Treating hepatitis C in difficult-to-treat patients

Posted on April 25, 2015

Interferon-free treatment regimens are highly effective, well-tolerated, and enable clinicians to treat patients with hepatitis C who cannot be treated with interferon-based regimens.

In a review article recently published in the journal Nature Reviews Gastroenterology & Hepatology, Peter Ferenci, MD, describes and assesses the application of interferon-free treatment in previously untreatable patients (Ferenci P. Nat Rev Gastroenterol Hepatol. 2015 Apr 21. [Epub ahead of print]). Dr. Ferenci notes that the term “difficult-to-treat” was first used when interferon-based regimens were standard of care and described patients who did not respond to treatment or who did not tolerate interferon (such as those with advanced cirrhosis, psychiatric problems, or comorbidities). Whether these patients remain difficult-to-treat with the new interferon-free treatments is the subject of ongoing studies.

Interferon-based hepatitis C treatment regimens cannot be used safely in patients with advanced liver diseases, and once a patient with chronic hepatitis C infection experiences late complications such as variceal bleeding, hepatic decompensation and hepatocellular carcinoma, only liver transplantation can improve survival. Dr. Ferenci notes that the rapid evolution of direct-acting antiviral (DAA)-based interferon-free treatment regimens has changed our perception of how to treat patients with chronic hepatitis C. He discusses DAA clinical trials in patients with compensated and decompensated cirrhosis and also patients with HCV genotype 3, which has emerged as a particularly difficult HCV genotype to treat. HCV genotype 3 is the second most prevalent genotype worldwide (accounting for approximately 30% of all patients infected with HCV) and is particularly common in the Indian sub­continent (72%).

Dr. Ferenci also highlights DAA studies in patients who have undergone liver transplantation, as unfortunately reinfection of the graft is unavoidable after successful liver transplantation for hepatitis C. He also discusses DAA clinical studies in patients with renal insufficiency and patients who have undergone kidney transplantation. The use of interferon-based therapies in kidney transplant recipients might result in rejection of the graft and is, therefore, not recommended. Ribavirin augments anemia owing to kidney failure and is also poorly tolerated in patients on hemodialysis. Eradicating HCV in the transplant setting will improve survival and graft preservation and treating patients with advanced stages of cirrhosis might even decrease the need for liver transplantation.

Dr. Ferenci notes the following in his conclusion to this review: “on the basis of currently available data, both the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver have issued and regularly update recommendations on how to use these agents. Currently, the main nonmedical hurdle is improving access to these effective but expensive therapies. Even in developed countries, economic pressure limits the number of patients who might receive interferon-free regimens.”

Key points derived from this review:

  • The availability of potent and safe direct-acting antiviral agents has substantially improved the treatment of chronic hepatitis C
  • Patients who are ‘difficult-to-treat’ can now be cured, including those with advanced cirrhosis before and after liver transplantation; studies in patients with kidney failure and after kidney transplantation are underway
  • Combinations of NS5B inhibitors (sofosbuvir, dasabuvir) with new protease inhibitors (simeprevir, paritaprevir) and NS5A inhibitors (ledipasvir, daclatasvir, ombitasvir) are becoming the standard of care for all patients with HCV
  • In patients post-liver transplantation, sofosbuvir, ledipasvir and daclatasvir are safe but protease-containing regimes should be avoided in patients with decompensated liver disease
  • The optimal treatment duration and the need for ribavirin require further studies
  • More effective antiviral agents than those currently available are needed for patient with cirrhosis who are infected with HCV genotype 3a

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