Hepatitis C

Hepatitis C

·        An enveloped ssRNA virus (used to be called non A non B).  6 geneotypes identified.

·        Damage is caused by immune response – not virus

Presentation

·        Incubation to onset of symptoms average 7 weeks (range 3 – 20)

·        HCV RNA detectable within 1 – 3 weeks of exposure.  Rises rapidly to 10E6 – 10E8 per ml

·        Only 1/3 have symptoms. .  Clinical illness (if any) lasts 2- 12 weeks

·        ALT elevation to 300 – 800

·        50% go on to chronic infection (ie higher than Hep B)

·        May present with end stage liver disease (e.g. may present for first time with variceal bleeding) 

·        Hepatocellular carcinoma found in 1/3, test with ultrasound. ?Evidence that interferon for 6 months ¯risk of HCC

Risk Factors

·        NZ prevalence: 0.47%

·        Low infectivity: mainly transmitted by blood

·        Transfusion

·        IV drugs (40-60% of cases)

·        Sexual contact (very low risk)

·        Maternal transmission to neonate in 5% of maternal infection (ie low risk)

Viral Serology

·        Acute HCV: Anti-HCV doesn’t appear for 3 months.  Can do PCR.  Exclude HAV, HBV, EBV, and

·        CMV

·        Chronic HCV: Anti-HCV antibody

·        Indications for HCV test:

o   Chronic hepatitis (raised ALT over 6 months)

o   History of Non-A, Non-B hepatitis but at least 3 months after acute infection

o   At risk groups: IV users, haemophiliacs

o   Donors: blood and organs 

·        Indications for HCV RNA test. Test if indeterminate Anti-HCV results, diagnosis in neonates and monitoring of interferon therapy.

·        80% of chronically infected have persisting viraemia

Tests  

·        LFT: bilirubin, Albumin

·        FBC: platelets

·        APTT/INR

·        Anti HCV antibodies

·        PCR for HCV RNA

·        Ultrasound for size (& to guide biopsy) 

·        ?Biopsy ® degree of fibrosis ® prognosis

·        Exclude: Hep A, Hep B, Iron studies, ANA

Progression

·        If self-limiting HCV RNA undetectable and ALT back to normal in 1 – 3 months

·        Wide spectrum: 1/3 persistently normal ALT. Majority fluctuating ALT (Þ immune system active and causing hepatocyte death). ALT height doesn‟t correlate with histological severity. Acute – ALT 10 times normal

·         Non-hepatic manifestations: arthritis, dry membranes, lichen planus (white plaques in mouth), glomerulonephritis, cryoglobulinaeamia, porphyria cutanea tarda (PCT – blisters on skin)

Prognosis

·        Contributing to progression:

o   Alcohol ® ­fibrosis

o   HBV

o   Age at infection  - younger have longer period of time with infection

o   Mode of acquisition: transfusion worse (?greater viral load) 

o   Genotype of virus: effects interferon treatment. Type 1 ® severe disease and poor response to interferon

Management

·        ¯Alcohol 

·        Have liver biopsy before commencing drug treatment. Also, intravenous drug users should have drug free urines (otherwise risk of reinfection)

·        Need strong motivation/compliance

·        Interferon - best for:

o  High ALT

o  Disease < 5 years

o  Non-cirrhotic

o  Not genotype 1

o  Low viral load

o  No history of depression (interferon can cause this) 

o  Causes flu like symptoms: ¯appetite, fever, myalgia. Largely resolves after 1-2 weeks. Given it up-regulates the immune system can also cause ­autoimmune diseases (e.g. thyroid) 

o  On it‟s own only 15% are PCR negative 6 months after completing treatment

·        Combination interferon/Ribavirin

o  Ribavirin is teratogenic: contraception needs to be VERY reliable

o  Purine nucleoside analogue

o  Stored and transported in red cells.  Dose dependent haemolysis Þ monitor HB and reticulocytes

o  Only useful in addition to interferon 

o  After 3 months, 35% non-responders. 65% complete responders. For geneotypes 2 & 3 most of these go on to be sustained responders

·        Transplantation:

o  Hep C most common indication

o  Recurrent (usually mild) infection of graft

o  Survival: 65% at 5 years