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Diagnosis and Testing

How and when is HCV diagnosed?

HCV infection is not infrequently diagnosed as a complete surprise and may cause considerable upset for patient and those around the patient including doctor.

The disease can have a broad spectrum of presentations such as:

• Major symptoms (swelling of legs and abdomen, confusion)and findings (abnormal laboratory tests (blood) or imagines (Ultrasound, CT scan).
• HCV can be diagnosed in a completely asymptomatic individual during health or life insurance check
• focused test result after someone's history indicated risk factor's (sometimes decades ago!)
• Asymptomatic individual may becomes more symptomatic once knowing that they carry HCV virus. This may due to prior denial of symptoms or occur against the background of increased anxiety about the diagnosis.
• As part of work-up for a variety of symptoms and findings, often - but not necessarily -including abnormal liver tests:
  • Fatigue
  • Jaundice (relatively rare)
  • Fluid retention in abdomen or legs
  • Skin and joint complaints
  • Red blood cells in urine
  • Abnormal looking liver and/or spleen on ultrasound or CT
  • Liver tumor on imaging
  • Mental status changes, disturbance of sleeping pattern

Testing for HCV

Historical aspects
Testing has dramatically improved safety of blood products

• In the seventies it became apparent that the world's blood supply was contaminated with a virus causing liver disease that was Hepatitis A nor Hepatitis B ("nonA-nonB hepatitis")
• In 1989 the cause of transfusion hepatitis was finally discovered: The HCV virus
• By lack of the availability of a specific diagnostic test, transaminase levels (ALT/SGPT, AST/SGOT) were often used to screen potential donors for the risk of infectivity of their blood. All with elevated enzymes were rejected as blood donors
• Since the availability of anti-HCV and HCVRNA testing it appeared
  • The virus can be present in spite of normal liver tests (enzymes): This was one of the sources of until then unrecognized infectious blood
  • Many with abnormal liver tests have no infection as a cause and not all need to be excluded from donating blood .
  • Fat accumulation causing steatohepatitis (NASH) is one of the most common non-infectious sources of blood

Current testing

• Key in diagnosis and therapy of HCV infection
  • HCV screening, typically by testing for the antibody (anti-HCV)
  • The presence of anti-HCV in blood means: the person was or continues to be exposed to the HCV virus. This is confusing and unlike anti-bodies in other diseases where the presence often indicates resolution/immunity for the disease (for example anti-HAV and anti-HBs indicating immunity for hepatitis A and B)
  • Molecular testing of the virus (HCVRNA testing ) proves the presence of the virus itself, circulating or present in cells
  • Presence of HCVRNA
  • Confirms the presence of virus / active infection
  • Monitoring of the level in blood (viral load) enables to assess response to therapy, or lack of response /persistence and therefore often the futility of continuation of a specific therapeutic regimen
  • To confirm eradication / sustained viral response to viral therapy
  • Should be considered in patients with a diminished immune response who may not develop HCV antibodies (Patients on dialysis of immunosuppressive therapy, patients with HIV infection)
• Chronicity of HCV infection is common - (50-85% of those infected)
  • Occurs when the body fails to spontaneously eradicate the virus
  • The younger acquired, the more benign the course and the higher the likelihood of spontaneous clearance
  • Once the body has failed to eradicate HCV, chronic viral presence leads to ongoing inflammation of variable severity. This may lead to scar formation (fibrosis)
  • Fibrosis may lead to cirrhosis in some 20% of infected individuals over a 20-30 years period, faster if subject to confounding risk factors (alcohol, obesity etc.)
  • Risk liver failure
  • Risk of hepatocellular carcinoma (a few % of all infected individuals!)
  • Important : HCV infection tends to be a very slowly progressive disease, rarely ever leading to major disease in the first 10-20 years.
• Therapeutic options
  • Rapidly increasing for suitable candidates
  • Cure now possible in 40-80% of selected individuals!
  • Major side effects of interferon and ribavirin
  • Very costly and also therefore beyond reach of too many world wide
  • Suitable candidates: No major co-morbid disease, not too advanced disease and able to tolerate side-effects
• HCV infection has become a leading cause of death in HIV co-infected individuals
  • Ironically: HIV infected patients used to die from horrible opportunistic infections that are now well controlled by HAART therapy. The greatly improved survival created to opportunity to develop complications of HCV infection, and often faster than in other HCV infected individuals.
• Too many infected individuals go unidentified until they present with complications
  • Missed opportunity for timely
    • Treatment
    • Elimination of risk factors for worse outcome (obesity/insulin resistance, alcohol)
    • Vaccination for HAV and HBV, diseases that may be disastrous in HCV infected individuals
• Transfusions of blood products
  • HCV infection is a blood borne disease
  • Contaminated blood products and equipment (dialysis machines) used to be a major source of transmission.
  • Transmission and disease were also a significant cause of disease and death in medical personnel
  • Effective measures to prevent transmission (screening of blood products, needle hygiene, separate dialysis equipment for specific patient categories etc) have dramatically increased the safety of blood products and needle associated procedures:
    Example, the risk of transmission through blood products in the USA is in recent decades reduced from 3-5 to less than 1:150,000 per 100 units of blood.

The Future

• HCV will continue to put a tremendous burden on future health care expenditures
• Many patient have already often irreversible damage.
• An enormous number of infected patients, many of them as yet unidentified and who contracted blood through blood products or past iv drug abuse are at risk of developing cirrhosis with all its complications including hepatocelluar carcinoma.
• Once advanced cirrhosis with complications, viral eradication (still) very difficult, often impossible or associated with detrimental complications
• Continued contamination / infection through needle transmission # illicit drug use
• A fraction of all patients will be eligible for liver transplantation: this is beyond the reach of most worldwide and if available: the organ shortage is tremendous