insights in hepatitis c virus (hcv) infection management · slide 4 of 44 staging liver disease •...
TRANSCRIPT
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Insights in Hepatitis C Virus (HCV)
Infection Management
David L. Thomas, MD, MPHProfessor of Medicine
The Johns Hopkins Medical InstitutionsBaltimore, Maryland
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Learning Objectives
After attending this presentation, learners will be able to:
• List the 3 approved methods of liver staging
• Identify the most important interactions between HCV and
HIV drugs
• List the medications that are approved to treat HCV in
renal disease
• Compare treatment of HCV in persons with cirrhosis to
those without
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Staging liver disease
• A hepatologist, ID doc, primary care provider, and
insurance executive go to a bar…
April 26, 2018, Washington, DC Page 1
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Staging liver disease
• A hepatologist, ID doc, primary care provider, and
insurance executive go to a bar…
• to discuss whether a 58 year old HCV infected
woman with well controlled HIV has cirrhosis.
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Liver disease staging is a necessary
inexact art
• Stage to rule out cirrhosis and get approvals
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Liver disease staging is a necessary
inexact art
• Stage to detect cirrhosis and get approvals
• 3 approved tests are liver biopsy, blood fibrosis
tests, and elastography
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Liver disease staging is a necessary inexact art
High sensitivity for excluding cirrhosis is with FIB-4
plus transient elastography
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
de Ledinghen et al. JAIDS 2006
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Elastography also can tell you something about how bad the
cirrhosis is
Vizzutti Hepatology 2007
Complications of cirrhosis among 144 with F3-4
Hepatovenous pressure gradient
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Liver disease staging is a necessary inexact art
• High sensitivity for excluding cirrhosis is with FIB-
4 plus transient elastography
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
Sterling Hepatology 2006; Vallet-Pichard
Hepatology 2007
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Liver disease staging is a necessary, inexact art
• Stage to detect cirrhosis and get approvals
• Blood tests and elastography (or biopsy)
• High sensitivity for excluding cirrhosis with FIB-4 plus
transient elastography
• When discrepant use higher (or MRE)
• Vibration-controlled equivalent to transient elastography
and gives US to rule out HCC
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment can vary
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment in the HIV infected person
• No differences (no 8 week SOF/LDV)
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment in the HIV infected person
• No differences (no 8 week SOF/LDV)
• Drug interactions
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HCV treatment in the HIV infected person
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment in the HIV infected person
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment in the HIV infected person
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment can vary
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment with cirrhosis
• F3 or F4
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment with cirrhosis
• F3 or F4
• G/P is always 12
(vs 8) weeks
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
Forns Lancet ID 2017 N=146
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HCV treatment with cirrhosis
• F3 or F4
• G/P is always 12 (vs 8) weeks
• Screen HCC and varices
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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HCV treatment with cirrhosis
• F3 or F4
• G/P is always 12 (vs 8) weeks
• Screen HCC and varices
• Treatment helps with decompensation
(CAUTION)
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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Slide 28 of 44Manns Lancet ID 2016; Charlton Gastro 2015
HCV treatment in persons with decompensated cirrhosis
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Change in MELD score baseline to post
treatment week 12 in those with SVR
Manns Lancet ID 2016
Pre-transplant
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Recommendation for when to treat HCV infected
person with decompensated cirrhosis
Terrault Transplantation 2017
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HCV treatment can vary
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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Grazoprevir/Elbasvir in genotype 1 or 4
and ESRD: C-SURFER
• 73% male, 46% AA, 80% naïve, 52% 1a, 6% cirrhosis
• 81% CKD stage 5 (GFR <15 or HD)
• 6 stopped treatment early + 11 in pK group (mITT N=116)
Roth Lancet 2015
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Roth Lancet 2015
• No serious drug related AE
• NS5 RAS in 17 (14.8%)
• ITT SVR12 – 115/122
(94%)
• 1 relapse in 1b with L31M
baseline
• RAS testing not
recommended
Grazoprevir/Elbasvir in genotype 1 or 4
and ESRD: C-SURFER
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Glecaprevir and pibrentasvir for 12 weeks in patients with stage 4-
5 renal impairment
N=104, 19% F4
82% dialysis
GT1=54; GT2=17; GT3=11;
GT4=20; GT5/6=2
NS5A RAS 24/96
No serious drug-related AE
No relapse
REC same as not ESRD
0
20
40
60
80
100
Gane NEJM 2017
% SVR 12EXPEDITION 4
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Treatment of patients with renal insufficiency
• When should you treat?
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Treatment of patients with renal insufficiency
• When should you treat?
From Up To Date 2015; U.S. Renal Data System, USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-
Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney
Diseases, Bethesda, MD, 2009.
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HCV treatment can vary
Sterling Hepatology 2006; Vallet-PichardHepatology 2007
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Treatment of acute hepatitis C
How?
– Treat the same as with chronic hepatitis C
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Treatment of acute hepatitis C
How?
– Treat the same as with chronic hepatitis C
– Can it be shorter?
63 with acute HCV (<24 weeks)
All but 3 HIV pos; GT 1 or 4
Single arm open label, grazoprevir/elbasvir qd for 8
weeks
SVR 12 in 52/53
Boerekamps CROI 2018; Abstract 128
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Treatment of acute hepatitis C
How?
– Treat the same as with chronic hepatitis C
– Can it be shorter?
27 HIV infected with acute hepatitis C treated with 8
weeks of SOF/LDV
100% SVR12
Naggie AASLD 2017; Abstract 196
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Treatment of acute hepatitis C
How?
– Treat the same as with chronic hepatitis C
When/whom?
not acute any more (6 months)
not likely to clear (HIV pos, IFNL4, male, Black, stable high
HCV RNA)
might transmit
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HCV is growing problem in pregnancy
Ly Ann Intern Med 2017
Number of reported cases of HCV among women in the USA
“estimated 29 000 women who gave birth to 1700
infants with HCV infection each year”
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HCV infection is growing problem in pregnancy
Ly Ann Intern Med 2017
Risk of mother infant transmission is 4-8% if HIV neg
and 10-20% if HIV positive
DAAs not known to be harmful to fetus
No recommendation for routine testing
No recommended prevention– No C section or maternal or infant treatment
Test infants born to HCV pos moms
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Treatment of the patient over 65 years of age is fine
Pooled analysis of G/P in 328 >65 yrs vs 2041 <65yrs
– No difference in adverse events
– SVR12 was 97.9% >65 yrs vs 97.3 in <65 yrs
Foster AASLD 2017; Abstract 1188
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Summary of HCV management
• List the 3 approved methods of liver staging
• Identify the top interactions between HCV and HIV drugs
• List the medications that are approved to treat HCV in
renal disease
• Compare treatment of HCV in persons with cirrhosis to
those without
April 26, 2018, Washington, DC Page 15