Understanding Spontaneous Hepatitis C Virus Clearance

Dewi Nur Aisyah

Among patients in the acute phase of hepatitis C virus (HCV) infection, a portion will spontaneously clear the infection without treatment, and HCV RNA will completely disappear from the serum. Estimates from various studies project that anywhere from 20% to 30% of patients will spontaneously clear HCV, with the biggest factors being sex, ethnicity, immune status, and genetics.

For those who do not clear the infection on their own, direct-acting antiviral (DAA) agents have become available, and over 90% of patients undergoing treatment with these drugs will achieve a cure. The biggest drawback to DAA treatment is the cost, with 1 course of treatment in the United States ranging from $51,000 to $84,000.

The question then remains as to which patients should be targeted to receive treatment with DAAs, with the goal of not just reducing the number of individual HCV infections but also the public health burden of the disease in the future.

Dewi Nur Aisyah, an epidemiologist at Emerging Zoonotic and Infectious Disease in the Health Policy Research Group, Universitas Indonesia, and a PhD candidate at the Institute of Health Informatics, University College London, recently undertook a systematic review and meta-analysis, along with several colleagues, to help answer this question.

“The aim of this review was to ascertain precise estimates of spontaneous viral clearance, and establish factors which are associated with spontaneous clearance to inform policy regarding the use of anti-viral agents for HCV,” wrote Aisyah and colleagues.

For the assessment of spontaneous HCV clearance, Aisyah and colleagues included only those studies with precise information on viral clearance at specific time intervals (3, 6, 12, and 24 months). Ultimately, a total of 6 studies, or 998 patients, were included in the analysis.

Aisyah and colleagues concluded that spontaneous clearance peaked at 12 months, with 36.1% of patients achieving spontaneous clearance of HCV by that point in time. They determined that spontaneous clearance beyond 12 months is unlikely.

For the examination of factors affecting spontaneous clearance of HCV, Aisyah and colleagues pooled data from 43 studies, or 20,110 patients.

The key factor affecting spontaneous clearance was intravenous (IV) drug use. IV drug users, who are at a high risk of infection and pose an ongoing risk for transmission of HCV to others, are less likely to experience spontaneous clearance of HCV. Other factors that reduce the likelihood of spontaneous clearance include HIV co-infection, non-hepatitis B co-infection, non-genotype 1 infection, asymptomatic infection, male sex, black or indigenous race, older age, and excessive alcohol use.

“These data provide support for a strategy of early treatment for high risk groups who are less likely to achieve spontaneous clearance, may pose a higher risk of onward transmission and who may be more likely to be lost to follow up,” researchers wrote.

Aisyah and colleagues also suggest active engagement of high risk groups, to encourage safe injection practices, condom use, and medication adherence to reduce the likelihood of transmission of HCV.

The study, “Assessing Hepatitis C Spontaneous Clearance and Understanding Associated Factors: A Systematic Review and Meta-Analysis” was published online in the Journal of Viral Hepatitis last month.

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