Hepatitis C Flashcards
Descrieb HCV
- 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
Describe HCV lifecycle
- HCV is endocytosed
- uncoated in cytoplasm
- replicated and assembled
- exocytosed
DEscribe natural history of infecton
- 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.
Describe Disease Progression in Chronic HCV
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Fibrosis
- Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
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Cirrhosis
- Over time, fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure
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Hepatocellular Carcinoma (HCC)
- HCC can develop after years of chronic HCV infection
List RFs for cirrhosis development
- HIV/HBV co-infection
- Diabetes mellitus
- Obesity
- Male gender
- Alcohol excess
List some extrahepatic manifestations of HCV infection
- 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
Describe epidemiology worlwide and patients at risk for infection in Au
- 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.
Describe diagnosis of HCV infection
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Screening Test:
- Serology: HCV Ab indicates exposure
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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
- HCV PCR
Compare and contrast acute and chronic infection features
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
Describe the assessment of a patient with chronic HCV infection prior to treatment
- 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
Why is identifying cirrhosis important?
- It influences treatment duration
- It identifies patients at risk for hepatocellular carcinoma who require ongoing surveillance
aSSESSMENT OF Patient iwth infections eg consult
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History:
- Fatigue, extrahepatic manifestations (rash, arthritis, neuropathy, etc.)
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Co-factors:
- Alcohol, co-infection, obesity/type II diabetes
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Examination:
- Evidence of cirrhosis (spider naevi, palmar erythema, hard liver edge, splenomegaly)
Assessment of patient with chronic infection - what investigations would you order?
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Investigations:
- LFTs
- Serology, virology
- Hepatic synthetic function (Albumin, coagulation studies)
- Evidence of portal hypertension (Platelet count, ultrasound scan)
- Fibroscan (transient elastography)
Describe treatment of chronic HCV
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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
Describe treatment uptake
- 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
