Hepatitis C management
Hepatitis C virus (HCV)
infection
4.1 Aetiology
Hepatitis C is a RNA virus in the flaviviridae family. It
is endemic worldwide
an estimated 185 million individuals infected and with
prevalence rates varying from 1% in Europe to as high as 4% in North
Africa/Middle East[125]. Recent national estimates suggest approximately 215000
individuals are chronically infected with HCV in the UK, but most are unaware of their infection. Most (90%) is due to infection with genotypes
1 and 3 [126].
4.2 Transmission in the UK
•
Parenteral spread accounts for the majority of
cases through shared needles/syringes in PWID (including the practice of
‘slamming’ recreational drugs – see 4.9 below), transfusion of blood or blood
products (pre1990s), re-use of needles in healthcare, renal dialysis,
needlestick injury, sharing a razor with an infected individual and sharing of
straws and notes for snorting recreational drugs. [125-135].
•
off of rates of sexual transmission of HCV among
HIV-positive MSM. [140] • There is also evidence of increased rates of
infection in sex workers [143]. • Other risk groups include former prisoners,
people from highly endemic countries, tattoo recipients, people who inject
steroids and recreational drugs, people who snort cocaine and alcoholics
[144-147].
•
Vertical (mother to infant) spread also occurs
at a low rate (about 5%), but higher rates (7% or more) are seen if the woman
is co-infected with HIV [148152]. In all
groups transmission risk correlates with the quantity of detectable HCV RNA in
the mother’s blood [148- 152].
•
Amongst blood donors, 25% of those with HCV
infection do not admit to having risk factors [153].
4.3 Incubation period
•
The incubation period is 4 to 20 weeks. HCV
serology is positive three months after exposure in 90%, but can take as long
as nine months. Occasional cases of infection proven by HCV RNA detection (see
“diagnosis”) do not result in positive antibody tests [154].
•
In the context of HIV-infection, the appearance
of HCV antibodies may be significantly delayed [155,156]
4.4 Symptoms [131, 132]
• The
majority of patients (>60%) have asymptomatic infection.
• The
uncommon cases of acute icteric hepatitis are similar to hepatitis A.
4.5 Signs
• Acute
icteric hepatitis see hepatitis A (Section 2.4).
• Chronic
hepatitis see hepatitis B (Section 3.4)
4.6 Complications
Acute hepatitis C
• Acute
fulminant hepatitis is rare (<1% of all
hepatitis C infections). Hepatitis A super-infection of chronic hepatitis C
carriers [28, 131, 132, 157] may cause a very severe hepatitis. However, acute
hepatitis A can reduce HCV replication [158].
• Approximately
50-85% of infected patients become chronic carriers; a state which is usually
asymptomatic but may cause nonspecific ill health
[153,159,160].
Patients with favourable polymorphisms around the IL28B gene are more
likely to clear virus spontaneously [161]
• Pregnancy:
complications of acute icteric hepatitis: as for hepatitis A [21].
Chronic hepatitis C
Once established (infected > 6 months), the chronic carrier
state rarely resolves spontaneously (0.02%/year)[131-2]. Symptoms/signs are worse if there is a high
alcohol intake or other liver disease [162,163]. Significant liver disease can be present in
the 35% of carriers who have normal serum aminotransferase levels, [131, 132,
164,165].
• Up
to 30% of chronic carriers will progress to severe liver disease after 14-30
years infection, with an increased risk of liver cancer (approximately 14% of
all patients and up to 33% of those with cirrhosis) [68, 69, 81, 131, 132, 164,
165, 166-168].
•HIV co-infection worsens the prognosis although this may
be ameliorated to some degree by ART [169-171].
Recent data suggests a deleterious effect of HCV on both overall and
HIV/AIDS related-morbidity/mortality [172]
4.7 Diagnosis (see also
Sexually Transmitted Infection Screening and Testing Guidelines Hepatitis A, B
and C)
4.7.1 Serology
Acute infection
•
This is defined as recent exposure to HCV
following which the patient is HCVRNA positive but anti-HCV negative or
seroconverts from anti-HCV negative to positive. An antibody test may not
become positive for several months after acute infection but a test for HCV-RNA
will usually be positive after two weeks [154-156, 173].
HCV core antigen is a surrogate marker of HCV replication.
HCV
core antigen detection can be used instead of HCV RNA detection to diagnose
acute or chronic HCV infection. HCV core antigen assays are less sensitive than
HCV RNA assays (lower limit of detection equivalent to approximately 500 to
3000 HCV RNA IU/ml, depending on the HCV genotype [154 a, 154 b])
Chronic Infection
•
A screening antibody or antibody/antigen test
such as an Enzyme immunoassay (EIA) or other immunoassay is initially performed
and RNA
detection confirms active infection [154-156,173,174]. (1A)
•
In HIV+ patients with a low CD4 count (<200
cells/mm3) the EIA may be negative and HCV RNA detection may be
needed for diagnosis (175).
•
Chronic infection is confirmed if an HCV RNA assay
is positive six months after the first positive test[154-156,173,174]. .
•
All patients should have a viral RNA test to
confirm viraemia and the HCV genotype should also be identified [129, 163,176].
(1A)
4.7.2
Other tests
•
Acute infection - as for hepatitis A (2.7.2).
•
Chronic infection - as for hepatitis B (3.7.2).
4.8 Management
4.8.1 General Advice
• Patients
should be reassured that hepatitis C is curable (1A) [127].
• Patients
should be told not to donate blood, semen or organs and given advice on other
routes of transmission (see below) (1D) [126,153].
• Patients
should be given a detailed explanation of their condition with particular
emphasis on the longterm implications for the health of themselves and their
partner(s). This should be reinforced by giving them clear and accurate written
information. (1D)
• Acute
hepatitis is a notifiable infection in England, Wales and Northern Ireland
[59,126].
• Refer
all HCV RNA+ve patients to a specialist for further management (1A)[127].
4.8.2 Further Investigations
• Screen
for other STIs in cases thought to have been sexually acquired
(1C)[136,137]
• Non-invasive
methods of assessing liver fibrosis such as
Hepatic elastography (e.g. fibroScan) and/or serum markers
(e.g. FibroTest, APRI, FIB-4, ELF) are the investigation of choice for disease
staging [177] although the liver biopsy remains the investigation of choice for
selected patients [178,179].
• A
liver imaging ultrasound should also be performed (1B)[180].
4.8.3 Treatment
The goal of treatment is to cure HCV infection and
to reduce the progression of liver
fibrosis, decompensation of cirrhosis, hepatocellular carcinoma and extrahepatic manifestations.
HCV cure
is defined by negative HCV RNA in blood 12 weeks after completion of HCV treatment.
Acute infection:
Most patients with
acute hepatitis C are asymptomatic
•
There is clear evidence that treatment given
during the acute phase reduces progression and will reduce the rate of
chronicity (1A) [181,182].
Spontaneous resolution of acute hepatitis C is defined as
loss of HCV RNA within the first six months.
Patients with acute HCV should be followed with fourweekly HCV RNA
quantitation; if there is less than a 2 log10 decline in HCV RNA at week 4 or the HCV RNA remains positive
at week 12, they should be considered for treatment in the acute phase.
Treatment in the acute phase generally has significantly higher success rates
than treatment in the chronic phase. (1A) [183,184]
•
Patients should be referred to a specialist
centre for monitoring and treatment and access to clinical trials (1A) [183,
184]. See algorithm below for the
management of Acute HCV (NEAT algorithm) (1A) [184].
4.8.4 Figure: Summary of NEAT Algorithm for the management
of Acute
HCV[183]
Chronic infection
We
recommend all patients with HCV should be assessed for treatment with
direct-acting antiviral agents (DAAs).
The DAAs target HCV non-structural proteins to prevent viral
replication.
•
Currently used DAAs target NS3/4A protease
inhibitors (simiprevir, ritonavir boosted ombitasvir, grazoprevir,
glecaprevir),
•
NS5A (ledipasvir, daclatasvir, ombitasvir,
velpatasvir, elbasvir, pibrentasvir)
•
NS5B inhibitors (sofosbuvir,dasabuvir).
With the advent of Directly Acting Antivirals (DAAs) the
treatment paradigm for chronic HCV is rapidly evolving ([185]. The need for
treatment should be managed in a specialist clinic with access to DAA-based
therapy and clinical trials (1A).
•
In the era of DAAs, HIV positive patients
respond to treatment as well as HIVnegative patients, and should be considered
for therapy, bearing in mind important drug-drug interactions between the DAAs
and antiretroviral therapy regimens (1A) [47,186].
•
Patient selection for therapy and
specific-therapy will depend on HCV genotype and viral load, liver disease
stage, prior HCV treatment history and
comorbidities [177,186].
· HCV resistance to NS5A inhibitors can be used to
guide certain treatment options. Duration of treatment and addition of
ribavirin can be considered based on the presence of resistance- associated
substitutions (RASs) (79b)
•
Given the potential for fulminant hepatitis in
co-infection with hepatitis A and C and the worse prognosis of hepatitis B and C co-infection, patients with hepatitis C
should be vaccinated against both hepatitis A and B (1A) [28, 131, 132, 157,187].
4.8.5 Pregnancy and Breast feeding
• At
present there is no clearly demonstrated intervention to reduce HCV
transmission from mother-to-child [149)
• Ribavirin
is teratogenic. Treatment of HCV in
pregnancy is not recommended
(1D)
• Women
should be informed of the small potential risk of transmission in pregnancy
(see transmission) (1D) [148-152].
• Breast
feeding: there is no firm evidence of additional risk of
transmission(1B)[148-152].
4.8.6 Sexual and Other Contacts
•Partner notification should be performed and
documented and the outcome documented at subsequent follow-up. Contract tracing
to include any sexual contact if the index patient or partner are HIV+
(penetrative vaginal or anal sex) or needle sharing partners during the period
in which the index case is thought to have been infectious (1D) [37]. If there
is no acute infection trace back to the likely time of infection (e.g. blood
transfusion, first needle sharing) although this may be impractical for periods
longer than two or three years. (1D) • Screen contacts for evidence of past or
current HCV infection (1D).
• Test
children born to viraemic women (1A) [148-152].
• For
other non-sexual contacts thought to be at risk, consider on a case-by-case
basis. (1D)
•There is currently no available vaccine or immunoglobulin
preparation that will prevent transmission. Spontaneous resolution of infection
and previous successful treatment do not provide protection if further HCV
exposure occurs. • In acute infection, patients should be advised to avoid
unprotected sexual intercourse (1D)
•In patients with chronic infection, sexual transmission should be discussed. It seems likely that if condoms are used consistently then sexual transmission will be avoided, but given the very low rates of transmission outside of HIV coinfection [136-142] (see above), monogamous partners may choose not to use them. Sexual contacts with HIV should be advised of the risk of sexual transmission, with regular testing and condom use encouraged (1D)[136-142].
•Advice for MSM and HIV+ MSM should include use of condoms,
gloves for fisting, single person only sex toys/condoms on sex toys and changed
between partners. Also not to share lube and avoid group sex situations (1D).
4.8.7 Follow-up
•
Patients with chronic untreated HCV should have
liver fibrosis assessments 612 monthly (1A)[177,178].
Patients
with advanced fibrosis/cirrhotic should have 6 monthly HCC screening with
ultrasound and alpha-feto protein (1A) [179].
•
Previous exposure to HCV does not confer
immunity and risk of re-infection and dual/super infection is well documented
[188,189].
4.9
Screening and Primary Prevention.
•
It may take three months or more for the
anti-HCV test to become positive after exposure (see “incubation period”). (1A)
•
Offer testing for hepatitis C in all PWID,
including people who inject steroids and ‘recreational’ drugs, all HIV-positive
patients, people with haemophilia or other patients who received blood or blood
products pre1990 and remain untested, (1A) [124-130, 138-140,188,189]. For
needlestick injury follow PHE guidelines.
|
• Offer the
test at least annually to MSM eligible for three monthly HIV testing |
|
|
and those taking or
eligible for PrEP (see BASHH MSM guidelines 2017) |
|
•
In the last few years, ‘chem-sex parties’,
largely attended by MSM and involving
multiple sexual partners and the use of ‘recreational drugs’ such as
gammahydroxybutyric acid/gamma-butyrolactone (GHB/GBL), mephedrone and crystal
methamphetamine have been described [190]. The drugs are frequently injected
(‘slamming’), leading to high risk of BBVs including HCV and HIV. They also
lead to a loss of attention to safer sex.
MSM with such risks should be screened for HCV and other BBVs and the
risks/prevention discussed (2D).
•
Other groups to be tested include: the sexual
partners of HCV positive individuals, sex workers, tattoo recipients, migrants
from highly endemic countries, alcoholics, people who snort cocaine and
ex-prisoners (1B)
[136,137,141-143,145,146]
•
Currently there is no evidence that HIV-negative
MSM without other risk factors should be routinely screened (1B) [191].
•
All HIV+ patients should be screened for HCV at
HIV diagnosis and every year thereafter. Patients with previous infection who
have cleared the infection (either spontaneously or through treatment) should
have annual HCV PCR (1D).
[192]
•
Offer additional HCV testing in HIV+ MSM if
other STIs have been diagnosed including syphilis and LGV or in situations of
traumatic anal sex, fisting and sharing of sex toys [138-140].
•
Since September 1991 all donated blood in the UK
has been screened for HCV [193].
•
Needle and syringe exchange schemes have led to
a fall in parenterally transmitted infections including HCV, HBV and HIV,
although not consistently, as this infection can be transmitted through sharing
other drug paraphernalia such as shared spoons, filters and
water.[127,194-196].
•
Non-sterile needle use in the healthcare setting
remains an important cause of HCV transmission in developing
countries[128].
•
Discuss how to reduce any risk of catching this
infection where appropriate (1D)
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