Managing Acute HCV in MSM in the Era of All Oral Therapy
Managing Acute HCV in MSM in the Era of All Oral Therapy
The most prominent clinical question at the moment of course is how to manage a patient who experiences an acute hepatitis C just now in this exciting but indecisive transitional phase where the guidelines still recommend a quite successful but rather toxic treatment regimen, and the more efficacious and well-tolerated DAAs have not been properly investigated or recommended for use in this setting, yet, and even more importantly will not be reimbursed by health insurances as there is no approved indication for use of DAAs in AHC, yet.
In our opinion, a decision in this situation can only be made on an individual basis in an open discussion between patient and physician. The data from EuroSIDA as well as reports from EASL 2014 tell us that the incidence of AHC and re-infections particularly among HIV-infected MSM are still high. If the patient is particularly worried about infecting someone else (having gotten used to the concept of hardly being infectious anymore under ART), then treatment with pegIFN + RBV should be discussed highlighting potential side effects and long treatment duration. If side effects occur, treatment should be discontinued as there will be several efficacious and safe treatment options in the next 12–24 months.
If the patient is interferon-ineligible or afraid of potential side effects, treatment can be deferred until the chronic phase. If treatment with DAAs over 12 weeks is then initiated early at the chronic stage, patients might reach an SVR even earlier than patients with response-guided pegIFN/RBV treatment of at least 24- up to 48-week duration. In addition, recent data from the European AHC Cohort should bring relief to patients and clinicians about the risk of liver fibrosis/cirrhosis after AHC as the investigators found no evidence for faster fibrosis progression rate assessed mainly by transelastography in 41 patients over a median follow-up period of 45 months after diagnosis of AHC.
In developed countries with full access to any of the upcoming DAA and not yet restricted financial health resources, it is unlikely that the HCV PIs will play a major role in AHC treatment. The role of a combination of just one DAA plus RBV cannot be defined at this moment in the absence of data from clinical trials. The most likely scenario would be that the gold standard of pegIFN + RBV will be followed by a 'platinum' standard consisting of 2 (or 3) DAAs (potentially as fixed-dose combination) given a successful performance in first pilot trials.
Most importantly, with the new DAAs, we will have powerful tools to really shape the course of the ongoing AHC epidemic. Data from larger AHC cohorts such as the European PROBE-C study have shown us that treatment uptake in the acute phase is just around 58% (279/478) reflecting concerns about IFN-related toxicities by both patients and physicians. The far less toxic DAA combination regimen with their short treatment duration would allow us to treat almost everyone and thus curtail further viral dissemination particularly in high-risk populations such as MSM and IVDU. In the past, successful HCV treatment in confined settings such as prisons has been shown to have a significant impact on new infections in a high-risk population. In addition, modelling data from chronic HCV infection showed a substantial impact on HCV-related morbidity and mortality if screening and treatment uptake with efficacious drugs were increased. Analogously, one should expect to see a similar thwarting effect on AHC incidence if a DAA-containing treatment regimen as prevention strategy is combined with intensified screening efforts.
Whom to Treat Now in 2014
The most prominent clinical question at the moment of course is how to manage a patient who experiences an acute hepatitis C just now in this exciting but indecisive transitional phase where the guidelines still recommend a quite successful but rather toxic treatment regimen, and the more efficacious and well-tolerated DAAs have not been properly investigated or recommended for use in this setting, yet, and even more importantly will not be reimbursed by health insurances as there is no approved indication for use of DAAs in AHC, yet.
In our opinion, a decision in this situation can only be made on an individual basis in an open discussion between patient and physician. The data from EuroSIDA as well as reports from EASL 2014 tell us that the incidence of AHC and re-infections particularly among HIV-infected MSM are still high. If the patient is particularly worried about infecting someone else (having gotten used to the concept of hardly being infectious anymore under ART), then treatment with pegIFN + RBV should be discussed highlighting potential side effects and long treatment duration. If side effects occur, treatment should be discontinued as there will be several efficacious and safe treatment options in the next 12–24 months.
If the patient is interferon-ineligible or afraid of potential side effects, treatment can be deferred until the chronic phase. If treatment with DAAs over 12 weeks is then initiated early at the chronic stage, patients might reach an SVR even earlier than patients with response-guided pegIFN/RBV treatment of at least 24- up to 48-week duration. In addition, recent data from the European AHC Cohort should bring relief to patients and clinicians about the risk of liver fibrosis/cirrhosis after AHC as the investigators found no evidence for faster fibrosis progression rate assessed mainly by transelastography in 41 patients over a median follow-up period of 45 months after diagnosis of AHC.
In developed countries with full access to any of the upcoming DAA and not yet restricted financial health resources, it is unlikely that the HCV PIs will play a major role in AHC treatment. The role of a combination of just one DAA plus RBV cannot be defined at this moment in the absence of data from clinical trials. The most likely scenario would be that the gold standard of pegIFN + RBV will be followed by a 'platinum' standard consisting of 2 (or 3) DAAs (potentially as fixed-dose combination) given a successful performance in first pilot trials.
Most importantly, with the new DAAs, we will have powerful tools to really shape the course of the ongoing AHC epidemic. Data from larger AHC cohorts such as the European PROBE-C study have shown us that treatment uptake in the acute phase is just around 58% (279/478) reflecting concerns about IFN-related toxicities by both patients and physicians. The far less toxic DAA combination regimen with their short treatment duration would allow us to treat almost everyone and thus curtail further viral dissemination particularly in high-risk populations such as MSM and IVDU. In the past, successful HCV treatment in confined settings such as prisons has been shown to have a significant impact on new infections in a high-risk population. In addition, modelling data from chronic HCV infection showed a substantial impact on HCV-related morbidity and mortality if screening and treatment uptake with efficacious drugs were increased. Analogously, one should expect to see a similar thwarting effect on AHC incidence if a DAA-containing treatment regimen as prevention strategy is combined with intensified screening efforts.