EASL 2015: Part 2 —Alan Franciscus, Editor-in-Chief

In part 2 of our European Association for the Study of the Liver (EASL) coverage I will wrap up with a brief overview of some of the remaining data. 

AbbVie:  Ombitasvir/Paritaprevir/Ritonavir for Treatment of HCV Genotype 1b In Japanese Patients with or without Cirrhosis: Results from Gift-I –K Chayama et al
In this current study, Japanese patients were treated with AbbVie’s 2D (paritaprevir/ritonavir plus ombitasvir) given once-a-day for 12 weeks.  This is different from the 3D regime given in the United States and elsewhere because Japanese patients metabolize AbbVie’s drugs differently.  With the 2D combinations Japanese patients reach high enough levels even without ribavirin or dasabuvir.    
In the study there were 215 HCV genotype 1b patients who received the study drugs, 42% were cirrhotic, and 35% were treatment experienced.  The overall cure rate was 95%.  The cure rates among those who had never been treated, as well as those who were treated previously (cirrhotic and non-cirrhotic) were all similar.  The most common side effects were headache, edema and sore throat. 

Comments:  Japan has a long history of hepatitis C.  AbbVie’s 2D combination will be a welcome addition to the drugs in Japan to treat Japanese patients.  For more information about HCV in Japan check out our HCV in Japan—HCV Around the World series.
NHANES:  Advanced Fibrosis is Common in Individuals whose Hepatitis C Has Not Been Diagnosed: Results from the National Health and Nutrition Examination Survey 2001-2012—P Udompap et al
This study has been reported at previous conferences, but it is worth discussing again.  The National Health and Nutrition Examination Survey (NHANES) used data from a group of 62,000 American adults of whom 45,000 were tested for hepatitis C antibodies—591 tested antibody positive and of those 420 were HCV RNA or viral load positive. 

Of the 420 who had chronic hepatitis C, 1 in 10 had cirrhosis and 1 in 5 had advanced fibrosis.  Approximately 50% did not know that they had hepatitis C. 

Comments:  This validates the recommendation for “Baby Boomer” testing.  This should WAKE UP the complacency among physicians and associations and start testing baby boomers NOW.  We want to test, monitor, treat, cure and save lives.
Gilead:  Ledipasvir/sofosbuvir treatment results in high SVR rates in patients with chronic genotype 4 and 5 HCV infection— A Abergel et al
A total of 44 HCV genotype 4 patients and 41 HCV genotype 5 patients were treated with the combination of sofosbuvir and ledipasvir for 12 weeks.  In both of the groups the patients were evenly divided between treatment experienced (TE) and those who had never been treated (TN) and those with and without cirrhosis (C & w/o C).  The cure rates in the HCV genotype 4 patients was TN =96% (21 of 22 pts); TE = 91% (20 of 22 pts); C= 100% (10 of 10 pts); w/o C = 91% (31 of 34 pts).  The most common side effects were fatigue and headache.
Comments:  These are very good cure rates with few side effects.  While the population of genotype 4 and 5 in the United States is very low—genotype 4 is very high in Egypt and other parts of the world (see HCV in Egypt in our HCV Around the World series).  Genotype 5 is primarily seen in South Africa and parts of Europe.  I will be writing an article on Genotype 5 for the June Mid-Monthly edition so stay-tuned.
Merck: The Phase 3 C-Edge Treatment-Naive (TN) Study of a 12-Week Oral Regimen of Grazoprevir (GZR, MK-5172)/Elbasvir (EBR, MK-8742) in Patients with Chronic HCV Genotype (Gt) 1, 4, or 6 Infection—S Zeuzem et al
This was a phase 3 study of a one pill, once-a-day grazoprevir and elbasvir pill taken for 12 weeks.  The study included treatment naïve (TN). The trial included a total of 421 infected HCV genotype 1, 4 or 6.  Most of the trial participants were male sex, and White.  Ninety-one percent were genotype 1.   Approximately 22% had cirrhosis. 

The overall cure rate was 95%: 92% for genotype 1a and 99% for genotype 1b; 100% (36 of 36 pts) of the genotype 4 patients were cured; 80% (5 of 6 pts) of genotype 6 patients were cured.  The most common side effects were headache, fatigue, nausea and joint pain.
Comments:  These are high cure rates with a low side effect profile and it will make a good addition to the treatment landscape of HCV in 2016.  In people with the genotype 1a NS5A resistance-associated variants (RAVs) it shows greater than a 5-fold loss in sensitivity to elbasvir (a protease inhibitor).  What this means in clinical practice in unknown at this time.


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