Transcript What is HCV?

Hepatitis C Update
Primary Care Guidance
Michael J. Tan, MD, FACP, FIDSA
Associate Professor of Internal Medicine
Northeast Ohio Medical University
Summa Health System
Akron, OH
Objectives
 Review basic epidemiology of HCV
 Understand testing and interpretation of HCV labs
 Review new therapeutics
 Primary source for recommendations is IDSA-AASLD,
accessible from www.hcvguidelines.org
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What is HCV?
 Non-A, Non-B
 small, single stranded, enveloped RNA virus
 Family: Flaviviridae
• Genera: Hepacivirus, HCV
• Genera: Flavivirus: Dengue, Yellow Fever, WNV
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Targets hepatocytes
Blood-borne
2-3% of world’s population (130-170mil)
US <2%, Egypt > 10%
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A and B, Electron microscopic images of hepatitis C virus (HCV) virions concentrated from human plasma by high-speed centrifugation. The virions are
identified by staining
with gold-labeled antibodies to the HCV envelope proteins. (From Kaito M, Watanabe S, Tsukiyama-Koham K, et al. Hepatitis C virus particle detected by
immunoelectron
microscopic study. J Gen Virol . 1994;75:1755-1760.)
(From Kaito M, Watanabe S, Tsukiyama-Koham K, et al. Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol . 1994;75:17551760.)
Hepatitis C
RAY, STUART C., Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 154, 2157-2185
Copyright © 2010 Copyright © 2010, 2005, 2000, 1995, 1990, 1985, 1979 Elsevier Inc.
Hepatitis C Virus
• Primary target hepatocytes
• Genome encodes a polyprotein consists of 3011 amino
acids
– Structural (core, E1, E2)and Non-structural (regulatory NS2, NS3,
NS4A/B, NS5A/B) proteins
– Robust viral replication ~10 trillion particles/day
– RNA-dependent RNA polymerase-lacks proofreading and no DNA
intermediates
– Does not integrate into host genomes (vs. HIV)
HIV vs. HCV
• RNA virus-Retrovirus
• CD4, macrophages, dendritic
cells
•  mutation rate
• Blood-borne, moderate sexual
transmission
• Fatal if untreated
• Treatable not curable
• Many drugs
• Life-long therapy
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RNA virus-Flavivirus
Hepatocytes
 mutation rate
Blood-borne, low sexual
transmission
Might be fatal (cirrhosis, HCC)
Both treatable AND potentially
curable
Few drugs (more to come)
Finite duration
Hepatitis C Virus
• Genotypes 1 to 6, multiple subtypes
• Geographical distribution differences around the world
• Genotypes important to stratify duration and dosing
– Genotype 1 harder and longer therapy
– Genotype 2,3 “easier” and shorter duration
– Less important with new and more potent agents
Geographic distribution of hepatitis C virus genotype. (Adapted from Fang JW, Chow V, Lau JY: Virology of hepatitis C virus. Clin Liver Dis 1997;1:493 - 514.)
(Adapted from Fang JW, Chow V, Lau JY: Virology of hepatitis C virus. Clin Liver Dis 1997;1:493 - 514.)
Viral Hepatitis
Cleveland Clinic,, Current Clinical Medicine, ${parentCitation.chapternum}, 539-551
Copyright © 2010 Copyright © 2009, 2010 by The Cleveland Clinic Foundation. Published by Saunders, a imprint of Elsevier Inc.
HCV Genotype (used to) matter
• Genotype 1 historically the most difficult type to treat
– Unfavorable characteristics
• Advanced fibrosis, especially cirrhosis
• African-American
• IL-28B CT or TT genotype
– Polymorphism encodes gene products for IFN-III
– Favorable response to CC genotype
• Baseline high viral load
• Prior non-responders
• New agents might relegate above characteristics,
except for cirrhosis
The Prevalence of Hepatitis C Virus Infection in
the United States, 1999 through 2002
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NHANES data->15,000
Prevalence ~1.6%
~4.1 million + HCV Ab
~3.2 million with chronic HCV
Peak age 40-49 (4.3%)
Between age 20-59 (48.4%)
Risk factors: IVDU, >20 life-time sex partners, blood
transfusions >1992
Ann Intern Med. 2006;144(10):705-714. doi:10.7326/0003-4819-144-10-200605160-00004
From: The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002
Ann Intern Med. 2006;144(10):705-714. doi:10.7326/0003-4819-144-10-200605160-00004
Figure Legend:
Prevalence of antibodies to hepatitis C virus (HCV) by age group (A) and year of birth (B) in the Third National Health and Nutrition
Examination Survey (NHANES III, 1988–1994) and the current NHANES (1999–2002).The vertical bars represent 95% CIs.
Date of download:
4/2/2014
Copyright © American College of Physicians.
All rights reserved.
From: The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007
Ann Intern Med. 2012;156(4):271-278. doi:10.7326/0003-4819-156-4-201202210-00004
Figure Legend:
Annual age-adjusted mortality rates from hepatitis B and hepatitis C virus and HIV infections listed as causes of death in the United
States between 1999 and 2007.
Because a decedent can have multiple causes of death, a record listing more than 1 type of infection was counted for each type of
infection.
Date of download:
4/7/2014
Copyright © American College of Physicians.
All rights reserved.
• Traditional risk factors
 Illegal drug injection (once or a
few times many years ago)
 Clotting factors before 1987
 Hemodialysis
 Abnormal ALT
 Prior transfusions or organ
transplantations before July 1992
 HCW after needle sticks or
mucosal exposures with HCV +
blood
 Children born to HCV + women
• Traditional risk factors
 Illegal drug injection (once or a few times many
years ago)
 Clotting factors before 1987
 Hemodialysis
 Abnormal ALT
 Prior transfusions or organ transplantations
before July 1992
 HCW after needle sticks or mucosal exposures
with HCV + blood
 Children born to HCV + women
 “Adults born during 1945-1965 should received onetime testing for HCV without prior ascertainment of HCV
risk”
 Brief alcohol screening and intervention, if indicated
 HIV-infected patients
Hepatitis C-not just an urban problem
 Notes from the Field: Hepatitis C Virus
Infections Among Young Adults-Rural
Wisconsin 2010
• Increased HCV infections among persons
<30 age in 6 contiguous rural counties
 2004-2008 ~8 cases/year
 2009-2010 ~24 cases/year
 Investigated all 25 patients-all HCV
Ab positive
 17 patients-sharing hypodermic
needles, drug preparation
equipment or drug snorting
equipment
 16 patients-injected/snorted/both
 6 specimens with similar NS5B
regions
 Subanalysis of quasispecies
not related
Staging
Histologic Stages of HCV Infection.
Lauer GM, Walker BD. N Engl J Med 2001;345:41-52.
Liver staging
 Important to identify cirrhotic patients
 Higher incidence of HCC
• Initiate surveillance, risk still present even patient is cured
 Decreased response rate
 Risk of liver decompensation (while on therapy)
 Candidacy for response-guided therapy (1st generation protease
inhibitors: boceprevir and telaprevir)
Distribution of hepatic fibrosis in patients with chronic hepatitis C virus infection and normal
or persistently elevated serum alanine aminotransferase (ALT) levels.
Shiftman M L et al. J Infect Dis. 2000;182:1595-1601
© 2000 by the Infectious Diseases Society of America
Distribution of hepatic fibrosis in patients with chronic hepatitis C virus infection and normal
or persistently elevated serum alanine aminotransferase (ALT) levels.
Shiftman M L et al. J Infect Dis. 2000;182:1595-1601
© 2000 by the Infectious Diseases Society of America
ALT not reliable to predict severity of liver
disease
Liver Biopsy
 Still considers as gold standard
 Might be replaced by serum markers
 Values:
 Best way to assess fibrosis
 Assess other liver disease(s)
 Definitive staging
Liver Biopsy
 Cons:
 Invasive
 Relative more expensive than serum markers
 Expertise in acquiring specimen and interpreting histopathology
• Adequacy of specimen
• Which classification is used (Metavir, Ishak, etc.)
 Bleeding risk
Fig. 5
Source: Journal of Hepatology 2007; 47:598-607 (DOI:10.1016/j.jhep.2007.07.006 )
Copyright © 2007 Terms and Conditions
Liver Biopsy-size matters!!
>3 cm
1.5 cm
1 cm
22.4±4.9
10.3±2.2
6.4±1.2
Mild (≤6)
80 (49.7%)
97 (60.2%)
133 (86.6%)
Moderate (7-12)
62 (38.5%)
63 (39.1%)
28 (17.4%)
Severe (≥13)
19 (11.8%)
1 (0.6%)
0
Mild (1-2)
95 (59%)
110 (68.3%)
120 (80.1%)
Moderate (3-4)
48 (29.8%)
39 (24.2%)
24 (14.9%)
Severe (5-6)
18 (11.2%)
12 (7.4%)
8 (4.9%)
No. of portal
tracts
Complete
Grading
Staging
Colloredo et al. Journal of Hepatology 39 (2004):239-244
FibroSure
• Serum biomarkers as surrogate to test for fibrosis
• Non-invasive
• Biochemical markers: α2 macroglobulin, haptoglobin,
bilirubin, GGT, apolipoprotein A1 and ALT
• Coupled with patient’s age and gender and using a
proprietary artificial intelligence algorithm to generate a
score
FibroSure
 Provides a numerical quantitative estimate of liver
fibrosis ranging 0.00 to 1.00-corresponds to Metavir
scroing F0-F4
 F0=no fibrosis, F1= portal fibrosis, F2= bridging fibrosis with septa,
F3= bridging fibrosis with many septa, F4= cirrhosis
 Provides a numerical quantitative estimate of
necroinflammatory activity from 0.00 to 1.00
corresponds to A0 to A3
 A0= no activity, A1= minimal activity, A2= moderate activity, A3=
severe activity
FibroSure
 Correlates fairly well with liver biopsy
 Multiple studies indicated AUROC predictive value
between 0.70 to 0.80
 Should not be used:
 Hemolysis, acute hepatitis, autoimmune hepatitis, low haptoglobin,
genetic liver disease
 Discordant liver biopsy vs. FibroSure
 Biopsy size (<15 mm)
Hepatitis C More Background
 Risks
 About 10% spontaneous clearance
 Non-cleared—risk of cirrhosis, liver failure, HCC
 Previous treatments: Peg-Interferon + Ribavirin
 Treatment up to 12mos
 Sustained virologic response:
• Genotype 1: 70% (less with HIV)
• Genotype 2-3: 80-90% (less with HIV)
 Anemia
 Influenza-like illness
 Depression
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Treatment
Ghany et al. Hepatology, Vol. 49, April 2009
Therapy
 For decades only two major classes of medications: interferon
and ribavirin
 Standard IFN-1991; Pegylated IFN-early 2000’s
 Response rate poor to fair at best (genotype 1 especially)
 Moderately significant side-effects
 Direct Acting Anti-virals (DAAs)-2011 revolutionized treatment
paradigm
Ribavirin
• Nucleoside purine analogs
• 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
• Broad spectrum of DNA and RNA viruses
– Exact mechanism on HCV not clear
• Major metabolite ribavirin-5’-triphosphate
– Erythrocytes lack necessary enzymes to degrade metabolite-leads to
 accumulation of metabolites
– Exerts oxidative damage to cell membrane and increased extravascular hemolysis by RE system
Gilbert et al. AAC, Aug 1986, p.201-205
Evolution of HCV Therapy
McHutchison NEJM 1998; 339:1485-1492
Fried NEJM 2002; 347:975-982
Manns Lancet 2001; 358:958-965
Boceprevir
Telaprevir
Simeprevir
Asunaprevir
Sofosbuvir
Ledipasvir
Daclastavir
Organization of the hepatitis C virus (HCV) genome and polyprotein. ( A ) Organization of the HCV genome with nontranslated RNA segments shown as
lines and the open reading frame as a box; the region encoding the nonstructural proteins required for replication is shaded. ( B ) Functional organization
and processing of the viral polyprotein, showing approximate membrane topologies of the mature HCV proteins. Sites of cleavage by host cell and viral
proteases are indicated by triangles. (Redrawn from Lemon SM, Walker C, Alter MJ, et al. Hepatitis C virus. In: Knipe DM, Howley PM, eds. Fields’
Virology, 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2007:1253.)
(Redrawn from Lemon SM, Walker C, Alter MJ, et al. Hepatitis C virus. In: Knipe DM, Howley PM, eds. Fields’ Virology, 5th ed. Philadelphia: Lippincott
Williams & Wilkins; 2007:1253.)
Viral Hepatitis C
Alter, Miriam J., Tropical Infectious Diseases: Principles, Pathogens and Practice, CHAPTER 65, 427-432
Anti-Hep C
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4/2011, Recommended for approval
5/2011, Telaprevir, boceprevir-APPROVED!
Approval for recurrence/treatment
New Agents for HCV
 Combination with PEG-IFN, RBV
 Anemia biggest AE
 Apparently better SVR than standard of care
 Cost? Role? Efficacy in HIV?
Anti-Hep C-Boceprevir
 N Eng J Med 2011;364:1195-206.
 Boceprevir for untreated HCV Genotype 1
• Gp 1: pegIFN-RBV + Placebo 44wks
• Gp 2: peg IFN-RBV + boceprevir 24 wks
• Gp 3: peg IFN-RBV + boceprevir 44wks
 SVR non-black: Gp 1 40% vs Gp 2 67% vs Gp 3 68%
 SVR black: 23% vs 42% vs 53%
 Anemia 13% controls vs 21% boceprevir
SVR rates improve with new DAAs
Adapted from: Poordad et al. NEJM 2011;364:1195; Jacobson et al. NEJM 20111:364:2405; Bacon et
al. NEMJ 2011;364:1207; Zeuzem et al. NEJM 2011;364:2417
Side-effects
 Boceprevir
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Fatigue
Anemia
Nausea
Dysgeusia
 Telaprevir
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Anemia
Rash
Fatigue
Pruritis
Nausea
Diarrhea
Vomiting
Hemorrhoids
Anorectal discomfort
Sofosbuvir (SOF, GS-7977)
 HCV-specific uridine nucleotide NS5B polymerase inhibitor
(chain terminator)
 Potent antiviral activity against
HCV genotypes 1–6
 High barrier to resistance
 Once-daily, oral, 400-mg tablet
 Favorable clinical pharmacology
profile
 No food effect
 Renally cleared - limited potential for drug interactions
 No CYP3A/4 metabolism
 limited potential for drug interactions
 Generally safe and well tolerated in clinical studies to date
(>3000 patients)
Gilead
Anti-HCV
 Simeprevir (Janssen)
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Oral 150mg q24 x12wk + Peg/Rib x24wk.
SVR 79-80%
Approval for naïve and treatment experienced Genotype 1
Once daily pill option
APPROVED
 Sofosbuvir (Gilead)
 Once daily nucleotide analogue
 Approval in chronic HCV in adults with GT2, 3
• PEGIFN + Riba + sofosbuvir, Chronic HCV 1 and 4 treatment Naïve
• Riba + sofosbuvir, Chronic HCV 2, 3 (24wk)
• SVR in as little as 12 weeks Sup or non-inf to current treatments.
Sofosbuvir
 Indications
 Genotype 1 and 4: P/R/SOF x 12 weeks
• If INF ineligible: SOF + RBV x 24 weeks
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Genotype 2: RBV + SOF x 12 weeks
Genotype 3: RBV + SOF x 24 weeks
Hepatocellular carcinoma awaiting transplant: RBV + SOF up to 48 weeks
HIV/HCV co-infection
Simeprevir (Olysio)
 NS3/4A protease inhibitor
 Combination therapy with PEG-IFN/RBV for genotype 1 only
 Treatment naïve/prior relapses:
 12 weeks then 12 more weeks with P/R
 Partial/null responders and cirrhotics:
 12 weeks then 36 more weeks with P/R
Simeprevir
 Off label use-combination of sofosbuvir + simeprevir (sim-sof
combo)
 As recommended by recent AASLD/IDSA joint guidelines for IFN intolerant
GT-1 patient
 Significant: interferon free!
 Data derived from ongoing study COSMOS
ledipasvir/sofosbovir (Harvoni)
 Approved for genotype 1 in adults (too early to be
added to guidelines)
 One tablet (90/400) PO q24h
 Naïve with or without cirrhosis 12 wk
 Experiencec without cirrhosis 12 wk
 Experienced with cirrhosis 12 wk
 Interferon sparing
 AE:
 Fatigue, Headache, nausea, diarrhea, insomnia
 GT-1 96-99% SVR with minimal relapse
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DAA
 daclatasvir (Daklinza,)
 paritaprevir/ritonovir/ombitasvir (daily) + dasabuvir
(twice/day) (Viekira Pak)
 sofosbuvir (Sovaldi)
 ledipasvir + sofosbuvir (Harvoni)
 Simeprevir (Olysio)
When and in Whom to Initiate
Therapy?
 All patients with chronic HCV except those with short
life expectancies that cannot be remediated by treating
HCV, by transplatation, or by other directed therapy.
 Prioritization tables have been removed
 Earlier treatment leads to augmented benefit of SVR
 Treatment in setting of fibrosis or cirrhosis and reduce
decompensation
Recommendations-Treatment
Naive
 Genotype 1
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daclatasvir + sofosbuvir x12 weeks (no cirrhosis) (1a, 1b)
daclatasvir + sofosbuvir x24 weeks +/- ribavrin (cirrhosis) (1a, 1b)
ledipasvir + sofosbuvir x12 weeks (1a, 1b)
paritaprevir/ritonovir/ombitasvir (daily) + dasabuvir (twice/day) x12
weeks (no cirrhosis) or 24 weeks (cirrhosis) (1a)
 paritaprevir/ritonovir/ombitasvir (daily) + dasabuvir (twice/day) x12
weeks (1b)
 simeprevir + sofosbuvir x12 weeks (no cirrhosis) or +/- ribavirin
(cirrhosis) x 24 weeks (1b)
 Not recommended:
• sofosbuvir + RBV x24wks
• PEG-IFN + RBV +/- Sofosbuvir, simeprevir, telaprevir, or boceprevir for 1248 weeks.
• Monotherapy with PEG-IFN, RBV, or DAA
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www.hcvguidelines.com
Recommendations-Treatment
Naive
 Genotype 2
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daclatasvir + sofosbuvir x12 weeks (2) *Intolerant of ribavirin
sofosbuvir + RBV x12 wks
Extend treatment to 16 weeks with cirrhosis
Not recommended:
• PEG-IFN + RBV x24wks
• Monotherapy with PEG-IFN, RBV, or DAA
• Telaprevir, boceprevir, or ledipasvir containing regimens
 Genotype 3
 daclatasvir + sofosbuvir x12 weeks (no cirrhosis) or 24 weeks +/- RBV
x24 weeks (cirrhosis)
 sofosbuvir + RBV + PEG-IFN x12wks (24 wks if no PEG-IFN)
 Not recommended:
• PEG-IFN + RBV x24-48wks
• Monotherapy with PEG-IFN, RBV, or DAA
• Telaprevir, boceprevir, or ledipasvir containing regimens
Recommendations-Treatment
Naive
 Genotype 4
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ledipasvir/sofosbuvir x12 weeks
paritaprevir/ritonovir/ombitasvir + RBV x12 weeks
sofosbuvir + RBV x24 weeks
Alternative: sofosbuvir + RBV + PEG/IFN x12 weeks.
Not recommended:
• PEG-IFN + RBV +/- simeprevir x24-48wks
• Monotherapy with PEG-IFN, RBV, or DAA
• Telaprevir, boceprevir, containing regimens
 Genotype 5/6
 ledipasvir/sofosbuvir x12 weeks
 Alternative: sofosbuvir + RBV + PEG-IFN x12wks
 Not recommended:
• PEG-IFN + RBV +/- simeprevir x24-48wks
• Monotherapy with PEG-IFN, RBV, or DAA
• Telaprevir, boceprevir, or containing regimens
Recommendations-Retreatment
 Genotype 1a, 1b, no cirrhosis, failed PEG-IFN-RBV
 daclatasvir + sofosbuvir x12 weeks
 ledipasvir + sofosbuvir x12 weeks
 paritaprevir/ritonovir/ombitasvir (daily) + dasabuvir (twice/day) x12
weeks
 simeprevir + sofosbuvir x12 weeks
 1a, 1b, compensated cirrhosis, failed PEG-IFN-RBV
 daclatasvir + sofosbuvir x24 weeks
 ledipasvir + sofosbuvir x24 weeks (or with RBV for 12 weeks)
 paritaprevir/ritonovir/ombitasvir (daily) + dasabuvir (twice/day) x12
weeks 1b, 24wks + RBV for 1a
 simeprevir + sofosbuvir x24 weeks (1a Q80k (-)), 1b
55
www.hcvguidelines.com
Recommendations-Retreatment
 Failed Sofosbuvir/RBV +/- PEG-IFN
 ledipasvir/sofosbuvir + RBV x12 weeks (no cirrhosis)
 ledipasvir/sofosbuvir + RBV x24 weeks (cirrhosis)
 Failed tela/bocep/simep + PEG-IFN/RBV or sim/sof (NoNS5A),
geno 1
 daclatasvir + sofos x12 weeks
 Ledipasvir/sofos x12 weeks
 Other combinations exist
 Avoid in GT 1 for any protease failure:
 Simepmrevir, sofosbuvir, telaprevir, or boceprevir with PEG-IFN/RBV or
PEG-IFN RBV alone
 DAA or PEG-IFN, RBV monotherpay
 PEG-IFN/RBV alone.
 Any IFN-Free regimen containing Simeprevir or Paritaprevir
Recommendations-Retreatment
 Genotype 2
 Failed PEG-IFN, RBV: Sofosbuvir + RBV x16-24 wks
•
Add RBV and PEG-IFN for 12 weeks if eligible to receive PEG-IFN
 Failed sofosbuvir and RBV:
• daclatasvir + sofosbuvir x24 wk +/- RBV
• Sofosbuvir + RBV + PEG-IFN x12 weeks.
 Not recommended:
• PEG-IFN + RBV with or without telap or bocep
• Monotherapy with PEG-IFN, RBV, or DAA
• Ledipasvir/sofosbuvir
 Genotype 3
 daclatasvir + sofosbuvir x12 weeks (no cirrhosis) or + RBV x24 weeks (cirrhosis)
 sofosbuvir + RBV + PEG-IFN x12 weeks
 Prior sofos/RBV: daclatasvir + sofosbuvir + RBV x24 wks or sofos + RBV +
PEG-IFN x12 weeks.
 Not recommended:
• PEG-IFN + RBV x24-48wks
• Monotherapy with PEG-IFN, RBV, or DAA
• Telaprevir, boceprevir, or ledipasvir containing regimens
Recommendations-Retreatment
 Genotype 4
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ledipasvir/sofosbuvir x12 weeks
paritaprevir/ritonovir/ombitasvir + RBV x12 weeks
Sofosbuvir x12 wks + RBV + PEG/IFN x12 weeks
sofosbuvir + RBV x24 weeks.
Not recommended:
• PEG-IFN + RBV +/- telaprevir or boceprevir
• Monotherapy with PEG-IFN, RBV, or DAA
 Genotype 5/6
 ledipasvir/sofosbuvir x12 weeks
 Alternative: sofosbuvir + RBV + PEG-IFN x12wks
 Not recommended:
• Monotherapy with PEG-IFN, RBV, or DAA
• Telaprevir, boceprevir, or containing regimens
Monitoring
 Drug-Drug interactions
 HCV Geno/Subtype, Qunatitative HCV
 Within 12 weeks prior to start
 CBC, INR, LFT, Calculated GFR
 TSH (if IFN)
 During therapy
 CBC, Creat, GFR, LFT after4 weeks
 TSH q12k weeks if IFN
 Discontinue Tx for 10 fold rise in ALT at week 4.
• If less than 10 fold rise, check LFT wk 6 and 8
 Quantitative @ 4 weeks, and 12 weeks after completion,
+/- 24 weeks after completion.
HCV and HIV
 Still want to treat HIV fully
 Follow guidelines for HCV
 Watch for drug interactions with HAART
HCV
 Decompensated disease has recommendations but
should be done with consultation with liver specialist
 Post-liver transplant has recommendations
 Specific recommendations for patients with impaired crt
cl <30
 Acute infection?
 HCV Ab and HCV RNA (viral load)
 Pre-exposure prophy and post-exp prophy not recommended
 F/U VL for clearance, no treatment for spontaneous clearance. (min
6 mos)
Monitoring
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If HCV detectable @ wk 4, repeat at wk 6
If HCV increases 10 fold at week 6, stop therapy
If comes down at week 6 and 8, no recommendation
Check serum HCG
RBV not recommended in pregnancy
No SVR:
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LFT, CBC, INR for disease progression
Surveillance for HCC q6mos
Endoscopic surveillance for varices if cirrhosis
Evaluate for retreatment as new alternatives become available.
SVR Achieved
 No fibrosis (f/u as if no HCV)
 Check Quant if ongoing risk of HCV or if unexplained
hepatic dysfunction
 If F3 or F4, ultrasound 2x/year surveillance for HCC
 Baseline endoscopy for varices if cirrhosis
 Assess for other causes of liver disease in those who
develop persistently abnormal LFT after SVR
 Not recommended to prospectively monitor for HCV
recurrence in those receiving immunosuppressive
therapy.
Conclusions
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HCV is a huge problem
Cases on increase, especially with screening
Therapy is easier than it used to be
Cure is possible
Cost is an issue