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Modeling the Impact of Deferring HCV Treatment [to F3/F4 vs F2 or sooner: 1 month/year after diagnosis) on Liver-Related Events in HIV+ Patients....outcomes: liver-related events & infectious duration....by Swiss HIV & HCV Cohort....model finds delay in treatment increased 2-times to 5 times risk in developing decompensation, HCC & liver-related death
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....model finds timely treatment is important...delay in treatment or imperfect treatment response: patients can result in "progress to end-stage liver disease"
Reported by Jules Levin
CROI 2015
Feb 23-26, Seattlw, WA
from Jules: the authors stated after the presentation during Q&A that the reason for doing this study was so they could go to the Swiss govt to discuss access to treatment for all patients rather than having restrictions & they said these data make discussions "easier".
Program Abstract-
Cindy Zahnd1, Luisa Salazar-Vizcaya1, Gilles Wandeler1, Barbara Bertisch1, Olivia Keiser1, Jean-Francois Dufour2, Andri Rauch2, Beat Mullhaupt3, Roger Kouyos3
1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland;2 University Hospital Bern, Bern, Switzerland;3 University Hospital Zurich, Zurich, Switzerland
program abstract-
Background: Successful treatment of HCV infections substantially reduces the risk of liver-related complications. However, cost considerations and the availability of better treatment options in the future often leads to the deferral of treatment of HCV infection in patients with limited liver fibrosis.
In this study, we modelled the impact of different treatment strategies on liver fibrosis progression among HIV-infected patients with incident HCV infection.
Methods: We developed an individual-based model of liver disease progression. We parameterized it with observed data on incident HCV infections among men who have sex with men from the Swiss HIV Cohort Study (SHCS) and with published data. We simulated patients from HCV infection through stages of liver disease: from fibrosis grade F0 to F4, decompensated cirrhosis, hepatocellular carcinoma and death. Liver disease progression was affected by age at HCV infection and alcohol consumption. Patients also progressed through the care cascade: they could be diagnosed, treated and succeed or fail treatment. We assumed treatment efficacy with Interferon (IFN)-free regimen was 90%. Successfully treated patients had a residual liver fibrosis progression of 0.1 times the rate of patients with detectable HCV. We compared liver-related events and duration of infectiousness (ie. detectable viral load) between the following strategies: treatment of all patients one month after diagnosis, one year after diagnosis or as they reach F2, F3 or F4.
Results: Delaying treatment until 1 year after diagnosis or until F2, F3 or F4 led to 14, 43, 142 and 418 additional cases of liver-related deaths per 1000 HCV infections as compared with treating all patients one month after diagnosis. The average time people were infectious increased from 5 years with early (one month after diagnosis) to 21 years with late (F4) treatment (Figure).
Conclusions: Our model suggests that timely treatment of HCV infection is important: Patients can progress to end-stage liver disease after HCV clearance if treatment is delayed until later stages of liver disease due to imperfect treatment responses and residual fibrosis progression in HIV-infected patients.
Delaying treatment also increases the risk of HCV transmission: the average time during which patients are infectious is four times higher if patients are treated in F4 than if they are treated one month after diagnosis.
webcast: http://www.croiwebcasts.org/console/player/25807?mediaType=slideVideo&
patients who received DAA treatment assuming 90% SVR the percent who experienced DC (decompensation), HCC or death was greatly reduced compared to what was expected in the model:
This chart shows the results of the model - if treating a patient 1 month or 1 year after infection, as you can see this results in very low rates of decompensation, HCC & liver death
Whether patients were treated in F2, F3 or F4 "really matters" - liver deaths were doubled if patients were treated in F3 vs F2 from 5% to 10%; and "if treatment was deferred from F2 to F4 then there was a 5-fold increase from 5% to almost 25% who died from liver-related complications"
Why were these increased death rates so high, they were surprised, so they figured "some of these events must have occurred after HCV clearance" - because many HIV+ "individuals have other risk factors than HCV that keep them at risk for progression despite HCV clearance, particularly true as you can see in graph for those treated in F4 because there risk for developing HCC remains significant even after successful treatment"
OF note:
for patients who cleared HCV, achieved SVR, dying of liver-related complications depending on when they were treated; if treated during F4 you can see the high rates of dying of liver-related complications: (decompensation, HCC, death) and the authors suggested this is in part due to other liver-related complications HIV+ individuals face including fatty liver perhaps due to ARTs, history of alcohol/substance abuse etc.
If treatment is deferred the average time for being infectious increases, treating at 1 month/year vs F4 increases duration of infectious 4-fold from 5 yrs to 20 yrs-
Cindy Zahnd1, Luisa Salazar-Vizcaya1, Gilles Wandeler1, Barbara Bertisch1, Olivia Keiser1, Jean-Francois Dufour2, Andri Rauch2, Beat Mullhaupt3, Roger Kouyos3
1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland;2 University Hospital Bern, Bern, Switzerland;3 University Hospital Zurich, Zurich, Switzerland
program abstract-
Background: Successful treatment of HCV infections substantially reduces the risk of liver-related complications. However, cost considerations and the availability of better treatment options in the future often leads to the deferral of treatment of HCV infection in patients with limited liver fibrosis. In this study, we modelled the impact of different treatment strategies on liver fibrosis progression among HIV-infected patients with incident HCV infection.
Methods: We developed an individual-based model of liver disease progression. We parameterized it with observed data on incident HCV infections among men who have sex with men from the Swiss HIV Cohort Study (SHCS) and with published data. We simulated patients from HCV infection through stages of liver disease: from fibrosis grade F0 to F4, decompensated cirrhosis, hepatocellular carcinoma and death. Liver disease progression was affected by age at HCV infection and alcohol consumption. Patients also progressed through the care cascade: they could be diagnosed, treated and succeed or fail treatment. We assumed treatment efficacy with Interferon (IFN)-free regimen was 90%. Successfully treated patients had a residual liver fibrosis progression of 0.1 times the rate of patients with detectable HCV. We compared liver-related events and duration of infectiousness (ie. detectable viral load) between the following strategies: treatment of all patients one month after diagnosis, one year after diagnosis or as they reach F2, F3 or F4.
Results: Delaying treatment until 1 year after diagnosis or until F2, F3 or F4 led to 14, 43, 142 and 418 additional cases of liver-related deaths per 1000 HCV infections as compared with treating all patients one month after diagnosis. The average time people were infectious increased from 5 years with early (one month after diagnosis) to 21 years with late (F4) treatment (Figure).
Conclusions: Our model suggests that timely treatment of HCV infection is important: Patients can progress to end-stage liver disease after HCV clearance if treatment is delayed until later stages of liver disease due to imperfect treatment responses and residual fibrosis progression in HIV-infected patients. Delaying treatment also increases the risk of HCV transmission: the average time during which patients are infectious is four times higher if patients are treated in F4 than if they are treated one month after diagnosis.
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