Real world experience in 150 genotype 1 HCV patients with triple therapy: severe adverse events and high rates of virological failure in cirrhotic patients with portal hypertension (platelets < 100.000/nl and albumine < 40 g/l)
Background and aim: Newly approved HCV GT1 triple regimens are complex and associated with additional toxicities. Besides RCT results, only limited data are available for BOC und TVR under real life conditions, especially for difficult to treat patients with non-response and advanced liver disease.
Methods: Data from 150 patients who initiated triple therapy apart from clinical studies or Early-Access-Programs with BOC (n = 73) or TVR (n = 77) at the IFI Institute were obtained from medical record review and analysed on an intention to treat basis. Hemoglobin level < 9 g/dl or a > 4.5 g/dl decrease from baseline defined severe anemia, fibrosis scores of > 3 by Fibroscan or ARFI defined advanced fibrosis.
Results: Median age of the study group was 55yrs with 31% of more than 60yrs, 67% males, 90% Caucasian, GT1a 39%, GT1b 60%, IL28 C/C 11%, non C/C 88%. 44% of patients showed advanced fibrosis, 26% of patients presenting with complete cirrhosis and platelets of < 100.000/ul. 26% were treatment-naïve, of 74% of patients with prior failure to therapy 50% were non-responders. In this ongoing study, severe adverse events (SAEs) were reported in 65% and 53% of patients during BOC and TVR therapy, respectively. All patients with cirrhosis and all patients above 60yrs of age developed SAEs. Severe anemia occurred in 65% of patients, 38% of patients received blood transfusions, all patients above 60yrs and all cirrhotic patients received blood transfusions. Discontinuation rate because of SAEs or virological failure was 33% (BOC) and 31% (TVR). Interestingly, virological failure was more often related to virological break throughs compared to failure in reaching primary stopping rules at week 4 (TVR) or 12 (BOC). The interim data suggest that SVR rates will be significantly lower compared to RCTs.
Conclusions: Despite improved efficacy with DAA triple therapies, real world data reflect the treatment complexity and concerns about side effects and safety in patients with advanced liver disease. In patients of older age with liver cirrhosis and portal hypertension reflected by low platelets (< 100.000/nl) or low albumin (< 40 g/l), the safety profile is poor for both drugs, SVR is low and clinical outcome remains questionable.