Tables

 

Table 1. Populations to consider for a hepatitis C virus (HCV) screening test
• People who inject drugs or who have ever injected drugs
• People in custodial settings
• People with tattoos or body piercing
• People who received a blood transfusion or organ transplant before 1990
• People with coagulation disorders who received blood products or plasma-derived clotting factor treatment products before 1993
• Children born to HCV-infected mothers
• Sexual partners of an HCV-infected person (individuals at higher risk of sexual transmission include men who have sex with men and people with HCV–HIV coinfection)
• People infected with human immunodeficiency virus or hepatitis B virus
• People with evidence of liver disease (persistently elevated alanine aminotransferase level)
• People who have had a needlestick injury
• Migrants from high-prevalence regions (Egypt, Pakistan, Mediterranean and Eastern Europe, Africa and Asia)

Table 2. 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 cofactors (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 barriers 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)
    • 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. antiHBc = 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. ELF = Enhanced Liver Fibrosis. * Online calculator available at: http://www.fibrogene.com/viral_hepatitis.html.
†  All three tests for HBV may be requested if the clinical notes indicate acute or chronic hepatitis.  
† Online calculator available at : http://www.fibrogene.com/viral_hepatitis.html.

Table 3. Treatment protocols for people with compensated liver disease and hepatitis C virus (HCV) genotype (Gt) 1 infection, including people with HCV–HIV coinfection
Treatment duration
No cirrhosisCirrhosis
RegimenHCV GtTreatment-
naive
Interferon-experiencedTreatment-
naive
Interferon-experiencedEfficacy (SVR)
Sofosbuvir 400 mg, orally, daily + Velpatasvir 100 mg, orally, daily1a/b12 weeks12 weeks12 weeks*12 weeks*≥ 95%
Sofosbuvir 400 mg, orally, daily + Ledipasvir 90 mg, orally, daily1a/b8 weeks OR 12 weeks12 weeks12 weeks24 weeks≥ 95%
Elbasvir, 50 mg, orally, daily + Grazoprevir, 100 mg, orally, daily ± Ribavirin 1000/1200 mg, orally, daily (weight-based)§1a12 weeks12 weeks (relapser)
OR
16 weeks + ribavirin (OTVF)
12 weeks12 weeks (relapser)
OR
16 weeks + ribavirin (OTVF)
> 95%
1b12 weeks12 weeks12 weeks12 weeks
Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
±
Ribavirin 1000/1200 mg, orally, daily (weight-based)§
1a/b12 weeks12 weeks
OR
24 weeks**
12 weeks + ribavirin OR 24 weeks (no ribavirin)12 weeks + ribavirin
OR
24 weeks
(no ribavirin)**
≥ 95 %
Paritaprevir–ritonavir (150 mg/100 mg), orally, daily
+
Ombitasvir 25 mg, orally, daily
+
Dasabuvir 250 mg, orally, twice daily
±
Ribavirin 1000/1200 mg, orally, daily (weight-based)§
1a12 weeks + ribavirin12 weeks + ribavirin12 weeks + ribavirin12 weeks + ribavirin††≥ 95 %
1b12 weeks12 weeks12 weeks12 weeks
HIV = human immunodeficiency virus. SVR = sustained virological response at least 12 weeks after treatment. Relapser = patient who failed to achieve SVR despite achieving an end-of-treatment response. OTVF = on-treatment virological failure (patient who has had a null response, partial response, virological breakthrough or rebound, or intolerance to prior treatment). pegIFN = peginterferon-alfa. PrOD = paritaprevir (ritonavir-boosted) + ombitasvir + dasabuvir.

* Addition of ribavirin may be considered for patients with Gt 3 HCV and compensated cirrhosis.

† 8 weeks may be considered if HCV RNA level is < 6 × 106 IU/mL in people with no cirrhosis who are treatment-naive; 8-week treatment duration is not recommended for people with HCV–HIV coinfection.

‡ Sofosbuvir + ledipasvir can be used to treat people in whom either pegIFN + ribavirin dual therapy or protease inhibitor + pegIFN + ribavirin triple therapy has failed.

§ Ribavirin dosing is weight-based; recommended dose is 1000 mg for people weighing < 75 kg and 1200 mg for people weighing ≥ 75 kg.

¶ Daclatasvir dose modification is required when used in combination with specific antiretroviral therapies for HIV (see Section 10.3.4). ** In people with cirrhosis, the recommended regimen is sofosbuvir + daclatasvir + ribavirin for 12 weeks or sofosbuvir + daclatasvir (no ribavirin) for 24 weeks; for people in whom a protease inhibitor + pegIFN + ribavirin has failed, sofosbuvir + daclatasvir (no ribavirin) for 24 weeks is recommended for all (with or without cirrhosis).

†† The recommended treatment duration for PrOD plus ribavirin in people with Gt 1a HCV and cirrhosis who have had a previous null response to pegIFN and ribavirin therapy is 24 weeks. PrOD therapy is not recommended for people who did not respond to previous therapy that included an HCV protease inhibitor or an NS5A inhibitor.

Notes: For Gt 1 HCV patients in whom treatment with a protease inhibitor + pegIFN + ribavirin has failed, the preferred treatment is sofosbuvir + ledipasvir or sofosbuvir + daclatasvir. Sofosbuvir is not recommended for patients with an estimated glomerular filtration rate < 30 mL/min/1.73m2. Dose reduction or dose interruption of direct-acting antiviral therapy is not recommended. Dose reduction of ribavirin for the management of symptomatic anaemia according to the product information is appropriate and will not reduce the likelihood of SVR.

Table 4. Treatment protocols for people with compensated liver disease and hepatitis C virus (HCV) genotype (Gt) 2 or 3 infection, including people with HCV–HIV coinfection
Treatment duration
No cirrhosisCirrhosis
RegimenHCV GtTreatment-
naive
Interferon-experiencedTreatment-
naive
Interferon-experiencedEfficacy (SVR)
Sofosbuvir 400 mg, orally, daily
+
Velpatasvir 100 mg, orally, daily
2/312 weeks12 weeks12 weeks*12 weeks*≥ 95%
Sofosbuvir 400 mg, orally, daily + Ribavirin 1000/1200 mg, orally, daily (weight-based)212 weeks12 weeks12 weeks24 weeks> 90%
Sofosbuvir 400 mg, orally, daily
+
Daclatasvir, 60 mg, orally, daily
±
Ribavirin 1000/1200 mg, orally, daily (weight-based)
312 weeks12 weeks12 weeks + ribavirin
OR
24 weeks
12 weeks + ribavirin
OR
24 weeks
> 85%
SVR = sustained virological response at least 12 weeks after treatment.
* Addition of ribavirin may be considered for patients with Gt 3 HCV and compensated cirrhosis.
† Ribavirin dosing is weight-based; recommended dose is 1000 mg for people weighing < 75 kg and 1200 mg for people weighing ≥ 75 kg.
‡ Daclatasvir dose modification is required when used in combination with specific antiretroviral therapies for human immunodeficiency virus (HIV; see text).
Notes: Dose reduction or dose interruption of direct-acting antiviral therapy is not recommended. Dose reduction of ribavirin for the management of symptomatic anaemia according to the product information is appropriate and will not reduce the likelihood of SVR.

Table 5. Treatment protocols for people with compensated liver disease and hepatitis C virus (HCV) genotype (Gt) 4, 5 or 6 infection, including people with HCV–HIV coinfection
Treatment duration
No cirrhosisCirrhosis
RegimenHCV GtTreatment-
naive
Interferon-experiencedTreatment-
naive
Interferon-experiencedEfficacy (SVR)
Sofosbuvir 400 mg, orally, daily
+
Velpatasvir 100 mg, orally, daily
4-612 weeks12 weeks12 weeks12 weeks≥ 95%
Elbasvir, 50 mg, orally, daily + Grazoprevir, 100 mg, orally, daily ± Ribavirin 1000/1200 mg, orally, daily (weight-based)*412 weeks12 weeks (relapser) OR 16 weeks + ribavirin (OTVF)12 weeks12 weeks (relapser)
OR
16 weeks + ribavirin
(OTVF
> 95%
HIV = human immunodeficiency virus. SVR = sustained virological response at least 12 weeks after treatment. Relapser = patient who failed to achieve SVR despite achieving an end-of-treatment response. OTVF = on-treatment virological failure (patient who has had a null response, partial response, virological breakthrough or rebound, or intolerance to prior treatment). * Ribavirin dosing is weight-based; recommended dose is 1000 mg for people weighing < 75 kg and 1200 mg for people weighing ≥ 75 kg.
Notes: Dose reduction or dose interruption of direct-acting antiviral therapy is not recommended. Dose reduction of ribavirin for the management of symptomatic anaemia according to the product information is appropriate and will not reduce the likelihood of SVR.

Table 6. 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, HCV RNA level (quantitative)
Week 4
  • FBE, urea and electrolytes, LFTs, HCV RNA level (quantitative)
  • LFTs
  • At each on-treatment visit assess for:
    • medication adherence
    • treatment adverse effects
    • drug–drug interactions
Week 12 (EOT)• LFTs
Week 12 after EOT (SVR)• LFTs, HCV PCR (qualitative)
• People treated with elbasvir plus grazoprevir should have LFTs at Week 8 to screen for hepatotoxicity. The Week 8 LFTs may be done as an alternative to Week 4 LFTs.
• 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 or if there are risk factors for reinfection.
• 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 HCC screening with liver ultrasound every 6 months.
• Patients with decompensated liver disease require close monitoring, with review every 2–4 weeks. Measurement of quantitative HCV RNA level is recommended at Weeks 4, 12 ± 24 on-treatment in these patients to confirm viral suppression.
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 and cirrhosis:
  • Patients with cirrhosis require long-term monitoring and should be enrolled in screening programs for:
    • HCC — liver ultrasound +/- serum α-fetoprotein level
    • oesophageal varices — gastroscopy
    • osteoporosis — dual emission x-ray absorptiometry
EOT = end of treatment. SVR = sustained virological response at least 12 weeks after treatment (cure). FBE = full blood examination. LFT = liver function test. PCR = polymerase chain reaction. HCC = hepatocellular carcinoma. ALT = alanine aminotransferase. ANA = anti-nuclear antibodies. ASMA = anti-smooth muscle antibodies. LKM = liver–kidney microsome. AMA = anti-mitochondrial antibody.

Table 7. Treatment protocols before liver transplantation for hepatitis C virus (HCV) infection in people with decompensated liver disease
HCV GtTreatment regimenDurationPBS listing
1–6Sofosbuvir 400 mg, orally, daily + Velpatasvir 100 mg, orally, daily + Ribavirin 600 mg, orally, daily*12 weeksThe combination of sofosbuvir + velpatasvir with ribavirin is PBS-listed for Gt 1 HCV in people with cirrhosis
1Sofosbuvir 400 mg, orally, daily + Daclatasvir 60 mg, orally, daily + Ribavirin 600 mg, orally, daily*12 weeks (24 weeks if ribavirin-intolerant)The combination of sofosbuvir + daclatasvir with ribavirin is PBS-listed for Gt 1 HCV in people with cirrhosis
1Sofosbuvir 400 mg, orally, daily + Ledipasvir 90 mg, orally, daily + Ribavirin 600 mg, orally, daily*12 weeks (24 weeks if ribavirin-intolerant)Ribavirin is not PBS-listed for use in combination with sofosbuvir + ledipasvir
3Sofosbuvir 400 mg, orally, daily + Daclatasvir 60 mg, orally, daily + Ribavirin 600 mg, orally, daily*24 weeksRibavirin is PBS-listed for use in combination with sofosbuvir + daclatasvir for the treatment of Gt 3 HCV in people with cirrhosis
Gt = genotype. PBS = Pharmaceutical Benefits Scheme. DAA = direct-acting antiviral. SVR = sustained virological response at least 12 weeks after treatment.
* Ribavirin starting dose should be 600 mg daily, with dose adjustment according to tolerance.

Notes: The combination of sofosbuvir + velpatasvir + ribavirin is the only DAA regimen to include a specific indication for treating decompensated HCV liver disease. A number of the DAA regimens evaluated in recent studies enrolling subjects with decompensated liver disease have not been submitted to the Therapeutic Goods Administration/Pharmaceutical Benefits Advisory Committee and are therefore not reflected in the PBS listing. All patients should be treated by a specialist experienced in the management of decompensated liver disease. SVR may be associated with improvement in liver function (see text). Paritaprevir–ritonavir + ombitasvir + dasabuvir, elbasvir + grazoprevir and peginterferon-alfa are all contraindicated in people with decompensated liver disease.

Table 8 (A). Treatment protocols after liver transplantation for hepatitis C virus (HCV) infection in people with compensated liver disease
HCV GtTreatment regimenDurationPBS listing
1–6Sofosbuvir 400 mg, orally, daily + Velpatasvir 100 mg, orally, daily*12 weeksThe combination of sofosbuvir + velpatasvir is PBS-listed for the treatment of Gt 1–6 HCV
1Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally, daily (weight-based)
12 weeks (24 weeks if ribavirin-intolerant)The combination of sofosbuvir + ledipasvir is PBS-listed for the treatment of Gt 1 HCV Ribavirin is not PBS-listed for use in combination with sofosbuvir + ledipasvir
1,3Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally, daily (weight-based)
12 weeks (24 weeks if ribavirin-intolerant)The combination of sofosbuvir + daclatasvir is PBS-listed for the treatment of Gt 1 and 3 HCV Ribavirin is PBS-listed for use in combination with sofosbuvir + daclatasvir
1a, 1b plus prior non-response to pegIFN plus ribavirinParitaprevir–ritonavir (150 mg/100 mg), orally, daily
+
Ombitasvir 25 mg, orally, daily
+
Dasabuvir 250 mg, orally, twice daily
+
Ribavirin 600–800 mg, orally, daily
24 weeksFor Gt 1a HCV, PrOD + ribavirin is PBS-listed for 24 weeks’ treatment duration only for people with cirrhosis and prior null response to pegIFN plus ribavirin PBS listing for other situations is for 12 weeks’ treatment duration
1b plus treatment-naive or prior relapse to pegIFN plus ribavirinParitaprevir–ritonavir (150mg/100 mg), orally, daily
+
Ombitasvir 25 mg, orally, daily
+
Dasabuvir 250 mg, orally, twice daily
24 weeksFor Gt 1b HCV, PrOD  ribavirin is PBS-listed for 12 weeks’ treatment duration only
Gt = genotype. PBS = Pharmaceutical Benefits Scheme. pegIFN = peginterferon-alfa. PrOD = paritaprevir–ritonavir + ombitasvir + dasabuvir. mTOR = mammalian target of rapamycin.

* Addition of ribavirin may be considered for all patients in the post-transplant setting.

† Ribavirin dosing is weight-based; recommended dose is 1000 mg for people weighing < 75 kg and 1200 mg for people weighing ≥ 75 kg.

‡ PrOD is associated with drug–drug interactions that require dose modification of calcineurin inhibitors; use in combination with mTOR inhibitors is not recommended.

Table 8 (B). Treatment protocols after liver transplantation for hepatitis C virus (HCV) infection in people with decompensated liver disease
HCV GtTreatment regimenDurationPBS listing
1–6Sofosbuvir 400 mg, orally, daily
+
Velpatasvir 100 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeksThe combination of sofosbuvir + velpatasvir with ribavirin is PBS-listed for the treatment of Gt 1 HCV in people with cirrhosis
1Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks if ribavirin-intolerant)
The combination of sofosbuvir + daclatasvir with ribavirin is PBS-listed for the treatment of Gt 1 HCV in people with cirrhosis
1Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks if
ribavirin-intolerant)
Ribavirin is not PBS-listed for use in combination with sofosbuvir + ledipasvir
3Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks if ribavirin-intolerant)
Ribavirin is PBS-listed for use in combination with sofosbuvir + daclatasvir for the treatment of Gt 3 HCV in people with cirrhosis†
Gt = genotype. PBS = Pharmaceutical Benefits Scheme. DAA = direct-acting antiviral. pegIFN = peginterferon-alfa. SVR = sustained virological response at 12 weeks after treatment.
* Where ribavirin starting dose is 600 mg daily, consider dose adjustment according to tolerance.
† Treatment duration is 12 weeks in people with compensated liver disease and 24 weeks in people with decompensated liver disease.
Notes: The combination of sofosbuvir + velpatasvir + ribavirin is the only DAA regimen to include a specific indication for treating decompensated HCV liver disease. A number of the DAA regimens evaluated in recent studies enrolling subjects with decompensated liver disease have not been submitted to the Therapeutic Goods Administration/Pharmaceutical Benefits Advisory Committee and are therefore not reflected in the PBS listing. All patients should be treated by a specialist experienced in the management of decompensated liver disease. SVR may be associated with improvement in liver function (see text). Recommendations are based on a limited number of studies with small sample sizes. There are insufficient clinical data available to support treatment recommendation for patients with Gt 4, 5 or 6 HCV infection; these recommendations are expert opinion based on in vitro data and small numbers of patients enrolled in clinical trials. PegIFN and paritaprevir–ritonavir + ombitasvir + dasabuvir are both contraindicated in people with decompensated liver disease.

Table 9. Definitions of hepatitis B virus (HBV) infection, by HBV test result
TestCurrent HBV infectionPast HBV infectionOccult HBV infectionVaccine-induced immunity
HBsAg+---
Anti-HBc+++-
Anti-HBs-+/-+/-+
HBV DNA+/--+ (typically very lowlevel-

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