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Copyright (c) 2014 Paul C.
Pinto, MD | Peak
Gastroenterology Associates,
PC

Hepatitis-C
What to Know in 2014
Clinical Presenter: Paul C. Pinto, MD

Southern Colorado GI Health and Wellness Summit & CME Event – February 22nd, 2014
Why should I care about Hepatitis C?
 Hepatitis C affects 3 million Americans
 It accounts for 40% of chronic liver disease in the US
 HCV-cirrhosis is the leading indication for liver

transplantation
 It disproportionately affects African-Americans and Latinos
 We CAN cure this infection in most individuals
 We will be caring for more patients cured of the infection

who have advanced fibrosis-they still need us!
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Most persons infected with Hepatitis C
are Baby Boomers
 75% of those infected were born between 1945 and 1965
 Persons with these years of birth should be screened once for

hepatitis C with an HCV-antibody test regardless of risk
factors
 Continue to screen high risk individuals
 A positive antibody test usually means chronic infection

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Natural history of Hepatitis C progression
 100 infections--80% (80) become chronic
 25% of the 80 (20) will develop cirrhosis (tell them this)
 5 will require transplant or die from liver disease
 Cirrhosis may not end life due to death from other causes
 Most who spontaneously clear infection do so early, leaving

them with little liver damage

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
How to test for Hepatitis C


ELISA or other test for antibodies against
Hepatitis C
• Antibody Positive---> Perform HCV-RNA
• Antibody Negative---> No further testing
required
(caveat: a negative antibody test can miss
acute infection)

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
What to tell a patient who is both antibody
and RNA positive
 Chronic infection is likely, and it will not resolve

spontaneously (< 1%)
 Blood is infectious; take steps to prevent

transmission
 Tell them the infection is curable in most

persons
 Help them remain positive-discuss steps to stay

healthy
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Advice and education for the Hepatitis Cinfected individual
 Limit alcohol consumption-it is synergistic with

hepatitis C
 Achieve normal body weight and control diabetes
 Limit marijuana use-it worsens hepatic fibrosis
 Stop smoking-it increases risk of liver cancer
 Get a HIV test done – co-infection worsens hepatitis C

outcomes
 Get vaccinated against hepatitis A and B
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Commonly used medications-The
relationship to Hepatitis C
 Acetaminophen
 limit to 2,000 mg per day
 NSAIDs - avoid in advanced liver disease
 idiosyncratic hepatotoxicity (uncommon)
 renal dysfunction (common)
 Statins - Acceptable in patients with compensated cirrhosis, and

stable liver disease-may improve response to antivirals
 Opiates and sedative-hypnotics
 Do not worsen liver disease, but their clearance is slowed by liver

disease-start with lower dose, increase slowly
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Antiviral treatment of Hepatitis CHistorical perspective
Drug-year first in use

Response-genotype 1

Interferon alfa-1991

15%

Interferon alfa and ribavirin-1998

25%

Pegylated Interferon & Ribavirin-200

40%

PIFN/R/Telaprevir or Boceprevir-2011

60%

PIFN/R/sofosbuvir-2013

70-80%

PIFN/R/simeprevir-2013

80%

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Eradication of Hepatitis C saves lives
• Data from the HALT-C Trial-patients with advanced fibrosis*
• Followed for 7.5 years after completion of PIFN/R treatment
140 patients who cleared virus

Death or transplant in 2.2%

309 patients who did NOT clear virus

Death or transplant in 21.3%

*Morgan TR; PMID 20364351
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Eradication of Hepatitis C helps prevent liver
cancer
 307 French patients with advanced fibrosis treated with

PIFN/R*
 Patients followed for an average of 3.5 years after treatment

completion

Incidence of Liver Cancer per 100-person years
 Those cured of infection

1.24

 Those NOT cured of infection

5.85

*Cardoso, et al. PMID 20546533
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Treatment of Hepatitis C may help
Hepatitis C comorbidities
 Fatigue - in a study of 431 patients, 59% of which had fatigue

at baseline-fatigue improved in 35% of responders, and 22%
of non-responders*
Little Data in the following conditions-consider treatment
 Mixed Cryoglobulinemia - and renal disease
 Porphyria Cutanea Tarda
 Leucocytoclastic Vasculitis
 Necrolytic Acral Erythema

*Cacoub P; J Hepatol: 2002; 36(6):812

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Regimens for Genotype 1 Hepatitis C in
2014
All Regimens are given with Pegylated Interferon and Ribavirin
Regimen

Best Response

Clinical Issues

Telaprevir/PIFN/R
24-48 weeks

65%

Rash, anemia-both can be severe
Drug-Drug interactions extensive
Pill burden-fat required with meds

Boceprevir/PIFN/R
32-48 weeks

60%

Anemia-can be severe
Many Drug-Drug interactions

Sofosbuvir/PIFN/R
12 weeks

80%

Untested in previously treated patients
Low pill burden
Side effects similar to PIFN/R alone

Simeprevir/PIFN/R
24-48 weeks

70-80%

Tested in previously treated patients
Low pill burden
Few side effects over PIFN/R alone

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Treatment of Genotypes 2 and 3
Hepatitis C-2014
Sofosbuvir/Ribavirin for 12-16 weeks

Clinical Parameters

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC

Genotype 2:

Response Rate

Treatment naïve
Naive with cirrhosis
Non-naïve
Non-naive with cirrhosis

97%
83%
90%
60%*

Genotype 3:

Sofosbuvir/Ribavirin for 16-24 weeks

Naïve
Non-naïve
Naive with cirrhosis
Non-naive with cirrhosis

93%
85%
92% (12 pts)
60% (24 pts)*

*may do better with a regimen that includes pegylated interferon
How to help someone taking Hepatitis C
treatment
 Fatigue-remain active both mentally and physically; consider interferon dose

decrease if severe

 Anemia -do not prescribe iron or vitamins-they will not work; consider dose

modifications of ribavirin and/or interferon

 Depression - treat as usual with SSRI or SNRI agents; avoid St John's Wort
 If depression occurred on previous treatment, begin antidepressant with the

antiviral treatment; Involve psychiatrist if concerned

 Any new medication should be reviewed for drug-drug interactions
 Discuss avoidance of pregnancy in both women and men who are on treatment
 Remind them to comply with laboratory tests needed on therapy-these help us

help them

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Exactly what do we mean by “Cure”?
 In clinical trials of hepatitis C treatment, cure means that HCV-RNA is non-

detectable in the serum when performed by an assay that can detect as few as 25
IU/ml of virus, 24 weeks after completion of treatment.

 The chance that the virus will return after this is less than 1% per year.
 I personally stop testing for virus recurrence after two years of treatment

completion.

 Hepatitis C is the ONLY curable chronic viral infection in 2014. It is the speaker's

experience that patients will frequently refer to themselves being in "remission"
after a course of therapy, regardless of viral test results. This term should not be
used in hepatitis C-you are either cured, or not-period.

 Avoiding vague terms may help those with persistent infection return for re-

treatment-speaker's opinion.

Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
What do we do after a patient is cured of
Hepatitis C?
 Test for thyroid disorders six months after treatment completion-

(hypothyroidism may occur)
 Wean off antidepressants as appropriate
 Repeat HCV-RNA one and two years after treatment completion

 Confirm that HIV testing as well as Hepatitis A and B vaccination

are completed
 Screen those with advanced fibrosis as follows:
 --for esophageal varices, with every two year upper endoscopy
 --for liver cancer with every six month imaging (US or TP-CT)
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC
Thank you!

We are available to assist you!
Peak Gastroenterology Associates, PC
719-636-1201

www.peakgastro.com
Copyright (c) 2014 Paul C. Pinto, MD | Peak
Gastroenterology Associates, PC

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what every PCP needs to know about Hepatitis C_Dr. Paul Pinto

  • 1. Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC Hepatitis-C What to Know in 2014 Clinical Presenter: Paul C. Pinto, MD Southern Colorado GI Health and Wellness Summit & CME Event – February 22nd, 2014
  • 2. Why should I care about Hepatitis C?  Hepatitis C affects 3 million Americans  It accounts for 40% of chronic liver disease in the US  HCV-cirrhosis is the leading indication for liver transplantation  It disproportionately affects African-Americans and Latinos  We CAN cure this infection in most individuals  We will be caring for more patients cured of the infection who have advanced fibrosis-they still need us! Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 3. Most persons infected with Hepatitis C are Baby Boomers  75% of those infected were born between 1945 and 1965  Persons with these years of birth should be screened once for hepatitis C with an HCV-antibody test regardless of risk factors  Continue to screen high risk individuals  A positive antibody test usually means chronic infection Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 4. Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 5. Natural history of Hepatitis C progression  100 infections--80% (80) become chronic  25% of the 80 (20) will develop cirrhosis (tell them this)  5 will require transplant or die from liver disease  Cirrhosis may not end life due to death from other causes  Most who spontaneously clear infection do so early, leaving them with little liver damage Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 6. Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 7. Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 8. How to test for Hepatitis C  ELISA or other test for antibodies against Hepatitis C • Antibody Positive---> Perform HCV-RNA • Antibody Negative---> No further testing required (caveat: a negative antibody test can miss acute infection) Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 9. What to tell a patient who is both antibody and RNA positive  Chronic infection is likely, and it will not resolve spontaneously (< 1%)  Blood is infectious; take steps to prevent transmission  Tell them the infection is curable in most persons  Help them remain positive-discuss steps to stay healthy Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 10. Advice and education for the Hepatitis Cinfected individual  Limit alcohol consumption-it is synergistic with hepatitis C  Achieve normal body weight and control diabetes  Limit marijuana use-it worsens hepatic fibrosis  Stop smoking-it increases risk of liver cancer  Get a HIV test done – co-infection worsens hepatitis C outcomes  Get vaccinated against hepatitis A and B Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 11. Commonly used medications-The relationship to Hepatitis C  Acetaminophen  limit to 2,000 mg per day  NSAIDs - avoid in advanced liver disease  idiosyncratic hepatotoxicity (uncommon)  renal dysfunction (common)  Statins - Acceptable in patients with compensated cirrhosis, and stable liver disease-may improve response to antivirals  Opiates and sedative-hypnotics  Do not worsen liver disease, but their clearance is slowed by liver disease-start with lower dose, increase slowly Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 12. Antiviral treatment of Hepatitis CHistorical perspective Drug-year first in use Response-genotype 1 Interferon alfa-1991 15% Interferon alfa and ribavirin-1998 25% Pegylated Interferon & Ribavirin-200 40% PIFN/R/Telaprevir or Boceprevir-2011 60% PIFN/R/sofosbuvir-2013 70-80% PIFN/R/simeprevir-2013 80% Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 13. Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 14. Eradication of Hepatitis C saves lives • Data from the HALT-C Trial-patients with advanced fibrosis* • Followed for 7.5 years after completion of PIFN/R treatment 140 patients who cleared virus Death or transplant in 2.2% 309 patients who did NOT clear virus Death or transplant in 21.3% *Morgan TR; PMID 20364351 Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 15. Eradication of Hepatitis C helps prevent liver cancer  307 French patients with advanced fibrosis treated with PIFN/R*  Patients followed for an average of 3.5 years after treatment completion Incidence of Liver Cancer per 100-person years  Those cured of infection 1.24  Those NOT cured of infection 5.85 *Cardoso, et al. PMID 20546533 Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 16. Treatment of Hepatitis C may help Hepatitis C comorbidities  Fatigue - in a study of 431 patients, 59% of which had fatigue at baseline-fatigue improved in 35% of responders, and 22% of non-responders* Little Data in the following conditions-consider treatment  Mixed Cryoglobulinemia - and renal disease  Porphyria Cutanea Tarda  Leucocytoclastic Vasculitis  Necrolytic Acral Erythema *Cacoub P; J Hepatol: 2002; 36(6):812 Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 17. Regimens for Genotype 1 Hepatitis C in 2014 All Regimens are given with Pegylated Interferon and Ribavirin Regimen Best Response Clinical Issues Telaprevir/PIFN/R 24-48 weeks 65% Rash, anemia-both can be severe Drug-Drug interactions extensive Pill burden-fat required with meds Boceprevir/PIFN/R 32-48 weeks 60% Anemia-can be severe Many Drug-Drug interactions Sofosbuvir/PIFN/R 12 weeks 80% Untested in previously treated patients Low pill burden Side effects similar to PIFN/R alone Simeprevir/PIFN/R 24-48 weeks 70-80% Tested in previously treated patients Low pill burden Few side effects over PIFN/R alone Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 18. Treatment of Genotypes 2 and 3 Hepatitis C-2014 Sofosbuvir/Ribavirin for 12-16 weeks Clinical Parameters Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC Genotype 2: Response Rate Treatment naïve Naive with cirrhosis Non-naïve Non-naive with cirrhosis 97% 83% 90% 60%* Genotype 3: Sofosbuvir/Ribavirin for 16-24 weeks Naïve Non-naïve Naive with cirrhosis Non-naive with cirrhosis 93% 85% 92% (12 pts) 60% (24 pts)* *may do better with a regimen that includes pegylated interferon
  • 19. How to help someone taking Hepatitis C treatment  Fatigue-remain active both mentally and physically; consider interferon dose decrease if severe  Anemia -do not prescribe iron or vitamins-they will not work; consider dose modifications of ribavirin and/or interferon  Depression - treat as usual with SSRI or SNRI agents; avoid St John's Wort  If depression occurred on previous treatment, begin antidepressant with the antiviral treatment; Involve psychiatrist if concerned  Any new medication should be reviewed for drug-drug interactions  Discuss avoidance of pregnancy in both women and men who are on treatment  Remind them to comply with laboratory tests needed on therapy-these help us help them Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 20. Exactly what do we mean by “Cure”?  In clinical trials of hepatitis C treatment, cure means that HCV-RNA is non- detectable in the serum when performed by an assay that can detect as few as 25 IU/ml of virus, 24 weeks after completion of treatment.  The chance that the virus will return after this is less than 1% per year.  I personally stop testing for virus recurrence after two years of treatment completion.  Hepatitis C is the ONLY curable chronic viral infection in 2014. It is the speaker's experience that patients will frequently refer to themselves being in "remission" after a course of therapy, regardless of viral test results. This term should not be used in hepatitis C-you are either cured, or not-period.  Avoiding vague terms may help those with persistent infection return for re- treatment-speaker's opinion. Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 21. What do we do after a patient is cured of Hepatitis C?  Test for thyroid disorders six months after treatment completion- (hypothyroidism may occur)  Wean off antidepressants as appropriate  Repeat HCV-RNA one and two years after treatment completion  Confirm that HIV testing as well as Hepatitis A and B vaccination are completed  Screen those with advanced fibrosis as follows:  --for esophageal varices, with every two year upper endoscopy  --for liver cancer with every six month imaging (US or TP-CT) Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC
  • 22. Thank you! We are available to assist you! Peak Gastroenterology Associates, PC 719-636-1201 www.peakgastro.com Copyright (c) 2014 Paul C. Pinto, MD | Peak Gastroenterology Associates, PC