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Objectives
• Discuss the importance of screening for chronic HCV
• Identify the target population of HCV screening• Understand what tests are needed to screen
patients and linkage to care• Examine the natural progression of chronic HCV
infection• Discuss long term management strategies
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• 170 Million Carriers Worldwide
• Global HCV Prevalence 3.0 %
Hepatitis C: A Global Health Problem
Most Patients with Chronic Hepatitis C in the US Are Not
Aware that They Are Infected
~3,300,000 individuals
are infected with the
hepatitis C virus in
the United States
825,000 (~25%)
AWARE
2,475,000 (~75%)
UNAWARE
Adapted from Colvin HM, Mitchell AE. Hepatitis and liver cancer: A national strategy for
prevention and control
of hepatitis B and C. Washington, DC: The National Academies Press; 2010.
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Deaths Due to HCV Infections Now ExceedThose Due to HIV Infection
7Ly KN et al. Ann Intern Med. 21 February 2012;156(4):271-278; Mahajan, IDSA 2013
Number of HCV-related
deaths may be over
60,000 because of
under-reporting on death
certificates
• In the United States, the annual number of deaths due to HCV infection are increasing, and have risen above that of HIV infection.
• While these data indicate the increasing mortality burden of chronic HCV infection, deaths due to HCV are frequently underreported; thus the accurate mortality is likely to be higher than is captured by death certificates
To
tal
No
. In
fec
ted
(millio
ns
)
Diagnosed
Undiagnosed
2.7 to 3.9 Million1
75% Unaware of Infection
1.1 Million1
21% Unaware of Infection
~800,000 to 1.4 Million1
65% Unaware of Infection
HIV HBV HCV
4
3
2
1
0
Prevalence of Chronic Viral Infections
HCV is Nearly 4 Times as Prevalent as HIV and HBV
• A 2011 study estimated that as many as 5.2 million persons are living with HCV in the United States2
HBV=hepatitis B virus; HCV=hepatitis C virus; HIV=human immunodeficiency virus. 1. Institute of Medicine. Washington, DC: The National Academies Press; 2010.2. Chak E, et al. Liver Int. 2011;31(8):1090-1101.
1. Ghany MG, et al. Hepatology. 2009;49(4):1335-1374.
HCV Can Now Be Cured in Most Patients
• Unlike HIV and HBV infection, HCV infection is a curable disease
• What does cure mean?• Sustained Viral Response
• Undetectable HCV RNA 12 weeks after completion of antiviral therapy for chronic HCV infection1
• Long term morbidity and mortality benefits
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Therapy for Hepatitis CProjected SVR Rates with Multiple DAAs
6
16
34
4239
55
70
90
0
20
40
60
80
100
IFN6m
IFN12m
IFN + RBV6m
IFN + RBV12m
PEG12m
PEG + RBV12m
PEG + RBV + PI6-12m
Multiple DAAs3m
Su
sta
ine
d V
iro
log
ic R
es
po
ns
e (
%)
Timeline
1986 1998 2001 2002 2011 2014
All-Cause Mortality
International, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada. Patients
with chronic HCV infection started an interferon-based treatment regimen between 1990 and 2003 (n=530).
van der Meer AJ, et al. JAMA. 2012;308:2584-2593.
SVR Was Associated With Reduced Long-Term Risk of All-Cause Mortality in an International, Multicenter Study
Impact of Treatment on Liver Failure
Van der Meer AJ, et al. JAMA. 2012;308:2584-2593.
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Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer
13
Chronic liver disease includes fibrosis, cirrhosis, and hepatic decompensation; HCC=hepatocellular carcinoma.
1. Highleyman L. Hepatitis C Support Project. http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Fibrosis.pdf. Accessed August 18, 2011; 2. Bataller R et
al. J Clin Invest. 2005;115:209-218;
3. Medline Plus. http://www.nlm.nih.gov/medlineplus/enxy.article/000280.htm. Accessed August 28, 2012; 4. Centers for Disease Control and Prevention.
http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed May 8, 2012.
Fibrosis1
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis1,2
Over time, fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
~75% of patients infected with HCV will develop a chronic infection and approximately 65% of those are expected to develop chronic liver disease
Decompensated cirrhosis: Ascites, bleeding gastroesophageal varices, hepatic encephalopathy, and jaundice.
Projected Numbers of Decompensated Cirrhosis and Cases of HCC to Rise Through 2020
14
Decompensated cirrhosis became more common after 1995 and is presently estimated at 11.7% of cirrhosis cases; the number of cases is expected to continue to increase through ~2020 to 2030.
HCC rose steeply after 1990. Based on the model, the incidence of HCV-related HCC is expected to peak after 219 at almost 14,000 cases per year if the risk in HCV-infected persons with fibrosis remains the same.
The best way to reduce the likelihood that someone will
develop severe complications of hepatitis C is to cure the
infection!
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Risk Factors for Acute Hepatitis C
Alter MJ. Presented at the NIH Consensus Development Conference, March 24, 1997.
United States, 1991-1995
*Other High Risk
Other non-injection, STDs,
and prison
Other
High Risk* 30.0%
Injection Drug Use 43.0%
Unknown 1.0%
Household 3.0%
Occupational 4.0%
Transfusion** 4.0%
Sexual (Multiple Partners) 15.0%
**None in 1995
The Morbidity and Mortality Weekly Report (MMWR)
Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945-1965
Source: CDC and Prevention. MMWR. 2012:RR61:1-32.
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NEW CDC Recommendation
– Adults born during 1945 through 1965 should receive one-time testing for HCV without prior ascertainment of HCV risk factor
– Benefits of therapy
• Reduces risk of liver cancer by 70%
• Reduces risk of all-cause mortality by 50%
Baby Boomers (Born in 1945–1965) Account for 76.5% of HCV in the US1
20
An estimated 35% of undiagnosed baby boomers with
HCV currently have advanced fibrosis (F3-F4; bridging
fibrosis to cirrhosis)3
1. Centers for Disease Control and Prevention. MMWR. 2012;61:1-32; Adapted from Pyenson B, et al. Consequences of Hepatitis C Virus (HCV): Costs of a baby boomer
Epidemic of Liver Disease. New York, NY: Milliman, Inc; May 18, 2009. http://www.milliman.com/expertise/healthcare/publications/rr/consequences-hepatitis-c-virus-RR05-
15-09.php Milliman report was commissioned by Vertex Pharmaceuticals; 3. McGarry LJ et al. Hepatology. 2012;55(5):1344-1355.
Screening of Baby Boomers May Prevent >120,000 Deaths Due to HCV Infection
› Birth-cohort screening in primary care would identify 86% of all undiagnosed cases in the birth cohort, compared with 21% under risk based screening1
› Cost effectiveness of HCV screening is comparable to cervical cancer or cholesterol screening (cost/QALY gained with protease inhibitor+IFN+RBV = $35,700)
21
Markov chain Monte Carol simulation model of prevalence of hepatitis C antibody stratified by age, sex, race/ethnicity, history of injection drug use, and natural history of chronic hepatitis C.*With pegylated interferon and ribavirin plus DAA treatment.†Deaths due to decompensated cirrhosis or hepatocellular carcinoma within 1945-1965 birth cohort. 470,000 deaths under birth cohort screening vs 592,000 deaths under risk-based screening1. Rein D et al. Ann Intern Med. 2012;156(4):263-270; 2. McGarry LJ et al. Hepatology. 2012;55(5):1344-1355.
1,070,840 new cases of HCV identified with birth-cohort screening
552,000 patients treated
364,000 patients cured*
121,000 deaths averted†
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Who Should Be Tested for HCV
CDC Recommendations• Everyone born from 1945 through 1965
(one-time)• Persons who ever injected illegal drugs• Persons who received clotting factor
concentrates produced before 1987• Chronic (long-term) hemodialysis• Persons with persistently abnormal ALT
levels. • Recipients of transfusions or organ
transplants prior to 1992• Persons with recognized occupational
exposures• Children born to HCV-positive women• HIV positive persons
USPSTF Grade B Recs*• Everyone born from 1945 through 1965
(one-time)
• Past or present injection drug use
• Sex with an IDU; other high-risk sex
• Blood transfusion prior to 1992
• Persons with hemophilia
• Long-term hemodialysis
• Born to an HCV-infected mother
• Incarceration
• Intranasal drug use
• Receiving an unregulated tattoo
• Occupational percutaneous exposure
• Surgery before implementation of universal precautions
22*Only pertains to persons with normal liver enzymes; if elevated liver
enzymes need HBV and HCV testing
Smith at al. Ann Intern Med 2012; 157:817-822. Moyer et al. Ann Intern Med epub 25 June 2013
Diagnosis
of infection
Assessment
of disease
Chronic HCV InfectionPersistence of HCV RNA for at least 6 months
Treatment
evaluation
HCV Diagnostic Algorithm
Modified from CDC Guidelines on Hep C Dx, MMWR 2003;52(RR03):1-16.
HCV RNA
Antibody Test
EIA for anti-HCV
Active HCV Infection
Medical Evaluation
No Current HCV
Infection
Spontaneous or
treated
HCV Genotype&
Linkage to Care
Born in age cohort
(1945-1965) or Risk
Factors
Negative for HCV Infection
Additional Testing Recommended if:
Acute HCV suspected
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Hepatitis C Antibody (HCV Ab)
• A positive antibody means that your body was exposed to the Hepatitis C virus and antibodies were made
• This does not mean that you have an active HCV infections
• HCV antibody is NOT protective
• HCV antibody will remain positive even after SVR
HCV RNA
• Referred to as “viral load”
• Available as qualitative and quantitative
• Confirms active HCV infection
• Quantitative testing is used to monitor HCV treatment
HCV RNA Testing Has No Prognostic Value
• The level of viremia does not correlate with the severity of liver disease (activity grade or fibrosis stage)
• Does not predict the outcome of HCV infection (resolution vs. persistence)
• Does not predict the natural course of the disease
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Repeated testing for HCV RNA
levels is not indicated in the
routine management and
monitoring of untreated
patients with hepatitis C
Prevalence of HCV Genotypes in the US
• 6 known genotypes.
• Little difference among them regarding transmission and natural history.
• Genotype 1 is most common in the United States. 73%
10%
8%
1%
4%
Genotype 1 Genotype 2 Genotype 3
Genotype 4, 5, 6 Mixed Genotype
Adapted from Blatt LM, et al. J Viral Hepatitis. 2000; 7:196-201.
Geographical Distribution of HCV Genotype
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Hepatic Fibrosis
FIBROSIS
Cholestatic
Disorders
Viral
Hepatitis
Excess
Vitamin A
Inherited
Metabolic
Disorders
Alcohol
Immune
Disorders
Drugs
NASH
Assessing Liver Damage—Liver Biopsy
Four Stages of Fibrosis
Desmet VJ et al., Hepatology 1994;19:1513
Four Stages of Fibrosis in Chronic Hepatitis: METAVIR
Stage 1 Fibrosis – Portal Stage 2 Fibrosis – PeriportalStage 3 Fibrosis – SeptalStage 4 Fibrosis – Cirrhosis (ultimate stage of scarring)
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Sampling can makethe difference between….
Desmet VJ et al., Hepatology 1994;19:1513
Or more advanced disease
Desmet VJ et al., Hepatology 1994;19:1513
Aspiration (Klatskin) needle Full core, 16g cutting needle
Desmet VJ et al., Hepatology 1994;19:1513
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Non-invasive Markers of Fibrosis
FibroTest / FibroSure Bili, gGT, g-globulin, haptoglobin, a2 M, apolipoprotein A
FibroSpect Hyaluronic acid, TIMP-1, a2 M
ELF (Bayer) HA, Procollagen III amino terminal peptide (PIIINP),TIMP1
HepaScore Hyaluronic acid, gGT, a2 M
Forns gGT, cholesterol, platelets, age
APRI AST /ULN X 100 / platelets (109/ L)
SHASTA; (HIV/HCV) AST, HA, albumin
FIB-4 AST, ALT, platelets, age
Fibroscan (elastography) is a rapid and non-invasive measure of hepatic stiffness
FIBROSCAN
39Ziol M et al. Hepatology 2005;41:48-54.
7.1 8.7 9.6 12.9 14.5
F1F2 F2 F3 F3F4 F4
kPa
F0F1
4 75...
Fibroscan results in kPa can be correlated with the metavir scale F0-F4
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PCP Education Example: Screening in Clinic
40
1,000
adult
patients
330
baby
boomers
10
HCV
antibody
positive
7 HCV
RNA
positive
3 with more
advanced
fibrosis
4 with mild
fibrosis
Efficiently identify birth cohort 1945-1965:• Electronic
prompt
~1/3 of
adults are
in 1945-
1965
cohort
• 1 of 30 baby
boomers
• 1 of 23 men
baby boomers
• 1 of 12 African
American men
baby boomers
15%-30% of
HCV antibody
patients will
spontaneously
clear
Up to 25% of
baby boomers
may have
cirrhosis
75% of cirrhotic
patients are
men
Davis, Gastro 2010; 138: 513
HCV Antibody Positive and HCV RNA Negative Patients
• If liver function tests are normal no further testing or follow up required
• Patients who have attained sustained viral response with treatment need not have repeated tests for HCV RNA to confirm a cure
• If liver function tests are elevated evaluate for other etiologies of liver disease
Approach to the Patient with Newly Diagnosed HCV
• Patients need to be educated on
• the natural history of disease
• modes of transmission of
• how to avoid transmission to family members
• the availability of effective treatment
• the reassurance that these new highly effective and safe interferon free treatments available are very well tolerated and nothing like the interferon days
• Screen for depression
• Reassurance
• Patients may benefit from referral to a support group
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Additional Measures for Newly Diagnosed Patients with HCV
• Vaccinate for hepatitis A and hepatitis B• Counsel for weight loss if appropriate. Obesity
increases likelihood of liver fibrosis• Recommend avoiding doses of acetaminophen
exceeding 1-2 grams per day• Determine presence or absence of cirrhosis• NSAIDs should be avoided in patients with
advanced fibrosis or cirrhosis
Measures to Avoid Transmission of Hepatitis C
• Avoid Sharing Razors or Toothbrushes
• Cover Bleeding Wounds
• Stop Injection Drug Use
• Advise Not to Share Needles and Paraphernalia
Sexual Transmission of HCV
• Risk of Sexual Transmission is Low in Monogamous Heterosexual Relationships
• Many Experts do not Recommend Barrier Protection for Couples that are in a Monogamous Long Term Relationship
• Patients with Multiple Sexual Partners, and Patients with HIV Should Use Barrier Protection
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Rate of Liver Progression is Affected by Several Patient Factors
• Male gender1
• Age at infection1
• Comorbidities such as HIV and HBV status1
• High levels of alcohol consumption1
• Immune status1
• Visceral obesity with steatosis2,3
• Diabetes4
• Insulin resistance5-7
• Synergy between risk factors8Metabolic Syndrome
Affects 37–54% of adults over 40
years old9
1. Chen SL, Morgan TR. Int J Med Sci. 2006;3(2):47-52. 2. Adinolfi LE, et al. Hepatology. 2001;33(6):1358-
1364. 3. Adinolfi LE. Expert Rev Gastroenterol Hepatol. 2013;7(3):205-213. 4. El-Serag HB, et al. Clin
Gastroenterol Hepatol. 2006;4(3):369-380. 5. Bugianesi E, et al. J Hepatol. 2012;56(suppl 1):S56-65. 6.
Mohamed HR, et al. Int J Health Sci (Quassim). 2009;3(2):177-186. 7. Khattab MA, et al. Ann Hepatol.
2012;11(4): 487-494. 8. Loomba R, et al. Am J Epidemiol. 2013;177(4):333-342. 9. Ervin RB. Natl Health Stat
Report. 2009;(13):1-7.
Steps to Slow Progress of Liver Disease
• Obesity and Smoking Increase Liver Fibrosis• Daily Marijuana Use Increases Fibrosis Progression
Rate. Odds Ratio = 3.4 (1.5 -7.4)• Patients Should be Counseled to:
• Lose Weight if Necessary• Stop Smoking• Discontinue Marijuana Use
Hu KQ: J Hepatol. 2004 Jan;40(1):147-54Hu SX: J Clin Gastroenterol. 2009 Sep;43(8):758-64Mallat A: J Hepatol. 2008 Apr;48(4):657-65Hezode C: Hepatology. 2005 Jul;42(1):63-71
Hepatitis C and Alcohol
• Hepatitis C Infection Rates in Alcoholics are Significantly Higher Than Controls
• Alcohol Use in Patients with HCV Infection Increases Fibrosis Progression Rate, Risk for Liver Cancer and Overall Mortality
• Abstinence from Alcohol is Recommended
• Educate on Synergistic Damage to liver by Alcohol and HCV
• Refer to Alcohol Rehab Programs if appropriate
Coelho-Little ME: Alcohol Clin Exp Res. 1995;19(5):1173
Chen CM: Alcohol Clin Exp Res. 2007;31(2):285
Delarocque-Astagneau E: Ann Epidemiol. 2005;15(8):551
Hassan MM: Hepatology. 2002;36(5):1206
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3’UTR5’UTR Core E1 E2 NS2 NS4BNS3 NS5A NS5Bp7
Ribavirin
Polymerase
Daclatasvir (DCV)Ledipasvir (LDV)Ombitasvir (OMV)Elbasvir (EBR)
Sofosbuvir(SOF)
Dasabuvir(DSV)
NS5B
NUC
Inhibitors
NS5A
Replication
Complex
Inhibitors
NS5B
Non-NUC
Inhibitors
(NNI)
Boceprevir (BOC)Telaprevir (TVR)Simeprevir (SMV)Paritaprevir (PTV)Grazoprevir (GZR)
NS3
Protease
Inhibitors
Protease
4A
No Cross Resistance Between Drug Classes
FDA Approved Direct-Acting Antiviral Agents (DAAs) from Multiple Classes
General Concepts About SelectingHCV Regimens
• Choice of regimen, treatment duration, and use of ribavirin depends on:
• Presence of cirrhosis
• Prior treatment experience
• PEG-RBV failure
• Prior protease inhibitor failure
• Prior sofosbuvir failure
• Genotype
• Genotype 1a vs 1b
• Genotypes 2-6
• Daclatasvir (DCV) + Sofosbuvir (SOF) (Daklinza + Sovaldi)
• Grazoprevir (GRZ)/Elbasvir (EBR) (Zepatier)
• Ledipasvir (LDV)/Sofosbuvir (SOF) (Harvoni)
• Paritaprevir/Ritonavir/Ombitasvir (PTV/RTV/OMV) + Dasabuvir (DSV) (Viekira Pak)
• Velpatasvir (VEL) + Sofosbuvir (SOF) (Epclusa)
• Ribavirin (RBV) required for some regimens in certain populations.
Approved Treatment Options Most Often Used for Genotype 1 Infection
(Most Common Genotype in US) (alphabetical)
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Cure (SVR12) in GT 1 Patients Treated with Daklinza + Sovaldifor 12 or 24 Weeks (FDA Approved for 12 Weeks)
0
20
40
60
80
100 100
SV
R12 (
%)
40/41 39/41 14/14 21/21 15/15 19/20
98 95 100 100 95
Treatment Naive Prior PI/PEG/RBV Failures
12 Weeks 24 Weeks
DCV/SOF + RBV DCV/SOF + RBVDCV/SOF DCV/SOF
Sulkowski MS et al., N Engl J Med 2014;370: 211-21
95 92 99 94 97
0
20
40
60
80
100
All Patients GT 1a GT 1b No Cirrhosis Cirrhosis
Pa
tien
ts,
(%)
299/ 316
144/ 157
129/ 131
231/ 246
68/ 70
Zeuzem, et al. Abstract #G07, EASL 2015; published online at Ann Intern Med (www.annals.org) on 24APR15.
Cure (SVR12) in GT 1 Patients Treated with Zepatier for 12 Weeks
94100
94100
0
20
40
60
80
10099 97 98 99
0
20
40
60
80
100
SV
R12 (
%)
179/
180
178/
184
181/
184
179/
181
12 Weeks 24 Weeks
LDV/SOF
+ RBVLDV/SOF
+ RBV
LDV/SOF LDV/SOF
Non-Cirrhotic Cirrhotic
32/
34
34/
34
31/
33
36/
36
LDV/SOF
+ RBVLDV/SOF
+ RBV
LDV/SOF LDV/SOF
12 Weeks 24 Weeks
SV
R12 (
%)
Afdhal, et al. N Eng J Med. 2014;370:1889-98.
Cure (SVR12) in GT 1 Patients Treated with Harvoni for 12 or 24 Weeks (FDA Approved for 12 Weeks Without RBV; 8 Weeks for
Some Patients)
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90 90
96 96
0
20
40
60
80
100
All Patients Treatment Naïve
SV
R1
2 (
%)
No Ribavirin
Ribavirin
Cure (SVR12) in GT 1a Patients Treated with Viekira Pak for 12 Weeks
94
10095
Relapse Null
Prior PegIFN/RBV Response
p=0.004 p=0.006
182/
202
569/
593
182/
202
403/
420
47/
50
36/
36
83/
87
Everson G, et al. Abstract #83, AASLD 2014
SVR
12
(%)
Most Recently Approved: Sofosbuvir/Velpatasvir(SOF/VEL) x 12 Weeks (Pangenotypic)
99 98 99 100 100 97 100
0
20
40
60
80
100
SVR
12
(%
)
618624
206210
117118
104104
116116
3435
4141
56
Total 1a 1b 2 4 5 6
Genotype
Feld JJ et al. Presented at: American Association for the Study of Liver Diseases 2015 Annual Conference; San Francisco, CA Nov 13-17, 2015.
SVR
12
(%)
More Pangenotypic Regimens in Development
Combination Treatment Phase Manufacturer
ABT-493 (NS3/4A protease inhibitor) +ABT-530 (NS5A inhibitor)
3 AbbVie
Sofosbuvir (nucleotide polymerase inhibitor) + Velpatasvir (NS5A inhibitor) + GS-9857 (NS3/4A
protease inhibitor)
3 Gilead
Grazoprevir (NS3/4A protease inhibitor), MK-3682(NS5B polymerase inhibitor) and elbasvir (NS5A
replication complex inhibitor)
2 Merck
Grazoprevir (NS3/4A protease inhibitor), MK-3682 (NS5B polymerase inhibitor) and MK-8408 (NS5A
replication complex inhibitor)
2 Merck
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Special Populations
• HIV/HCV Coinfection• ESRD• Decompensated cirrhosis• Post liver transplant
• These patients do have options and need to be referred to a provider that can treat them.
• www.hcvguidelines.org is living document and regularly updated
So now you suspect that your patient has cirrhosis…
Diagnosis of Cirrhosis Changes Approach to Patients with HCV
• Screen for HCC every 6 months• Evaluate for esophageal varices with endoscopy• Avoid all hepatotoxic drugs• Absolutely no alcohol• Refrain from use of NSAIDs including aspirin,
ibuprofen, naproxen, and others due to an increased risk of gastrointestinal bleed, potential for renal toxicity, and impaired response to diuretic therapy.
• Tylenol is ok to use in patients with cirrhosis• Recommend weight loss for obese patients
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• Primary complications include:
– Ascites
– Jaundice
– Variceal hemorrhage
– Portosystemic encephalopathy
• Other possible complications include:
– Spontaneous bacterial peritonitis
– Hepatic hydrothorax
– Hepatorenal syndrome
– Portopulmonary hypertension
– Hepatocellular carcinoma
– Portal vein thrombosis
Decompensated Cirrhosis
Lefton HB et al. Med Clin N Am. 2009;93:787-799.
Points
1 2 3
Encephalopathy None Grade 1 - 2(or precipitant-induced)
Grade 3 - 4(or chronic)
Ascites None Mild/Moderate(diuretic-responsive)
Severe(diuretic-refractory)
Bilirubin (mg/dL) <2 2-3 >3
Albumin (g/dL) >3.5 2.8 - 3.5 <2.8
Prothrombin Time (seconds prolonged)
<4 4-6 >6
Total Numerical Score
Child-Pugh Class
5 - 6 A
7 - 9 B
10 - 15 C
Classification of Cirrhosis Severity Determinants for Child-Turcotte-Pugh (CTP)
Adapted from Garcia-Tsao G et al. Am J Gastroenterol. 2009;104:1802-1829.
Patients in Class A are considered “compensated”
Patients in Classes B and C are considered “decompensated”
Classification of Cirrhosis Severity Model for End Stage Liver Disease score
• MELD - determines the severity of liver disease based on:
• serum bilirubin,
• serum creatinine
• international normalized ration (INR)
• developed in 2002 by UNOS
• Calculation:
• [0.957 x (Serum creatinine mg/dL) + 0.378 loge (Total bilirubin mg/dL) + 1.12 loge (INR) + 0.64] x 10
• Range: 6 – 40
• equates to estimated 3-month survival rates from 90% to 7%respectively
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Summary: Role of Primary Care
• HCV screening• Risk-based and one-time birth cohort screening with
HCV Ab.
• Confirmation of HCV infection• HCV RNA testing required to confirm infection.
• Counseling• HCV transmission/prevention• Risks of alcohol use
• Screening in HCV-infected individuals• HIV/HAV/HBV• Alcohol and substance use disorders
Summary: Role of Primary Care
• Vaccination• Hep A and B
• Baseline liver assessment• CBC, INR, albumin, AST/ALT, bilirubin, alkaline
phosphatase, GFR
• Treatment and Referral• Patients need to be informed of current effective,
well tolerated treatments and referred appropriately.
Case Study
• Mr. R is a 66 year old Hispanic male who comes in for a routine physical exam. He has never seen a doctor regularly as he feels great and never gets sick. His children urged him to establish a PCP.
• ROS all negative; VSS, however BP 145/87; BMI 35.2
• PMH unremarkable
• Family history• Father – DM, HTN, HLP, and died in his 70s from an MI
• Mother – HTN & DM
• Brother – HTN & cirrhosis of the liver secondary to ETOH
• Social Hx – Drink 2-3 12 oz beers on the weekends
• What tests should we order?
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MR. R
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• Thank you for your attention!
• Questions?
