ANALYSIS OF QUANTITATIVE INDICATORS OF LEADING
CLINICAL SIGNS OF ICTERIC CHOLESTASIS IN OPTIMIZATION
OF ITS THERAPY EFFICIENCY
Lola Izzatilloyevna Makhmudova* and Nilufar Sharipovna Akhmedova
Department of Faculty and Hospital Therapy, Bukhara State Medical Institute.
ABSTRACT
Assessing the competence of the information potential of quantitative
indicators of the leading clinical and biochemical signs of icteric
cholestasis (ICh) and optimizing its therapy. The material for the study
was quantitative indicators of clinical signs of cholestasis of 66
patients (18 male persons, and other persons of female) with chronic
diffuse liver diseases. Indicators leading clinical signs – (SICH)
jaundice and pruritus were quantified using a Likert scale. The number
of points was allocated to assess the range from 1 to 3, and it depended
on the severity of clinical signs leading SICH. The results showed that
the information potential of quantitative indicators of clinical signs
SICH was quite competent to differentiate into individual grades. At the same time, among
other clinical symptoms of cholestasis were the most informative indicators of jaundice.
From the perspective of clinical practice, it is claimed SICH division into separate
independent gradation. Leading clinical symptoms SICH possess sufficient information
potential to delineate it’s severity for certain types.
KEYWORDS: Icteric Cholestasis, Main Clinical Signs, Jaundice, Pruritus, Evaluation.
INTRODUCTION
Syndrome of intrahepatic cholestasis (SICH) is understood to mean a slowdown or cessation
of bile secretion associated with changes either in its consistency (thickening) or in the lumen
of the intrahepatic bile duct (narrowing) ducts.[1,2,3] Theoretically, any liver pathology can be
complicated by the development of ICh and only cases with a duration of more than 6 months
are classified as chronic. Between the concepts of cholestasis and hepatic jaundice should not
Volume 8, Issue 13, 236-243. Research Article ISSN 2277– 7105
*Corresponding Author
Lola Izzatilloyevna
Makhmudova
Department of Faculty and
Hospital Therapy, Bukhara
State Medical Institute. Article Received on 10 Oct. 2019,
Revised on 31 Oct. 2019, Accepted on 21 Nov. 2019
be equated. For, the term cholestasis is a broader concept, and hepatic jaundice is just its
integral part. Moreover, cholestasis can occur clinically with or without jaundice.[4,5,6] It is
clear that both forms of cholestasis, even within the same type of liver pathology, can
manifest themselves in various forms of its severity.[7]
The problem of the treatment of ICh continues to be one of the most important, due to the
low effectiveness of both nearby and long-term results of its treatment. Currently, the most
widely used regimen is ursodeoxycholic acid (UDChA), in which the daily dose is
determined based on body weight (12-15 mg / kg / day) of patients.
Clinical practice suggests the need to divide the severity of ICh into separate subunits with
their own range of variation. Theoretically, such an approach is able to enhance the
information potential of individual gradations, hence, their role in assessing the severity of
SICH. Consequently, the process of diagnosing ICh in the clinical practice of doctors who by
the nature of service often encounter them will be noticeably facilitated. Along with this,
favorable conditions will be created for early recognition of ICh and optimization of the daily
dose of the drugs used in its therapy.
Despite the obvious need, to this day practitioners do not have a convenient way to
differentiate the severity of ICh. For this reason, they are forced to experience not entirely
mandatory difficulties in the management of patients with liver pathology, accompanied by
ICh. Hence, any study, the vector of which is aimed at developing a competent method for
distinguishing the severity of ICh into separate species, is justified and in demand.
Assessment of the competence of the information potential of quantitative indicators of the
leading clinical and biochemical signs of ICh and optimization of its therapy.
MATERIALS AND METHODS
To achieve the objectives, a group of patients was examined, consisting of 66 people (of
which 18 were men and the rest were female), with chronic diffuse liver diseases,
accompanied by clinical and biochemical manifestations of SICH. In 20 patients, intrahepatic
cholestasis of pregnant women was verified, in 25, primary biliary cirrhosis (PBC) of the
liver, and in the remaining 21 patients, drug-induced cholestasis (DICH). The diagnosis was
bilirubin (TB) and its fractions, cholesterol (Ch), alkaline phosphatase (ALP) and γ -
glutamyltranspeptidase (GGTP) were studied using conventional methods.
Patients included in the study were prospectively selected from October 2016. until May
2019. The presence of skin itching and an increase in at least one of the following laboratory
parameters TB> 20.5 mlmol/l, Ch> 5.7 mlmol/l, ALP> 130 IU/l, GGTP> 61 IU/l served as
the basis for the inclusion of patients in the study circle. The reasons for the exclusion were:
chronic liver diseases without clinical and biochemical signs of cholestasis, cases of severe
cholelithiasis, skin diseases, allergic reactions.
Relying on specific indicators of the content of biochemical indicators of cholestasis: alkaline
phosphatase, hydrochlorothiazide, hydrochlorothiazide, and their values were divided into
separate gradations. The first pair of cholestasis indicators was relatively sensitive than the
second. Therefore, it was classified as an indicator of ICh of the first, and the next - as a
second order. The growth of the content of TB to 100 mlmol/L (N = 4 - 20.5), Ch to 6
mlmol/L (N = 3.3 - 5.7) and the activity of GGTP enzymes to 80 IU/L (N = 11 - 61) and
alkaline phosphatase up to 200 IU/L (N = 45 - 130) was evaluated as light (+) gradation.
Cases of increasing the TB content to 200 mlmol/L, Ch to 8 mlmol/L and GGTP activity to
100 IU/L and alkaline phosphatase to 300 IU/L were taken as the average (++) gradation. For
a pronounced (+++) gradation, cases of increasing concentration were perceived: TB = 300
and ↑ mlmol/l, Ch to 10 and ↑ mlmol/l and GGTP activity to 120 and ↑ ME/l and alkaline
phosphatase to 400 and ↑ ME/l. Indicators of KBP cholestasis were quantified depending on
their severity. The sum of the allotted points for the assessment of each individual cholestasis
CBC ranged from 0 to 3 units.
The patients involved in the study circle were informed orally about the research nature of the
work. The study was approved by the ethics committee of the Bukhara Medical Institute and
was conducted in accordance with the requirements of the Helsinki Declaration.
Statistical analysis was performed using the program STATISTICA 5.0. (Stat soft, USA).
The results were expressed as mean ± standard deviation (SD). Parametric data with a normal
type of distribution were compared using Student's t-test. A value of p <0.05 was considered
RESULTS
The task before this study obliged, first of all, to find opportunities for quantitative
assessment of the leading clinical signs of cholestasis. For this purpose, a modified Likert
scale for quantifying parameters was used. Using this scale, it is convenient to calculate the
quantitative parameters of various indicators, including medical ones. Moreover, they relied
as much as possible on the real parameters of the evaluated clinical signs of cholestasis. At
the same time, aspects of the involved quantitative assessment criteria, such as prostate and
convenience, were carefully considered.
The process of quantitative assessment of indicators of biochemical markers of them was not
particularly difficult. In order to successfully implement the latter, the only necessary
condition was the establishment of a boundary for varying the indicators of biochemical
indicators of cholestasis, characteristic of one or another type of their severity. Next, it was
necessary to calculate the number of corresponding points for each type of severity of
indicators of biochemical markers of cholestasis and summarize their amount.
As expected, the process of quantitative assessment of the main clinical signs of SICH:
jaundice and skin itching turned out to be somewhat laborious in terms of finding criteria for
their division. For its actual implementation, an indispensable condition was the
establishment of the possibilities of objective differentiation of the severity of clinical signs
of cholestasis into independent species. The most acceptable differentiating condition: for
jaundice, the extent of its distribution turned out to be, and for skin itching, the intensity of its
manifestations. If the spread of the jaundice symptom was limited to sclera, then it was
referred to as local. Cases of a symptom of jaundice not only in the sclera, but also in the
mucous membrane of the pharynx were called regional. When the spread of the symptom of
jaundice covered the sclera, the mucous membrane of the oral cavity and skin, then it was
recognized as total.
The basis for distinguishing a symptom of skin itching into individual species was its
intensity. The manifestation of skin itching with a frequency of 1 - 2 times during: the last 10
days was called - moderate (+), weeks - expressed (++), day with a predominant
manifestation in the evening - night time - painful (+++). The divided fragments of the
The basis for distinguishing a symptom of skin itching into individual species was its
intensity. The manifestation of skin itching with a frequency of 1 - 2 times during: the last 10
days was called - moderate (+), weeks - pronounced (++), day with a predominant
manifestation in the evening - night time day - painful (+++). The divided fragments of the
clinical signs of cholestasis were given the corresponding number of evaluation points.
Depending on the number of points scored, a gradation of the severity of a particular clinical
sign of cholestasis was established.
Leading clinical signs of cholestasis, taking into account their severity, were evaluated
quantitatively from 1 to 3 points. It should be noted that the information potential of
indicators of jaundice and pruritus was quite competent for the differentiation of the
syndrome of intrahepatic cholestasis into separate grades. At the same time, the most
informative were indicators of jaundice (Table 1).
The severity of the leading clinical and biochemical parameters of cholestasis: jaundice,
pruritus, alkaline phosphatase, GGTP, TB and Ch were also differentiated into separate
gradations based on their specific quantitative indicators.
Cases of growth of the TB content to 100 mlmol/l, Ch to 6 mlmol/l, GGTP to 80 IU/l and
alkaline phosphatase to 200 IU/l and the severity of pruritus to moderate intensity and
limitation of jaundice with sclera (+) were classified as mild (1-3 points) the severity of these
indicators. It was also recognized as average (3.1-6 points) with an increase in TB content to
200 mlmol/l, Ch to 8 mlmol/l, GGTP to 100 IU/l, alkaline phosphatase to 300 IU/l in the
presence of severe skin itching and staining yellow not only the sclera, but also the mucous
Table 1: Quantitative Assessment of Clinical Signs of the Syndrome of Intrahepatic
Cholestasis.
№ Clinico - biochemical
indicators of ICh
Short name of the component
of ICh
The value of the
attribute Poin
ts The value
of the
attribute Poin
ts The value
of the
attribute poin
ts
Clinical signs of ICh
1. Priritus P + 1-3 ++ 3,1-6 +++ <6,1
2. Jaundice J + 1-3 ++ 3,1-6 +++ <6,1
Biochemical signs of ICh
3. Total bilirubin (mlmol/l) TB 21 – 100 1-3 101 - 200 3,1-6 <201 <6,1 4. Cholesterol (mlmol/l) Ch 5,7 – 6,0 1-3 6,1 – 8,0 3,1-6 <8,1 <6,1
5. Alkaline phosphatase
(UЕ/l) ALP 131 – 200 1-3 201 – 300 3,1-6 <301 <6,1
6. γ -
glutamyltranspeptidase (UЕ/l)
GGTP 61 – 80 1-3 81 – 100 3,1-6 <101 <6,1
For a severe (<6 points) severity, cases of increasing TB, Ch, GGTP, and alkaline
phosphatase by 200 and ↑ mlmol/l, 10 and ↑ mlmol / l, 100 and ↑ ME / l and alkaline phosphatase 300 and ↑ ME / l, respectively, were taken with the presence of excruciating skin
itching, yellow sclera, visible mucous membranes and skin integument (+++). From a
practical point of view, such a division justified itself, because in complicated cases the
differentiation of their gradations was noticeably simplified.
The effectiveness of urotherapy was evaluated every 10-12 days on the basis of monitoring of
clinical (skin itching, jaundice, xanthomas and xanthelasma) and biochemical manifestations
of ICh. The main criterion for effectiveness was a decrease in the intensity of pruritus by
more than 50% and jaundice, not less than 30%, during the first 18–20 days of therapy. As
well as the positive dynamics of biochemical markers of cholestasis. A decrease in the
number and size of xanthomas and xanthelasm during 1 month of therapy was also evaluated.
In an alternative UDChA regimen, the daily therapeutic dose of the drug, in contrast to
traditional methods (where it is established taking into account body weight), was selected
taking into account the specific gradation of ICh (Table 2).
Table 1: Optimization daily dose ursodeoxycholic acid.
Gradation ICh Daily dose
DISCUSSION
Clinically, SICH is characterized by skin itching or jaundice with an increase in serum levels
of alkaline phosphatase (ALP), gamma glutamyltranspeptidase (GGTP), conjugated
bilirubin.[8,9,10] Symptoms of bile deficiency in the intestines are steatorrhea (light stool) and
diarrhea with loss of fluid, electrolytes and fat-soluble vitamins. Steatorrhea and diarrhea lead
to the development of malabsorption and subsequent weight loss. A deficiency of vitamins A,
D, E and K develops, a violation of bone mineralization. The elimination of endotoxins is
also reduced, as a result of which renal function suffers.[11,12] The mechanism of pruritus has
not been fully studied: there is a hypothesis about the role of a high concentration of bile acid
inherent in cholestasis, which can play an independent role or release unidentified
pruritogens.[13,14]
In our studies the frequency of clinical signs - pruritus was somewhat different and
significantly different from those of jaundice. If icteric syndrome occurred exclusively in all
patients included in the examination group, then pruritus was observed in 58 persons out of a
total of 66 patients, which amounted to 87.9%. In 25 (43.2%) cases of the study, disturbed
patients on average 1-2 times in the last 10 days. Syndrome pruritus similar intensity was
quantified to 1 point, which corresponded to a light (+) gradation. In 19 (32.7%) patients,
pruritus was more pronounced and more than 1–2 times weekly made itself felt. Similar cases
of pruritus itching were quantified more than 1, but not more than 2 points, which
corresponded to the average (++) gradation. In 14 (24.1%) cases of the study, the severity of
pruritus syndrome was very pronounced, sometimes painful with a daily manifestation,
mostly in the evening - night time. These cases of pruritus were evaluated from 2.1 to 3
points and corresponded to severe (+++) gradations of severity.
Thus, preliminary data obtained in the course of the present study allow us to conclude that,
from a practical point of view, it is very expedient to divide the of the syndrome of
intrahepatic cholestasis into separate gradations. At the same time, quantitative indicators of
clinical and biochemical signs of cholestasis proved to be a very useful criterion in their
adequate differentiation.
CONCLUSIONS
Based on the studies, it can be concluded that the proposed method for optimizing the daily
dose of UDChA contributed to a more pronounced manifestation of their therapeutic
signs of ICh were stopped twice as fast, the time to normalize biochemical markers of
cholestasis was reduced, and the amount of drugs consumed per course of treatment was
markedly reduced. This increased the economic profitability of the proposed regimen and,
together with it, reduced the import-oriented need for the region's pharmaceutical industry.
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