Natural History

Acute hepatitis C (HCV) infection is defined as the 6-month time period following exposure to the hepatitis C virus. After initial infection, the virus clears spontaneously in an estimated 20 to 35% of patients. These patients never develop chronic hepatitis C infection.

Epidemiology

The CDC tracks confirmed cases of acute hepatitis C virus infection each year, which are reported by each state on a voluntary basis. The CDC requires that a confirmed case of acute HCV meet both clinical criteria (discrete onset of symptoms such as nausea or malaise plus either jaundice or a peak elevated serum alanine aminotransferase (ALT) level >200 IU/L) and laboratory criteria (positive HCV RNA). The HCV antibody can be negative during the first 6 weeks after exposure. A case can also be classified as acute HCV if the patient has a documented negative HCV test followed by a positive test within 12 months. The CDC also computes an estimate of the true number of new HCV infections per year after taking into account the fact that acute infections are likely to be asymptomatic and underreporting by clinicians is high. New cases of acute hepatitis C have increased rapidly in the US since 2010, and have most often been associated with injection drug use. CDC reported 44,700 cases (adjusted number) of acute infections in 2017.

Treatment

Treatment of acute hepatitis C should be considered to prevent complications of chronic HCV infection and reduce transmission among high-risk populations. Because most HCV seroconversions are asymptomatic, screening for acute hepatitis C infection should be performed following known or suspected exposures and periodically among populations with ongoing exposure. Acute HCV infection is confirmed when a patient has a negative hepatitis C antibody and a detectable HCV viral load or when an individual with a recent exposure seroconverts from a negative to a positive hepatitis C antibody. Patients with known or suspected acute HCV infection should also receive screening for acute hepatitis A, acute and chronic hepatitis B (± delta virus), and HIV infection. Testing for acute non-viral hepatitis (e.g. autoimmune) should also be considered. Patients with suspected or confirmed acute HCV infection should be counseled on the avoidance of needle sharing (including injection equipment) and avoiding high-risk sexual practices. Patients who continue injecting drugs should be referred to an addiction specialist.

Patients with acute HCV infection can be treated with DAAs upon initial diagnosis (based on detectable HCV RNA) without awaiting spontaneous resolution. The treatment regimens recommended for chronic HCV are the same as recommended for acute HCV (see section on Initial Treatment of HCV Infection from the Chronic Hepatitis C Virus (HCV) Infection: Treatment Considerations from the Department of Veterans Affairs National Hepatitis C Resource Center and the HIV, Hepatitis, and Related Conditions Program in the Office of Specialty Care Services). Pangenotypic regimens are recommended if HCV genotyping is unavailable or if concern of exposure to more than 1 genotype exists.

Treating acute HCV without waiting 3-6 months for potential spontaneous clearance is a departure from prior recommendations. There are pros and cons to immediate vs. deferring treatment until after infection has become chronic. Immediate treatment greatly increases the likelihood of the patient receiving treatment at all and reduces the risk of new HCV transmission to others. However, patients with acute HCV are likely to have high risk behaviors and may not complete the intended DAA treatment course, or follow up for laboratory testing and appointments. If treatment is deferred for months, the opportunity to treat the patient may be lost. On the other hand, the primary downside of immediate treatment is the use of DAA treatment for 30-50% of patients who may otherwise spontaneously clear the infection. Prescribing unnecessary medication creates a potential for unnecessary adverse effects and medication costs. Weighing these considerations, along with the overall simplicity of the DAA regimens, extremely high SVR rates, and low side effect profile, the clinical benefit of immediate treatment is very high to the patient and the public and therefore, the overarching recommendation is for immediate treatment. Providers should discuss the benefits and risks of immediate treatment with the patient to make a shared decision.