Today, almost all HCV-infections can be successfully treated in clinical routine - even those patients who have not responded to pre-therapies or who have shown failure in therapy. This is also confirmed by new studies, the results of which were presented at the International Liver Congress (ILC) in 2019.
Given the good response of hepatitis C to antiviral therapies and the availability of a vaccine against hepatitis B virus (HBV), these viral hepatitis C virus (HCV) may be eradicable in the foreseeable future, more important a possibility given the ambitious targets set by the WHO for 2030 on the issue.
The number of new infections with hepatitis B and C is to be reduced by 90%, and 80% of patients with HBV or HCV infections suitable for treatment are to be actually treated. This may result in a reduction of deaths by 65%, according to Prof. Dr. Alessandra Mangia of the IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
However, these objectives will be difficult to achieve in many countries. According to Dr. Mangia, "most countries are not on track, and all steps of the strategy need to be improved." Dr. Mangia explained that among other things, effective and simple therapies are in demand. For hepatitis C, this would mean the use of pan-genotypic regimen to treat large numbers of patients.
The nucleotide NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir are available as a fixed combination and are effective against all known HCV genotypes as well as different degrees of fibrosis. "That means one pill a day and no interaction with food," Dr. Mangia explained. Therapy over 12 weeks is approved for a wide range of patient groups.
Dr. Mangia presented the results of a Real World study based on 12 cohorts in a total of 8 countries (the USA and Europe). The primary endpoint of the integrated analysis was sustained virologic response (SVR) 12 and 24 weeks after the end of treatment in per-protocol analysis excluding non-virologic failure. The secondary endpoint was SVR 12 and 24 weeks after the end of therapy in the Intention-to-Treat (ITT) analysis including virological and non-virological failures. The population included was as large as possible, including known difficult patient groups such as those with persistent intravenous drug use.
Only patients with decompensation in anamnesis, pre-therapy with an NS5A inhibitor, more than 12 weeks of therapy or ribavirin therapy were excluded. A total of 5760 patients with HCV genotype 1-6 were included in the analysis; at the time of evaluation, 4491 patients had completed treatment.
Of these, 4442 (98.9%) had achieved SVR. SVR rates were high for all genotypes and fibrosis grades. The SVR rate for the difficult genotype 3 was 97.6%. In the ITT population, the most common reason for failure was lost to follow-up, i.e. loss of contact with the patient. According to Mangia, this is to be expected under clinical everyday conditions (see source 1).
Two other real-world studies presented as posters at the ILC 2019 investigated the efficacy of another pan-genotypic fixed combination, namely the triple combination sofosbuvir/velpatasvir/voxilaprevir (an NS3 protease inhibitor) in a population that is particularly difficult to treat, namely in patients who had not previously responded to therapy with direct antiviral substances (DAA).
The combination is approved in Europe for patients of all genotypes following prior DAA failure. The studies showed SVR rates of 93 - 100%, confirming the efficacy of the combination under everyday clinical conditions (see sources 2, 3)
The first of the two studies was based on the German Hepatitis C Registry (German acronym: DHC-R). Patients previously had paritaprevir/ ritonavir/ ombitasvir ± dasabuvir ± RBV (PrO ± D ± RBV [n=30]), Ledipasvir/Sofosbuvir ± RBV (LDV/SOF ± RBV [n=35]), SOF/Velpatasvir ± RBV (SOF/VEL ± RBV [n=18]), Daclatasvir + SOF ± RBV (DCV + SOF ± RBV [n=13]), Elbasvir/Grazoprevir (EBR/GZR [n=8]), SOF + RBV (n=2) or Simeprevir + SOF + RBV (n=1) not responded or relapsed and were now treated with SOF/VEL/VOX + RBV, 27% of patients suffered from cirrhosis. In this cohort, where data were already available, the SVR was 100% (see source 2).
Data on 196 patients were analyzed for the American study. Therapeutic patients (11%) were also included, some of the patients were treated with ribavirin. The most frequent pre-therapies were LDV/SOF ± RBV (n=92), SOF/VEL ± RBV (n=20), EBR/GZR ± RBV (n=19). Other SOF-based therapies" (n=17) were also reported.
The per-protocol analysis showed an SVR of 98% (183/186), in the intention-to-treat analysis, 93% (183/196) of the patients reached an SVR (see source 3). "These real-life data show that almost all patients with chronic hepatitis C, including pre-therapized patients, can now be cured," commented Prof. Dr. Markus Cornberg of the Hannover Medical School, a member of the EASL Governing Board.
Sources:
1. Mangia A et al.: Global real-world evidence of sofosbuvir/velpatasvir as a simple, effective regimen for the treatment of chronic hepatitis C patients: integrated analysis of 12 clinical practice cohorts. ILC 2019, GS-03.
2. Multiplying J et al: Retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C virus infection and prior DAA failure: an analysis from the German Hepatitis C-Registry (DHC-R). ILC 2019, THU-188.
3. Bacon B et al.: Effectiveness of the salvage therapy sofosbuvir-velpatasvir-voxilaprevir (SOF-VEL-VOX) in chronic hepatitis C: clinical practice experience from the TRIO Network. ILC 2019, THU-116.