Daily Highlights from EASL 2017 - 
Friday, April 21, 2017

 Don't Miss  "Reporting on EASL 2017 - Advances in Chronic Hepatitis C Management and Treatment: Comprehensive Expert Review and Discussion of Key Presentations"

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Friday, April 21, 2017
EXPEDITION-I: efficacy and safety of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus genotype 1, 2, 4, 5 or 6 infection and compensated cirrhosis (GS-006):

The combination of gelcaprevir/pibrentasvir was shown to be highly effective in compensated cirrhosis patients with genotypes 1, 2, 4, 5, and 6.  In this study reported by Dr Xavier Forns 146 patients with compensated cirrhosis (48 genotype 1a, 39 genotype 1b, 34 genotype 2, 16 genotype 4, 2 genotype 5 and 7 genotype 6) were treated with 12 weeks of glecaprevir/pibrentasvir.  25/146 had failed PEG/RBV, 11/146 failed SOF based regimen with IFN or RBV.  The SVR rate was 99% with just one relapse in a genotype 1a patient. The regimen was well tolerated and high SVR rates were achieved regardless of pre-treatment characteristics across the 5 genotypes including the presence of NS5a variants in 40% of individuals prior to therapy.  
Tumor recurrence after Interferon-free treatment for hepatitis C in patients with previously treated hepatocellular carcinoma discloses a more aggressive pattern and faster tumor growth (Abstract PS-031):
While all oral DAAs are highly effective in achieving SVR in patients with cirrhosis, there are emerging data that suggest that some individuals with HCC and hepatitis C infection may develop a more aggressive recurrence pattern after SVR. Reig and colleagues extended their previous report of individuals with HCC and HCV by reporting on 77 individuals with confirmed radiological assessment of HCC after starting DAA therapy. In their cohort, 21/77 had HCC radiological recurrence after starting DAAs with 5 deaths with median f/u of 12 months, the median time between start of DAA and 1st HCC recurrence was 3.5 months with a median time of 2nd HCC recurrence of 6 months.  While not all reports from major centers have replicated this finding, more data are required to understand what the relationship is between HCC and HCV eradication and DAAs. In the meantime, rigorously survey your patients with HCC when you treat their hepatitis C infection.

No increase in the occurrence rate of hepatocellular carcinoma in Chinese treated by direct-acting antivirals compared to Interferon after eradication of hepatitis c virus: A long-term follow-up (Abstract PS-037)

Occurrence of hepatocellular carcinoma in patients with hepatitis C virus related liver disease treated with direct-acting antivirals (Abstract PS-038):

These studies report in Chinese and Italian cohorts that SVR with DAAs does not raise the risk of developing de novo HCC. These reports differ from the Reig study in that these patients did not have HCC that had been eradicated by loco regional therapy or other means.   The main concern that needs to be sorted out is whether DAAs affect HCC behavior in those with pre-existing HCC prior to treatment with DAAs.
A phase 2 dose-optimization study of lonafarnib with ritonavir for the treatment of chronic delta hepatitis-end of treatment results from the LOWR HDV-2 study (GS-008):

Lonafarnib shows promise in chronic hepatitis D.  Lonafarnib is an oral prenylation inhibitor that was previously studied in oncologic trials and   interferes with a critical step in HDV replication that involves prenylation. This study looked at doses of 25 and 50 mg BID of lonafarnib as mono therapy or in combination with peg interferon. 24 weeks of lonafarnib at 25 or 50 BID suppressed HDV RNA to below quantification in 5/14 individuals. Lonafarnib with PEG IFN at week 24 suppressed HDV RNA to below quantification in 4/5 and undetected HDV RNA in 3/5.  ALT levels normalized in up to 78% of patients. While results are still preliminary, lonafarnib holds promise in those with HDV infection with best results seen in combination with PEG IFN thus far.