Acute Hepatitis C

Etiology and PathogenesisTop

1. Etiologic agent: Hepatitis C virus (HCV). Hepatocyte damage is mainly caused by a strong cell-mediated immune response (and probably also by nonspecific responses).

2. Reservoir and transmission: The only HCV reservoir is patients with hepatitis C. The routes of transmission include contact with blood, blood products (nonsterile medical instruments or nonmedical equipment, such as razor blades, tubes for inhaling cocaine, needles and syringes in injection drug users, toothbrushes), and sexual contacts. Perinatal infection is possible.

3. Epidemiology: In 2013, the estimated prevalence of chronic hepatitis C infection in Canada was ~250,000. Risk factors are present in <50% patients and most commonly associated with injection drug use. The risk of HCV transmission to a sexual partner is ~1.5% per year of nontraumatic sexual activity or 1% to 11% for partners in long-term relationships. The risk of neonatal infection from a seropositive mother is ~2%; 4% to 7% in the case of mothers with positive serum HCV RNA on the day of delivery; and 15% in mothers with HIV coinfection.

4. Incubation and contagious period: The incubation period is 15 to 160 days (average, 50 days). Patients are contagious starting ≥1 week before the onset of symptoms and remain contagious as long as HCV RNA is positive. HCV particles are contagious on environmental surfaces for up to 6 weeks.

Clinical Features and Natural HistoryTop

Most patients with HCV infection are asymptomatic. In others the clinical features resemble mild hepatitis A or B. In the prodromal period serum sickness–like symptoms associated with immune complexes may be observed; these improve with the onset of jaundice. Physical examination may reveal moderate hepatomegaly.

HCV clearance in acute hepatitis C is observed in 15% to 50% of patients, particularly those with symptomatic disease. Patients with uncomplicated acute hepatitis C return to normal daily activities and work within 6 months. The remaining patients develop chronic hepatitis C, out of which 5% to 20% may progress to liver cirrhosis within 20 to 25 years.

DiagnosisTop

Diagnostic Tests

1. Virologic tests: HCV RNA can be detected in serum as early as 1 to 3 weeks from infection (because it is detectable intermittently, HCV infection cannot be excluded on the basis of a single test result and repeat testing is necessary).

2. Serologic tests: Anti-HCV antibodies are detected 4 to 10 weeks from infection (average, 7 weeks). At the onset of symptoms, anti-HCV are detectable in 50% to 70% of patients, and at 3 months, in >90%. The results may be negative in patients who are immunocompromised or treated with hemodialysis.

3. Other laboratory tests: Abnormalities are as in acute hepatitis A but less severe.

4. Liver biopsy is not routinely indicated.

Diagnostic Criteria

Criteria:

1) Documented exposure to HCV (based on risk factors; see Etiology and Pathogenesis, above) within the prior 4 months.

2) Documented anti-HCV seroconversion (2 results of serologic tests with the first result negative and the second positive).

3) A positive HCV RNA test result.

4) Serum alanine aminotransferase (ALT) levels ≥10 × upper limit of normal (ULN) with documented results within normal values from the prior 12 months.

Because the above criteria are rarely met simultaneously in a given patient, it is sometimes difficult to distinguish acute from chronic hepatitis C. Histologic examination of specimens obtained during liver biopsy that is performed after resolution of acute hepatitis may be helpful in such situations if it is needed for prognosis or treatment. Gradual resolution of features of inflammation and absence of fibrosis indicate resolving acute hepatitis, whereas presence of fibrosis is generally a proof of chronic hepatitis.

Differential Diagnosis

As in hepatitis A.

TreatmentTop

1. General measures and symptomatic treatment as in hepatitis A.

2. Antiviral treatment was previously recommended after 24 weeks of diagnosis and the regimen was similar to chronic hepatitis C. However, the 2017 guidelines from the European Association for the Study of the Liver (EASL) recommend treatment at the time of diagnosis with a direct-acting antiviral (DAA) regimen that is similar to that used in chronic hepatitis C but with a shortened duration of 8 weeks (see Chronic Hepatitis C).

Follow-UpTop

As in hepatitis A. Perform follow-up virologic studies (HCV RNA levels) at 6 months to exclude chronic hepatitis even if ALT levels are normal. Patients should be tested for hepatitis B virus, HIV, and other sexually transmitted infections, if appropriate. Provide education and counseling regarding prevention of further transmission, especially avoiding blood donation and avoiding sharing needles in IV drug users. Encourage vaccination against hepatitis A and B if the patient is not immune.

ComplicationsTop

1. Fulminant hepatitis (<1% of patients).

2. Complications caused by immune complexes: Glomerulonephritis, mixed cryoglobulinemia (more frequent in patients with chronic hepatitis C).

3. Progression to chronic hepatitis C.

PrognosisTop

Mortality is low and mainly due to the rare fulminant hepatitis (primarily in patients with HCV and hepatitis virus A or B coinfection). Risk factors for the development of chronic hepatitis C include infection caused by transfusion of blood or blood products (in developed countries this has been extremely rare since 1989), asymptomatic acute HCV infection, multiphasic course of ALT activity, male sex, infection at an age >40, and immunosuppression.

PreventionTop

1. No specific vaccines or immunoglobulins are available.

2. The key prevention method is adherence to the general rules of prevention of blood-borne infections. Instruct the patient how to reduce the risk of infecting others by preventing contact with the patient’s personal belongings that may be contaminated with blood (eg, toothbrushes, razors, needles, syringes and other paraphernalia in the case of persons who inject drugs). Patients should adhere to safe-sex practices. HCV-positive women may continue breastfeeding. Contact notification is recommended with permission of the infected patient.

3. Disease reporting is subject to local regulations.