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Diagnosis of Hepatitis C

A complete HCV diagnosis requires collecting all information needed to make recommendation with respect to treatment of the virus and/or complications of the disease. It provides important clues for the outcome of the disease.

This requires assessment / selection of a variety of options in the diagnostic armamentarium

1. Cause(s) identification by history and specific testing
   • Is it HCV alone, or HCV + other causes such as HBV, alcohol, fat or iron overload
   • Viral load
   • Genotype
   • Co-existing HIV (risk factors often identical!)
2. Severity
   • Clinical symptoms (fatigue, fluid retention, gastrointestinal bleeding, mental confusion etc)
   • Blood tests: bilirubin, transaminases, albumen, INR, Hemoglobin, white blood cells, platelets, (see also: liver tests explained)
   • Imaging: US, CT, MRI (likely cirrhosis, spleen enlargement, abnormal circulation in abdomen, fluid overload (ascites))
   • Histological findings or equivalents (what looks liver tissue like?)
   • Liver biopsy (the classical assessment)
   • Fibrosis markers in blood
   • Elasticity assessment (scar formation) with Fibroscan (widely in Europe, not yet approved by FDA)
   • Alternative scar assessment with MRI etc.
   • Presence of varices (abnormal vessels causing bleeding: often needs endoscopy)
3. Other patient characteristics
   • Other disease such as kidney failure, heart disease
   • Psychiatric disease
   • Ongoing addiction problems

This information enables a physician to provide an opinion and make recommendations with respect to

• The need and feasibility of therapy
  • Not all need treatment now (Minimal disease: wait until better therapy?)
  • Not all can be treated (Too advanced disease/contraindications)
  • Treatment can often be deferred to fit into plan (see below)
• The recommended therapy (dosage, duration vary depending further details)
• Preventative recommendations including
  • Vaccination needs (for HAV, HBV)
  • Infection prophylaxis needed in case of fluid overload
  • Bleeding prophylaxis medication in case of varices
  • Use of medications that may harm (high dosage Tylenol)
  • Screening for development of HCC (AFP, US/US/MRI)

How is the information used in making treatment recommendations?

This is best illustrated by discussing a few patients

Example 1: Janice
Janice is a 27 year old customer service clerk at a car dealership. She felt fatigued and saw her PCP. He found her to have abnormal liver tests and subsequently diagnosed her with hepatitis C infection: She had HCV antibodies in her blood (anti-HCV) and virus was detected by PCR testing. She was very upset, and frustrated that she had to wait 8 weeks to be seen by a HCV specialist because "the harm needed to be stopped promptly". Various friends had told her that HCV was incurable and you would die if no timely liver transplant would be done. Also, she felt uncomfortable, putting her partner at risk: Should they rather have protected intercourse with condoms?

The HCV specialist saw her and obtained some further information:

• She tended to be depressed, particularly in the fall, and depression was running in her family.
• She had always been in excellent health and had no other diseases whatsoever.
• She had on occasions (at the suggestion of her subsequently fired boy friend) between the ages of 20-22 years experimented with needles/cocaine
• She was now in a stable relationship with a great guy, and in fact engaged with the plan to get married 7 month from now. They could not wait to conceive but was there a future with HCV...?
• She had rarely had any sip of alcohol in her life.

The HCV specialist did a little further assessment (blood work including HIV testing, ultrasound) and then was able to provide information and suggestions/recommendations that should help to alleviate concerns:

• Fatigue is often a symptom of HCV, but there are many other causes of fatigue.
• Although IV drug users are at risk of contracting HIV, she had no HIV infection.
• Where she very likely contracted HCV less than 10 years ago, more advanced disease was most unlikely. Major harm typically would occur20-30 after getting infected. Even if she had been drinking more, 8 years would be very short to develop advanced disease.
• Being in a stable/monogamous relationship would barely justify condoms. HCV - unlike hepatitis B - is under most circumstances not an easily transmitted disease.
• Because HCV infection progresses slowly, treatment hurry is relative.
• Her HIV test was negative: reassuring.
• Her genotype was 1a, her viral load 2,3 million IU/L; the more difficult to treat case with need for 1 year of therapy if she wanted therapy
• Side effects are potentially a considerable setback. Depression is a major one: If the urge for treatment is somewhat relative, is it wise in a stressful period of life (planning the wedding) to add a major risk factor for ruining the wedding events? Note: there are many equivalents for wedding plans: just starting a new job or business, preparing for an exam and other important moments.
• Conceiving during or the first 6 months after HCV therapy is absolutely contraindicated because of the risk of fetal malformations. They should make up their mind: first conceiving and deferring therapy (from the hepatologist's view no objection), or first therapy and deferring conceiving.
• Pregnancy and delivery are as a rule without any significant risk for transmission of HCV from mother to child. Breast feeding is safe and not even contra-indicated.

Follow-up: After hearing all this, Janice deferred treatment and the hepatologist received a birth announcement of Xavier some 11-month later with a comment: Thanks for your encouragement; we want first a second one. Two years later she reappeared for an appointment. After some discussion ("I wanted to know what my liver looks like now") she underwent a liver biopsy. It showed mild inflammation and scarring. She wanted to be done with the virus. She was treated. It was a rough year and close monitoring by the nurse practitioner and the psychiatry team with use of anti-depressants led to permanent eradication of the virus. A year after therapy she was declared cured and only suggested to have in a few years once more HCVRNA testing done to reconfirm cure.

Her fatigue was quite a bit less after reassurances during her first visit and would come and go over time. She had her children tested and they had no virus.