Hepatitis C

Question 1

HCV structure & classification

Answer 1

Family: Flaviviridae
Genus: hepacivirus

8 genotypes. Subgenotypes depicted by letters.

(+)ssRNA enveloped

Baltimore: IV

Question 2

HCV natural course

Answer 2

30% clear spontaneously
70% CLD in 20-30 years
1-5% HCC

Question 3

HCV diagnostics

Answer 3

1. Serology: ELISA/EIA - these generally detect anti-HCV core antibodies by using recombinant antigens from the core and the nonstructural proteins NS3, NS4, and NS5 as targets

NOTE - IgG can take up to 6 months to seroconvert.

2. Antigen/quantitative PCR - architect core Ag or Roche Cobas RT-PCR

Reflex testing is recommended. HCV RNA NAAT performed on the same sample as the original screening assay streamlines the HCV care pathway and avoids losing the 20-30% of patients with positive screening tests

Question 4

HCV vertical transmission rate & screening

Answer 4

Risk: 5%

All pregnant persons with HCV infection should receive prenatal and intrapartum care that is appropriate for their individual obstetric risk(s) as there is no currently known intervention to reduce MTCT.

SEE BABY SCREENING ALGORITHM IN ALBUM

BABY GETS HEP A VACCINE

Question 5

HCV treatment

Answer 5

WHO recommends offering treatment to all individuals diagnosed with HCV infection who are 3 years of age or older, irrespective of disease stage (EXCEPT PREGNANT WOMEN)

WHO recommends the use of pangenotypic DAA regimens for the treatment of persons with chronic HCV infection aged 3 years and above

DAAs are considered pangenotypic when they achieve high treatment efficacy across all six major HCV genotypes (1-6).

For adults without cirrhosis, the following pangenotypic regimens can be used:
• Sofosbuvir/velpatasvir 12 weeks
• Sofosbuvir/daclatasvir 12 weeks
• Glecaprevir/pibrentasvir 8 weeks

For adults with compensated cirrhosis, the following pangenotypic regimens can be used:
• Sofosbuvir/velpatasvir 12 weeks
• Glecaprevir/pibrentasvir 12 weeks
• Sofosbuvir/daclatasvir 12 weeks
• Sofosbuvir/daclatasvir 24 weeks if previously treated

Nucleic acid testing for qualitative or quantitative detection of HCV RNA should be used as the test of cure at 12 or 24 weeks (i.e. sustained virological response [SVR12 or SVR24]) after completion of antiviral treatment.

Systematic reviews of the effectiveness of DAAs for the treatment of chronic HCV infection indicate that SVR rates generally exceed 90%

Question 6

HCV Re-treatment

Answer 6

Currently, there is one pangenotypic regimen approved for the retreatment of persons who have been previously treated with any combination of DAAs. This is the FDC of sofosbuvir, velpatasvir and the protease inhibitor voxilaprevir

Question 7

HCV drug classes

Answer 7

1. NS3/4A protease inhibitors: Voxilaprevir – a potent, pangenotypic protease inhibitor that is only available in combination with the NS5B inhibitor sofosbuvir and the NS5A inhibitor velpatasvir

Glecaprevir

2. NS5A inhibitors: The NS5A protein plays a role in both viral replication and the assembly of HCV

●Velpatasvir – a pangenotypic NS5A inhibitor

●Daclatasvir

●Ledipasvir

3. NS5B RNA-dependent RNA polymerase inhibitors:

There are two classes of polymerase inhibitors: nucleoside/ nucleotide analogues (NPIs) and non-nucleoside analogues (NNPIs)

A. NPI: Sofuabuvir
B. NNPI: Tegobuvir

Question 8

HCV reporting

Answer 8

Report as: Evidence of active infection with HCV, please send repeat sample to confirm

Advise referral to an appropriate specialist for further assessment/treatment. Hepatitis A and B vaccine recommended if appropriate.

Question 9

HCV RAS

Answer 9

SEE IMAGE.

resistance-associated substitutions

NS5As:
L31MV - 1a & 1b
Y93HN - 1a, 1b, 3a
Q30R - 1a

Question 10

HCV D*/R-

Answer 10

SEE ALBUM.