adults spontaneously clear the virus without treatment, compared with only about 10% of infants infected at birth.

L.T. Yeung and colleagues assessed the rate of spontaneous HCV clearance in 157 children with hepatitis C identified between 1990 and 2001; most were infected via transfusions. Clearance was defined as at least 2 positive HCV antibody tests combined with undetectable HCV RNA. Results were reported in the November 2007 Journal of Viral Hepatitis.

Results

44 children (28%) cleared HCV without treatment.

The spontaneous clearance rate was similar in children infected via transfusions and those infected through other routes (28% vs 29%).

In general, younger age at follow-up predicted a greater likelihood of spontaneous clearance (P < 0.0001).

However, just 25% of children with neonatal infection cleared HCV after 7 years.

Normal alanine aminotransferase (ALT) predicted HCV clearance (P < 0.0001)

In contrast with adults, sex was not found to be a significant predictor of HCV clearance

Conclusion

“The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and non-transfusional cases,” the study authors concluded. “If clearance occurs, it tends to occur early in infection, at a younger age.”

Unlike hepatitis B, spontaneous hepatitis C clearance seems to occur at similar rates in adults and children.

Rouge Valley Health System; Division of Gastroenterology and Nutrition; Hospital for Sick Children; Population Health Sciences; and Department of Paediatrics, University of Toronto, Ontario, Canada.



CC Wang, E Krantz, J Klarquist, and others. Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. Journal of Infectious Diseases 196(10): 1474-1482. November 15, 2007.

LTF Yeung, T To, SM King, and others. Spontaneous clearance of childhood hepatitis C virus infection. Journal of Viral Hepatitis 14(11): 797-805. November 2007.
* JM Micallef, JM Kaldor, GJ Dore. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. Journal of Viral Hepatitis 13(1): 34-41. January 2006.