HEPATITIS C TRAINING

MODULE FOR PRIMARY

CARE IN MALAYSIA
DR HJH ROSAIDA BINTI HJ MD SAID
Senior Consultant Gastroenterologist &
Hepatologist
Hospital Serdang
Content
01 Introduction
• The disease and natural history
• Epidemiology
• National Strategic Plan for Viral
Hepatitis
• Transmission and Risk Factors
02 Screening and Diagnosis
• Screening
• Diagnosis
• Assessment
03 Management
• Counselling
• Treatment options-SOP
• Post treatment follow up
 INTRODUCTION
 Hepatitis C is a liver disease caused by Hepatitis C virus (HCV)

 The virus is a small (55-65nm)size, enveloped single stranded RNA virus

 HCV causes acute and chronic hepatitis infection

 Wide spectrum severity: mild illness (few weeks) to serious, lifelong illness
 HEPATITIS C
VIRUS
STRUCTURE
 Enveloped RNA virus
 Flaviviridae family
 6 genotypes (GT)
 GLOBAL DISTRIBUTION OF
HEPATITIS C VIRUS
GENOTYPES
 HCV has been classified into six major genotypes
Prevalence of Genotypes in Different Areas
1a : Northern Europe, United States
1b : Global, Southern Europe
2 : Europe, North Africa
3 : Southeast Asia
4 : Middle East
5 : South Africa
6 : Asia

 Some genotypes (genotypes 1, 2 and 3) are distributed

globally, while others (genotypes 4, 5 and 6) are
endemic in different geographically restricted areas.
 Malaysia – mainly Genotype 1(30%) and
Genotype 3(70%)
 NATURAL HISTORY
Acute HCV HEPATITIS C VIRUS
Chronic HCV
Resolved 85% INFECTION
15% Cirrhosis
Stable 15%
80% HCC
Slowly Liver failure
progressive 25%
75%
10 20 30
Time/year
Reference : Nancy Reau. ID Week 2015
HCC = hepatocellular carcinoma
 The Disease
Acute Hepatitis C Chronic Hepatitis C
15% 85%
 Clinically mild and typically  Is one of the leading cause of end stage
unrecognized and undiagnosed liver disease (ESLD), Hepatocellular
carcinoma (HCC) and liver related
 Acute resolution of HCV is not deaths
associated with any long term sequelae
 The effect of chronic hepatitis extend
 Treatment is indicated in patients who beyond liver related morbidity and
are deemed to develop chronic hepatitis impact on the overall quality of life

 Achievement of sustained virologic

response (SVR) is associated with a
reduction in portal hypertension, hepatic
decompression, HCC and liver related
mortality

Reference : Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014;61:S58–S68.

 The Natural History of Chronic
Hepatitis C
Generally a slowly progressive disease. Characterized by persistent hepatic
01 inflammation, leading to cirrhosis in 10–20% patients over 20–30 years of HCV
infection.

Once cirrhosis developed:

02  Annual risk of HCC is 1–5%.
 Annual risk of hepatic decompensation is 3–6%.

03 Following an episode of decompensation the risk of death in the following year is

15%-20%.

Reference : Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014;61:S58–S68.

 FACTORS ASSOCIATED WITH
HEPATITIS C VIRUS
PROGRESSION
Alcohol consumption
>30g/d in men Steatosis
>20g/d in women

Acquisition at age Immunocompromise

≥40 years +40 d state

HIV or HBV
Male gender
coinfection
EPIDEMIOLOGY
 HEPATITIS C VIRUS ~70 million people with
active/viraemic HCV
is the silent global epidemic of the
21st Century
Reference : Blach S, et al. Lancet Gastroenterol Hepatol 2017;2:161–76; The Polaris Observatory HCV Collaborators, Homie Razavi and team, (authours include Rosmawati M, SSTan and Rohani J.
The Polaris Observatory. Hepatitis C. Available at: http://polarisobservatory.org/polaris/hepC.htm (accessed July 2017)
 NATIONAL STRATEGIC PLAN
FOR
VIRAL HEPATITIS
NATIONAL STRATEGIC PLAN FOR
VIRAL HEPATITIS
VISION
Viral hepatitis transmission is halted and
everyone has access to prevention, care
and treatment for viral hepatitis.

GOAL
To eliminate viral hepatitis as a major
health threat by 2030.
NATIONAL STRATEGIC PLAN FOR
VIRAL HEPATITIS

OBJECTIVE
• To achieve 90% population living
with viral hepatitis are diagnosed.
• To achieve 90% reduction of
new cases of viral hepatitis.
• To reduce mortality due to viral
hepatitis by 65% by 2030.
• To ensure 90% of those ‘eligible
population for treatment’ are
treated by 2030.
Notification Rate for Hepatitis C

Compulsory notification of
chronic HCV cases
(in addition to acute cases)
 Large burden of undiagnosed
and untreated individuals with HCV
Majority of individuals living with Hepatitis C are
NOT AWARE that they are infected

Chronic
HCV

<15% of those infected with

Hepatitis C are diagnosed
World population Family Medicine Specialists/Primary Care Clinicians have a
6.7 billion Critical Role in Hepatitis C screening
Reference : Wei L, Lok AS. Impact of new hepatitis C treatments in different regions of the world. Gastroenterology 2014;146:1145–1150.
 Routes of Transmission

*Nosocomial, iatrogenic and perinatal

Reference : Centers for Disease Control and Prevention
 Hepatitis C Transmission Risk by
Exposure Type
EXPOSURE Risk per exposure (unless otherwise stated)

Needlestick Healthcare setting, source patient (serology) 0-10%.20-22 Average 1.8%

injury known Increased risk if - hollow needle21, deep injuries,
co-infection with HIV, high viral load.
Healthcare setting, source patient unknown, or Unknown source – negligible risk.
unable to test source patient (serology unknown) Risk assessment required
Community setting Risk not accurately determined. Risk assessment
required.
If local PWID population has a seroprevalence of 50-90%,
the estimated risk of HCV transmission in a community
needlestick injury is 1.62%
Exposure prone procedure by infected healthcare worker 0-3.7%. Risk may increase to 6% for certain procedures,
e.g. open heart surgery. Risk assessment required.
Non healthcare related occupational sharp injuries Risk not accurately determined, but transmission
possible.
Risk assessment required.
Tattoos Risk not accurately determined. Pooled odds ratio 2.73
(95% CI 2.38-3.15) Risk assessment required. Increased
 Hepatitis C Transmission Risk by
Exposure Type
Mucous membrane exposure to blood
Intact skin exposed to blood
Non-intact skin, body fluid exposure
Human bite injuries
Heterosexual exposures in general
MSM
Very low risk. Case reports only. 34, 35 Risk assessment required
No recognized risk
Very low risk. Case report describes transmission of HIV and HCV from co-infected source.
Risk assessment required
Very low risk. Case reports only. Risk assessment required.
Possible higher risk of transmission of HCV than HIV if the source patient is co-infected
with
HCV and HIV.
Inefficient transmission, but transmission possible as seen in stable heterosexual
relationships, and in those with history of multiple sexual partners. Possible increased risk
of transmission if source co-infected with HIV.
5-8%
 A large number of HCV patients
are UNDIAGNOSED

 Most nations fail to identify a large proportion of

patients with chronic HCV infection[1]
• As few as 15-25% of patients are diagnosed
• ? Asian patients detected
• HCV screening program
http://www.thewellingtonliverunit.com/treatments-hepatitis-c.asp; Schlosser et al. EASL
 Survey of 4000 primary care physicians[2] 2009; Vermehren et al. DGVS 2010;
Gane. New Zealand Doctor. 2007; http://www.hepatitiscmsg.org/hep-c-facts--stats.html.

• Only 59% of 1412 respondents asked patients

about HCV risk factors

Reference : 1. Kim WR. Hepatology. 2002;36:S30-S34.

Reference : 2. Shehab TM, et al. J Viral Hepat. 2001;8:377-383.
Reference : 3. Ghany MG, et al. Hepatology. 2009;49:1335-1374.
 Gaps Along the HCV Care
Continuum
For Malaysia, this is the largest gap i.e. up to 90-95% individuals living with
HCV are UNAWARE that they are infected

Left side of the cascade equally/

more important

DAAs only help

once you get here
9%

Chronic HCV Diagnosed and Access to HCV Liver Disease Prescribed HCV Achieved
Infected Aware Care Confirmation assessment Treatment SVR
 TARGETED PERSON/
POPULATIONS
AT INCREASED RISK OF
HCV INFECTION
 WHO TO SCREEN
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.
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. number of
injections/person/year). A study
reported that 53.9% of patient
on dialysis from 1985 and
September 1991 were positive
for anti-HCV.
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.
HEPATITIS
C
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. In 1992,
Ministry of Health Malaysia has outlined that all
donated blood and blood products are to be screened
for HCV.
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
Persons who were ever incarcerated Persons with HIV infection, in particular MSM, are at
Persons who were incarcerated are at risk for Hepatitis C increased risk of HCV infection through unprotected
because many people in jails or prisons already have sex
Hepatitis C Persons with HIV infection, in particular MSM, are at
increased risk of HCV infection through unprotected sex.

Unexplained chronic liver disease and/or Children born to HCV infected women
chronic hepatitis including elevated ALT levels
HCV transmission risk is estimated as 4–8%
among mothers without HIV infection
Approximately 60% to 70% of chronically Transmission risk is estimated as 17-25%
(HCV) infected person will eventually develop among mothers with HIV infection.
chronic liver disease.

People with sexual partners who are HCV infected Solid organ donors (deceased and living)
There is a risk of HCV infection in unscreened
There is low or no risk of sexual transmission of HCV organ donors.
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.

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).
Self-resolving HCV Infection

Reference : WHO Feb 2017

Natural Course of Chronic HCV

Reference : WHO Feb 2017

 Which Serological Assay to Use?
Screening for HCV infection should be based on the detection of anti-HCV antibodies in serum or plasma by
means of enzyme immunoassay(A1) .

Rapid Diagnostic Tests(RDTs) using serum, plasma, fingerstick whole blood or crevicular fluid (saliva) as
matrices can be used instead of classical enzyme immunoassays at the patient’s care site to facilitate
anti-HCV antibody screening and improve access to care(A2).
EASL Recommendations on Treatment of Hepatitis C 2018, JOURNAL OF HEPATOLOGY

Currently Malaysia uses RDT SD Bioline by fingerprick or

venous whole blood sample.
 Screening Test
 HCV serological testing.

 Marker: anti HCV (HCV Antibody).

 Interpretation: positive HCV antibody indicates evidence of past or present infection.

 Antibody-based assays are unable to detect infection soon after acquisition of HCV
infection, as antibodies may not be detected for 2–3 months in an individual who
has been recently infected.

Hepatitis C, Screening, testing And treatment guidelines, MOH 2017

 Detection of Viraemic Infection

If anti-HCV antibodies are detected, the presence of HCV RNA, or alternatively HCV
core antigen (if HCV RNA assays are not available and/or not affordable) in serum or
plasma should be determined to identify patients with ongoing infection (A1).
EASL Recommendations on Treatment of Hepatitis C 2018, JOURNAL OF HEPATOLOGY
 TESTING ALGORITHM FOR
DETECTION
HCV INFECTION

EASL Recommendations on Treatment of Hepatitis C 2018, JOURNAL OF HEPATOLOGY

Reference : Organization WH. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection 2018.
 EASL 2018 Recommendations on
Treatment of HCV
 HCV RNA detection (qualitative) and quantification should be made by a sensitive assay with a lower limit of
detection of ≤15 IU/ml (A1).
A1 = high level of evidence and strong recommendation

 If HCV RNA testing is not available or not affordable, HCV core antigen detection and quantification by EIA
can be used as a surrogate marker of HCV replication (A1).

**Useful to know what HCV confirmation test is available to you

In general (cost per test in Malaysia) i. HCV RNA qualitative test costs less than some
quantitative HCV RNA test.
ii. Certain HCV RNA quantitative test costs similar to qualitative HCV RNA test.
iii. HCV core Ag is costs less than HCVRNA test.
Guidelines Recommendation
“An assay to detect HCV core (p22) antigen, which has comparable clinical sensitivity to NAT, is an
alternative to NAT to diagnose viraemic infection.”

“HCV core antigen is a surrogate marker of HCV replication. Core antigen detection can be used
instead of HCV RNA detection to diagnose acute or chronic HCV infection (core antigen assays
are slightly less sensitive than HCV RNA assays for detection of viral replication) (A1).”
A1 recommendation = high level of evidence and strong recommendation

“HCV antigen assays, another method of detection of active HCV infection, have been
commercially available for a couple of years and can detect both free antigen and antibody-
combined antigen”
 Reflex Testing

Reflex testing for HCV RNA in patients found to be anti-HCV antibody-positive should
be applied to increase linkage to care (B1).
EASL Recommendations on Treatment of Hepatitis C 2018, JOURNAL OF HEPATOLOGY
 Clinical Value Overview Diagnostic HCV Markers
and Disease Stages
Early stage Early acute Acute Resolved Chronic Occult*
ALT - + + - + (+)
Anti-HCV - - + + + (+)
HCV RNA + + + - + -
Symptoms - (+) + - - -
Contagious + + + - + (+)
*Occult HCV infection is defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum
(+) = potentially present
Reference :
1. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002;36:S21–S29.
2. Carreño V, Bartolomé J, Castillo I, Quiroga JA. New perspectives in occult hepatitis C virus infection. World Journal of Gastroenterology: WJG 2012;18:2887.
 Interpretations of Results and Further
Actions
Results Interpretations Actions
 Counselling; do’s and don’ts.
 Health promotion/modifiable factors:
Anti-HCV + ETOH, obesity, DM, vaccination,
Active infection
NAT+ OST, harm reduction.
 Assess fibrosis.
 Enrollment to care and treatment.
 Repeat HCVRNA in 3 months
 If HCVRNA still negative:
Anti-HCV+ False positive anti-HCV or
 No active infection
NAT- previous HCV infection with spontaneous clearance
 Health education especially risk behavior
 Discharge
Anti-HCV+ False positive anti-HCV or
Nat testing
HCV Core Ag –ve previous HCV infection with spontaneous clearance

Reference : Jülicher P, Galli C. Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting. Journal of Medical Economics 2018;21:1–10.
 CONCLUSION

A combined pattern of HCV Ab screening followed by sequential confirmation with Ag

and RNA on Ag negatives would provide equal or better diagnostic performance at
lower cost over a broad range of scenarios.

Reference : Jülicher P, Galli C. Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting. Journal of Medical Economics 2018;21:1–10.
 NOTIFICATION

All anti-HCV antibody positive

 ASSESMENT
 The contribution of comorbidities to the progression of liver disease must be
evaluated and appropriate corrective measures implemented (A1).

 Liver disease severity must be assessed prior to therapy (A1).

 Patients with cirrhosis must be identified, as their treatment regimen must be

adjusted and post-treatment surveillance for HCC is mandatory (A1).
EASL Recommendations on Treatment of Hepatitis C 2018, JOURNAL OF HEPATOLOGY
 Staging of Hepatic Fibrosis is Essential Prior to
HCV Treatment: Do Not Miss Cirrhosis!
Non-invasive tests can simplify fibrosis assessment
Liver biopsy: Transient Elastography / fibroscan:
Gold standard > 12.5 kPa = cirrhosis
Rarely done
Serum Biomarkers of Fibrosis:
In resource-limited settings, WHO recommends that the assessment of liver fibrosis should be performed using
non-invasive tests (e.g. aspartate/platelet ratio index (APRI) score or FIB-4 test).

Very good negative predictive value. APRI < 0.5, FIB-4 < 1.45 rule out cirrhosis.

Online calculators:
APRI at http://www.hepatitisc.uw.edu/page/clinical-calculators/apr
FIB-4 at http://www.hepatitisc.uw.edu/page/ clinical-calculators/fib-4
 Staging of Hepatic Fibrosis is Essential Prior to
HCV Treatment: Do Not Miss Cirrhosis!

Online calculators:
APRI at http://www.hepatitisc.uw.edu/page/clinical-calculators/apr
FIB-4 at http://www.hepatitisc.uw.edu/page/ clinical-calculators/fib-4
 Staging of Hepatic Fibrosis is Essential Prior to
HCV Treatment: Do Not Miss Cirrhosis!
The presence of thrombocytopenia (platelet count below the lower limit of normal) was the
single most useful laboratory investigation for identifying cirrhosis

Reference : Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, et al. Does this patient with liver disease have cirrhosis? Jama 2012;307:832–842.
 SUMMARY
 Promotion and training
 Screening
 High index of suspicious.
 Strategise eg 100% among MMT clients, RVD, health care staff and STI.
 OPD/MCH with risk factors-IVDU, blood donors prior 1994, NSI, Tatoos, body piercing,
interested public.

 Testing
 RDTs in KK.
 Immunoassay with reflex testing.

 Assesment with serum biomarkers

 Notification
GOALS
OF TREATMENT
 Goals of HCV Treatment

Primary Goal Secondary Goal

Slow disease
Prevent progression
Eradicate HCV Complications
from HCV Improve histology
Infection by
achieving "Virologic Infection
Reduce risk of HCC
Cure" (SVR)
Improve health-
related QOL

The goal of treatment: reduce all-cause mortality and liver-related health

adverse consequences, including end-stage liver disease and hepatocellular
carcinoma, by the achievement of virologic cure as evidenced by an SVR
 Chronic Hepatitis C - the Solution
Antiviral therapy is effective, can achieve permanent eradication of Hepatitis C virus = Cure

Sustained Virological Response (SVR12)

 Undetectable Hepatitis C virus (HCVRNA) 3 months after completion of treatment. This is considered a cure
as the virus remains undetectable in 99% of cases.

More than 99% of patients

achieve a durable response
 WHO TO TREAT AT
PRIMARY CARE ?
 Recommendation for When and
Whom to Treat
 Treatment is recommended for all patients with HCV infection, except for those with a short life expectancy
that cannot be remediated by HCV therapy, liver transplantation or another directed therapy.

 Patients with a short life expectancy owing to liver disease should be managed in consultation with an expert
(Level 1A 2017 AASLD).
 Age of ≥ 18 years old

+1
8WHO TO
TREAT AT
PRIMARY
CARE ? Non cirrhotic
treatment naive HIV/
Non cirrhotic HCV
treatment naive co-infection
 Factors to Be Considered in
Prioritising Treatment
 Patient’s willingness to start and adhere strictly to treatment and follow up.

 Risk of accelerated fibrosis (e.g. HIV or HBV co-infection, metabolic syndrome).

Referral to secondary/tertiary centres:

 Patients with increased risk of death (e.g. advanced fibrosis and cirrhosis, post-liver or other organ
transplantation).

 CHC/CHB co-infection.

 All treatment naïve and treatment experienced patients with compensated or decompensated chronic liver
disease.

 Extrahepatic manifestations and evidence of end-organ damage (e.g. debilitating fatigue, vasculitis and
lymphoproliferative disorders).
 PRE-TREATMENT

SCREENING
and
COUNSELLING
 PRE-TREATMENT SCREENING ASSESSMENT
Role of Physicians/FMS
A. Document patient’s medical history
 Risk Factors for HCV acquisition

 Medical Comorbidies e.g. NAFLD/DM

 Review concomitant medications including over the counter (OTC)/herbal dietary supplements (HDS)/oral
contraceptive pills (OCP)

 Co-infections (CHB/RVD)

 Complication of Liver Disease if cirrhotic

 Prior Treatment for hepatitis C, types of treatment received previously and type of response

 HBV and HAV vaccination should be proposed to patients who are not protected

 Extra-hepatic manifestations of HCV infection should be identified in case of symptoms

 PRE-TREATMENT SCREENING ASSESSMENT
Role of Physicians
B. Perform the baseline investigation
 Confirmatory test --> HCV core antigen

 Full Blood Count/Liver Function Test including Aspartate (AST)/Creatinine

 APRI Score or FIB-4 to determine if there is cirrhosis. If cirrhosis --> to refer to secondary centre

 Hepatitis B Surface Antigen and HIV Antibody

 Ultrasound liver - if available

 Other relevant investigation based on clinician’s discretion

C. Explain on treatment flow and follow-up schedule

 PRE-TREATMENT SCREENING ASSESSMENT
Role of Nurses/Medical Assistance
 Vital signs

 Perform Hepatitis Education

 Pre-pregnancy care for women in reproductive age group, advise on contraception

TREATMENT
OPTIONS
STANDARD OPERATING
PROCEDURE (SOP)
SOFOSBUVIR RIBAVIRIN

DACLATASVIR
 Sofosbuvir
 HCV nucleotide polymerase NS5B inhibitor.

 Approximately 80% of sofosbuvir is renally excreted, whereas 15% is excreted in faces.

 Used in patients with eGFR of > 30ml/min/1.73m2. Latest EASL 2018 states that can be used with cautious
in eGFR of less than 30ml/min/1.73m2 and even haemodialysis patients.

 Not metabolized by cytochrome P450.

 Sofosbuvir should not be administered with known P450 inducers, such as rifampin, carbamazepine,
phenytoin or St. John’s wort. Other potential interactions may occur with rifabutin, rifapentine and modafinil.

 Contraindicated in patients who are being treated with the anti-arrhythmic amiodarone due to the risk of life-
threatening arrhythmias.
 Daclatasvir
 First-ever approved HCV NS5A replication complex inhibitor with pangenotypic activity.

 The dose of 60 mg (one tablet) or 30 mg (one tablet) when a reduced dose is needed, once daily dose.

 May interact with other drugs e.g. Anti TB, antibiotics, herbals containing St John Worts.

 Generally well tolerated, not known side effects (SE) of its own.

 The most common SEs combination Sofosbuvir and Daclatasvir are fatigue, nausea and headache (10%).
Genotype Treatment naive/experience Non cirrhosis Compensated cirrhosis Decompensated cirrhosis
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 1a 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RBV
Genotype Treatment naive 12 weeks 12 weeks 12 weeks with RBV
1b Treatment experience 12 weeks 12 weeks 12 weeks with RBV
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 2
Treatment experience 12 weeks 12 weeks 12 weeks with RBV
Treatment naive 12 weeks 24 weeks with RBV 24 weeks with RBV
Genotype 3 12 weeks with RBV or
Treatment experience 24 weeks with RBV 24 weeks with RBV
24 weeks without RBV
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 4 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RB
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 5 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RB
Treatment naive 12 weeks 12 weeks 12 weeks with RBV
Genotype 6 12 weeks with RBV or 12 weeks with RBV or
Treatment experience 12 weeks with RBV
24 weeks without RBV 24 weeks without RB

Hepatitis C : Screening, testing & treatment guidelines; MOH October 2017

EASL Recommendations on Hepatitis C Treatment 2016
 Management of Drugs with Potential Interaction

 Stop the particular related drug for the period of treatment (2 weeks prior to treatment/half life drug should
be considered for longer withhold) e.g.: statin.

 Replace the drug with an alternative product without a drug interaction in the same therapeutic class.

 Adapt the dose with a clear monitoring plan.

 Dosage adjustment.

Example: Daclatasvir-Decrease dose to 30mg: Coadministration with strong CYP3A

inhibitors, Increase dose to 90mg: Coadministration with strong CYP3A inducers.
 APPS TO CHECK DRUG
drug interaction
 TREATMENT INITIATION
Role of Pharmacist
 Drug Dispensing for 8-4 weeks supply

 Counsel on:
 Adherence.
 Missed dose management.
 Administration time.
 Drug Storage: room temperature (Below 30°C).
 Suggest patient diary card to record each drug intake.
 Bring back all balance medications and empty bottle for each visit.
 Use of any medication or herbal/supplement product not prescribed by a licensed physician is
prohibited.
 FOLLOW UP VISIT

WEEK 4 WEEK 12 WEEK 24

Assessment on Assessment on HCV RNA for

side effects/ side effects. SVR12.
concurrent Blood
medication. investigations (FBC,
Blood creat, ALT, AST)
investigations
(FBC, creat, ALT,
AST)

HCV RNA at 12 weeks post treatment

If HCV RNA not detected--> achieve SVR--> no other liver comorbidities-->
discharge
 POST
TREATMENT
FOLLOW UP
 Post Treatment Follow Up
NOT CIRRHOTIC CIRRHOTIC NO SVR12
ACHIEVE SVR12 ACHIEVE SVR12
Patients who achieve SVR12 can Continue follow up for HCC Should monitor for progression
be discharged but patients with surveillance: 6 monthly US liver of liver disease and considered
remains abnormal liver function and blood for AFP. Endoscopy for retreatment once alternative
test should be evaluated for for OV surveillance. treatment is available.
other causes of transaminitis.
 HOW TO TREAT
NON
CIRRHOTIC
TREATMENT
NAIVE
HCV/HIV CO-INFECTION
 HCV/HIV CO-INFECTION (WHO 2018)
 Generally have more rapid disease progression and hepatic decompensation than monoinfected persons,
even among persons in whom ART leads to successful control of HIV infection (i.e. undetectable HIV viral load)
.

 Priority for HCV treatment.

 Treatment outcomes with DAAs are comparable.

 DAAs are safe and effective for people with HIV/HCV, there is no longer any need to consider them as a
special or difficult-to-treat population.

 However, there are important DDIs with pangenotypic HCV regimens and ART. Therefore, checking for DDIs
between HIV and HCV medications needs to be emphasized.
Sofosbuvir needs NO dose adjustment
Daclatasvir:
Decrease dose to 30mg: Coadministration with strong CYP3A
inhibitors (Indinavir, Azatanavir/ Ritonavir)
Increase dose to 90mg: Coadministration with strong CYP3A inducers
(e.g. Efavirenz, Nevirapine)
WHO on HCV July 2018
THANK YOU