Microbiology

Life Cycle

Worldwide about 170 million cases
Genotype varies by geography
- Genotype 1a and 1b common in Canada
  - Disproportionate burden in Indigienous Canadian population
  - Very high burden of disease in Canada, causing more years of life lost in Ontario than any other infectious disease
- Genotype 3 more common in injection drug use and south-east Asia
- Genotype 4 common in Egypt (15% prevalence)
Modes of transmission
- Injection drug use (most important population, highest risk)
- Tattoos
- Blood transfusions before 1992
- Cocaine use from blood on the straws
- Rarely, sexual transmission especially HIV-infected MSM
- Vertical transmission rare (3-5%)
- Iatrogenic or medical transmission, from multi-use vials
In Canada, about 245,000 chronic hepatitis C, about half are undiagnosed
- Risk factors: injection drug use (highest risk), prior transfusion, and hemophilia
- Increasing burden of disease as patients progress to cirrhosis

In the acute phase, the viral load and liver enzymes fluctuate over months
- Anti-HCV-Ab develops at 12 weeks
- Acute phase lasts 6 months to 2 years
Spontaneous clearance is rare after 2 years
- Anti-HCV-Ab positive and HCV RNA negative
- Repeat to confirm, but no need to follow it
- No complications, though it is a surrogate for risk behaviours
- Not protected from reinfection
If it isn't cleared, it becomes chronic
- Lifetime risk of cirrhosis is 50-60%, with 20% having cirrhosis at 20 years
- Liver cancer develops in 1-4%

After exposure, may clear infection, but 70-80% become chronically infected
Progresses slowly and asymptomatically until they develop liver fibrosis, compensated cirrhosis, then decompensated cirrhosis
- ~20-25% progress to end-stage liver disease within 20 years

All individuals should be considered for antiretroviral treatment
Assess readiness for treatment, as good adherence is necessary
Alcohol, drug use, and mental health disorders are not containdications to treatment

Confirm active infection with HCV RNA then get genotype and subtype
- Two positive HCV RNA tests 6 months apart documents chronic infection
- May need resistance testing
Baseline bloodwork, including CBC, liver enzymes, liver function, and creatinine
Serology to exclude HIV and HBV
Transferrin saturation to exclude hemochromatosis, and IgG levels to exclude autimmune hepatitis
Baseline liver ultrasound
If not clearly cirrhotic, assess liver fibrosis
- Bloodwork: AST:platelet ratio index (APRI), FIB-4, FibroTest
- Imaging: FibroScan
- Gold standard: biopsy

Include nonstructural 3/4A (NS3/4A) serine protease (-previr), the NS5B RNA dependent RNA polymerase (-buvir) and the NS5A protein (-asvir)
Assess drug-drug interactions with [[1]]
- PPI and Epclusa/Harvoni
- Statins require dose reduction; atorvastatin and Maviret is no-no
- Anti-epileptics except leviteracetam
Choice of treatment regimen depends on genotype, previously-failed treatments, and cirrhosis
- All protease inhibitors (-previr) are contraindicated in decompensated cirrhosis, which refers to ascites, esophageal variceal hemorrhage, jaundice, or hepatic encephalopathy
- Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) is indicated for previously-treated patients

Regimen	1a	1b	2	3	4	5	6
Ledipasvir/sofosbuvir (Harvoni)	12 wk ± ribavirin	12 wk	–	12 wk + ribavirin	12 wk	12 wk	12 wk
Elbasvir/grazoprevir (Zepatier)	12-16 wk ± ribavirin	12 wk	–	12 wk + sofosbuvir	12 wk	–	–
Sofosbuvir/velpatasvir (Epclusa)	12 wk	12 wk	12 wk	12 wk	12 wk	12 wk	12 wk
Glecaprevir/pibrentasvir (Maviret)	8 wk	8 wk	8 wk	8 wk	8 wk	8 wk	8 wk
...

Counsel to avoid sharing products like needles or razors, safe sex, avoid alcohol
Vaccinate for Hep A and B

Majority of cases of chronic hepatitis C occur in baby boomers (born 1945 to 1975), though screening for this population appears to be controversial