Hepatitis C

Organism

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver.

Clinical presentation

During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain and jaundice occur.

Acute infection progresses to chronic disease in up to 75% of cases.

Chronic infection is usually asymptomatic. However, without treatment, around 20–30% of people with chronic HCV infection will develop cirrhosis, generally after 20–30 years of infection. In some cases, those with cirrhosis will develop complications such as portal hypertension, liver failure and liver cancer.

Investigations

Laboratory investigations of HCV infection include:

  • tests to diagnose HCV infection
  • tests for pre-treatment assessment of people with chronic hepatitis C infection
  • follow up tests to monitor liver function +/- response to treatment (see ‘Follow up’)

Tests for diagnosing HCV infection

HCV diagnosis in Australia is based on detecting antibodies to HCV in a blood sample. A positive antibody test indicates past or current infection; these patients should have HCV RNA (NAAT)/HCV PCR testing to distinguish current/active infection (positive HCV RNA (NAAT)/HCV PCR) from past infection (negative HCV RNA (NAAT)/HCV PCR).

Window period

The screening test detects antibody to HCV. There is a period after infection, when the screening test will not detect antibody they are yet to be produced or are present at a level that cannot be detected. This is called the window period. The time after infection at which antibody is identified can be up to three months, although it is usually six weeks.

A negative screening test for HCV excludes HCV infection provided that the last potential exposure was at least 12 weeks before the test. If not, the test must be repeated at an appropriate time.

Pre-treatment assessment of people with chronic hepatitis C virus (HCV) infection

History
  • Estimated duration of HCV infection
  • Previous HCV treatment experience – date, regimen and response
  • Cofactors for liver disease progression: alcohol intake, marijuana use, virological confactors (HIV, HBV), diabetes, obesity
  • For those planned to receive ribavirin, note history of ischaemic heart disease or cardiovascular risk factors
  • Vaccinations against HBV and HAV
  • Physical and psychiatric comorbidities
  • Ongoing risk factors for viral transmission and reinfection
  • Social issues – potential barries to medication adherence
Medication
  •  Concomitant medications (prescription, over-the-counter, illicit)
Physical examination
  •  Features of cirrhosis: hard liver edge, spider naevi, leukonychia
  • Features of decompensation or portal hypertension: jaundice, ascites, oedema, bruising, muscle wasting, encephalopathy
  • Body weight and body mass index
Virology
  • HCV genotype and subtype
  • HCV RNA level (quantitative)
  • HBV (HBsAg, anti-HBc, anti-HBs), HIV, HAV serology
Investigations
  • Full blood examination, liver function tests, urea and electrolytes, eGFR, INR
  • Pregnancy test for women of childbearing potential
  • Liver fibrosis assessment, eg:
    • Elastography (FibroScan, ARFI, SWE)
      OR
    • Serum biomarker (APRI*, Hepascore, ELF test, FibroGENE**)
  • Liver ultrasound should be performed in people with cirrhosis to exclude hepatocellular carcinoma
  • Electrocardiogram should be performed if ribavirin therapy is planned and patient is
    > 50 years of age or has cardiac risk factors

HIV = human immunodeficiency virus. HBV = hepatitis B virus. HAV = hepatitis A virus. HBsAg = hepatitis B surface antigen. anti-
HBc = hepatitis B core antibody. anti-HBs = hepatitis B surface antibody. eGFR = estimated glomerular filtration rate. INR = international normalised ratio. ARFI = acoustic radiation force impulse. SWE = shear wave elastography. *APRI = aspartate aminotransferase to platelet ratio index = (AST [IU/L] x 100) ÷ platelet count (x109/L) Online calculator available at Hepatitis C Online (external site). ELF = Enhanced Liver Fibrosis. ** Online calculator available at Fibro Gene (external site).

See: Australian recommendations for the management of hepatitis C virus infection: a consensus statement (January 2017) (external site)

Gastroenterological Society of Australia (GESA) (external site)

Treatment

GPs and other medical practitioners experienced in the treatment of chronic hepatitis C infection are eligible to independently prescribe hepatitis C treatment under the PBS without consulting an infectious diseases physician, hepatologist or gastroenterologist.

Medical practitioners NOT experienced in the treatment of chronic hepatitis C infection may initiate hepatitis C treatment in consultation with an infectious diseases physician, hepatologist or gastroenterologist by submitting, the remote consultation request for initiation of Hepatitis C treatment form (Word 46KB) or (PDF 451KB).

Please forward the Remote Consultation Request form to the Central Referral Service by:
Secure Messaging: HealthLink secure messaging – crefserv (email)
Fax: 1300 365 056
Post: Central Referral Service
PO Box 3462
Midland WA 6056

All patients with evidence of cirrhosis should be referred via the Central Referral Service to an infectious diseases physician, hepatologist or gastroenterologist for hepatitis C treatment

Treatment protocols for people with hepatitis C virus (HCV) infection and compensated liver disease

As it is likely that new hepatitis C treatments will continue to be made available through the PBS, please check the following sources to determine the most appropriate treatment regimen for your patient:

Education, counselling and prevention

Alcohol and other drugs

Abstinence from alcohol and other drugs is best, tailor according to previous intake and stage of disease.

Early disease with no risk factors for progression, consistently normal ALT and normal clinical examination - alcohol advice as per general population, NHMRC Australian guidelines (external site) to reduce health risks from drinking alcohol.

Significant fibrosis - one standard drink/day and no bingeing.

Cirrhosis - aim for total abstinence.

Refer to alcohol and drug services (external site) as necessary for alcohol withdrawal, opiate substitution treatment, etc.

If your patient is continuing to engage in injecting drug use refer to the WA Substance Users' Association (external site).

Note that patients who are using alcohol and other drugs can be treated successfully. The best way of predicting adherence with treatment is to discuss treatment options with the patient over two consultations and if they attend both appointments conduct a pre-treatment work-up at the third consultation. Patients who attend all three appointments as scheduled are likely to complete treatment successfully even if they are not totally abstinent from alcohol and/or other drugs.

Dental care

Optimise oral health. Visit Dental Health Services (external site) for more information.

Immunisation

People with hepatitis C should be offered HAV and HBV vaccination, if not immune. See Operational Directive OD 0392/12 (external site).

Nutrition

General recommendations for a healthy diet see Australian Dietary Guidelines (external site) refer to a dietician as necessary.

Psychological support

For patient and their family/partners, telephone support, education and support groups are available through Hepatitis WA (external site).

Smoking

Quitting will lead to improved general health. Visit Quit Now (external site) for more information.

Weight management

Aim for an ideal body weight (BMI 18.5-25kg/m2) or in overweight patients a gradual but sustained loss of at least 5-10% body weight. For more information visit Live Lighter (external site).

Work

Patients with chronic HCV who are health care workers must not perform exposure prone procedures (EPPs) while they are HCV RNA or HBV DNA positive, but they may be permitted to return to EPPs after successful treatment or following spontaneous clearing of HCV RNA. For further information see the CDNA guideline (external site).

Management of partners

Avoid behaviours that risk re-infection/super-infection and transmission to others, such as sharing injecting equipment. A superinfection is generally defined as a second infection superimposed on an earlier one, especially by a different microbial agent of exogenous or endogenous origin that is resistant to the treatment being used against the first infection.

Avoid sharing equipment that could be contaminated with visible or microscopic amounts of blood, e.g. injecting equipment, razor, toothbrush, dental floss, nail clippers, tweezers.

Counsel patients with chronic HIV or HBV co-infection about safe sex practices.

Follow up

Recommended follow-up for people not on treatment.

Ongoing

Review every 6 to 12 months and monitor for signs and symptoms of liver disease e.g. palmar erythema, spider naevi, jaundice, ascites, encephalopathy, hepato-splenomegaly, pruritis, weight loss and/or lethargy.

Monitor FBC, ALT, INR, albumin and bilirubin every 6 to 12 months.

Screening for hepatocellular carcinoma: Ultrasound and AFP every 6 months for those with cirrhosis.

Symptom management

Fatigue: advise planning rest periods during the day and the addition of light to moderate exercise into their routine to reduce fatigue.

Important: Provide immunisation and advice on how to reduce transmission.

Recommended follow-up for people on treatment or post-treatment

Monitoring of patients receiving antiviral therapy for hepatitis C virus (HCV) infection: (A) on-treatment and post-treatment monitoring for virological response; and (B) monitoring after SVR.

A. On-treatment and post-treatment monitoring for virological response 
Routine monitoring for a 12 week treatment regimen:
Week 0
  •  FBE, urea and electrolytes, LFTs, INR, HCV RNA level (quantitative)
Week 4
  • FBE, LFTs
Week 12
  • FBE, LFTs, HCV PCR (qualitative)
 

At each treatment visit, assess for:

  • medications adherence
  • treatment adverse effects
  • drug-drug interactions.
Week 12 after EOT (SVR)
  • FBE, LFTs, HCV PRC (qualitative)
  • Routine on-treatment HCV RNA testing is not mandated but may be considered where there is a clinical concern about non-adherence to treatment, especially in people with cirrhosis.
  • The need for increased frequency of review should be individualised.
  • Patients taking ribavirin may require FBE at Week 2 and Week 4 and then every 4 weeks.
  • Patients with cirrhosis require monitoring every 4 weeks, including FBE, LFTs and assessment for hepatic decompensation. Measurement of quantitative HCV RNA level is recommended at Weeks 4, 12 ± 24 on-treatment in patients with cirrhosis.
  • Patients with decompensated liver disease require close monitoring, with review every 2–4 weeks.
  • Patients taking hepatitis C treatment need monitoring for drug-drug interations (external site).
B. Monitoring after SVR

SVR, no cirrhosis and normal LFT results (males, ALT < 30 U/L; females, ALT < 19 U/L):

  • Patients who are cured do not require clinical follow-up for HCV

SVR and abnormal LFT results (males, ALT ≥ 30 U/L; females, ALT ≥ 19 U/L):

  • Patients with persistently abnormal LFT results require evaluation for other liver diseases and should be referred for gastroenterology review. Investigations to consider include: fasting glucose level, fasting lipid levels, iron studies, ANA, ASMA, anti-LKM antibodies, total IgG and IgM, AMA, coeliac serology, copper level, caeruloplasmin level and α-1-antitrypsin level

SVR, cirrhosis:

  • Patients with cirrhosis require long-term monitoring and should be enrolled in screening programs for:
    • hepatocellular carcinoma — liver ultrasound ± serum α-fetoprotein level
    • oesophageal varices — gastroscopy

EOT = end of treatment. SVR = sustained virological response at least 12 weeks after treatment (cure). FBE = full blood examination. LFT = liver function test. INR = international normalised ratio. PCR = polymerase chain reaction. ALT = alanine aminotransferase. ANA = anti- nuclear antibodies. ASMA = anti-smooth muscle antibodies. LKM = liver–kidney microsome. AMA = anti-mitochondrial antibody.

See: Australian recommendations for the management of hepatitis C virus infection: a consensus statement (January 2017) (external site) 
Gastroenterological Society of Australia (GESA) (external site) 


Referral

Refer to a PBS approved specialist for the following (see metro and regional list of approved specialists):

1. If the patient is suspected of having cirrhosis or the hepascore is >0.8;
2. If the ALT following treatment remains elevated;
3. All people with decompensated cirrhosis should urgently be referred.

Hepatitis C and HIV infection

Refer to specialist for treatment.

Hepatitis C in pregnancy and breastfeeding

There are no safety data for the use of any DAA regimen during pregnancy, with all PBS-listed DAA regimens classed as Category B. Treatment of pregnant women with DAA therapy is therefore not recommended.

Hepatitis C in children

Children under the age of 18 years are not currently eligible for treatment with the new HCV medications under the PBS.

People under the age of 18 years should be referred to a paediatrician who is experienced in the treatment of HCV for discussion about therapy.

Public health issues
  • No specific prophylaxis or vaccine is available for HCV.
  • Notify WA Health of any cases.
  • Contact tracing is generally not carried out for all HCV cases.
  • Consider testing for other STIs and blood-borne viruses (HIV and HBV).
  • Provide information about other sources of information and support, such as HepatitisWA (see contacts for specialist advice on STIs and HIV for contact details).
  • Hepatitis A and B vaccination is recommended.
Notification

This is a notifiable infection. Medical practitioners must complete the appropriate notification forms for all patients diagnosed with a notifiable STI/HIV, as soon as possible after confirmed diagnosis.