Man With Newly Diagnosed Hepatitis C

Hepatitis C virus (HCV) infection was recently diagnosed in an asymptomatic 53-year-old African American fireman. He had applied for a new life insurance policy prior to retirement some months earlier, and routine blood testing revealed an elevation of serum alanine aminotransferase (ALT) to approximately twice normal values, confirmed by repeated testing.

HISTORY

His health is otherwise excellent, and he has routinely performed in the top quartile in physical and cardiovascular fitness. He sustained job-related trauma several times and required blood transfusions for multiple trauma in 1988. He does not smoke but does occasionally drink beer at social events. He denies arthritis symptoms or rash.

PHYSICAL EXAMINATION

Vital signs are normal. No scleral ictus or adenopathy is noted. Heart and lungs are normal. Abdominal examination reveals no masses and no enlargement of either the liver or spleen; no ascites is noted. Examination of the extremities and skin is negative for arthritis, rash, and spider angiomas.

LABORATORY RESULTS

Hemogram and routine chemistry panel results are normal. Biochemical profile shows bilirubin, 1.2 mg/dL; aspartate aminotransferase (AST), 75 IU/L; and ALT, 200 IU/L. INR is 1.

HCV infection was diagnosed by initial enzyme immunoassay. Viral load is 200,000 IU/mL. The patient was told he may require treatment for hepatitis C, and he now wishes to discuss the risk-benefit issues of the disease itself as well as diagnostic and therapeutic considerations.

Which of the following statements about this patient’s condition is incorrect?

A. His age, race, and sex are not favorable predictors for response to antiviral therapy.
B. His viral load is a positive factor with regard to treatment response.
C. A liver biopsy can add significant information regarding the need for and response to therapy.
D. Hepatocellular carcinoma risk will not be affected by antiviral therapy.

(Answer and discussion on next page)

Correct answer (ie, incorrect statement): D, Hepatocellular carcinoma risk will not be affected by antiviral therapy.

This patient has well-documented HCV infection. He is in a high-risk population, having received a blood transfusion before 1992, which until recently was the major risk factor in developed countries. The predominant risk factor today is history of injection drug use; among those who have such a history, the prevalence of hepatitis C is 45%.¹

This patient has a classic presentation: he has had no obvious symptoms for a prolonged period after infection. The elevated ALT was the clinical clue that liver disease was present, and the appropriate current serologic screening assay—enzyme immunoassay—was performed, was positive, and confirmed HCV infection. Since the patient has a significant risk factor (blood transfusion before 1992), the test can be considered a true positive without need for further confirmation by recombinant immunoblot assay, as might be needed in patients without risk factors or without clinical or laboratory evidence of liver disease.

INITIAL EVALUATION

Extensive literature exists regarding the initial evaluation in an asymptomatic but ALT-positive patient with newly diagnosed hepatitis C. There has been an explosion in both methods of measurement and characterization of HCV infection as well as viral load. Assays based on molecular detection of HCV RNA can quantitate the presence and degree of viremia (viral load). This patient has a viral load of 200,000 IU/mL, a level not considered high.² Such assays are relevant to the outcome of and response to anti-HCV therapy but do not always correlate with either extent of liver damage already present or likelihood of disease progression. A high viral load (more than 600,000 to 800,000 IU/mL) is correlated with diminished sustained virologic response to antiviral therapy.² Thus, his low viral load is a positive predictor of good response, and choice B is a correct statement.

Age, race, and sex are also determinants of the response to therapy; the favorable determinants are age younger than 40, Caucasian race, and female sex.^2,3 In this demographic, the patient is in an unfavorable subset, so choice A is indeed correct.

The “gold standard” for determining viral activity in the liver and degree of damage remains liver biopsy. Tissue sampling also is the only reliable means of determining the prognosis and likelihood of HCV-related liver disease progression.² Liver biopsy can detect the degree and extent of active inflammation as well as the presence or absence of bridging fibrosis or cirrhosis. Many investigators use biopsy results in making decisions about antiviral therapy.⁴ Therefore, liver biopsy is usually recommended for initial assessment of patients with chronic HCV infection, and choice C is an appropriate, correct response.

TREATMENT

Once a decision to proceed with therapy is made, a vast and growing literature exists to aid in assessing the likelihood of a durable response (and even a cure) as well as specifics of antiviral regimens.^2,3 Some convenient markers for the likelihood of response include²:

• HCV genotype other than 1.
• Low baseline viral titer.
• Caucasian race.
• Minimal fibrosis.
• Female sex.
• ALT quotient ≥ 3.

Thus, our case has several favorable but also unfavorable prognostics (choices A and B). Less defined but likely more important are innate genetic/immune characteristics in any given patient. Such allelic polymorphisms and lymphocyte characteristics will assume more importance as they are defined and clinically evaluated.²

Peginterferon and ribavirin remain the cornerstone of all antiviral therapies. Currently, the list of different regimens with newer-generation antivirals^2,3,5 and varying durations of therapy continues to grow, but a comprehensive discussion is beyond the scope of this vignette. Actuarial analysis suggests that response rates approaching 80% are attainable, which would reduce cirrhosis rates to 12% to 25% of chronic hepatitis C cases.²

One area that has already been established is that interferon therapy indeed reduces the incidence of hepatocellular carcinoma in patients with hepatitis C in general and very markedly so in those with viral eradication.⁶ Thus, choice D is not a true statement and is the appropriate answer here.

OUTCOME OF THIS CASE

After discussion, the patient elected to undergo a liver biopsy, which revealed lymphocytic infiltration of parenchyma and reactive bile duct changes but no fibrosis. He will shortly begin therapy with telaprevir and peginterferon-ribavirin and will be evaluated for response at 12 weeks. 

1. Armstrong GL, Wasley A, Simard BP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-714.
2. Rosen HR. Chronic hepatitis C infection. N Engl J Med. 2011;364:2429-2438.
3. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management and treatment of hepatitis C—an update. Hepatology. 2009;49:1335-1374.
4. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med.2006;355:2444-2451.
5. Hoofnagle JH. A step forward in therapy for hepatitis C. N Engl J Med. 2009;360:1899-1901.
6. Shiratori Y, Ito Y, Yokosuka O, et al. Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med.2005;142:105-114.