Prediction of Liver Cirrhosis in Patients with HCV Chronic Infection
through Routine Laboratory Parameters: Myth or Reality?
Ivan Gentile*and Guglielmo Borgia
Department of Clinical Medicine and Surgery, University of Naples Federico II, Italy
- *Corresponding Author:
- Ivan Gentile
Department of Clinical Medicine and Surgery (Ed. 18)
University of Naples Federico II
I-80131 Naples, Italy
E-mail: [email protected]
Received date: August 28, 2013; Accepted date: September 02, 2013; Published date: September 04, 2013
Citation: Gentile I, Borgia G (2013) Prediction of Liver Cirrhosis in Patients with HCV Chronic Infection through Routine Laboratory Parameters: Myth or Reality? J Mol Genet Med 7:76.
Copyright: © 2013 Gentile I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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Noninvasive; Cirrhosis; HCV; Liver biopsy
About 150,000,000 people worldwide are estimated to be chronic
carriers of Hepatitis C virus (HCV) . Roughly, a quarter of
these patients evolve toward liver cirrhosis . Once cirrhosis has
been established, 4% per year of these patients progress toward a
decompensated disease with an annual death rate as high as 30%, and
about 1.6% per year develop a hepatocellular carcinoma (HCC) .
Therefore the presence of cirrhosis is a boundary layer that marks a
dramatic drop in the life expectancy and quality of life of HCV-positive
patients. Moreover, the diagnosis of cirrhosis prompts mandatory
screening for esophageal varices and HCC, and influences decisions
about timing of antiviral treatment.
How do physicians diagnose liver cirrhosis? Excluding the most
advanced stages of the disease, in which the diagnosis is based on
clinical observation (e.g. presence of ascites) and, in the absence of
clear signs of cirrhosis on ultrasound examination, endoscopy or on
blood count (e.g. low platelet count), liver biopsy, and the subsequent
histological evaluation of the liver tissue, is the most widely used
method for the assessment of liver cirrhosis. However, liver biopsy is
invasive and consequently it is associated with a not negligible rate of
complications (0.3-0.8%) and even death (0.01-0.3%) [4-7].
Several researchers have proposed non-invasive means to diagnose
liver cirrhosis [8-10]. Some procedures need an expensive machine to
measure liver stiffness (FibroScan) , others are based on a panel of
blood tests and a proprietary algorithm called “Fibro Test” . On
the other hand, other groups have devised scores based on routinely
available analytes [8,13-28]. Some scores were devised and validated
to predict advanced fibrosis (e.g., AP, FIB-4, CDS, the Pohl score and
the Forns score); some scores were able to predict also or exclusively
liver cirrhosis (e.g., GUCI, aspartate aminotransferase (AST)/alanine
aminotransferase (ALT) ratio, platelet count (PLT), APRI, CISCUN,
the Lok score, the Fibrosis index and the King’s College score).
The most frequently used scores able to predict cirrhosis and the
formulae used to calculate them are reported in Table 1. The table
also shows the sensitivity and specificity as calculated in the original
report of each method. No score has both 100% sensitivity and specificity.
However, some of these scores can be useful in diagnosing cirrhosis,
namely those with a high positive predictive value (PPV), and others in
ruling out it, namely those with a high negative predictive value (NPV).
Almost all scores listed in the table have a relatively low PPV. Only the
AST/ALT ratio by Sheth et al.  had a PPV of 100%. This finding
was not confirmed in other studies [27,29]. Although some scores have
a high NPV, but this value should be very close to 100% to make this
score a reliable screening test. Notably, positive likelihood ratios(i.e.
the probability of a positive test in patients with the disease divided by
the probability of the same finding in patients without the disease) arequite low except in the cases of the Fibrosis index and CISCUN ≥ 4,
and the negative likelihood ratio(i.e. the probability of a negative test in
patients with the disease divided by the probability of the same finding
in patients without the disease) are acceptably low only for CISCUN
≤ 1 and APRI ≤ 1.Interestingly, some scores (namely, Lok, CISCUN
and APRI) provide two cutoff values to identify patients at a high and
low risk of cirrhosis, respectively [13,27]. According to the authors,
the patients in the two tails could be spared liver biopsy because of
their high or low risk of cirrhosis. Patients in the middle (“gray zone”)
should undergo liver biopsy because they have an intermediate a priori calculated risk of cirrhosis. However, neither of these scores had a NPV
of 100% for the low-risk cutoff value and even the PPV was relatively
Table 1: Scores used to predict cirrhosis based on noninvasive, routinely-available parameters.
The real drawback of all these studies is that the comparison
was made with the standard method for assessing cirrhosis (i.e. liver
biopsy) which is per se in accurate . The “true gold standard” is
the histological evaluation of large surgical biopsies , which is
difficult to obtain in everyday clinical practice. Classical liver biopsy
had a 20% false negative rate for the diagnosis of liver cirrhosis when
compared with laparoscopic biopsy in an Italian study . This can
occur because the distribution of fibrosis is patchy, and a liver biopsy
sample represents only from one hundred-thousandth to one thirtythousandth
of the whole organ, and gives no information about the
remaining part of the liver. In fact, histology of long and thick samples
provides a better estimate of liver fibrosis than histology of short and
thin samples [31,33,34].
In conclusion, the ideal non-invasive procedure for the evaluation
of cirrhosis, namely one that is based on routinely-available markers,
that is easy-to-calculate, and, above all, that accurately discriminates
between patients with or without cirrhosis is not yet within our grasp.
Therefore, studies comparing the diagnostic accuracy of the abovedescribed
scores with that of the Fibro scan or the Fibro test and liver
biopsy are needed to identify the best, if not the ideal, score with which
to diagnose non-invasively liver cirrhosis in patients with chronic
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