Hepatitis C

Question 1

Descrieb HCV

Answer 1

• HCV is an RNA virus of the Flaviviridae family
• It is an enveloped virus that has a limited range of hosts including humans and chimpanzees
• Comprised of core, RNA, and surface E protein

Question 2

Describe HCV lifecycle

Answer 2

• HCV is endocytosed
• uncoated in cytoplasm
• replicated and assembled
• exocytosed

Question 3

DEscribe natural history of infecton

Answer 3

• 7 genotypes described 1-7
• Genotypes 1 and 3 are most common in Australia
• HCV rarely causes an acute illness (5-10% cases)
• 15-40% of people will spontaneously clear HCV, treatment reserved for chronic disease
• Chronic hepatitis C is defined as the presence of HCV in the bloodstream for >6 months

Natural History of HCV Infection
- exposure results in 15% resolved
- 85% chronic
- 80% stable
- 20% cirrhosis
- 75% slowly progressive
- 6%/yr ESLD, 4% HCC/yr
- both of these ending in transplantation or death

Note that HIV, HBV, alcohol and steatosis can accelerate progression rate and increase chances of poorer outcomes e.g. cirrhosis.

Question 4

Describe Disease Progression in Chronic HCV

Answer 4

• Fibrosis
  
  • Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
• Cirrhosis
  
  • Over time, fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure
• Hepatocellular Carcinoma (HCC)
  
  • HCC can develop after years of chronic HCV infection

Question 5

List RFs for cirrhosis development

Answer 5

• HIV/HBV co-infection
• Diabetes mellitus
• Obesity
• Male gender
• Alcohol excess

Question 6

List some extrahepatic manifestations of HCV infection

Answer 6

• haematologic: mixed cryoglobulinaemia, aplastic anaemia, thrombocytopenia, non-Hodgkin’s
• dermatologic: porphyria cutanea tarda, lichen planus, vasculitis
• renal: GHitis, nephrotic syndrome
• endocrine: DM, thyroid dysfunction
• salivary: sialadenitis
• ocular: uveitis, corneal ulver
• vascular: necrotising vasculitis, polyarteritis nodosa
• neuromuscular: weakeness/myalgia, peripheral neuropathy, arthritis/arthralgia
• autoimmune phenoma: CREST

Question 7

Describe epidemiology worlwide and patients at risk for infection in Au

Answer 7

• Global prevalence of 1-2%:
  
  • 71 million chronic HCV
  • 350,000 deaths/year

Patients at Risk for HCV Infection in Australia
- People who inject drugs or who have ever injected drugs (79% of all HCV)
- People in custodial settings
- People with tattoos or body piercings
- People who received a blood transfusion or organ transplant before 1990
- Children born to HCV-infected mothers
- People with HIV or HBV infection
- Aboriginal or Torres Strait Islanders
- Migrants from high prevalence regions (Egypt, Pakistan, Eastern Europe, Africa, and SE Asia)
- Sexual partners of an HCV-infected person

• epidemiology will change as migration influences demography

80% of these in total are PWID. Important to identify, screen and treat, not only to reduce burden of disease but reduce community transmission.

Question 8

Describe diagnosis of HCV infection

Answer 8

• Screening Test:
  
  • Serology: HCV Ab indicates exposure
• Confirmation of Current Infection:
  
  • HCV PCR
    
    • PCR: a positive polymerase chain reaction confirms presence of virus in the bloodstream
    • note genotyping not as important as good pan-genotype drugs exist

Question 9

Compare and contrast acute and chronic infection features

Answer 9

Acute HCV Infection
- Most asymptomatic
- Develops 2-24 weeks after exposure
- Symptoms include jaundice, nausea, dark urine, and RUQ abdominal pain

Chronic HCV Infection
- Evidence of infection for >6 months
- LFTs may be normal, or mildly elevated ALT/AST
- Symptoms, if present, include fatigue
- Most patients asymptomatic until cirrhosis develops

Question 10

Describe the assessment of a patient with chronic HCV infection prior to treatment

Answer 10

• Confirm current infection
• Identify genotype
• Assess for presence of cirrhosis
• Co-morbidities (e.g., renal dysfunction)
• Concomitant medications
• Consideration of compliance
• Contraception/pregnancy - drugs contraindicated in pregnancy

Question 11

Why is identifying cirrhosis important?

Answer 11

• It influences treatment duration
• It identifies patients at risk for hepatocellular carcinoma who require ongoing surveillance

Question 12

aSSESSMENT OF Patient iwth infections eg consult

Answer 12

• History:
  
  • Fatigue, extrahepatic manifestations (rash, arthritis, neuropathy, etc.)
• Co-factors:
  
  • Alcohol, co-infection, obesity/type II diabetes
• Examination:
  
  • Evidence of cirrhosis (spider naevi, palmar erythema, hard liver edge, splenomegaly)

Question 13

Assessment of patient with chronic infection - what investigations would you order?

Answer 13

• Investigations:
  
  • LFTs
  • Serology, virology
  • Hepatic synthetic function (Albumin, coagulation studies)
  • Evidence of portal hypertension (Platelet count, ultrasound scan)
  • Fibroscan (transient elastography)

Question 14

Describe treatment of chronic HCV

Answer 14

• Direct Acting Antivirals (DAAs)
  
  • Inhibit replication of HCV
  • Well-tolerated, effective oral medications
  • Achieve eradication of the virus in 90-95% of patients after an 8-16 week course, varies depending on severity of disease and lines of treatment used
  • DAAs used in combination to reduce viral resistance
    Examples include drugs that inhibit NS3/4A protease, that cleaves the HCV polyprotein e.g. glecaprevir, and drugs that inhibit the NS5A/B polymerases such as velpatasvir and dasabuvir respectively.

Older drugs include ribavirin which may inhibit HCV polymerase, and PEGylated interferon alpha.

Current Treatment Options
- Pan-genotypic Regimens Include:
- Sofosbuvir + velpatasvir (12 weeks)
- Glecaprevir + pibrentasvir (8 weeks)
- Precautions:
- Drug-drug interactions
- Contraindicated in pregnancy
- Poor compliance may lead to resistance

Question 15

Describe treatment uptake

Answer 15

• Great uptake on release of hepatitis C drugs on PBS, but steady drop
• Challenge now to identify those who are not aware/have not been diagnosed

Question 16

What is a cure?

Answer 16

• Cure defined as negative HCV PCR 12 weeks after completion of treatment (sustained virological response = SVR)
• Patients will remain HCV Ab positive
• HCV Ab does not confer immunity – hence patients must be routinely testing for RNA
• Increased treatment uptake aims to achieve eradication of HCV infection in Australia!

Complications of HCV Can Be Prevented Through Treatment