S. Anand, Maria Velez, Department of Medicine, V. A. Medical
Center and Baylor College of Medicine, Houston, Texas 77030, USA
Correspondence to: Bhupinder S. Anand, MD, Digestive Diseases
Section (111D), VA Medical Center, 2002 Holcombe Blvd. Houston,
Texas 77030, USA. firstname.lastname@example.org
AIM: The significance of hepatitis C virus (HCV) serum titers
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
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).
All subjects were men, with a mean±SD age of 47±7.8 years. The
mean HCV RNA level in the blood was 76.3×105 ±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
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
Anand BS, Velez M.
Assessment of correlation between serum titers of hepatitis c virus
and severity of liver disease. World J Gastroenterol 2004; 10(16): 2409-2411
Hepatitis C virus (HCV) is a bloodborne pathogen that is endemic
in most parts of the world, with an estimated overall prevalence of
nearly 3%. Approximately 80% patients with hepatitis C
virus develop chronic infection, and progression to cirrhosis occurs
in nearly 20% of these subjects. Moreover, patients
with HCV-related cirrhosis are at an increased risk of developing
hepatocellular carcinoma, which is estimated to occur at the rate of
1.5% to 4% per year. In most individuals, liver
disease progresses slowly over several decades, but the rate of
progression is highly variable[3-5]. Whereas some
patients develop cirrhosis and end-stage liver disease within one to
two years of exposure, others may die of old age or an entirely
unrelated cause. Although it is mostly unclear why
some patients progress more rapidly than others, several factors
have been identified as having a role in disease severity. HCV
patients co-infected with hepatitis B virus (HBV) have an increased
risk of developing cirrhosis and ecompensated liver disease
as well as hepatocellular carcinoma. Several
researches have noted more severe clinical and histological
abnormalities in HCV infected chronic alcoholics compared to
non-alcoholics with HCV infection[9-12]. Other factors
associated with a more rapid course of liver disease include age at
acquisition of HCV infection, gender of the patient and presence of
Several studies have assessed the correlation between serum
HCV viral titers and different clinical and laboratory parameters.
Perinatal transmission of HCV from mothers to infants has been found
to be related to maternal HCV titers. The risk of HCV transmission
was found to be significantly higher (36%) among infants born to
women with HCV RNA titers of at least 106 per mL compared to none if
the titers were <106 per mL. HCV titers have been
found to be associated with responses to anti-viral treatment.
Patients with a baseline HCV viral load of ≤2×106
copies per mL have significantly better responses to anti-viral
therapy compared to those with higher viral titers.
Patients with HCV genotype 1 have been found in some studies to have
higher viral loads than those with HCV genotype 2[15,16],
although other studies have failed to observe such an association[17-19].
Previous attempts to assess the effect of viral titers on the
severity of liver disease have produced conflicting results and the
present study was designed to examine this issue in more detail.
Patients with chronic hepatitis C virus infection diagnosed on
the basis of a positive recombinant immunoblot assay (Riba) were
included in the study. All patients were negative for other causes
of chronic liver disease including hepatitis B virus infection.
Patients were interviewed with respect to alcohol use, and in those
with a positive history an assessment was made of the duration of
alcohol abuse and amount of daily consumption. Physical findings and
results of laboratory tests were recorded. All patients were
treatment-naive and were tested before the administration of
Quantitative HCV analysis
assay of hepatitis C virus levels was performed by the
branched-chain DNA (bDNA) technique (Quantiplex HCV-RNA; Chiron
Corporation, Emeryville, USA). The bDNA assay incorporates a series
of steps involving viral nucleic acid hybridizations to obtain
signal amplification. This technique is unlike the polymerase chain
reaction (PCR)-based assays in which the viral genome is amplified.
The results of viral RNA titers in clinical samples are expressed as
viral or genome milliequivalents per mL (mEq/mL). When the study was
first initiated, only the initial version of the bDNA assay (Quantiplex
1.0), which had a lower limit of detection of 350 000 viral mEq/mL,
was available commercially. Subsequently, the Chiron Corporation
upgraded the technique and the latest version of the assay (Quantiplex
2.0) was employed which has a lower limit of detection of 200 000
Descriptive statistical analyses were performed, and the
results are presented as mean±SD. Comparison of quantitative
measurements between groups was performed using Wilcoxon Rank Sum
Test. The Students t-test was used to assess changes in HCV RNA
levels in the same individual. Linear regression analysis was
employed to examine the presence of any correlation between serum
HCV RNA levels and different laboratory and clinical parameters
including the amount of daily alcohol consumption.
total of 50 patients were included in the study. These comprised of
34 patients with a history of alcohol use and 16 non-alcoholics. All
subjects were men, with a mean±SD age of 47±7.8 years. The mean
HCV-RNA level in the blood was 76.3×105
±109.1 genome equivalents/mL. There was no correlation between HCV
RNA levels and the age of the patients (r = 0.181), a history
of alcohol use or the amount (g/day) of alcohol consumption (r =
0.07). Furthermore, no correlation was observed between 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.
To further assess the effects of viral titers on the severity
of liver disease, the study subjects were arbitrarily divided into
two groups: patients with low viral titers (≤50 genome mEq/mL)
and those with high titers (>50 mEq/mL). The results are shown in
Table 1. Again, no difference was observed between the two groups
with respect to any of the parameters examined.
1 Comparison of
patients with low and high hepatitis C virus serum titers
HCV RNA level
genome mEq/L) n =
HCV RNA level
genome mEq/L) n
are expressed as mean±SD.
Several factors have been incriminated in predicting the rate of
progression of HCV-related chronic liver disease. These include age
at acquisition of HCV infection, gender of the patient, alcohol
abuse and co-infection with HBV and HIV infections[5-12].
Studies assessing the relationship between serum viral titers and
the severity of biochemical and histological abnormalities have
produced conflicting results. Some found no correlation between HCV
viral loads, and serum ALT values and the extent of histological
damage[16,17,19-21]. On the other hand, Kato et al.
observed significantly higher HCV RNA titers in patients with
chronic active hepatitis and cirrhosis compared to those with milder
histological abnormalities such as chronic persistent hepatitis.
Similarly, Fanning et al. in a study on Irish women who
acquired their HCV infection through the administration of
contaminated anti-D immunoglobulin, obtained a significant
correlation between serum HCV viral loads and the degree of hepatic
inflammation in liver biopsy specimens.
In the present study, we further assessed the association
between serum HCV RNA titers and several clinical and laboratory
factors. Linear regression analysis showed a complete lack of
correlation between the viral loads and age at presentation of the
patients and the extent of alcohol consumption.
Moreover, none of the laboratory tests showed any correlation
with HCV viral count. For the purposes of statistical analysis, we
subdivided the patients into those with low (≤50 genome mEq/L)
and high (>50 genome mEq/L) viral loads. Again, there was no
correlation between any of the clinical and laboratory parameters
and HCV viral loads (Table 1).
results indicate that the severity of liver disease is independent
of serum levels of hepatitis C virus. The precise mechanism by which
hepatitis C virus damages the liver remains poorly understood. Until
recently, a direct cytopathic effect of the virus was considered as
the primary form of liver injury caused by the virus. It has been
suggested that the degree of liver damage is the result of a
complicated interaction between the virus and immune response of the
host. Immune mediated liver damage is believed to be
initiated by HCV-specific T cells and is enhanced by HCV-induced HLA-A,
B and C and intracellular adhesion molecules[25,26]. The
results of the present study are important since they argue against
a direct cytopathic effect of HCV and support the hypothesis that
the pathogenesis of HCV-related liver damage is immune-mediated.
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