What to Do for Patients With Hepatitis C?

No matter what primary care demographic your practice represents, it would be most unusual not to encounter patients infected with hepatitis C virus (HCV). Since HCV infection is chronic and can lead to cirrhosis (occurring in 20% of patients over a period of 10 to 20 years), decisions regarding its management, referral, and follow-up are of the utmost importance. A recent issue of the New England Journal of Medicine focused attention on a “typical” category of hepatitis C patients: those who are otherwise healthy and who have an incidentally discovered infection.1

A “TYPICAL” CASE OF HEPATITIS C
The “Top Paper” begins with a case vignette. A 25-year-old African American woman is incidentally discovered to be HCV-positive when she volunteers to donate blood. She is sent to her primary care physician to determine a course of action. History, medications, and physical findings are unremarkable. She does not drink alcohol or use illicit drugs, and she does not have multiple sex partners. All liver-related laboratory results are normal. She is immune to hepatitis B, and she does not have HIV infection. Her hepatitis C viral load is 2.3 million IU/mL and is characterized as genotype 1. She is vaccinated for hepatitis A.

THREE DIFFERENT APPROACHES
Three experts in hepatitis C management then discuss 3 different approaches to her care:

•Expectant management with periodic assessment of liver function.
•Liver biopsy with treatment contingent on biopsy results.
•Therapy with peginterferon and ribavirin.

Watchful waiting. First, what are the pros and cons of expectant management? The discussant proceeds to explain why a biopsy is not indicated. None of the major risk factors for fibrosis—obesity, alcohol use, hepatitis B, HIV infection, and diabetes—are present in this case. The liver enzyme levels are normal. The second reason that a biopsy is not proposed is the genotype of the virus and the patient’s race. For this specific patient, the likelihood of a “sustained” response to therapy (ie, a negative polymerase chain reaction assay for HCV at 6 months) is only 25% to 30%. The discussant then offers hope for the future treatment of hepatitis C. Recent data show that a new drug (telaprevir) increases the response in persons infected with HCV genotype 1.2-4 Waiting, albeit with careful follow-up, may allow a better treatment regimen if and when it is needed.

Liver biopsy. The second discussant favors liver biopsy. She cites a study comprising 486 patients with hepatitis C who had normal liver enzyme values on 3 separate measurements over 18 months. However, biopsy results showed 25% of the patients had moderate to severe inflammation and 30% had significant fibrosis.5 The discussant then reviews more sensitive and specific tests to identify liver fibrosis, and she alludes to the potential improvement in response with newer drugs in patients who have HCV genotype 1 infection.

Treatment. The last discussant argues for treatment. Since the patient has the more “stubborn” genotype 1, he suggests 48 weeks of therapy to eradicate the virus before it can cause irreversible complications. He observes that a sustained virologic response ensures a reduced rate of adverse outcomes later.6

HOPE FOR THE FUTURE
Readers were then asked to submit their choice for the course of action. I chose No. 1, expectant management, partly because I suspect there will be newer and better treatment choices for HCV genotype 1 infection in the near future. However, clinical wisdom and empiric data support the second choice as well.

Although this exercise did not address all hepatitis C scenarios (ie, concurrent infection with hepatitis B, alcohol use, steatosis, etc), it helped me with one common category of patients. Hepatitis C care is complicated and has to be approached in multiple installments.

References

1. Afdhal NH, Lok AS, Di Bisceglie AM. Clinical decisions. Management of incidental hepatitis C virus infection. N Engl J Med. 2009;360:1902-1906.
2. McHutchison JG, Everson GT, Gordon SC, et al; PROVE1 Study Team. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection [published correction appears in N Engl J Med. 2009;361:1516]. N Engl J Med. 2009;360:1827-1838.
3. Hézode C, Forestier N, Dusheiko G, et al; PROVE2 Study Team. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360:1839-1850.
4. Hoofnagle JH. A step forward in therapy for hepatitis C. N Engl J Med. 2009; 360:1899-1901.
5. Zeuzem S, Diago M, Gane E, et al; PEGASYS Study NR16071 Investigator Group. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. 2004;127:1724-1732.
6. Mallet V, Gilgenkrantz H, Serpaggi J, et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med. 2008;149:399-403.