Snapshots Lucinda K. Porter, RN

Article: Utility of Hepatitis C Viral Load Monitoring on Directly Acting Antiviral Therapy - S Sreetha Sidharthan, et al
  Source: Clinical Infectious Diseases first published online March 2, 2015

The National Institutes of Health (NIH) funded this small study. Researchers enrolled 114 subjects with chronic hepatitis C virus infection (HCV) who had genotype 1 and no prior treatment. The goal was to see if HCV RNA levels (viral load) at the end of treatment (EOT) negatively or positively predicted sustained virologic response (SVR12). Two viral load tests were used: The Roche COBAS TaqMan HCV test and the Abbott RealTime HCV assay.

To understand the results, it may help to define a couple of terms:

• LLOQ is lower limit of quantification, which is the lowest amount of virus that can be precisely counted.
• PPV is positive predictive value, which predicts the probability that the test will be positive. For instance, if there are 100 people and the PPV is 90%, this means that it is likely that 90 will test positive.
• NPV is negative predictive value, which predicts the probability that the test will be negative. If there are 100 people and the NPV is 2%, this means that it is likely that two will test negative.

Here are the various treatment arms and the results:

• Sofosbuvir and ribavirin for 24 weeks (n=55):
  All patients treated with sofosbuvir and ribavirin (55/55) had HCV RNA <LLOQ at EOT by the Roche and Abbott tests, but only 38 achieved SVR12 (PPV: 69%). Simply put, this means that if your viral load at EOT is less than the LLOQ, you have a 69% chance of having an SVR12.
• Harvoni (sofosbuvir and ledipasvir) for 12 weeks (n=20); Harvoni and GS-9669 for 6 weeks (n=20); Harvoni and GS-9451 for 6 weeks (n=19):
  In the Harvoni-based regimens +/- GS-9669 or GS-9451, 100% of the subjects (59/59) had HCV RNA <LLOQ at EOT, with one relapse (PPV: 98%). The Abbott assay had 90% (53/59) with HCV RNA <LLOQ with one relapse (PPV: 98%).

Here is the most important part: Six patients with HCV RNA ≥LLOQ at EOT achieved SVR12 (NPV: 0%).

The Bottom Line: In the past when using interferon-based treatments, a detectable viral load at EOT meant that treatment wouldn’t be successful. With Harvoni-based HCV treatment, this rule no longer applies—a detectable viral load at EOT DOES NOT mean that treatment will not be successful.

Editorial Comment: This research leads me to two points. First, don‘t despair if you have detectable virus during or at the end of HCV treatment. Second, be sure your doctor doesn’t stop treatment just because you have detectable HCV RNA. The HCV guidelines recommend viral load testing after 4 weeks of therapy and at 12 weeks following treatment completion.  If quantitative HCV viral load is detectable at week 4 of treatment, repeat viral load testing at treatment week 6. If viral load has increased by greater than 10-fold on repeat testing at week 6 (or thereafter), then discontinuation of HCV treatment is recommended. There are no other recommendations to stop or extend therapy based on viral load results.

Article: Treating HCV Infection in Children - Christine K. Lee and Maureen M. Jonas
  Source: Clinical Liver Disease January 2015; Volume 5, Issue 1, pages 14–16

Noting the successful treatment rate of adults with HCV, this study assessed treatment options in children with HCV. However, the newer, more effective, easier to tolerate HCV medications have not been approved for children.

The Bottom Line: Children don’t usually progress to advanced liver disease, so the researchers recommend deferring HCV treatment for children until interferon-free regimens are approved, or until children become adults. If treatment cannot be deferred, therapies using peginterferon and ribavirin can be given to children with compensated liver disease.

Editorial Comment: In last month’s HCV Advocate, I wrote about children with hepatitis C, chronicling the lack of safe HCV treatment options for kids. This new research supports my opinion that children need better options, and soon.

Article: Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment with Sofosbuvir and Ledipasvir in the United States - Jagpreet Chhatwal, et al.
  Source: Annals of Internal Medicine March 17, 2015; 162(6):397-406

HCV treatment using Harvoni (sofosbuvir and ledipasvir) is safer and has higher cure rates than the old interferon-based treatments, but Harvoni is substantially more expensive. This NIH-funded study evaluated the cost-effectiveness and budget impact of Harvoni.

The Bottom Line: This research found that HCV treatment using Harvoni is cost-effective in most patients, but noted limitations of their research.

Editorial Comment: While I understand the value of measuring the financial impact of new HCV medications compared to the older drugs, I am reminded by words purportedly said by former U.S. Surgeon General, Julius Richmond, “Statistics are people with their tears wiped dry.”

Article: Predictors of poor mental and physical health status among patients with chronic hepatitis C infection: The Chronic Hepatitis Cohort Study - Joseph A. Boscarino
  Source: Hepatology March 2015; Volume 61, Issue 3, pages 802–811

The purpose of this study was to evaluate the extent and risk factors for depression and poor physical health among HCV patients. They collected survey data from 4,781 participants, averaging 57 years old, 71% White, and 57% male. Slightly more than half reported past injection drug use, a third were current smokers, and nearly 18% had abused alcohol in the previous year. Around, 47% had been previously treated for HCV and 15% had an SVR.

The Bottom Line: Nearly 30% of HCV patients met criteria for current depression and 25% were in poor physical health. These risks increased among men, Blacks, less educated, unemployed, stress, and little social support. These risks were lower in those who achieved an SVR.

Editorial Comment: Over the years, similar studies to this one have been done, yielding similar results. Depression scores tend to be higher even among HCV-positive people who are unaware that they have HCV. Reading this study on the heels of the previous one about the cost-effectiveness of HCV treatment, I can only shake my head, and ask, “When are we going to treat all HCV patients?”

http://hcvadvocate.org/news/newsLetter/2015/advocate0415.html#4