hepatitis management

1. Hepatits C Management in
Primary Care
Ong Jee Tat

4. Chronic HCV
Infected
Diagnosed and
Aware
Access to
Care
HCV
Confirmation
Liver Disease
assessment
Prescribed HCV
Treatment
Achieved
SVR
9%
For Malaysia, this is the largest gap i.e. up to 90-95% individuals living with
HCV are UNAWARE that they are infected
DAAs only help
once you get here
Left side of the cascade
equally/more important
Gaps Along the HCV Care Continuum
4

5. Background
• Most chronic hepatitis C Virus (HCV) infected individuals are asymptomatic
& thus unaware of their infection. Many remained undetected.
• Failure to identify them prevents linkage to care & successful control of
HCV.
• Therefore, screening of HCV is an important step towards improving
detection & ultimately treatment & cure of infected individuals.
5

6. Stable
80% (68%)
HCC
Liver failure
25% (4%)
Slowly
progressive
75% (13%)
Resolved
15% (15%)
Acute HCV
Cirrhosis
20% (17%)
Chronic HCV
85% (85%)
HCC
Time/yr
10 20 30
Source: Nancy Reau. ID Week 2015 HCC: Hepatocellular Carcinoma
HCV Infection - Natural History
6

7. Timely Treatment Can
Arrest The Disease
Progression And
Prevent Death
7
50% F3 in 10 years 28% in 10 years
HCV Infection - Natual History

10. 2. Healthcare, emergency medical, and
public safety workers after needle
sticks, sharps, or mucosal
exposures to HCV-infected blood
Risk of HCV infection varies depending
upon the frequency of medical
procedures (i.e. number of
injections/person/year) and level of
infection control practices. High frequency
of injections and low level of infection
control can result in high prevalence of
HCV in the general population.
HEPATITIS
C
3. Recipients of blood / blood products /
clotting factor concentrates / organ
transplant before July 1994
There is a high risk of HCV infection via
transfusion of unscreened blood and blood
products.
1. People who inject drugs (PWID)
PWID have the highest risk of infection.
Globally, the prevalence of HCV is 67%
among PWID. In Malaysia, 59% HCV
infection acquired through injecting drugs.
WHO TO SCREEN?
10

11. 4. Persons on long-term
hemodialysis (ever)
Risk of HCV infection among dialysis
patient is high in condition where
level of infection-control practices
is low / ignored. Risk of HCV infection
also varies depending upon the frequency
of medical procedures (i.e.no of
injections/person/year). A study reported
that 53.9% of patient on dialysis from
1985 and September 1991 were positive
for anti-HCV.
HEPATITIS
C
5. Intranasal illicit drug use
Non-injecting drug use (e.g. through
sharing of inhalation equipment for
cocaine) is associated with a higher risk of
HCV infection. The present of blood and
HCV RNA in the nasal secretions of HCV-
positive long-term drug sniffers can be
transferred onto sniffing implements (i.e.,
straws) during simulated intranasal drug
use.
WHO TO SCREEN?
11

12. 9. Children born to HCV infected
women
HCV transmission risk is estimated as 4 –
8% among mothers without HIV
infection. Transmission risk is estimated
as 17-25% among mothers with HIV
infection.
7. Persons who were ever incarcerated
Persons who were incarcerated are at risk
for Hepatitis C because many people in jails
or prisons already have Hepatitis C
6. Persons with HIV infection, in
particular MSM, are at increased
risk of HCV infection through
unprotected sex
Persons with HIV infection, in particular
MSM, are at increased risk of HCV
infection through unprotected sex.
8. Unexplained chronic liver disease
and/or chronic hepatitis including
elevated ALT levels
Approximately 60% to 70% of chronically
(HCV) infected person will eventually develop
chronic liver disease.
WHO TO SCREEN?
12

13. 10. People with sexual partners
who are HCV infected
There is low or no risk of sexual
transmission of HCV among HIV-
uninfected heterosexual couples and HIV-
uninfected men who have sex with men
(MSM). The risk of sexual transmission is
strongly linked to pre-existing HIV
infection.
11. Solid organ donors
(deceased and living)
There is a risk of HCV infection in
unscreened organ donors.
12. Persons with percutaneous/parenteral exposures in an unregulated setting
Tattoo recipients have higher prevalence of HCV compared with persons without tattoos (odds ratio =
2.24, 95% CI 2.01, 2.50).
WHO TO SCREEN?
13

15. • Prior to initiation of treatment, hepatitis C must be assessed to
identify presence of co morbidity and to determine cirrhosis status.
• The following investigations need to be performed:
o full blood count (FBC)
o liver function test (LFT)
o serum creatinine
o international normalisation ration (INR)
o HIV & HBsAg screening
Pre-treatment Assessment
15

16. 1.5 3.25

19. 19
Formula

24. Sustained Virological Response (SVR)

28. Direct-acting
antivirals (DAAs)
28

29. Pharmacological Treatment
29
Duration (weeks)

30. Pharmacological Treatment
30
Decompensated
Cirrhosis

40. Pharmacological Treatment
40
Duration (weeks)

41. Pre-treatment assessment of concomitant medication should be
done to avoid DDI
Prescribers may consult the University of Liverpool webpage on hepatitis drug
interactions at https://www.hep-druginteractions.org/checker
Drug-drug Interactions (DDIs)
41

47. • HIV Co-infection
• Hepatitis B Co-infection
• Chronic Kidney Disease/End-Stage Renal Disease (CKD/ESKD)
• Pregnancy
• Acute hepatitis C
• Hepatitis C in children & adolescents
Introduction: Special Groups
47

48. HIV Co-infection
48

49. • People with HIV/HCV co-infection are advised to start ART soon after
being diagnosed with HIV (WHO 2016).
• This is especially so if CD4 cell count is below 350 cells/µL; to improve
immune function.
• Treatment of these patients requires special attention due to the
complexity of drug-drug interactions (DDI) that can occur between
DAAs & antiretroviral medications.
• HIV treatment should not be interrupted in order to start hepatitis C
treatment.
When to start DAAs?
49

50. • SOF/DCV has no significant DDI with NRTIs.
• SOF/LDV increases tenofovir levels when given as tenofovir disoproxil
fumarate (TDF), which may increase the risk of tenofovir-associated
renal toxicity.
• SOF/VEL increases tenofovir levels when given as TDF, which may
increase the risk of tenofovir-associated renal toxicity.
o These combinations should be used with caution with close monitoring of renal
profile in patients with an eGFR <60 ml/min/1.73 m2.28
DDIs - NRTIs
50
28. AASLD-IDSA HCV Guidance Panel. Clin Infect Dis. 2018;67(10):1477-92.

51. • The dose of DCV should be increased from 60 mg to 90 mg when
used with potent inducer of cytochrome P450 (CYP) 3A4 e.g.
efavirenz (EFV), etravirine (ETV) or nevirapine (NVP).
• LDV’s AUC decreases by 34% when co-administered with EFV-
containing regimes.
o Although no dose adjustments of LDV are recommended to account for these
interactions, the combinations should be used with cautions & frequent renal
monitoring.28
• SOF/VEL is not recommended to be used in patients on EFV, NVP
or ETV.
DDIs - NNRTIs
51

52. • HBV/HCV co-infection is more common among people who
inject drugs (PWID) or in areas where these 2 viruses are
endemic.
• Co-infection of HBV/HCV increases risk for HCC by 13.3%.46
• HBV/HCV co-infected patients should be treated similar to
HCV mono-infected once HBV status has been assessed.
52
Hepatitis B (HBV) Co-infection
46. Tsai JF et al. Br J Cancer. 1997;76(7):968-74.

53. Why Need to Treat?
Meta-analysis of 17 cohort studies on HBV/HCV co-infection:47
• When receiving DAAs treatment, HBV reactivation occurred more frequently in
patients with chronic 24% [hepatitis B surface antigen (HBsAg)] than resolved 1.4%
[HBsAg-negative/hepatitis B core antibody (HBcAb)-positive] infection.
• In chronic HBV infection, the risk of HBV-reactivation-related hepatitis was
significantly lower in patients with HBV DNA below the lower limit of quantification
at baseline than in those with quantifiable HBV DNA (RR=0.17, 95% CI 0.06 to 0.50).
Hepatitis B (HBV) Co-infection
53
47. Mücke MM et al. Lancet Gastroenterol Hepatol. 2018;3(3):172-80.

54. Source: Centres for Disease Control and Prevention. Available at: https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm
Hepatitis B (HBV) Co-infection
54

55. • HCV infection in CKD is associated with:
o increased liver-related morbidity & mortality rates
o accelerated progression to ESRD
o risk of cardiovascular events
o increase the morbidity & mortality rates of both dialysis &
kidney transplant (KT) patients
CKD/ESKD
55

56. • Studies showed:63 - 64
o once-daily oral regime of GZV/EBR for 12 weeks achieved high rates of SVR
97.4 - 99%
o an acceptable safety profile in patients with HCV genotype 1 infection &
advanced CKD with or without dialysis
• Treatment with GLE/PIB for 12 weeks:65
o resulted in an SVR of 98% (95% 95 to 100) in patients with stage 4 or 5 CKD &
HCV infection.
CKD/ESKD
56
63. Bruchfeld A et al. Lancet Gastroenterol Hepatol 2017;2(8):585-59.
64. Roth D et al. Lancet. 2015;386(10003):1537-45.
65. Gane E et al. N Engl J Med. 2017;377(15):1448-55

57. • A meta-analysis of 21 cohort studies of moderate quality showed that:62
o regime including SOF could be proposed for HCV-infected CKD patients with
or without HD
o it should be associated with close clinical, biological, cardiovascular &
therapeutic drug monitoring.
CKD/ESKD
57
62. Li M et al. Virol J. 2019;16(1):34.

58. Treatment Algorithm of CKD using DAAs
according to HCV Genotype & eGFR
58
Source: Kim SM et al. Korean J Intern Med. 2018 Jul;33(4):670-678.

59. • Treatment of hepatitis C should not be initiated until pregnancy has been excluded due to the lack
of safety & efficacy data.28
Adapted: Kushner et al. Hepatology Communications. 2019;3(1).
Pregnancy
59
28. AASLD-IDSA HCV Guidance Panel. Clin Infect Dis. 2018;67(10):1477-9

60. • Women of reproductive age with HCV should be counselled about the benefit
of antiviral treatment prior to pregnancy to improve the health of the mother &
eliminate the low risk of mother-to-child transmission (MTCT).
• Women who become pregnant while on DAA therapy (with or without ribavirin)
should discuss the risks versus benefits of continuing treatment with their
physicians.
• Ribavirin is contraindicated in pregnancy due to its known teratogenicity. In
addition, the risk for teratogenicity persists for up to 6 months after ribavirin
cessation & applies to women taking ribavirin & female partners of men taking
ribavirin.
Pregnancy
60

61. • Most patients with acute hepatitis C are asymptomatic. Spontaneous
viral clearance varies from 14% to 50%.
• A minimum of 6 months of monitoring for spontaneous clearance is
recommended before deciding to initiate treatment .
• If decision is to initiate treatment during the acute infection period,
HCV RNA monitoring for at least 12 to 16 weeks before starting
treatment is recommended.
• Patients who spontaneously clear after acute hepatitis C, antiviral
treatment is not recommended.
Acute Hepatitis C
61

62. CPG Recommendation
62

63. • The United Nations Convention on the Rights of the Child defines a child as an
individual below the age of 18 years; WHO defines an adolescent as a person
between the ages of 10 & 19.
• Major route of infection in:
o mother-to-infant transmission in children
o adolescents are at risk of infection via injecting drug use.
• Numerous trials of PEG-IFN & RBV in children but current treatment options with
DAAs are limited.
• The use of SOF/LDV for 12 weeks in children ages 12 - 17, weighing greater than
35 kg (genotype 1, 4, 5 and 6) have resulted in SVR rate of 98%.11,14
• Combination of SOF & RBV has also been proposed for genotypes 2 & 3 for
adolescents.11,14
Hepatitis C in Children & Adolescents
63
11. World Health Organization. Geneva: WHO; 2018.
14. European Association for the Study of the Liver. J Hepatol. 2018;69(2):461-511.

64. • Adolescents aged ≥12 years, infected with genotype 2 or 3, who are
treatment-naïve or treatment-experienced, without cirrhosis or with
compensated cirrhosis (CPS A*) can be treated with other regimens
approved for adults, with caution pending on more safety data in this
population.11,14
• In children younger than 12 years, treatment should be deferred until
DAAs, including pan-genotypic regimens, are approved for this age
group.11,14
*CPS A: Page 10 in CPG
Hepatitis C in Children & Adolescents
64

65. 65
• A treatment interruption was defined as treatment interruption for
>7 days or treatment discontinuation.
• If the interruption of treatment was for ≤7 days, treatment was
continued for the remaining duration as prescribed & SVR12 was
assessed 12 weeks after the completion of treatment.
• If interruption of treatment was >7 days & the patient had taken
treatment for <4 weeks, then the treatment was started afresh.
• If interruption of treatment was >7 days & the patient had taken
treatment for ≥4 weeks or more, then HCV RNA was measured
after 12 weeks of cessation of drug to assess for SVR12.
Monitoring During DAAs
6
5
Missed Dosing

66. When to Refer
• cirrhosis
• treatment failure
• hepatitis B co-infection
• CKD stage 4 & 5
• extrahepatic manifestation
• haemoglobinopathies
• solid organ transplantation
66
Patient with compensated cirrhosis,
treatment-naïve should be able to be treated at Klinik Kesihatan or any
physician base clinic.
When to Refer
66

67. When to Refer
• CPG Management of Chronic Hepatitis C in Adults
• EASL Recommendations on Treatment of Hepatitis C 2018
67
Referance
67

68. Thank you