Liver Disease: Monthly Essentials August 2017

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The 4 essential studies on Liver Disease this month, selected from 300 peer-reviewed studies

1. The US Food and Drug Administration has approved once-daily Vosevi for the treatment of HCV genotypes (GT) 1-6 in patients with mild or no cirrhosis. The fixed-dose combination tablet adds voxilaprevir, a new agent, to sofosbuvir/velpatasvir (SOF/VEL; Epclusa). This is the first option approved for patients who fail treatment with sofosbuvir (Sovaldi) or NS5A inhibitors. Approval was granted priority review and breakthrough therapy designation. See our essential synopsis of the article from FDA below.

2. Grazoprevir/uprifosbuvir/ruzasvir, with/without ribavirin, is highly effective for clearing HCV after failure of NS5A inhibitor-containing all-oral direct-acting antiviral (DAA) regimens. Patients who fail DAAs have limited options. Grazoprevir/uprifosbuvir/ruzasvir combines a NS3 protease inhibitor, a nucleotide NS5B polymerase inhibitor, and an NS5A inhibitor. See our essential synopsis of the article from Hepatology below.

3. An electronic health record-embedded best practice alert significantly boosts HCV testing among baby boomers (born between 1945 and 1965). Linkage to treatment remains problematic. One-time HCV testing is recommended for all baby boomers, but uptake remains low. See our essential synopsis of the article from Hepatology below.

4. Anemia, hypotension, ascites, and model for end-stage liver disease (MELD) score predict acute-on-chronic liver failure (ACLF) in outpatients with cirrhosis. Identifying high-risk patients opens the door for surveillance and prevention strategies. Anemia represents a potential new target for preventive measures. See our essential synopsis of the article from J Hepatol below.

1. HCV: FDA greenlights Vosevi salvage therapy



Source: FDA

Takeaway
  • The US Food and Drug Administration has approved once-daily Vosevi for the treatment of HCV genotypes (GT) 1-6 in patients with mild or no cirrhosis.
  • The fixed-dose combination tablet adds voxilaprevir (VOX), a new agent, to sofosbuvir/velpatasvir (SOF/VEL; Epclusa).
Key results
  • In POLARIS-1 (N=415; 41% cirrhotic), 12 wk of SOF/VEL/VOX yielded an SVR12 rate of 96% (vs 0% for placebo) in patients with GT 1-6 previously exposed to NS5A inhibitors.
  • In POLARIS-4 (N=333; 46% cirrhotic), 12 wk of SOV/VEL/VOX was superior to SOV/VEL overall (98% vs 90%) in patients with GT 1, GT 2, or GT 3 previously exposed to SOF-based regimens, including those with cirrhosis (98% vs 86%).
Study design
  • The approval was based on data from a couple of phase 3 randomized clinical trials: POLARIS-1 and POLARIS-4.
  • Primary endpoint was sustained virologic response at 12 wk posttherapy (SVR12).
  • Funding: Gilead.
Why this matter
  • This is the first option approved for patients who fail treatment with sofosbuvir (Sovaldi) or NS5A inhibitors.
  • Approval was granted priority review and breakthrough therapy designation.

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2. HCV: triplet salvage therapy yields impressive results



Source: Hepatology

Takeaway
  • Grazoprevir/uprifosbuvir/ruzasvir, with/without ribavirin (RBV), is highly effective for clearing HCV after failure of NS5A inhibitor-containing all-oral direct-acting antiviral (DAA) regimens.
Key results
  • Overall sustained virologic response at 12 wk posttherapy (SVR12) was 98.3% (115/117).
  • C-SURGE: SVR12 rate in HCV-1 (1a, 86%) was 100% with 24-wk RBV-free regimen (n=49), and 97.7% with 16-wk RBV-included regimen (n=43/44); 1 patient was lost to follow-up.
  • C-CREST: SVR12 rate with 16-wk RBV-included regimen was 100% in HCV-1 (n=2), 92.9% in HCV-2 (n=13/14), and 100% in HCV-3 (n=8); 1 patient stopped treatment after 1 dose because of serious vomiting/tachycardia.
  • Presence of baseline resistance associated substitutions (RAS) had no effect on SVR12; in C-SURGE, 84% had an NS5A RAS and 65% had an NS3 RAS.
Study design
  • 2 open-label, international phase 2 studies of patients with relapse after all-oral NS5A inhibitor-containing regimens: C-SURGE (N=93) and C-CREST Part C (N=24).
  • All received salvage therapy with grazoprevir/uprifosbuvir/ruzasvir for 16 wk (with RBV) or 24 wk (RBV-free).
  • Primary endpoint: SVR12.
  • Funding: Merck.
Why this matters
  • Patients who fail DAAs have limited options.
  • Grazoprevir/uprifosbuvir/ruzasvir combines a NS3 protease inhibitor, nucleotide NS5B polymerase inhibitor, and an NS5A inhibitor.

View Abstract

3. EHR alert increases HCV screening in baby boomers



Source: 
Hepatology 

Takeaway
  • An electronic health record (EHR)-embedded best practice alert (BPA) significantly boosts HCV testing among baby boomers (born between 1945 and 1965).
  • Linkage to treatment remains problematic.
Key results
  • In the 3 y preceding BPA, 52,660 baby boomers saw a primary care provider; 28% were screened.
  • In the 6 mo preceding BPA, the screening rate was 7.6%.
  • With 1 y of BPA, screening rates rose to 71% (P<.001; N=52,832).
  • Detectable HCV RNA was significantly less common in the BPA period (33% vs 74%; P<.001).
  • All 53 HCV-diagnosed patients were referred to specialists; 11 had advanced fibrosis/cirrhosis.
  • Of 31 patients (58.5%) prescribed direct-acting antivirals, 20 (65%) started treatment; thus far, 18 (90%) have achieved virologic clearance.
  • For the remaining 11 patients, 6 were pending insurance approval, 4 were denied access, and 1 was treated at an outside facility.
Study design
  • US study of BPA implementation at 13 primary care clinics sharing an EHR system.
  • BPA prompted clinicians to order testing for previously untested/undiagnosed baby boomers.
  • Funding: Bristol-Myers Squibb; Gilead; NIH; AASLD Advanced/Transplant Hepatology Fellowship.
Why this matters
  • One-time HCV testing is recommended for all baby boomers, but uptake remains low.

View Abstract

4. Cirrhosis: anemia included among predictors of ACLF



Source: J Hepatol

Takeaway
  • Anemia, hypotension, ascites, and model for end-stage liver disease (MELD) score predict acute-on-chronic liver failure (ACLF) in outpatients with cirrhosis.
Key results
  • 25% of patients developed ACLF (grade 1, 48%; grade 2, 28%; grade 3, 24%).
  • Probability of ACLF at 1, 5, and 10 y was 14%, 29%, and 41%, respectively.
  • Patients who developed ACLF had lower baseline Hb and mean arterial pressure (MAP), higher MELD score, and were more likely to have ascites (P<.001 for all).
  • In multivariate analysis, predictors of ACLF at 1 y included baseline Hb (HR, 0.07; P=.012), MAP (HR, 0=.96; P=.012), ascites (HR, 02.53; P=.019), and MELD score (HR, 1.26; P<.001).
  • 3-mo transplant-free survival rate in ACLF was 55%.
Study design
  • Study of 466 consecutive patients (69% male; mean age, 55±12 y) with cirrhosis at an Italian tertiary hospital outpatient clinic; 54% were in Child-Pugh class A.
  • Esophageal varices present in 64% and 36% of patients, respectively; 56% had anemia.
  • Cirrhosis etiologies included HCV (42%), alcohol (34%), and HBV (16%).
  • Mean follow-up: 45±41 mo.
  • Funding: None.
Why this matters
  • Identifying high-risk patients opens the door for surveillance and prevention strategies.
  • Anemia represents a potential new target for preventive measures.

View Abstract