Diagnosis of Hepatitis C
A proper evaluation of HCV requires collecting all information that is needed to make recommendations with respect to treatment of the virus and complications of the disease. It provides important clues for the outcome of the disease (prognosis).
This may require a variety of diagnostic tools after initial history taking and physical examination.
- Cause(s) confirmation by history and specific testing
- HCV alone, or HCV + other causes such as co-existing HBV, alcohol, fat or iron overload
- Viral load (the amount of virus in the blood)
- Genotype (strain of the virus)
- Co-existing HIV (risk factors often identical!)
- 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, US etc.
- Presence of varices (abnormal vessels in wall of esophagus or stomach causing bleeding: often needs endoscopy)
- 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: Consider waiting 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 (for HAV, HBV)
All patients with chronic liver disease should be vaccinated for HAV and HBV if not immune
- Infection prophylaxis in case of fluid overload
- Bleeding prophylaxis medication in case of varices (β-blocker)
- Review use of medications that may do harm such as high dosage acetaminophen (tylenol)
Most drugs can be used but in case of more severe disease drugs interfering with clotting, kidney function etc. should be avoided (aspirin, NSAIDS).
In patients on concomitant HIV therapy, interactions need to be considered.
- Screening for development of HCC (AFP, US/US/MRI)
This is very important in patients with cirrhosis.
- Vaccination (for HAV, HBV)
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 in her blood by PCR testing. She was very upset, and frustrated that she had to wait 8 weeks to be seen by a liver specialist (a gastroenterologist with a focus on liver disease and also called hepatologist) because "the harm needed to be stopped promptly". Various friends had told her that HCV was incurable and she would die if a liver transplant was not done at some stage. Also, she felt uncomfortable, putting her partner at risk: Should they rather have protected intercourse with condoms? Could they conceive?
The liver specialist saw her and obtained further history:
- 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 suggestions of 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 4 months 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 liver specialist did further testing (blood work including HIV testing, ultrasound) and now was able to provide information and 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 and she at least had a perfect ultrasound. Major harm typically would occur 20-30 years 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 she lacked antibodies against HAV and HBV, she was recommended to be vaccinated for HAV and HBV.
- Because HCV infection progresses slowly, a rush for treatment is not necessary and waiting a couple of years unlikely to be harmful.
- Her genotype is 1a, her viral load 3,3 million IU/L. It indicates that she has the more difficult to treat type of disease with a pretty high viral load and with need for 1 year of therapy if given. Depending her initial response, she may if treatment be given qualify for addition of one of the newer agents.
- 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, in healthy females as a rule, without any major 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. Her hepatologist received a birth announcement of Xavier some 11-months later with the comment: "Thanks for your encouragement: We would now like a second child ". A healthy second child was born a year later.
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 pretty mild scarring. She wanted "to be done with the virus". She was treated after extensive information and education. It was a pretty rough year. Close monitoring and support by 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, as expected.
Example 2: Keith
Keith is a 44 years old male, working in home construction and also doing plumbing work. He is divorced but maintains great relationships with his former wife and 2 teenage kids. He had noted swelling of his legs that got worse over time and particularly bad by the end of the day. His friends noted that he really did not look that good lately. He had lost some 15 lbs of weight with no specific effort. He went to see his PCP who send him after limited testing right away to a liver specialist.
- Used i.v. drugs at high school during a brief period and now some 38 years ago
- Some 30 years of alcohol use, typically 3 -4 beers after work, and on weekends often a few more
- Gained significant weight (some 60 lbs since he got married)
- Family history of diabetes and an overweight father and grandmother
- Increasingly an impotence problem, frustrating
- Frequent use of ibuprofen because of pain in joints/legs/skin
- Greyish appearing male, very overweight, BMI 32
- Little spider-like vessels upper chest ("spider naevi")
- Distended belly with features suggesting fluid ("ascites")
- Small testicles ("testicular atrophy")
- Big legs with easily leaving thumbprint when pressing ("edema")
- Peculiar painful red spots and little red vessels on skin (fitting with cryoglobulinemia")
- Low albumin, slightly prolonged INR
- Low Hgb (anemia), low platelets (as often seen with enlarged spleen). High MCV (increased size of red blood cells, often in advanced liver disease)
- Elevated transaminases
- Abnormal proteins (cryoglobulins), RhF (Rheumatoid factor) present
- Glucose minimally elevated
- Kidney function normal, electrolytes normal, urine exam normal
- Anti-HBs and anti-HAV +ve, consistent with passed infection and indicating viral clearance (immunity)
- Anti-HCV +ve, HCVRNA 1,4 million IU/mL, genotype 2b
- alfa-fetoprotein 244 ng/ml (elevated and could indicate inflammation/regeneration or a tumor (Hepatocellular carcinoma)
Imaging: MRI of abdomen
- small shrunken liver, but no tumor
- big veins around in upper part belly
- big spleen
- abundant free fluid (ascites)
Impression of liver specialist
Very advanced liver disease ("decompensated cirrhosis") due to a combination of chronic HCV infection with excessive alcohol use. Joint/skin complaints caused by abnormal proteins (cryoglobulins).
Right now no possibility to treat with antivirals (very risky because of ascites). Impotence likely secondary to liver disease + alcohol (impaired testosterone production, testicular atrophy, more female hormone)
With him and family was discussed:
- Needs to stop alcohol completely. Was told that after stopping alcohol considerable improvement may occur.
- Needs endoscopy to see if varicose veins are present and if treatment is needed (bleeding risk)
- Needs to stop NSAIDS completely (provoke or worsen fluid retention) and avoid excessive salt
- Start low doses of spironolactone (50 mg)
Follow-up: Three weeks later he had another office visit. He had lost some 20 lbs of weight. This is likely loss of his excessive fluid retention. His kids had motivated him to stop and he had been successful without any specific counseling. He had still swollen legs and some abdominal fluid. Spironolactone was increased to 100 mg, and furosemide 40 mg was added. An endoscopy showed varices that were treated with rubber band ligation and therapy was initiated with nadolol to reduce pressure with a fu band ligation scheduled.
Four weeks afterwards he had lost a further 13 lbs and felt a lot better. Energy and appetite had improved.
Two months later an ultrasound conformed complete disappearance of fluid in his belly and legs had minimal fluid only. His protein in the blood (albumin) had increased to near normal values and his Hgb had increased. His varices were completely eradicated. His joints continued to hurt him intermittently. A few weeks in the South had been a major relieve, being back in the North had worsened his complaints.
Comments: Although HCV is a major contributor, this patient came really under attention due to the combined effects of alcohol and NSAIDS superimposed on the likely already HCV damaged liver. It may take 4-8 months but stopping alcohol can dramatically improve symptoms and chances.
Completely stopping NSAIDS is key in controlling fluid retention.
We now could consider to carefully try to eradicate the HCV virus, but with such advanced disease, it is tricky. If he is lucky, he tolerates therapy and the cryoglobulins may disappear and relieving him from the skin and joint problems. He needs future control for the development of new varicose veins. He remains at high risk for developing liver cell cancer (HCC) and he may deteriorate and need a liver transplant. His chances of becoming a candidate are much better now that he is off alcohol for a prolonged period. In addition he has started a weight loss program to lose real weight instead of excessive fluid overload.