The safety and efficacy of dual therapy for Hepatitis C among Cirrhotic patients – Is there a future for dual therapy?
Daniel Schmidt-Martin1, Omar El-Sherif1, Audrey Dillon4, Orla Crosbie2, Susan Corbett2, Diarmaid Houlihan3, Steve Stewart4, Susan McKiernan1, Aiden McCormick3, and Suzanne Norris1.
1Department of Hepatology, St James’s Hospital, Dublin 2Department of Hepatology, Cork University Hospital 3The Liver Unit, St Vincent’s University Hospital, Dublin 4Department of Hepatology, Mater Misericordiae University Hospital, Dublin.
The recent publication of the French Early access programme also known as the CUPIC study which targeted Hepatitis C patient patients with advanced liver disease identified worryingly high rates of serious complications and a number of deaths among cirrhotic patients with platelet counts below 100,000 and albumin <35g/L who were treated with triple therapy. New interferon free regimens offer higher response rates in genotype 1 patients but genotype 3 has become the new challenge.
To evaluate the safety and efficacy of dual therapy with pegylated interferon and ribavirin among patients with established cirrhosis.
We performed a multicentre retrospective review of treatment outcomes among cirrhotic patients in the period between 2003 and 2012 in four of the leading centres for HCV treatment in the Republic of Ireland.
Among the 202 patients with cirrhosis who underwent treatment with dual therapy we identified no mortalities and 5.4% discontinued treatment due to drug related side effects. Patients with low platelet counts were associated with lower SVR rates in the entire cohort (p<0.01), genotype 3 patients (p<0.05) and genotype 1 (p<0.05). Patients with low albumin achieved lower SVR rates (p<0.05) though this was not statistically significant when the patients were stratified by genotype. Genotype 1 patients with both low platelets and albumin had a non response rate of 86% (p<0.01). SVR rates were markedly lower among patients with both low platelet and albumin levels for both genotype 1 (14%) and genotype 3 patients (25%) when compared with patients without these baseline characteristics (42% and 66% respectively). SVR rates among subjects with preserved platelets counts and albumin levels were comparable to published rates for non cirrhotic patients and this was also true for when analysed by genotype. This may suggest that the CUPIC group represents a form of liver decompensation which has not to date been recognized.
Dual therapy with ribavirin and interferon has a satisfactory safety profile among patients with low platelets and albumin levels. Cirrhotic patients with normal platelets and albumin levels achieve SVR rates with dual therapy which are equivalent to non cirrhotic patients. Where access to interferon free regimens is limited due to cost, the early treatment of genotype 3 cirrhotic patients with dual therapy should be considered.