Viral load tests are blood tests that measure HCV ribonucleic acid (RNA, or genetic material) in the blood. The presence of viral RNA indicates that the virus is actively replicating (reproducing and infecting new cells). A viral load test is usually first done after a person has tested positive for exposure to HCV based on an antibody test. A blood sample is taken and the amount of HCV RNA in a milliliter of blood is measured. Viral load tests confirm whether an individual is actively infected with HCV. Viral load test results were previously measured in number of copies, but are now typically reported in terms of International Units per milliliter (IU/mL).

Types of HCV Viral Load Tests
There are two categories of HCV viral load tests:

Qualitative viral load tests — These tests determine the presence of HCV RNA in the blood. This type of test is usually used to confirm chronic infection with HCV. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative.

Quantitative viral load tests — These tests measure the amount of virus in one milliliter of blood. They are often used to assess whether or not treatment with interferon or interferon plus ribavirin is likely to be successful and, later, if treatment is working.

There are currently three tests commonly used for HCV viral load testing:

Polymerase chain reaction (PCR) — PCR tests detect HCV RNA in the blood, which indicates current active infection. This type of quantitative PCR test is very sensitive, and can measure as few as 50 IU/mL.

Branched-chain DNA (bDNA) — The bDNA method quantitative viral load testing is easier (and cheaper) to use for a large number of samples, but only measures viral loads greater than 500 IU/mL. This means that if a person has a viral load below 500 IU/mL, HCV could be present in the blood but not detected by the test.

Transcription-mediated amplification (TMA) — TMA technology allows for the amplification and detection of nucleic acids (components of genetic material) in the blood. This test can measure as few as 5-10 IU/mL. This newer test appears easier and cheaper to use, streamlining test processing and producing consistent, reliable, and more rapid results.

Interpreting Viral Load Test Results
HCV viral load is often reported as low or high.
Expressed as copies/mL:
·Low: less than 2 million copies
·High: more than 2 million copies

Expressed as International Units (IU/mL):
·Low:less than 800,000 IU/mL
·High:more than 800,000 IU/mL

If no HCV RNA is found by a test, a person’s viral load is said to be undetectable. Note that whether viral load is undetectable depends on which test is used. PCR and TMA tests can measure viral loads much lower than those a bDNA test can detect. Importantly, the blood of an individual with a very low viral load may still contain HCV even though the current tests cannot measure it; that is, the virus may not have been truly eradicated from the body.

Viral load test results can vary depending on how a blood sample is handled and stored. Furthermore, results may vary from lab to lab. For this reason, most experts recommend that people should get their viral load testing done by the same laboratory each time, so that results are more comparable.

Changes in viral load are sometimes expressed in terms of logs. A log change is a 10-fold increase or decrease. For example, a change from 1,000,000 IU/mL to 10,000 IU/mL is a 2-log decrease.

Converting copies per milliliter to Inter-national Units
There is no standard conversion formula for converting the amount of HCV RNA reported in copies per milliliter to the amount reported in International Units. The conversion factor ranges from about one to about five HCV RNA copies per IU. Usually the lab report will list the conversion from IU/mL to copies/mL.

See Table 1 for a conversion of common viral load tests from IUs to copies.

Table 1: Conversion Chart

Assay	Conversion Factor
Amplicor HCV Monitor v2.0 (manual procedure)	1 IU/mL = 0.9 copies/ml
Cobas Amplicor HCV Monitor v2.0 (semi-automated procedure)	1 IU/mL = 2.7 copies/ml
Versant HCV RNA 3.0 Quantitative Assay	1 IU/mL = 5.2 copies/ml
LCx HCV RNA Quantitatiive Assay	1 IU/mL = 3.8 copies/ml
SuperQuant	1 IU/mL = 3.4 copies/ml

Viral load given in IU

Giving the viral load in IU probably soon will replace all other ways to express the viral load - until recently it was expressed most frequently in eq or Meq. But at the moment and in old lab reports a wide variety of ways to give the viral load still can be found.

The IU = International Unit for the hepatitis C viral load is a unit more or less arbitrarily fixed. Labs now can take part in international comparison tests using a calibrated sample and thereby normalize their results to an international standard. So, in the future results from different laboratories should be directly comparable.

For converting numbers from eq to IU and vice versa, different labs use different conversion factors, in the range from 2 to 5 viruses per IU. If you do not know the factor that your lab uses, using a factor of three might be reasonable. That means: Viral loads given in eq/ml have to be divided by three to get the viral load in IU/ml. And, viral loads given in IU/ml have to be multiplied by three to get the result in eq/ml.

Uses of Viral Load Test Results
Viral load test results have many uses, such as confirming active HCV infection, and predicting and measuring HCV treatment response before, during, and after therapy. Higher HCV viral loads may be associated with a greater risk of HCV transmission, particularly transmission from mothers to infants during pregnancy or birth. Viral load has not been correlated with the risk of sexual transmission. Furthermore, a correlation between HCV viral load and disease progression has not been shown.

Confirming active HCV infection — After a person has tested positive for HCV antibodies, an HCV viral load test is usually performed to confirm active HCV infection. This test is necessary because in up to 25% of people exposed to HCV, the virus can be cleared on its own.

Before treatment — Viral load measurement can help predict how well HCV treatment will work.

The lower the pre-treatment viral load, the more likely it is that a person will respond to current HCV therapies.

During treatment — A decrease in viral load while on therapy indicates that treatment is working. A treatment is said to produce a complete virological response if it reduces viral load to an undetectable level. After 12 weeks of antiviral treatment, a 2-log drop in viral load or elimination of detectable HCV is an indication that the medications are working. If a person does not achieve a 2-log drop in viral load or elimination of detectable HCV after 12 weeks, it is unlikely that he or she will be able to eradicate HCV from his or her body. Viral load tests during treatment can also detect viral breakthrough, or increases in viral load that occur after a previous undetectable test result.

Note: A log drop in viral load is measured by decreasing the number by one zero. For instance, a one log drop in a viral load of 1,000,000 International Units is 100,000 International Units; a two log drop in a viral load of 1,000,000 International Units is 10,000 International Units.

After treatment — Viral load measurements can be used after cessation of therapy to monitor for relapse—that is, to see if the virus becomes detectable again after being undetectable when treatment was completed.

http://www.hcvadvocate.org/news/newsLetter/advocate1003.html

Viral Load Tests

The viral load test measures the amount of HCV virus in your blood. There are different techniques for doing this:

PCR - Polymerase Chain Reaction. Is the most accurate test available at present. It involves the amplification of the nucleic acid associated with the virus several million times, by using the "chain reaction", in order to bring it up to measurable levels. As the amplification process is fully controlled, the quantity of original material present in the sample (the viral load) can be calculated with a great degree of accuracy.bDNA - Also tests for the presence of the virus in the blood, but is less sensitive than the PCR test, picking up only levels over 200,000 virus equivalents/ml.

Viral Load

by Albrecht Ernst ernst@infp.fzk.de

I.) What is Viral Load ?

Your viral load is the amount of viruses present in a given volume of your blood (usually 1 millilitre = 1 cubic centimeter). More precisely, it means that the amount of hepC genetic material found in your blood corresponds to as many hep C viruses as the given number says. Therefore the given number denotes 'viral equivalents'.

And now, of course, you would like to know whether your viral load is low or high....

Although there is no general consensus on the definition of 'low' and 'high' with respect to the viral load, data from the Web pages of the National Genetics Institute give you an idea: As can be seen there, the average viral load is at 3.2 Million eq/ml. - So, to make a simple scheme I would propose the following classification:

Viral Load Chart

Viral Load in eq/ml	Classification	Remarks
below 200.000	very low	below detection limit of bDNA test
200,000-1,000,000	low
1,000,000-5,000,000	medium	average viral load at 3,200,000 eq/ml
5,000,000-25,000,000	high
above 25,000,000	very high

Expressed in IU, the average viral load is at 1 Million IU/ml. All these classifications of viral load of course make sense only for patients that are not being treated against HCV.

II.) "Not detected"

The viral load can range from "not detected" to hundreds of millions. The meaning of "not detected" or "negative" differs, depending on the test used. In my lab, the detection limit for the "quantitative" HCV RNA test by "PCR" is 200 virus equivalents/ml (and with the "qualitative" test they can detect down 100 virus equivalents/ml ). The less expensive quantitative "bDNA" test has a detection limit of about 200,000 virus equivalents/ml, which makes it less sensitive, but above its detection limit it is more accurate than the PCR test.

So, when you are "negative", maybe you have no hepatitis C virus in your blood. But maybe also, you do have hepatitis C virus in your blood, but the number of viruses is lower than the detection limit.

III.) "Positive" - What's important to note, besides the pure numbers

When you get back the result of your HCV RNA quantitative test, and when the lab was able to determine the amount of virus in your blood, then it is important to write down not only the number, but also in what units this number is given.

A) Volume
The volume of blood that the number refers to is usually one millilitre. But some labs give the number for 20 microlitres = 1/50 millilitre. So in these cases you have to multiply the result of the viral load by 50 to get the number for 1 millilitre.

B) Amount of Virus
Unfortunately, there are several ways to express the viral load. So, in order to be able to compare different results, you have to know how to convert these numbers to some standard format, which I would say is just the plain number of viruses per millilitre, like 1.5 Million/ml, or 1,500,000/ml.

1.) By weight
Sometimes, the lab reports the amount of genetic material found by its weight. 1 pg (pico-gram) of genetic material corresponds to about 1 million virus equivalents, so, if your lab result is given in picograms, just multiply the lab result by 1,000,000, and you have the number of viruses.

2.) By virus count

a.) Plain numbers
Often the virus count is expressed as a plain number, like 1.73 million, or 1,730,000 or 1730000. Millions sometime are abbreviated by the prefix "M" (Mega). So when you see 1.73 Meq/ml, it means 1.73 Mega-equivalents/ml or again 1730000 equivalents/ml.

b.) Exponential format
Large numbers are often expressed in exponential form, that means a number, multiplied by 10 with an exponent. To convert this to normal numbers, append as many zeroes to a "1" as the exponent says, and multiply this with the number. In some lab report, the viral load was "Hep C RNA Quant 17.3 x 10(exp) 5 equivalents/ml". So, with 5 as exponent, you have to append 5 zeroes to an "1", that gives 100000, and multiply this with the number 17.3, that gives 1730000 as the viral load. Normally this would be written 1.73x10(exp)6, or 1.73x10⁶ , which are the same number. At the same time, 17.3x10⁵ = 1.73x10⁶ = 1,730,000

c.) Logarithmic format
Now, recently some people express these numbers also in logarithmic form (logarithmic transformed number).

log(1730000)=6.24

6.24 is the logarithmic transformed number of the viral load of our above example.

A result of 3.5 for a viral load, that someone reported, seems to be such a number (unless he forgot to write down a "10" and an exponent). You need a calculator to convert this. You have to use the function 10^x, where you have to replace x with the logarithmic number, in the above case 3.5. The result would be 10^3.5 = 3162 virus equivalents per milliliter. When you take the logarithmic number from the first example, 6.24, you have to calculate 10^6.24 = 1730000 , and here we have the original number of virus equivalents again.

If you don't have a calculator, you can estimate the order of magnitude of a viral load expressed as a logarithmic number. From the logarithmic number, you take the first digit (to the left of the point ) and add 1 to this number. This gives you the number of digits that your viral load has (expresses as a plain number).

Example: Logarithmic number 6.24
Left of the point is "6". 6+1 = 7
The number that gives the viral load is 7 digits long, that means it is between 1,000,000 and 9,999,999 (digit # 1 234 567).

The next digit ( right of the point of the logarithmic number ) shows whether you are high or low in the range.

In case ( but I have never seen that ) you have a logarithmic number and a blood volume other than 1 ml, you have to convert the logarithmic number to a plain number *first*, and then correct it to correspond to 1 ml !

Therefore it is important to have a close look at your lab report and see in what units the result is given !

Viral Load Chart

Viral Load Equivalents per Milliliter (EQ/ML)

Conversion to Logarithmic Form

(Viral Load is how many viral particles per ML of blood)

*[HCV-RNA (qPCR)-negative] is defined as less than 100 copies/ml of hepatitis C viral RNA as measured by the National Genetics Institute assay. Keep in mind, different labs do the PCR test differently. There is no set protocol for this test as of yet so results vary from lab to lab.

Viral Load in eq/ml	Classification	Remarks
below 200.000	very low	below detection limit of bDNA test
200,000-1,000,000	low
1,000,000-5,000,000	medium	average viral load at 3,200,000 eq/ml
5,000,000-25,000,000	high
above 25,000,000	very high

Conversion to Logarithmic Form

EQ/ML	Log (EQ/ML)	EQ/ML	Log (EQ/ML)
100,000	5.000	5,250,000	6.720
150,000	5.176	5,500,000	6.740
200,000	5.301	6,000,000	6.778
250,000	5.398	6,250,000	6.796
300,000	5.477	6,500,000	6.813
350,000	5.544	7,000,000	6.843
400,000	5.602	7,250,000	6,860
450,000	5.653	7,500,000	6,875
500,000	5.699	8,000,000	6.903
550,000	5.740	8,250,000	6.916
600,000	5.778	8,500,000	6.929
700,000	5.584	9,000,000	6.954
750,000	5.875	10,000,000	7.000
800,000	5.903	10,500,000	7.021
850,000	5.929	11,000,000	7.041
900,000	5.954	11,500,000	7.060
950,000	5.978	12,000,000	7.079
1,000,000	6.000	12,500,000	7.097
1,050,000	6.021	13,000,000	7.113
1,100,000	6.041	13,500,000	7.130
1,150,000	6.060	14,000,000	7.146
1,200,000	6.079	15,000,000	7.176
1,250,000	6.097	16,000,000	7.204
1,300,000	6.113	17,000,000	7.230
1,350,000	6.130	18,000,000	7.255
1,400,000	6.146	19,000,000	7.278
1,450,000	6.161	20,000,000	7.301
1,500,000	6.176	21,000,000	7.322
1,550,000	6.190	22,000,000	7.342
1,600,000	6.204	23,000,000	7.361
1,650,000	6.217	24,000,000	7.380
1,700,000	6.230	25,000,000	7.398
1,750,000	6.243	26,000,000	7.414
1,800,000	6.255	27,000,000	7.431
1,850,000	6.267	28,000,000	7.447
1,900,000	6.278	29,0500,000	7.362
1,950,000	6.290	30,000,000	7.477
2,000,000	6.301	35,000,000	7.544
2,200,000	6.342	40,000,000	7.602
2,250,000	6.352	45,000,000	7.653
2,500,000	6.398	50,000,000	7.699
3,000,000	6.477	55,000,000	7.740
3,250,000	6.511	60,000,000	7.778
3,500,000	6.544	70,000,000	7.845
4,000,000	6.602	75,000,000	7.875
4,250,000	6.628	80,000,000	7.903
4,500,000	6.653	90,000,000	7.954
5,000,000	6.699	99,000,000	7.995

What do viral loads mean?

By Tamra B. Orr/Jan 2009

Most of us carry around a long list of important numbers in our heads, ready to be pulled out whenever they are needed. We remember our social security numbers, telephone numbers, addresses and zip codes, birth dates and others such as checking account numbers or lock combinations. For patients living with chronic hepatitis B or C, there is another number that joins the ranks: their viral load. It’s a number they usually learn soon after they are diagnosed with the condition, and over the years, although the number typically goes up and down, it remains an important one to remember.

Simply put, a viral load is the amount of virus found in each milliliter (mL) of a person’s blood. “It is reported as copies/mL, or more recently as IU/mL, or international units per milliliter,” explains Dr. Paul Thuluvath, director of the Institute of Digestive Health and Liver Disease at Mercy Medical Center in Baltimore. Converting IU/mL to copies /mL is complicated because several different assays can be used to measure viral load. According to Hepatitis C Support Project’s “HCSP Fact Sheet,” 1 IU can equal between 0.9 copies and 5 copies of the hepatitis C virus, depending on which test was used.

“Most labs give both values, and in the future it may be given only as IU/mL,” says Dr. Philip Rosenthal, medical director of the pediatric liver transplant program at University of California, San Francisco. “Viral load refers to the number of viral particles or amount actually present in the blood or other body fluids. Obviously, the more viral particles present in the blood or fluid, the more likely the virus can be spread to another person.”

The number does not stay constant, however. “It fluctuates and is not considered absolute,” says Dr. Silvia Degli-Esposti, hepatologist and gastroenterologist at the perinatal hepatitis program at the Women and Infants Hospital in Providence, R.I.

One of the first steps following the initial diagnosis of either hepatitis B or C is establishing a beginning viral load. It is typically done through specific blood tests known as quantitative HCV RNA or HBV DNA. This number helps determine what – if anything – is going to happen next.

Knowing the numbers

“Viral load is a measure of the severity of the viral infections,” says Dr. Rosenthal. “The higher the viral load, the more virus that is present and the more chance for the virus to cause harm or injury.

”For those with HBV, knowing the viral load is an essential element in deciding on treatment strategy. An HBV patient’s viral load “could be billions or many millions,” says Dr. Thuluvath. “When it is less than 10,000 IU/mL, the standard practice is not to treat it. We monitor the levels during treatment. Viral loads in HCV could be many thousands or millions.” Treatment for either virus is assessed by a decrease in viral loads; it’s a key to judging overall treatment response – hopefully all the way to where the virus is undetectable.The viral loads in hepatitis B and C are different. Dr. Ned Snyder, chief of clinical gastroenterology and hepatology at the University of Texas Medical Branch in Galveston, explains, “In hepatitis B, there is a close correlation between the height of the viral load and prognosis. The higher the viral load, the more likely one is to develop cirrhosis or hepatocellular carcinoma (primary liver cancer). Also there are minimal levels of the virus below which treatment in most cases is not necessary.

“On the other hand, the viral load in chronic hepatitis C has nothing to do with prognosis,” Dr. Snyder continues. “There is no correlation between the level of virus and the state of the disease.

One may have 100,000 IUs and cirrhosis, and someone with 5 million IUs may have minimal disease. In hepatitis C, the viral load is primarily useful in guiding treatment. The goal of treatment is to make the viral load undetectable and have it remain undetectable after treatment is completed.” The viral load in hepatitis C has a direct connection to treatment success. Research indicates that for a patient with a high hepatitis C viral load, pegylated interferon and ribavirin are only about 40 percent effective, while those with low viral loads have an effectiveness rate closer to 56 percent. The success of various treatments also depends on other factors including the amount of liver damage already present when the diagnosis is made and how long the person has had the virus, as well as the person’s weight, age and ethnicity. While liver damage can be significantly influenced by lifestyle choices and diet, the viral load for hepatitis B and C patients is not. “Unfortunately, there is not much patients can do themselves to alter their viral load,” Dr. Snyder says. “Milk thistle and other herbs have not been shown to make a difference.” So although they do not change the viral load, Dr. Rosenthal reminds patients to avoid “medications, herbs or drugs such as alcohol that are known to be hepatotoxic” because they increase the damage being done to the liver.

Other tips

What other information should patients and their families know about viral load? Drs. Rosenthal, Snyder, Thuluvath and Degli-Esposti suggest the following:

For either virus, the higher the viral load, the more likely the virus can be transmitted to another person.
Viral loads should always decrease with appropriate treatment.
It is not useful to monitor hepatitis C viral loads when you are not receiving any treatment.
High viral loads do not necessarily indicate severe disease in hepatitis C.
The HCV RNA or viral load will vary significantly from month to month in patients not receiving interferon/ribavirin, but this does not mean anything.
Do not panic if you hear the viral load is in six or seven figures as this is the usual range with hepatitis C.
In hepatitis B, high viral loads may predispose patients to liver cancer even in the absence of cirrhosis.
In adults with chronic hepatitis B, there is some evidence to suggest that the longer the viral load is high, the more the risk of development of hepatocellular carcinoma.
The field of hepatitis B has changed markedly in recent years, and many generalist physicians are not aware of some of the new concepts and treatments in hepatitis B.

Viral loads can be complicated and confusing for many of us. Dr. Degli-Esposti says, “Explaining viral loads to patients is one of the hardest things I do. They rarely ever understand exactly what I am trying to convey to them.” Instead, our viral load is just one more number we tuck away on our individual internal lists and recall whenever it’s time for a new test. But understanding the significance of that number can help us make informed treatment decisions.

http://www.liverhealthtoday.org/viewarticle.cfm?aid=392

Albrecht Ernst ernst@infp.fzk.de

Hepatitis C Viral Load Is About More Than Numbers

A DGReview of :"Hepatitis c viral load does not predict disease outcome:
going beyond numbers"
Revista do Instituto de Medicina Tropical de São Paulo
06/05/2002
By Anne MacLennan

Hepatitis C viral (HCV) load does not correlate with the histological
evolution of the disease, and use of viral RNA quantification as a predictor
or determinant of severity of this disease is incorrect and of relative
value.

These are the views of Evaldo Stanislau Affonso de Araujo and colleagues
following an analysis of 58 patients at the Hepatitis Outpatient Clinic,
Department of Infectious and Parasitic Diseases, Faculty of Medicine,
University of Sao Paulo, (DMIP/FMUSP), Sao Paul, Brazil.

Participants all had chronic hepatitis C confirmed by liver biopsy and
detection of viral RNA in serum by nested polymerase chain reaction (PCR).
They were followed from 1997 to 1998.

They received interferon-alpha subcutaneously three times per week for 12
months, blood samples were collected and processed before treatment, and six
and 12 months after. The virus was serotyped.

A predominance of male patients with a mean age of 40 years was found and
although most patients acquired the infection through blood transfusion and
blood derivatives or through drug use, one third of the cases did not report
any suspected epidemiology. Diagnosis was mainly made upon blood donation.

Serotype 1 was the most common HCV subtype (30 cases, one co-infected with
serotype 4), although 34 percent of the patients were non-1 (4 were type 2
and 16 type 3). In most cases, viral load was below 500,000 copies/ml.

There was a predominance of patients with elevated HAI and slight structural
alterations. Median viral load decreased during the first six months of
treatment, but this reduction did not persist to the end of treatment.

A virological response was obtained in 21 cases and was sustained in 10
(17.2 percent), and a biochemical response was obtained in 19 cases and
sustained in nine (15.5 percent).

Histological analysis revealed a reduction in inflammatory activity and
maintenance of the favourable architectural profile.

These researchers conclude HCV RNA quantification plays a role in viral
dynamics and can provide an early prediction (24h to 48h) of a sustained
virological response. However, disease progression is more complex and does
not simply depend on viremia.

Interferon based therapies can reverse fibrosis in
HCV infected patients 05/31/2002
Progressive deposition of scar tissue (fibrosis) is the hallmark of chronic
hepatitis C infection. In its most severe form, the normal architecture of
the liver is distorted and cirrhosis is present. Over the last few years,
the mainstay of therapy for chronic HCV infection has been the use of
interferon in its unmodified or modified (pegylated) alone or in
combination with ribavirin. A new study reported recently in
Gastroenterology evaluates the role of the multiple interferon-based
regimens of the last decade on disease progression in treated patients. The
authors of this study evaluated pre- and post-treatment biopsies of over
3,000 patients who had been treated with interferon based regimens (10
regimens were evaluated). The analysis of these biopsies showed that the
degree of inflammation improved in 39% (regular interferon alone for 24
weeks) to 73% (optimal weight based pegylated interferon and ribavirin). In
addition, the rate of progression of cirrhosis was reduced in all treatment
regimens. The most astonishing finding though was that cirrhosis reversal
was evident in 75 of 143 patients (49%) who had histologic evidence of
cirrhosis prior to treatment. This study supports already existing ideas
that cirrhosis may be reversed. More importantly, it offers enormous hope
to patients who brave months of therapy in order to achieve viral
suppression. Maybe it is no longer too late to treat.
Reference:
Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH,
Albrecht J. Impact of pegylated interferon alfa-2b and ribavirin on liver
fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002
May;122(5):1303-13

Quest Diagnostics Incorporated Quest Diagnostics Announces Availability of HEPTIMAX Ultra-Sensitive Quantitative Hepatitis C Virus Test

TETERBORO, N.J., July 23 /PRNewswire/ -- Quest Diagnostics Incorporated (NYSE: DGX - news), the nation's leading provider of gene-based medical testing, information and services, announced the availability of a new ultra-sensitive viral load test for hepatitis C virus (HCV) that is approximately 10 times more sensitive than any other commercially available test. The test detects the level of hepatitis C virus based on an innovative application of transcription mediated amplification (TMA) technology to HCV testing. Quest Diagnostics developed the test and is the first laboratory in the world to offer it.

The new offering, called the HEPTIMAX(TM) viral load test, is capable of detecting minute quantities of hepatitis C virus down to as few as 5 International Units (IUs) per milliliter (ml). The ability to detect minute quantities of virus is useful to physicians in monitoring the effectiveness of various treatments for hepatitis C in patients. The HEPTIMAX(TM) viral load test not only delivers the maximum sensitivity but also offers the maximum range (5 IUs/ml to 8.3 million IUs/ml).

This proprietary test is ordered by physicians to monitor and confirm hepatitis C viral infection and to demonstrate post-treatment resolution of the infection. Because the HEPTIMAX(TM) viral load test combines the new TMA technology with traditional quantitative viral load testing using branched DNA technology, it simplifies patient management by allowing physicians to order just one test to cover the complete range of possible viral load values from 5 IUs to 8.3 million IUs per ml.

``The improved sensitivity of the HEPTIMAX(TM) viral load test is particularly relevant to physicians with the advent of new forms of hepatitis C therapeutics,'' said Jorge Leon, Ph.D., Vice President for Applied Genomics at Quest Diagnostics. ``New combination therapies utilizing sustained-action forms of interferon have shown better treatment responses in clinical trials that translate to lower levels of virus in patients.''

``Preliminary studies comparing the HEPTIMAX(TM) viral load test to other technologies and laboratories confirm it has superior sensitivity,'' said Dr. Peter Heseltine, Medical Director of Infectious Diseases for Quest Diagnostics. ``We are planning additional studies with other outside investigators to confirm and publish our findings.''

A study published in the October 2000 issue of the journal ``Hepatology'' utilizing a hepatitis C qualitative version of the TMA test, showed it to be a better predictor of end-of-treatment resolution than the other methods.

The new test was developed by Quest Diagnostics at Nichols Institute and is offered exclusively through Quest Diagnostics' national laboratory network. The highly sensitive HEPTIMAX(TM) HCV assay utilizes reagents from Bayer Diagnostics, based on proprietary TMA technology made available through Bayer's exclusive agreement with Gen-Probe, San Diego, CA.

The HEPTIMAX(TM) viral load test is the latest addition to Quest Diagnostics' comprehensive test menu for hepatitis C disease management. Quest Diagnostics provides a complete selection of tests for initial diagnosis, treatment monitoring and managing HCV infected patients. The menu also features the DupliType(TM) HCV genotype test, which helps physicians establish the appropriate duration of HCV therapy. Quest Diagnostics introduced the HCV DupliType(TM) test to provide subtyping for a broader range of hepatitis C viral isolates than was previously available using other technologies.

An estimated 4 million people are infected with hepatitis C virus in the United States, and approximately 130,000 patients currently receive treatment. Physicians monitor viral loads in infected patients to test the effectiveness of various types of combination therapies.

Quest Diagnostics' gene-based testing focuses on infectious disease, oncology and heritable conditions, and helps physicians target individual treatment regimes, monitor resistance to therapies and predict predisposition to various genetic conditions. Quest Diagnostics is a leading innovator in genomics testing, through its research and development center and esoteric testing laboratory, the world-renowned Nichols Institute, as well as through alliances with leading academic and commercial technology developers.

About Quest Diagnostics

Quest Diagnostics is the nation's leading provider of diagnostic testing, information and services with annual revenues of $3.4 billion in 2000. The company's diagnostic testing yields information that enables health care professionals and consumers to make better decisions to improve health. Quest Diagnostics offers patients and physicians the broadest access to diagnostic testing services through its national network of approximately 30 full-service laboratories, 150 rapid response laboratories and more than 1,300 patient service centers, where specimens are collected. Quest Diagnostics is the leading provider of esoteric testing, including gene-based testing, and is the leader in routine medical testing, drugs of abuse testing, and non-hospital-based anatomic pathology testing. Through partnerships with pharmaceutical, biotechnology and information technology companies, Quest Diagnostics provides support to help speed the development of health care insights and new therapeutics. Additional company information can be found on the Internet at: http://www.questdiagnostics.com

The statements in this press release which are not historical facts or information may be forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the outcome to be materially different. Certain of these risks and uncertainties are described in the Quest Diagnostics Incorporated 2000 Form 10-K and subsequent filings.

The HEPTIMAX viral load test and DupliType HCV genotype test are trademarks of Quest Diagnostics Incorporated.

SOURCE: Quest Diagnostics Incorporated

Understanding Log Changes in your Viral Load

( What is a 2 log Increase or Decrease ?)

An easy way to figure out log changes is to either drop the last "0"or add "0"to the original number. Drop one "0" for one log drop and two "00" for a two log drop.

Changes in viral load are often reported as logarithmic or "log changes." This mathematical term denotes a change in the value of what is being measured by a factor of 10. For example, if the baseline viral load by PCR were 20,000 copies/ml plasma, then a 1 log increase equals a 10-fold (10 times) increase or 200,000 copies/ml plasma. A 2 log increase equals 2,000,000 copies/ml plasma, or a 100-fold increase.

Using the same starting point of 20,000 copies/ml plasma, a 1 log decrease means that the viral load has dropped to 2,000 copies/ml. A 2 log decrease equals a viral load of 200 copies/ml plasma. An easy way to figure out log changes is to either drop the last "0"or add "0"to the original number.

Any change of less than one-half log is considered insignificant. More simply, if the viral load measurement has not tripled or dropped to one-third of its previous level, the difference might be unimportant. For example, if the baseline viral load were 20,000 copies, a rise to 60,000 or a fall to 7,000 copies might just be the result of transient changes. Repeat testing of a single specimen may give two quite different results and natural biological day-to-day variability of samples from the same person may cause measurements to vary slightly. Researchers believe that clinical decisions made on the basis of changes in viral load ideally should be based on measurements taken 2-3 weeks apart.
http://vhaaidsinfo.cio.med.va.gov/aidsinfo/newsletters/phe/phe6.htm

Hepatitis C and Viral Load

Are you confused about what viral load actually indicates regarding Hepatitis C? One of the most common misconceptions among Hepatitis C patients I speak with is that a higher viral load indicates a greater severity of the disease. This leads many to conclude that if their viral load is high they are in much more serious trouble than if it was low.

The study referenced at the bottom of this email finds that there is absolutely no correlation between viral load and the severity or progression of Hepatitis C.

It has previously been shown, in numerous studies, that lower viral load responds better to current interferon therapies. Doctors, therefore, often believe that people with higher viral load have a more serious condition---just because they are not good candidates for interferon.

High viral load does not, however, indicate that these patients have any more to worry about than anyone else with Hepatitis c.

In fact, I have spoken with people who have a viral load below 200,000 who could not get out of bed because of their physical reaction to the disease, as well as people in the tens of millions who feel just fine.

It seems, then, that viral load levels are only relevant as an indicator of possible interferon treatment success or when used to track treatment progress while trying to achieve a sustained virilogic response with interferon---NOT as an indicator of disease severity.

Incidentally, regardless of your viral load, Maximum Milk Thistle helps protect your liver 8 to 10x more effectively than any standardized milk thistle product. If you are taking any other milk thistle, you are not getting near the protection and support you should be. Go to MaximumMilkThistle.com for more info.

Is There a Correlation Between HCV Viral Load and Severity of Liver Disease?

The significance of hepatitis C virus (HCV) serum titers (HCV viral load) has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels.

Moreover, a direct association has been observed between serum titers of HCV and transmission rates of the virus.

The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease.

Fifty patients with HCV infection were included in the study. These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics.

Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique. Linear regression analysis was performed between serum viral titers and liver tests.

In addition, for the purpose of comparison, the subjects were divided into two groups: those with low viral titers (<=50 genome mEq/mL) and high titers (>50 mEq/mL).

Results

All subjects were men, with a mean+/-SD age of 47+/-7.8 years. The mean HCV RNA level in the blood was 76.3X10(5)+/-109.1 genome equivalents/mL.

There was no correlation between HCV RNA levels and age of the patients (r = 0.181), and the history or amount (g/d) of alcohol consumption (r = 0.07).

Furthermore, no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r = 0.175), bilirubin (r = 0.217), ALT (r = 0.06) and AST (r = 0.004) levels.

Similarly, no significant difference was observed between patients with low viral titers and high titers with respect to any of the parameters.

Conclusion

The authors conclude, “Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus. These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.”

Digestive Diseases Section (111D), VA Medical Center, 2002 Holcombe Blvd. Houston, Texas.

Reference
B S Anand and M Velez. Assessment of correlation between serum titers of hepatitis c virus and severity of liver disease. World Journal of Gastroenterology 10(16):2409-12411. August 15, 2004.

http://www.hepatitis-central.com/mt/archives/2004/10/

Hepatitis C (HCV) and Viral Load Questions and Answers

If you're being treated for hepatitis C virus (HCV) infection, your doctor is keeping track of your viral load.

What is HCV viral load? Why does it matter? WebMD got answers to your most frequently asked questions from two experts:

Frank Anania, MD, associate professor of medicine and director of hepatology at Emory University School of Medicine in Atlanta.
Brian L. Pearlman, MD, medical director of the center for hepatitis C at the Atlanta Medical Center, Atlanta; and associate professor, Medical College of Georgia in Augusta.

What is HCV viral load

Dr. Pearlman:Viral load is [the number of] viral particles floating in the blood. These are copies of the genetic material of the virus circulating though the body.

Dr. Anania: Viral load is based on technology that lets us measure extremely small quantities of hepatitis C virus RNA, the building block of the virus.

Can I be positive for hepatitis C if I don't have any measurable viral load?

Dr. Pearlman: Being "hepatitis C positive" means you have anti-HCV antibodies in your blood. Having HCV antibodies just means you've been exposed to the hepatitis C virus. You can certainly be antibody positive and not have any measurable viral load. One lucky thing this might mean is that you are one of the 15% to 40% of people who naturally clear the virus from their bodies. The other possibility is that the virus, during the time blood is drawn, was only temporarily undetectable. HCV viral load in the blood goes up and down, and the test might have caught it on a downswing. So before we tell someone they are negative, we ask them to have the test repeated.

Dr. Anania: After hepatitis C treatment, people still have antibodies to HCV. But if they have no detectable HCV viral load, that indicates recovery from infection -- that is, response to treatment and sustained remission. Over a period of time, if a later viral load test comes back detectable, that patient is in remission.

What is a low viral load and what is a high viral load? What does this mean?

Dr. Pearlman: Anything over 800,000 IU/mL is high. Anything under that is low viral load…Those with low viral load have a better chance of responding to treatment.

If my viral load is rising, am I getting sicker?

Dr. Anania: Not necessarily. With HCV, viral burden in hepatitis C does not necessarily predict the natural history of clinical disease. And therefore, patients need to understand that we use that measurement to help us guide therapy and response to therapy. We use it in conjunction with other types of laboratory data -- liver enzymes, liver biopsies sometimes, and viral genotype. Taken all together, these tests give us a snapshot of what is going on. But viral load numbers do not predict disease.

Dr. Pearlman: Unlike HIV, HCV viral copies do not directly affect a patient's prognosis and how fast disease is progressing in the liver. Remember, we are measuring blood levels, not what is happening in liver cells. HIV viral load does have a lot to do with quicker progression to AIDS. But HCV viral load does not tell you how fast hepatitis is progressing.

Does a drop in my HCV viral load mean my treatment is working?

Dr. Pearlman: We often talk about viral load numbers, but we really look at this in terms of logarithms. A "1 log" change is a 10-fold difference. Significant changes in viral load are a 2-log difference or a 100-fold change. This can be deceptive. If you have a viral load of 800,000 and it drops to 400,000, that seems like a big drop. But it's only changed by a factor of two. A change from 800,000 to 8,000 would be significant. This is important when we look at response to treatment. Twelve weeks after starting treatment, we see if a person's viral load has dropped 2 logs or more from baseline. If it has not, we are almost sure the treatment is not going to work.

How many months of no detectable viral load have to pass before I'm "cured?"

Dr. Anania: Generally we like to see six months of continued undetectable viral load after treatment to say a patient's virus is in remission. I cannot say they are "cured."

Dr. Pearlman: The best we can tell patients in 2004 is that after treatment, they have a "sustained virologic response" or SVR. That is defined as undetectable viral load by PCR to under 50 IU/mL for 24 weeks after treatment is complete. If that is the case, that is an SVR. SVR means it's 98% certain you are cured. But there are very rare cases where people relapse if you check their viral load a year or two out. But it doesn't mean you can't get hepatitis C again if you engage in high-risk behaviors.

Does the viral load respond differently to different brands of hepatitis C treatments?

Dr. Pearlman: The two major pegylated interferon products for treating hepatitis C -- Pegasys and Peg-Intron in combination with ribavirin -- in general show similar response rates. Slight variations may be reported in different clinical trials with different subsets of patients.

What are the different ways of measuring HCV viral load?

Dr. Pearlman: RNA is the genetic material all these tests measure. Most experts measure it by a technique called RNA polymerase chain reaction or PCR. There's also a technique called branched chain DNA, and a newer technique called transcription mediated amplification or TMA. These are just different ways of measuring HCV RNA. TMA probably gets down to detecting the fewest number of copies, but most labs use PCR.

HCV viral load used to be measured in number of copies. Now they use international units. What gives?

Dr. Pearlman: Different laboratories don't use the same standard for counting copies of HCV RNA. So we're now moving to an international standard.

Dr. Anania: You can still get a copy number. But using international units (IU) is a way to uniformly report data throughout the world. Many lab tests are reported in this way. It standardizes test results between different labs."

http://www.webmd.com/hepatitis/c-hcv-viral-load?page=2