Professor Michael P. Manns, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany, is scheduled to speak on the Unmet Need for the Patients with Chronic Hepatitis C - genotype 3, DAA resistance, HCV recurrent post transplantation, decompensated liver disease and renal insufficiency, etc.

 

　　Therapy for chronic hepatitis C virus (HCV) infection has been revolutionized due to interferon free all oral combinations with direct acting antiviral agents (DAA) targeting the HCV protease, polymerase and NS 5A protein. Sustained virological response (SVR) rates of more than 90 % for most HCV patients have become a reality and these results have been confirmed in real life experiences. The average treatment duration is 12 weeks, for some difficult to treat patients 24 weeks seem necessary while 8 weeks are sufficient for treatment na?ve non cirrhotic HCV genotype 1 patients with viral load < 6 MIO IU/ml with sofosbuvir (SOF) plus ledipasvir (LDV). Even shorter durations are presently explored for future regimen. Preliminary results suggest that 6 weeks may become possible at least for easy to treat patients. While this seems to be the limit for chronic HCV patients, 4 weeks seem realistic for acute HCV.

 

　　HCV genotype 3 patients are now the most difficult to treat population. In particular for cirrhotic and treatment experienced patients effective and safe 12 week regimen are still needed.

 

　　Preexistent NS 5A mutants indicate a significant risk for treatment failure and they persist long term after treatment cessation. The relevance of viral resistance has to be studied further in DAA failure patients that are a very heterogeneous group. Neverthess, pretreatment routine testing for resistance-associated variants (RAV) seems not to be necessary for the average HCV patient.

 

　　With the advent of DAA therapies prevention of recurrent HCV infection after liver transplantation has become possible. If patients achieve SVR before transplantation or are at least 30 days negative while under therapy HCV recurrence is prevented. Eradication of HCV infection in the post-transplant population should be achieved soon in the years to come and a decline of transplantations for HCV induced liver disease should happen within the next decade.

 

　　SOF based DAA therapies have also been explored in decompensated liver disease, i.e. Child B and C cirrhosis. The majority of patients improve their MELD and CPT scores after achieving SVR. However, there are a proportion of patients that does not improve or even deteriorates. The definition of the point of no return is a major unmet need and still an unsolved problem. Renal insufficiency is another yet unsolved problem in particular in the decompensated patient since SOF based regimen cannot be given to patients with GFR< 30 ml/min. On the other hand the so-called 3D combination (Paritasvir, Ombitasvir, Dasabuvir) can be given to patients with renal insufficiency but is either not recommended or contraindated in decompensated liver disease. Novel regimens are needed for patients with decompensated liver disease and renal insufficiency. Whether SVR following successful DAA therapies protects from de novo infections at least in a proportion of patients also needs to be clarified.

 

　　But all the above issues might be a piece of cake when compared with the last but the most important unmet need: the global access to HCV therapies. A global strategy for HCV eradication is urgently needed.

 

Symposium 3: HCV Treatment in Special Situation - "Unmet Need for the Patients with Chronic Hepatitis C"

 

15:50-16:10

 

Room 1ABCD