Introduction

First discovered in 1989, the hepatitis C virus (HCV) is blood-borne form of viral hepatitis. The incubation period is 6-9 weeks.

Transmission is usually via blood products or vertical transmission from mother to foetus. Sexual transmission is possible but rare.

HCV infection can be acute or chronic. The acute infection is usually asymptomatic, and often not discovered for years after infection (frequently discovered incidentally). Chronic infection is often discovered when patients develop serious liver disease later in life. It can cause cirrhosis, decompensated liver disease, and death.

50% – 80% of those exposed to the virus will develop chronic infection. Spontaneous late clearance of the disease is very rare.

There is no vaccine available for the prevention of HCV.

In many cases, chronic HCV can be cured with antiviral combination therapy. Previously this involved genotyping of the HCV virus for each individual, and complex medication regimens, often self-administered SC (subcutaneous) injections, under the supervision of a gastroenterologist. However, in recent years, new oral agents (DAA – direct acting antivirals) which are effective against all strains (and thus don’t require genotyping) have been developed, with a cure rate of >90%, and in some cases (e.g. in certain circumstances in Australia) can even be prescribed by a GP. It is likely that the NHS in the UK will adopt a similar model (some areas in the UK may already be doing this).

Epidemiology

  • Prevalence in the UK is about 0.02%. In Africa it is about 6%, and in Egypt is as high as 19%.
  • About 80% of those in the UK with haemophilia have hepatitis C – as a result of previously blood transfusion, received before hepatitis C was recognised or screened for.
  • Worldwide it is the leading cause of liver disease.
    • 180million people thought to be infected worldwide
  • 95% of new cases in UK are due to IV drug use. Sexual transmission is also possible but less common.
  • 6 genetic subtypes – genotyping for the type of Hep C is important for treatment (less so with the advent of new oral treatments)
    • 90% of cases are either type 1 or type 3

Risk factors

  • IV drug use
  • Blood transfusion before 1991
  • Haemodialysis
  • Sexual contact with an infected partner
  • Needlestick injuries in healthcare workers
  • Vertical transmission from mother to baby
  • Co-existing HIV
  • Medical or dental treatments in countries where sterilisation procedures may be inadequate – particularly in high prevalence countries

Household transmission is extremely rare.

Presentation

The vast majority of patients are asymptomatic. Many cases are discovered after LFTs show raised amintransferase (ALT). Any patient with persistently elevated ALT should be screened for HCV.

  • 85% anicteric (not jaundiced).
  • 10-15% of patients will have jaundice and perhaps other general symptoms suggestive of hepatitis: jaundice, malaise, abdominal pain, nausea & fever – mild

Diagnosis

Blood tests

  • Abnormal LFTs
    • Raised ALT
    • Low albumin, raised bilirubin, raised INR
      • Signs of liver synthetic dysfunction and suggest cirrhosis
  • Positive anti-HCV antibodies
    • If positive – perform HCV PCR, and viral load
    • HCV antibodies do not give information about cure. HCV antibodies typically remain positive for life. HCV viral load status is required to know if cure is successful.
    • Also test for HBV and HIV if HCV is positive – vaccinate as appropriate depending on the results
  • FBC
    • Check for anaemia
    • Low platelets may be a sign of portal hypertension
    • AST to platelet ratio (APRI) can be used to screen for cirrhosis. A score of <1.0 with no other signs of cirrhosis indicates low risk
  • U+Es
    • Some treatments are not recommended if eGFR low

Liver Assessment

  • If the APRI (see above) is <1.0 and no other signs of cirrhosis, then no further investigations are required- as the risk of liver damage is negligible
    • APRI calculator
    • If APRI >1.0 – further investigation and specialist referral is required
  • Liver USS
    • Helps assess for hepatocellular carcinoma, portal hypertension, and evidence of cirrhosis
  • Fibroscan
    • A special type of ultrasound that measures the “stiffness” (elasticity) of the liver, and is used to diagnose cirrhosis
    • Shear wave elastograhpy is another similar technique, but less well evaluated. It can be performed in some centres as part of a liver USS. Fibroscan requires different equipment to regular USS.
  • If any evidence of cirrhosis – patient will need to be referred to a gastroenterologist for further management

Further Investigations

Consider these if known chronic HCV, and signs of liver failure

  • Gastroscopy – to exclude varices
  • Bone densiometry for osteoporosis

Other Signs

  • Acute liver failure rare – < 0.1%
  • Chronic infection very common – 85%.
    • 1 – 4 % of these patients will have HCC (hepatocellular carcinoma) as a result

Management

Antiviral therapy is the mainstay of treatment for chronic infection. Treatment with Interferon has largely been superseded by use of DAA (direct-acting antivirals)

DAA:

  • Cure rate>90%
  • Oral medication – usually a daily regimen (may be poor adherence)
  • Treatment usually lasts 8-12 weeks
    • Sometimes up to 24 weeks
  • Does not require intensive monitoring (unlike interferon)
  • Side effects are uncommon and usually mild and include:
    • Fatigue
    • Headache
    • Insomnia
    • Nausea
  • Essential for patients to have follow-up blood test at 12 weeks to determine if treatment has been successful (re-check HCV viral load)
  • Exact medications used often depends on the HSV genotype
  • Examples include:
    • Sofosbuvir plus ledipasvir (Harvoni®)
    • Sofosbuvir + Valpatasvir
    • Sofosbuvir + ribavirin
  • Side effects:
    • Usually well tolerated
    • Side effects may include headache, fatigue, nausea, cough. All are usually mild
    • Ribavarin is often associated with more significant and troublesome side effects (anaemia (haemolytic), rash, anxiety, insomnia, dyspnoea). Avoid is Hb is low before treatment is started. Strongly teratogenic for both male and female patients – advise to use two forms of contraception whilst taking the medication and for 6 months afterwards. Contraindications include pregnancy, anaemia, heart disease.
    • Be wary of patients with low eGFR (<30) as they may need adjusted doses or alternative drugs. Seek specialist advice
  • Monitoring
    • Check FBC, LFTs and U+Es every 4 weeks, and again 12 weeks after the end of treatment
    • Abnormal LFTs typically resole after infection has been treated. If they persist, look for another cause
    • If tests are normal at 12 weeks after treatment, no further ongoing monitoring is required
    • If FBC declines on ribavirin then reduce dose, or consider stopping ribavirin (discuss with specialist)
    • Sustained virological response (SVR) is the term used to describe a successful treatment, as determined by a negative HCV PCR at 12 weeks after the end of treatment
  • Advise safe drinking limits and living alcohol intake (to reduce the risk of developing cirrhosis)
  • Ensure testing and vaccination for HIV and HBV before commencing treatment
  • In Australia, patients are suitable for GP initiated treatment if:
    • No cirrhosis
    • No HIV or HBV
    • Not pregnant
    • Referral anybody else who does to meet the above criteria to a gastroenterologist
    • GPs need prior experience in prescribing under the supervision of a specialist before prescribing independently
  • Failure of treatment is rare. Consider:
    • Poor adherence
    • Re-infection
    • Drug resistance

Reducing transmission risk

  • Counsel the patient about methods of transmission
  • Blood-to-blood contact only – e.g. mother to baby, can occur sexually (not common), and receive blood products (blood screened in most but not all countries)
  • Cannot be caught through normal social contact, hugging, kissing, sharing food or cutlery, or shared toilet facilities. Mosquitos do not transmit HCV
  • Avoid sharing items used in intimate personal care:
    • Toothbrushes
    • Razors
    • Tweezers
    • Jewellery that involves body piercings
    • Scissors
    • Nail clippers
  • Cuts and abrasions
    • Cover with a waterproof dressing
  • Blood spills and contamination (e.g. after simple cuts at home)
    • Wash hands before and after cleaning up the blood spill
    • Use disposable gloves
    • Use disposable materials (e.g. paper towels) to mop up with
    • Clean the area with detergent and then with bleach
  • Remind them not to donate blood or organs

Pregnancy and Breastfeeding

  • Mother to baby transmission risk is about 5%
    • C-section does not reduce the risk of transmission
  • Test babies after the age of 18 months – as maternal antibodies can persist until this age
  • Breastfeeding is safe – unless nipples are bleeding or cracked – advise mums to discard this breast milk in these circumstances and can resume once nipples have recovered

Prognosis

  • 30% of chronic HCV develop cirrhosis within 20 – 30 years
  • Male patients are more likely to develop fibrosis with chronic infection.
  • Progression from chronic hepatitis to cirrhosis takes 20-40 years. This happens more quickly in male patients, immunosupressed patients, and those who drink a lot of alcohol.
  • About 20% of HCV patients will develop cirrhosis within 20 years
    • 5 year survival once cirrhosis has set in is 95%. 10-year is 81%
    • ¼ of patients will develop complications, such as ascites. Once these have developed, 5-year survival drops to 50%
    • 2-5% of cirrotic patients will develop hepatocarcinoma.
  • Successful treatment:
    • Removes infection risk
    • Can lead to regression of cirrhosis and liver fibrosis
    • Reduces risk of hepatocellular carcinoma
    • Reduces mortality
    • Does not prevent re-infection. Patients can contract HCV again.
  • If cirrhosis present, then even despite successful treatment, it is recommended patients have the following follow-up monitoring:
    • Liver USS every 6 months (screening for HCC)
    • Gastroscopy every 1-2 years (screening for varices)
    • Bone densitometry (DEXA) at diagnosis and every 2-3 years (screening for osteoporosis)

References

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