Tables

 

Table 1. Populations to consider for a hepatitis C virus (HCV) screening test
• People who inject drugs or who have ever injected drugs
• Sex workers
• People in custodial settings
• People with tattoos or body piercing
• People who received a blood transfusion or organ transplant before 1990
• Children born to HCV-infected mothers
• Sexual partners of an HCV-infected person
• 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.

 

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
Gt
Treatment - naiveTreatment - experienced*Treatment - naiveTreatment - experienced*Efficacy
(SVR)
Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
1a/b8 weeks
OR
12 weeks‡
12 weeks§12 weeks24 weeks§≥ 95%
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 + ribavirin 12 weeks + ribavirin 12 weeks + ribavirin ≥ 95%
1b12 weeks12 weeks12 weeks12 weeks
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
(on-treatment virological failure)
12 weeks12 weeks (relapser)
or
16 weeks + ribavirin
(on-treatment virological failure)
≥ 95%
1b12 weeks12 weeks12 weeks12 weeks
HIV = human immunodeficiency virus. SVR = sustained virological response at least 12 weeks after treatment. PBS = Pharmaceutical Benefits Scheme. pegIFN = peginterferon-alfa. PrOD = paritaprevir (ritonavir-boosted) + ombitasvir + dasabuvir.
* Treatment experience may include a number of different treatment regimens; PBS eligibility and recommended duration for specific regimens varies according to the treatment history.
† Daclatasvir dose modification is required when used in combination with specific antiretroviral therapies for HIV (see Section 10.3.3).
‡ 8 weeks may be considered if HCV RNA level is < 6 × 106 IU/mL in people with no cirrhosis who are treatment-naive.
§ Sofosbuvir + ledipasvir can be used to treat people in whom either pegIFN + ribavirin dual therapy or protease inhibitor + pegIFN + ribavirin triple therapy has failed.
¶ Sofosbuvir + daclatasvir (no ribavirin) for 12 weeks is recommended for people with no cirrhosis in whom pegIFN + ribavirin or sofosbuvir + ribavirin has previously failed; 24 weeks (no ribavirin) is recommended for people with cirrhosis in whom pegIFN + ribavirin has previously failed; 24 weeks (no ribavirin) is recommended for all people in whom a protease inhibitor + pegIFN + ribavirin has failed.
** 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.
†† Ribavirin dosing is weight-based; recommended dose is 1000 mg for people weighing < 75 kg and 1200 mg for people weighing ≥ 75 kg.
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/1.73 m2 . At the time of writing, the combination of PrOD ± ribavirin was approved by the Therapeutic Goods Administration but not yet available for prescription under the PBS. 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
RegimenHCV
Gt
No cirrhosisCirrhosisEfficacy
(SVR)
Treatment-naiveTreatment-experienced*Treatment-naiveTreatment-experienced*
Sofosbuvir 400 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally,
daily (weight-based)**
212 weeks12 weeks§12 weeks12 weeks§> 90%
Sofosbuvir 400 mg, orally, daily
+
Daclatasvir, 60 mg, orally, daily
312 weeks12 weeks24 weeks24 weeks> 85%
Sofosbuvir 400 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally,
daily (weight-based)**
324 weeks24 weeks§24 weeks24 weeks§58%–
95%‡
Sofosbuvir 400 mg, orally, daily
+
PegIFN, subcutaneously, weekly
+
Ribavirin 1000/1200 mg, orally,
daily (weight-based)**
312 weeks12 weeks12 weeks12 weeks> 85%
SVR = sustained virological response at least 12 weeks after treatment. PBS = Pharmaceutical Benefits Scheme. pegIFN = peginterferon-alfa.
* Treatment experience may include a number of different treatment regimens; PBS eligibility and recommended duration for specific
regimens varies according to the treatment history.
† Daclatasvir dose modification is required when used in combination with specific antiretroviral therapies for human immunodeficiency virus
(HIV; see text).
‡ SVR rates vary from 90%–95% for treatment-naive individuals with no cirrhosis to 58%–76% for treatment-experienced individuals with
cirrhosis.
§ Sofosbuvir + ribavirin can be used to treat people with Gt 2 or Gt 3 HCV in whom pegIFN + ribavirin dual therapy has failed.
¶ Sofosbuvir + daclatasvir (no ribavirin) for 12 weeks is recommended for people with no cirrhosis in whom pegIFN + ribavirin or sofosbuvir + ribavirin has previously failed; 24 weeks (no ribavirin) is recommended for people with cirrhosis in whom pegIFN + ribavirin or sofosbuvir +
ribavirin has previously failed.
** 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 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
RegimenHCV
Gt
No cirrhosisCirrhosisEfficacy
(SVR)
Treatment-naiveTreatment-experienced*Treatment-naiveTreatment-experienced*
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 (on- treatment viro- logical failure12 weeks12 weeks (relapser) OR 16 weeks + ribavirin (on- treatment viro- logical failure> 95%
Sofosbuvir 400 mg, orally, daily
+
PegIFN, subcutaneously, weekly
+
Ribavirin 1000/1200 mg, orally, daily (weight-based)†
4, 5, 612 weeks12 weeks12 weeks12 weeks> 90%
HIV = human immunodeficiency virus. SVR = sustained virological response at least 12 weeks after treatment. pegIFN = peginterferon-alfa. * Treatment experience generally refers to pegIFN + ribavirin ± first-generation protease inhibitor (relapser = patient who failed to achieve SVR despite achieving an end-of-treatment response; 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. ‡ Of 35 treatment-naive patients with Gt 4, 5 or 6 HCV enrolled in the NEUTRINO study, 34 (97%) achieved SVR. 47 Treatment-experienced patients were not enrolled in the NEUTRINO study. 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, INR, HCV RNA level (quantitative)
Week 4• 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.
• 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 8 (A). Treatment protocols after liver transplantation for hepatitis C virus (HCV) infection
in people with compensated liver disease
HCV GtTreatment regimenDurationPBS listing
1, 4, 6Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally,
daily (weight-based)*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + ledipasvir is only PBS-listed for the treatment of Gt 1 HCV

24-week treatment duration is only PBS-listed for the treatment of Gt 1 HCV in people with cirrhosis who are treatment-experienced

Ribavirin is not PBS-listed for use in combination with sofosbuvir + ledipasvir
1–6Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally,
daily (weight-based)*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + daclatasvir is only PBS-listed for the treatment of Gt 1 and 3 HCV

24-week treatment duration is PBS-listed for people with Gt 1 or 3 HCV and cirrhosis, or people with Gt 1 HCV and no cirrhosis who have not responded to previous treatment with a protease inhibitor + pegIFN + ribavirin

Ribavirin is PBS-listed for use in combination with sofosbuvir + daclatasvir for the treatment of Gt 1 HCV only
1a,
1b plus
prior nonresponse

to pegIFN
plus
ribavirin
Paritaprevir–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 weeksPrOD + ribavirin is PBS-listed for 24 weeks’ treatment duration only for people with Gt 1a HCV with cirrhosis and prior null response to pegIFN plus ribavirin
PBS listing for other situations is for 12 weeks
1b plus
treatmentnaive
or prior
relapse to
pegIFN
plus
ribavirin
Paritaprevir–ritonavir
(150mg/100 mg), orally, daily†
+
Ombitasvir 25 mg, orally, daily
+
Dasabuvir 250 mg, orally, twice
daily
24 weeksPrOD ± ribavirin is PBS-listed for 12 weeks’
treatment duration only for Gt 1b HCV
Gt = genotype. PBS = Pharmaceutical Benefits Scheme. pegIFN = peginterferon-alfa. PrOD = paritaprevir–ritonavir + ombitasvir + dasabuvir. mTOR = mammalian target of rapamycin.
* 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 7. Treatment protocols before liver transplantation for hepatitis C virus (HCV) infection
in people with decompensated liver disease
HCV GtTreatment regimenDurationPBS listing
1Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
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 ribavirinintolerant)
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 not PBS-listed for use in
combination with sofosbuvir + daclatasvir for
the treatment of Gt 3 HCV
2Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + daclatasvir
with ribavirin is not PBS-listed for the
treatment of Gt 2 HCV
4, 6Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + ledipasvir
with ribavirin is not PBS-listed for the
treatment of Gt 4 or 6 HCV
4-6Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + daclatasvir
with ribavirin is not PBS-listed for the
treatment of Gt 4–6 HCV
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: None of the currently available DAAs in Australia 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. Paritaprevir–ritonavir + ombitasvir + dasabuvir and peginterferon-alfa are both contraindicated in people with decompensated liver disease.

Table 8 (B). Treatment protocols after liver transplantation for hepatitis C virus (HCV) infection in people with decompensated liver disease
HCV GtTreatment regimenDurationPBS listing
Decompensated liver disease
1Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
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 ribavirinintolerant)
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 not PBS-listed for use in combination
with sofosbuvir + daclatasvir for the treatment of
Gt 3 HCV
2Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + daclatasvir with
ribavirin is not PBS-listed for the treatment of Gt 2
HCV
4, 6Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + ledipasvir with
ribavirin is not PBS-listed for the treatment of Gt 4
or 6 HCV
4–6Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
The combination of sofosbuvir + daclatasvir with
ribavirin is not PBS-listed for Gt 4-6 HCV
Fibrosing cholestatic hepatitis (FCH)
1–6Sofosbuvir 400 mg, orally, daily
+
Daclatasvir 60 mg, orally, daily
+
Ribavirin 1000/1200 mg, orally, daily
(weight-based)†
24 weeksSofosbuvir + daclatasvir is PBS-listed for:
• 12 weeks in Gt 1 and 3 HCV in people with no
cirrhosis, or
• 24 weeks in Gt 1 and 3 HCV in people with
cirrhosis, or
• 24 weeks in Gt 1 HCV in people with no
cirrhosis in whom treatment with a protease
inhibitor + pegIFN + ribavirin has previously
failed
1, 4, 6Sofosbuvir 400 mg, orally, daily
+
Ledipasvir 90 mg, orally, daily
+
Ribavirin 600 mg, orally, daily*
12 weeks
(24 weeks
if ribavirinintolerant)
Ribavirin is not PBS-listed for use in combination
with sofosbuvir + ledipasvir
The combination of sofosbuvir + ledipasvir is not
PBS-listed for the treatment of Gt 4 or 6 HCV
Gt = genotype. PBS = Pharmaceutical Benefits Scheme. pegIFN = peginterferon-alfa. SVR = sustained virological response at least 12 weeks after treatment.
* Where ribavirin starting dose is 600 mg daily, consider dose adjustment according to tolerance.
† Ribavirin dosing is weight-based; recommended dose is 1000 mg for people weighing < 75 kg and 1200 mg for people weighing ≥ 75 kg.
Notes: None of the currently available direct-acting antivirals (DAAs) in Australia 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.

 

Supplementary Table 1. Non-invasive serum markers for assessing liver fibrosis stage currently available in Australia
MethodFormulaKey threshold for excluding cirrhosis*
APRIAPRI = (AST [IU/L] ÷ AST ULN [IU/L] × 100) ÷ platelet count (× 109/L) Online calculator: http://www.hepatitisc.uw.edu/ page/clinical-calculators/apriAPRI < 1.0
HepascorePatented formula combining bilirubin, GGT, hyaluronate, α-2-macroglobulin, age and sexHepascore < 0.80
FibroGENEPatented formula based on age, platelet count, AST, GGT and IL28B rs12979860 genotype Online calculator: http://www.fibrogene.com/viral_hepatitis.htmlThreshold not published but online calculator available
ELF testPatented formula combining age, hyaluronate, MMP-3 and TIMP-1ELF < 9.8
APRI = AST to platelet ratio index. AST = aspartate aminotransferase. ULN = upper limit of normal. GGT = gamma-glutamyl transferase.ELF = Enhanced Liver Fibrosis. MMP-3 = matrix metalloproteinase-3. TIMP-1 = tissue inhibitor of metalloproteinase-1.
* These thresholds have good performance characteristics for excluding the presence of cirrhosis. Patients in whom results exceed these thresholds should be referred for further assessment for the presence of cirrhosis by a specialist with experience in assessing liver disease severity and managing patients with advanced liver disease. These thresholds alone should not be used to diagnose cirrhosis.
Note that the performance of Hepascore and APRI for predicting the presence of cirrhosis may be less accurate in people with HIV coinfection than in people with HCV mono-infection (be aware of false positive results due to HIV-induced thrombocytopaenia with APRI, or antiretroviral treatment-related hyperbilirubinaemia with Hepascore).
References:

  • EASL-ALEH clinical practice guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63 (1): 237-264.

  • World Health Organization. Guidelines for the screening, care and treatment of persons with hepatitis C infection.April 2014. (http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1)

  • Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology 2011; 53 (3): 726-736.

  • Adams LA, Bulsara M, Rossi E, et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem 2005; 51 (10): 1867-1873.

  • Eslam M, Hashem AM, Romero-Gomez M, et al. FibroGENE: a gene-based model for staging liver fibrosis. J Hepatol 2016; 64: 390-398.

  • Parkes J, Guha IN, Roderick P, et al. Enhanced Liver Fibrosis (ELF) test accurately identifies liver fibrosis in patients with chronic hepatitis C.J Viral Hepat 2011; 18: 23-31.

 

Supplementary Table 2. Child–Pugh and Model for End-Stage Liver Disease (MELD) scoring systems for predicting prognosis in people with decompensated liver disease
A. Child–Pugh score
Points
Clinical measure123
Albumin (g/dL)> 3528–35< 28
Bilirubin (μmol/L)< 3434–51> 51
INR< 1.71.7–2.3> 2.3
AscitesNilSlightModerate
EncephalopathyNilGrade 1–2Grade 3-4
Interpretation
Classification1-year mortalityConsider transplant centre referral
Class A (5–6 points)0No
Class B (7–9 points)20%Yes
Class C (10+ points)55%
B. MELD score
MELD = 10 × ((0.957 × Loge (creatinine/88.4)) + (0.378 × Loge (bilirubin/17.1)) + (1.12 × Loge (INR))) + 6.43 Online calculators are available.
Classification3-month mortalityConsider transplant centre referral
MELD < 101.9%No
MELD 10–196.0%Yes if MELD ≥ 13*
MELD 20–2919.6%
MELD 30–3952.6%
MELD 40+71.3%
INR = international normalised ratio.
* Indications for assessment by a liver transplant centre include Child–Pugh score ≥ B7, MELD score ≥ 13 or one of the following clinical events: refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent or chronic hepatic encephalopathy, small hepatocellular carcinoma or severe malnutrition.

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