Hello folks, Clinical Care Options (CCO) launched a series of video modules with three different case scenarios exploring HCV treatment choices, durations, and outcomes in genotype 3, 2, and 1 patients.
For instance in the first module the panel weighs in on the clinical trial data of investigational agents sofosbuvir and simeprevir in treatment naïve and experienced genotype 3 patients. The text only for "Case 1 " is provided below, an expert video discussion for each case is available in the module.
Other topics include; treatment options for a new class of null responders who failed telaprevir or boceprevir and treating recurrent HCV after liver transplantation.
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Advanced HCV Treatment Topics
Fred Poordad, MD, moderates a case-based panel discussion exploring complex management issues in HCV-infected patients with Nezam H. Afdhal, MD, FRCPI, Douglas T. Dietrich, MD, Paul Y. Kwo, MD, and Norah Terrault, MD, MPH.
Released: 11/7/2013
Case 1: A Treatment-Experienced Patient With Genotype 3 HCV
Fred Poordad, MD:The patient is a 57-year-old white male with genotype 3a HCV infection and previous treatment failure on peginterferon 2a and ribavirin. He is now asking about his options for retreatment. He has no specific records of his past treatment, and his previous HCV RNA levels are unknown. He indicates he developed anemia while on therapy, with ribavirin being held for an unknown period. His current HCV RNA is 1.2 million IU/mL; liver enzyme studies determine his alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated at 125 U/L and 114 U/L, respectively, but the rest of his laboratory examinations are within normal limits. His ultrasound shows his liver and spleen to be of normal size and a FibroTest identifies F0-F2 fibrosis.
The first consideration is whether you would perform any additional tests to evaluate the patient’s liver histology?
Douglas T. Dieterich, MD:I would certainly want more information because my own experience with FibroTest has been less than ideal. At my center, we typically use transient elastography because we have it available. I wouldn’t order a liver biopsy.
Paul Y. Kwo, MD:My view is that the results of a liver biopsy would be helpful. The serum markers present 1 part of the picture; however, in this instance, the management approach will depend on the liver histology, making the biopsy results very helpful.
Norah Terrault, MD, MPH:I agree that the patient’s fibrosis stage is critical information, and the F0-F2 score on the FibroTest leaves considerable room for uncertainty. The patient’s platelet count is also concerning. A biopsy may be useful to help determine whether to delay treatment.
It is important to remember that every test has an error rate, and all the available data have to come together and make sense when you evaluate a given patient. If 1 of the tests does not seem consistent with other aspects of the patient presentation, it is important to seek more information until you are confident in making the right decision.
Fred Poordad, MD:In this case, we did biopsy the patient, and the results indicated Stage 3 fibrosis by Metavir score.
Disease Outcomes and Treatment Outcomes in Genotype 3 HCV
Fred Poordad, MD:Until recently, genotype 2 and genotype 3 HCV have been classified as a single entity. However, in recent years, differences between these genotypes have become more clearly recognized. Disease progression rates are faster in genotype 3 compared with genotype 2.[1] As long ago as 2007, Shiffman and colleagues[2] demonstrated that patients with genotype 2 HCV treated with peginterferon/ribavirin experience an approximately 10% higher rate of sustained virologic response (SVR) compared with those infected with genotype 3 HCV with the same regimen. Importantly, rapid virologic response (RVR) rates are lower in genotype 3 and, especially in patients with genotype 3 without RVR, 16 weeks of therapy is inadequate to achieve SVR.[2] Further, patients experience higher relapse rates with genotype 3.[3]
Nezam H. Afdhal, MD, FRCPI:Disease progression rates are really a difficult question and determining disease progression rates is complex. There are no good cohort studies that have followed untreated patients for 20 or 30 years to show this kind of retrospective data. However, numerically speaking, patients with genotype 3 HCV infection tend to have more liver disease at the time of presentation—whether that means the true rate of progression is different or not is unclear. Additionally, genotype 3 HCV infection is associated with more hepatic steatosis; does that affect progression? Genotype 3 HCV infection in the United States and Europe is a disease of young intravenous (IV) drug users, while in the rest of the world it is very predominant in India and Pakistan, where there is significant morbidity and mortality associated with cirrhosis, liver cancer, and liver failure from this disease. Overall, we do see a lot more disease in patients with genotype 3 HCV infection, but I am not sure if this is due to a difference in the rate of progression in this patient population.
Norah Terrault, MD, MPH:I agree that it is difficult to judge disease progression, but there are some emerging data that the genotype might be a predictor of outcomes. Whether this outcome is driven by genotype 3 HCV itself or by accompanying cofactors is unclear.
Fred Poordad, MD:Van der Meer and colleagues[4] demonstrated an approximately 2-fold increased risk of mortality in patients with genotype 3 HCV infection compared with patients without genotype 3 infection. Importantly, curing genotype 3 HCV results in a significantly lower mortality rate compared with patients who are treated but do not achieve an SVR. Furthermore, older patients with genotype 3 HCV, higher levels of fibrosis, diabetes, or a history of alcohol use are less likely to do well.[4]
Douglas T. Dieterich, MD:That has been my experience as well. Alcohol, diabetes, and genotype 3 HCV infection are all associated with steatosis in the liver which may increase the fibrosis rate, leading to higher mortality. As a consequence, patients with genotype 3 HCV who fail treatment with peginterferon/ribavirin are some of the most difficult to treat outside of a clinical trial.
Emerging Treatment Options for Genotype 3 HCV
Fred Poordad, MD:The interferon-free combination of the nucleoside analogue sofosbuvir with ribavirin has shown promise in the treatment of genotypes 2 and 3 HCV, and at the time of writing has been submitted for approval for these genotypes.
The phase III Fission trial was a randomized, open-label, active-control, noninferiority study comparing 12 weeks of sofosbuvir plus ribavirin with 24 weeks of peginterferon/ribavirin in treatment-naive patients with genotype 2 or 3 HCV infection. The overall SVR rates were 67% for both sofosbuvir plus ribavirin and peginterferon/ribavirin.[5] Subanalysis based on HCV genotype found that patients with genotype 2 infection had a 97% SVR rate with sofosbuvir plus ribavirin compared with 78% SVR rate with peginterferon/ribavirin. However, the sofosbuvir plus ribavirin regimen for patients infected with genotype 3 HCV achieved an SVR of 56% vs a 63% SVR rate with peginterferon/ribavirin. These results indicate the noninferiority endpoint was met, but for genotype 3 HCV infection, the data are clearly not as satisfying as hoped.
The blinded, active-controlled phase III FUSION study explored treatment with 12 weeks of sofosbuvir plus ribavirin, followed by 4 weeks of matching placebo, or 16 weeks of sofosbuvir plus ribavirin in treatment-experienced patients with genotype 2 or 3 HCV infection. After 12 weeks of treatment in patients with genotype 3 HCV infection, the SVR rate was only 30%.[6] However, the additional 4 weeks of treatment doubled the SVR rate to 62%.
Now, go to the next page to see a video of the faculty discussion of these data.
Continue to CCO........
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