Transcript Does this patient have hepatitis C?

Hepatitis B and C
What’s new
Thomas C. Mahl, MD
Professor, Medicine
University at Buffalo
Chief, Gastroenterology
VA Western New York
Disclosure
• No financial conflicts to disclose
• No off label uses will be discussed
Does this patient have hepatitis C?
• 56 y/o man with a history of needle sharing
about 30 years ago. He has no complaints
suggestive of hepatitis and his liver feels
normal on exam. He has elevated
aminotransferases.
What is the most common chronic
viral hepatitis?
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Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
What is the most common chronic
viral hepatitis?
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Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Hepatitis C - The Plague
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0.6-2.4 % of US population
3.8 million Americans infected
15-20 thousand in Western New York
7.5% of US Veterans
18% of Viet Nam era Veterans
– “Dr. Mahl’s retirement plan”
• 3% world wide!!!!
How could you confirm he has
hepatitis C?
• Hepatitis C Antibody by EIA
• Hepatitis C Antibody by RIBA
• Hepatitis C RNA by PCR or branched chain
assay
• Measure HBcAb
How could you confirm he has
hepatitis C?
• Hepatitis C Antibody by EIA
• Hepatitis C Antibody by RIBA
• Hepatitis C RNA by PCR or branched chain
assay
• Measure HBcAb
Who Should You Screen for HCV?
• Anyone with elevated liver tests
• Anyone with risk factors
• Everyone born 1945-1965 (Baby-boomers)
Does he Also Have Hepatitis B?
• His serology notes:
• HBsAg – negative
• Anti-HBs –positive
• Anti-HBc - positive
Does he Also Have Hepatitis B?
• No!
• HBsAg – negative
• Anti-HBs –positive
• Ant-HBc - positive
Diagnosis of Hepatitis B
• Hepatitis B surface antigen –HBsAg
• Indicates infection
• No HBsAg? Not infected
• Hepatitis B surface antibody – anti-HBs
• Protective
• Anti-HBs? Can’t have HBsAg
• Follows natural infection and vaccination
Diagnosis of Hepatitis B, con’t.
• Hepatitis B core antibody –anti-HBc
• Not protective
• Infected or resolved infection
• Hepatitis B viral DNA
• Gold standard
• Quantifiable
• Followed during treatment
Case 2
• 59 y/o Irish woman is noted to have elevated
liver enzymes during a routine blood draw.
She recalls no episodes of jaundice but did
receive an injection of contaminated RhoGAM
after her daughters delivery in 1973. Her liver
is enlarged and slightly firm.
What is the most common risk factor
for becoming infected with HCV?
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Transfusion?
Needle sharing?
Sexual congress?
Tattoos?
Occupational exposure (HCW)?
What is the most common risk factor
for becoming infected with HCV?
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Transfusion
Needle sharing
Sexual congress
Tattoos
Occupational exposure (HCW)
What is the most common risk factor
for becoming infected with HBV?
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Transfusion?
Needle sharing?
Sexual congress?
Tattoos?
Occupational exposure (HCW)?
What is the most common risk factor
for becoming infected with HBV?
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Transfusion?
Needle sharing?
Sexual congress?
Tattoos?
Occupational exposure
(HCW)?
What is this Woman’s Prognosis?
• Good?
• Bad?
• Ugly?
What is this Woman’s Prognosis?
• Good?
• Bad?
• Ugly?
Predictors of Poor Prognosis
• Alcohol: use - abuse
• Acquisition via transfusion
• Male gender
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HCV Prognosis: Bottom Line
• HCV is a very slowly progressive disorder in
many patients
• Significant numbers of patients develop
cirrhosis
• However, only about 10% patients will ever
develop symptoms or will die of liver disease
Case 3
• 37 y/o developed HCV after experimenting
with IVDA about 20 yrs ago. He feels well and
is in good health. Liver enzymes are elevated
and bilirubin is slightly elevated.
What further information would be
helpful before considering treatment?
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HCV RNA
HCV Genotype
Liver biopsy
His net worth and health insurance plan
What further information would be
helpful before considering treatment?
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HCV RNA
HCV Genotype
Liver biopsy
His net worth and health insurance plan
Molecular Tests
• HCV genotype
– 6 different genotypes
– Very predictive of response
to treatment
• ‘Non-one’ genotype’s do best
• ‘Non-one’ genotypes –
uncommon in US!
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60
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0
1
2
3
4
Genotypes
in USA
Liver biopsy - Chronic HCV
Normal
Chronic inflammation
Cirrhosis
Case 3 - further information
• HCV RNA 567,345 IU/ml
• Genotype 1a
• Liver biopsy
– Grade – moderate inflammation
– Stage – moderate fibrosis
• Very wealthy!!!
What is the optimal treatment for this
man?
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Interferon alpha
Pegylated interferon alpha
Pegylated interferon, ribavirin
Pegylated interferon, ribavirin and telaprevir
or boceprevir
• Milk thistle
What is the optimal treatment for this
man?
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Interferon alpha
Pegylated interferon alpha
Pegylated interferon, ribavirin
Pegylated interferon, ribavirin and telaprevir
or boceprevir
• Milk thistle
Treatment of Hepatitis C
10 Years of Progress
>50% ‘Cure’!
Sustained Virologic Response (SVR) = Cure
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40
30
20
10
PEG Interferon
and Ribavirin
Interferon and
Ribavirin
0
Interferon
Alone
Percent response
60
Telaprevir
$50,000!!!!
Telaprevir
Telaprevir
 Oral inhibitor of HCV
serine protease
 Used in combination
with PEG/riba
 Sustained response –
67% overall
◦ 89% in those who
completed treatment
 FDA approved
Telaprevir Associated Rash
Localized rash with
or without pruritus.
Diffuse rash with some superficial
skin peeling, pruritus, mucosa
involvement but no ulceration.
Try oral antihistamines, good skin care, topical
corticosteroids
Data extracted from Vertex Presentation to FDA Advisory Committee
Monitor
Closely
Ulcer, vesicles, bullae
or systemic symptoms
STOP
Telaprevir
Boceprevir
Interferon –Adverse Effects
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Depression/suicide
Psychosis
Thrombocytopenia
Leukopenia
Hair loss
So…
Not a terrible disease in most
Treatments difficult and expensive
Who should you refer for treatment?
 Everybody except those not able to be treated
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Substantial mental illness
Ongoing substance abuse
Significant medical comorbidities
Unreliable patient
Hepatitis C Drug Development: 2011
On Market
Phase 3
PSI 7977
Phase 2
MK7009
Boceprevir
BI-201335
GS9190
IFN & PEG IFN
Ribavirin
Albumin-IFN alfa
Thymalfasin
Locteron
GS-9256
TCM-700C
RG7227
ME-3738
RG7128
SCV-07
DA-3021
ITMN 191
Research/
Preclinical
celgosivir
IPH-1101
PF-868554
JTK-652
ANA598
Silibinin
NIM811
Infradure
Belerofon
Alinia
PYN-17
EMZ702
VCH-759
VX-222
oglufavide
CYT 107
Phase 1
BMS-790052
A-831
Omega IFN
BMS-650032
Viramidine
TMC-435
MK5172
Debio25
Telaprevir
BIT225
MK-3281
IL-29
Amarillo
BMS-791325
EGS21
Many others including
Immune stimulants
Gene therapy
Note: Not a complete list of products in development!
interferons
ribavirins
protease inhibitors
polymerase inhib.
immunomodulators
others
Case 4
• A 38 y/o man with bipolar illness is noted to
have elevated liver tests – including bilirubin.
He has sex with men. His HBsAg is positive and
HBV DNA is >108 . Appropriate treatment
would include?
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Observation
Vaccination for HCV
Oral entecavir
Pegelated Interferon
Case 4
• A 38 y/o man with bipolar illness is noted to
have elevated liver tests – including bilirubin.
He has sex with men. His HBsAg is positive and
HBV DNA is >108 . Appropriate treatment
would include.
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Observation
Vaccination for HCV
Oral entecavir
Pegelated Interferon
Adefovir Dipivoxil for HBV
Hadziyannis, NEJM 2003
Case 5
• 63 y/o man, infected with HCV while shooting
heroin in Vietnam. Cirrhosis by clinical findings
(low plts, cutaneous stigmata and firm liver).
On going depression, low plts and alcoholism
prevented treatment.
• Developed ascites and tap noted bloody fluid.
CT noted mass in the liver.
What type of tumor does he have?
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Metastatic adenocarcinoma?
Hepatic adenoma?
Hepatocellular carcinoma?
Focal nodular hyperplasia?
What type of tumor does he have?
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Metastatic adenocarcinoma?
Hepatic adenoma?
Hepatocellular carcinoma?
Focal nodular hyperplasia?
HCC Among In-Care Cirrhotics
4000
3500
HCC among in-care
cirrhotics
3000
2500
2000
1500
1000
500
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
J Dominitz, M Chang, et al. HCRC Liver Disease Database, reported 03/2011
How could you confirm the diagnosis?
• Check alpha fetoprotein?
• Biopsy?
• Classic imaging findings?
How could you confirm the diagnosis?
• Check alpha fetoprotein?
• Biopsy?
• Classic imaging findings?
What Treatments are Available?
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Transarterial chemoembolization (TACE)?
Radiofrequency ablation (RFA)?
Transplant?
Sorafinib?
Sorafenib tosylate
How do you screen for HCC?
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CT scan every year?
Ultrasound?
AFP?
AFP and ultrasound every 6 months?
How do you screen for HCC?
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CT scan every year?
Ultrasound?
AFP?
AFP and Ultrasound every 6 months?
Case 6
• 47 y/o man with longstanding HBV and stable
cirrhosis slowly deteriorates developing
ascites and liver failure.
• He is otherwise in good heath and has no hx
of mental illness or recent substance abuse.
• What is the optimal treatment for this man?
Case 6
• Transplant
Transplant
• Just about any liver disease is amenable to tpl
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HCV
PBC
NASH
HBV
Alcohol – if abstinent for 6-12 mo minimum
Small hepatocellular carcinoma
Transplant
• Contraindications
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Mental illness that would compromise compliance
Active substance abuse
Poor cardiopulmonary status
Poor social support
Active infection
Extra hepatic tumor
MELD
• Bilirubin
• INR
• Creatinine
• MELD Score = 0.957 x Loge(creatinine mg/dL)
+ 0.378 x Log e(bilirubin mg/dL)
+ 1.120 x Loge(INR)
+ 0.643∗
• (http://www.mayoclinic.org/gi-rst/mayomodel5.html)
What are the Criteria for Liver
Transplantation?
• MELD : >15
– Average MELD at transplant 24
Break point ~18
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