Answers:

1. In this case, what are the some clinical features that are typical for acute HCV?

Most often, Hep C transmission occurs parenterally. Recent h/o of IV drug abuse suggests the possibility of hepatitis B, C, and D infection in this patient. For hepatitis C, the incubation period between the exposure and the appearance of clinical and serological evidence of acute hepatitis is between 4 and 20 weeks. The majority of patients, 40-75 %, remain asymptomatic or have mild symptoms not leading to medical attention. Our patient was asymptomatic and would not have been identified if he had not required lab follow-up for his valproate therapy.

2. How is the diagnosis of acute hepatitis C made?

Clinically, acute hepatitis C is indistinguishable from other types of viral hepatitis; therefore it is important to exclude the possibility of other types of viral hepatitis by testing for HAV, HBV, and HDV markers, as was done in our patient.  Laboratory diagnosis of acute HCV infection is made by documenting HCV antigen being present (going from anti-HCV negative to anti-HCV positive supports the diagnosis but can take up to 1 year to occur!).

3. What is the natural history of HCV infection?

An important feature of HCV is that up to 80% of patients will develop chronic hepatitis C. Chronic disease is usually diagnosed 10 or more years after the acute illness. More than 20% of those with chronic hepatitis C infection will progress to cirrhosis and eventually will develop end-stage liver disease in about 20 years. Some patients will develop hepatocellular carcinoma ~30 years after initial infection.

4. What are the treatment strategies for acute HCV infection?

Management of acute hepatitis is mostly supportive. Patients need to be advised to maintain healthy diet, avoid alcohol and hepatotoxic drugs. In our patient, consideration of discontinuation of valproate should be discussed with the psychiatrist. It is important to monitor patients with acute HCV for development of chronic disease (seropositive for anti-HCV> 6 months.). Interferon therapy has been tried for the treatment of acute HCV, and results have been mixed and unimpressive. Immune serum globulin does not work either.

5. When is therapy initiated in chronic HCV patients and what is an example of a treatment regimen?

When the patient is seropositive for anti-HCV for greater than 6 months, patient is also seropositive for HCV RNA and patient has evidence of liver disease (LFTs are elevated).

One example: PEG INF alpha-2a or 2b + ribavirin is “standard of care” today (ribavirin dose used depends on genotype)

6. What are some of the limitations of available therapies?

Not all patients respond to interferon + ribavirin therapy. Response is usually monitored by HCV RNA testing.  If patient is not HCV RNA negative after 12 wk.of therapy, treatment should be D/C. Treatment must be continued for 2-4 years to produce reasonable sustained response rates (i.e. response after therapy has been D/C'd).

Interferon side effects include fever, headache, arthralgias, myalgias, depression, irritability and decreased white blood cell count and thyroiditisàthyroid function tests should be monitored monthly.  In our patient, interferon may worsen his existing depression and even precipitate suicide. Hence, IFN is contraindicated in our pt., potentially complicating his treatment (should he develop chronic HCV) greatly!