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January 15, 2013 Issue

Clinical Practice Points

Comparative Effectiveness of Antiviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review

This systematic review examines the effectiveness of antiviral regimens on sustained virologic responses in hepatitis C infection.

Use this article to:

  • Review the different antiviral regimens available and their effectiveness
  • Discuss the value of a surrogate end-point (the sustained virological response) in evaluating clinical outcomes for treatment of hepatitis C infection
  • Start your teaching session with a question about heptatitis C treatment from MKSAP – we’ve provided one below.
  • Use the recent In The Clinic on Hepatitis C to review issues related to hepatitis C (e.g., should clinicians screen patients for hepatitis C infection? What test should clinicians use for screening? And many more).

Selective D-dimer Testing for Diagnosis of a First Suspected Episode of Deep Vein Thrombosis: A Randomized Trial

D-dimer testing is sensitive but not specific for diagnosing DVT. This clinical trial examines if varying D-dimer cut-off values based upon clinical pre-test probability results in a more efficient strategy for diagnosing DVT.

Use this article to:

  • Review and reinforce the appropriate use of D-dimer testing
  • Incorporate discussions on High Value Care by reviewing costs of D-dimer testing and lower extremity Doppler ultrasound.
  • Discuss the importance of estimating disease prevalence to improve the tradeoff between sensitivity and specificity. Definitions are provided at the bottom of this email.

Quality Improvement

Accuracy of Electronically Reported “Meaningful Use” Clinical Quality Measures: A Cross-sectional Study

This study found a wide variation in accuracy may be expected when electronic health records are used to report compliance with quality measures. 

Use this article to: 

  • Discuss with residents how they would measure the quality of care provided in a practice, and the problems that might threaten the validity of a selected measure
  • Use the tables in this article to review currently used quality measures and whether your residents’ practices meet them
  • Develop or expand QI projects in your own program

Humanism and Professionalism

On Being a Doctor: The Cost of Quality

Take a break from teaching diagnostic skills and patient management, and encourage your residents to pay attention to the human interactions and feelings that make practicing medicine so challenging, and worthwhile. Play a reading of this issue’s On Being a Doctor  and discuss the unintended consequences to “quality measures” as experienced by patients. This might be a wonderful follow-up to a discussion on how we measure quality (see above).

Online Professionalism Investigations by State Medical Boards: First, Do No Harm

This study explored the likelihood by US state medical boards to investigate violations of online professionalism using ten hypothetical vignettes.

Use this article to:

  • Highlight standards for online professionalism
  • Start (or continue) discussions about the importance of life-long professionalism, as this study highlights that these are issues they will encounter not only during training, but also for the rest of their professional careers

MKSAP Question

This question was derived from MKSAP® 16, the latest edition of the Medical Knowledge Self-Assessment Program.

Begin a teaching session on Hepatitic C Treatment with the following question:

A 55-year-old man is evaluated for chronic hepatitis C infection. He takes no medications.

On physical examination, temperature is 36.8 °C (98.2 °F), blood pressure is 135/82 mm Hg, pulse rate is 66/min, and respiration rate is 16/min. BMI is 30.

Abdominal ultrasound demonstrates cholelithiasis but is otherwise normal. Liver biopsy demonstrates mild inflammation and advanced fibrosis without established cirrhosis.

Which of the following is the most appropriate management?

A: Corticosteroids
B: Initiation of antiviral therapy [CORRECT]
C: Referral for liver transplantation
D: Repeat liver biopsy in 6 months
E: Serial aminotransferase monitoring

Answer: B: Initiation of antiviral therapy

Educational Objective: Treat chronic hepatitis C infection.

Critique: In this patient with chronic hepatitis C virus (HCV) infection and advanced fibrosis, antiviral therapy with peginterferon and ribavirin is indicated. Chronic HCV infection is often progressive and may result in cirrhosis and hepatocellular carcinoma. Effective therapy for active HCV infection can delay or prevent these complications. The best available therapy for chronic hepatitis C is the combination of peginterferon and ribavirin, as well as an NS3/4A protease inhibitor if the patient has genotype 1 hepatitis C. The ideal candidate for therapy is the patient with detectable virus, some indication of hepatic inflammation (elevated liver chemistry tests or inflammation on the biopsy), and no contraindication to therapy (decompensated liver disease [ascites, hepatic encephalopathy, jaundice], pregnancy, severe psychiatric disease, or severe preexisting cytopenias). The goal of therapy is to achieve a sustained virologic response, which is defined as undetectable HCV beyond 6 months after the end of treatment. Antiviral therapy for hepatitis C is associated with significant morbidity; therefore, careful consideration should be made regarding which patients are candidates for antiviral therapy.

Extrahepatic manifestations of chronic HCV infection include hematologic conditions (mixed cryoglobulinemia, lymphoma), skin diseases, autoimmune diseases (thyroiditis), and kidney disease. Some of these conditions may benefit from corticosteroid and antiviral therapy, but this patient has no indication for corticosteroid therapy. Corticosteroid therapy results in increased viral replication and should not be given to patients with hepatitis C unless there is a defined indication for corticosteroids.

Liver transplantation is performed when patients with hepatitis C develop decompensated cirrhosis. This patient has good liver function without signs or symptoms of liver decompensation; therefore, referral for liver transplantation is not warranted at this time.

Repeating the liver biopsy in 6 months will provide no additional information that will be helpful in this patient's management.

Serial monitoring of aminotransferases without consideration of antiviral therapy is not appropriate because this patient has advanced fibrosis. Although the overall risk of developing cirrhosis from hepatitis C is up to 25%, one of the risk factors for progression to cirrhosis is advanced fibrosis. Therefore, this patient's lack of established cirrhosis should not be reassuring that cirrhosis will not develop.

Key Points: The best available therapy for chronic hepatitis C is the combination of peginterferon and ribavirin, with the addition of an NS3/4A protease inhibitor for genotype 1 hepatitis C virus.

Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374. [PMID: 19330875]


Sensitivity: The proportion of patients with the target disorder who have a positive test result (a/[a + c]) (Figure 1).

Specificity: The proportion of patients without the target disorder who have a negative test result (d/[b + d]) (Figure 1).

Figure 1. Comparison of test results with a diagnostic standard.


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