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dOI 10.11603/IJMMR.2413-6077.2019.2.10886

GOUT AND NONALCOHOLIC FATTY LIVER DISEASE:  
EFFECT OF ENTEROSORpTION’S ADDITION TO COMMON TREATMENT

U.O. Mudra 
I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY, TERNOPIL, UKRAINE

Background. Gout is still one of the major health problems despite significant advances in treatment in 
recent years. It has been proved that pathogenetic mechanisms of development and progression of gout are 
associated with nonalcoholic fatty liver disease. Complex pathogenic treatment of patients aimed at different 
parts of the pathological process has recently been supplemented with the enterosorbents.

Objective. The aim of the research is to study the clinical features of gout with concomitant nonalcoholic 
fatty liver disease (NAFLD) and to evaluate the effect of carbon enterosorbent on its course.

Methods. 123 patients were involved in the study. They were divided into 2 groups: group 1 included patients 
with gout without liver damage, and group 2 included patients with concomitant NAFLD. Each of these groups 
was divided into subgroups, in which the patients received carbon enterosorbent carboline plus basic treatment. 
The control group consisted of 30 healthy persons. Anamnesis, physical examination, uric acid (UA), C-reactive 
protein (CRP) content, erythrocyte sedimentation rate (ESR) in serum were determined. Gout activity was evaluated 
using the Gout Activity Score (GAS).

Results. Basic treatment in combination with carbon enterosorbent contributed to faster cure of intoxication, 
pain and joint syndromes, as well as decrease of the inflammatory process activity.

Conclusions. The course of gout in the patients with concomitant NAFLD is more severe. Adding of carbon 
granular enterosorbent carboline in the complex treatment of patients with gout with or without concomitant 
NAFLD in the exacerbation phase contributes to a faster cureing dynamics of clinical and laboratory manifestations 
of the disease.

KEY WORDS: gout; nonalcoholic fatty liver disease; enterosorbent; treatment.

*Corresponding author: Mudra Uliana, Department of Internal 
Medicine Propedeutics and Phthisiology, 1 Maidan Voli, I. 
Horbachevsky Ternopil National Medical University, Ternopil, 
Ukraine, 46001.
E-mail: heliosmuo@gmail.com

Introduction
Pathology of the articular apparatus is one 

of the most frequent and common human 
diseases. Salt arthropathy accounts for a large 
share, among which gout is the most common. 
Gout is a chronic progressive disease associated 
with impaired uric acid metabolism, which is 
clinically manifested by recurrent arthritis, tophi 
formation and internal organs damage [1].

Gout is certainly an urgent health issue and 
a significant social and economic burden for 
the country. According to the Ministry of Health 
of Ukraine, the number of gout patients in 
Ukraine has increased in recent years. Thus, in 
2013, the prevalence of this disease was 167.6 
per 100 thousand population, whereas in 2017 
this figure reached 190.4 per 100 thousand 
population, and 113.9 – among the able-bodied 
population. The cost of treating new cases of 

acute gouty arthritis in the United States is 
estimated at $ 27.4 million annually [2, 3].

Pain and swelling of the joints during 
exacerbations of gout can lead to a significant 
deterioration and disability, which affects the 
patient’s productivity and social activity. 
According to Edwards N.L. et al., a patient with 
gout, who is under 65 years of age, has an 
average of 25.1 working days a year due to the 
illness [4].

Uncontrolled administration of medicines 
for comorbid diseases, as well as malnutrition, 
alcohol abuse, hypodynamia, physical or 
psycho-emotional overload play an important 
role in increasing the incidence [5].

In recent years, researchers have paid 
particular attention to the multifaceted clinical 
manifestations of gout, which is not limited to 
damage of the musculoskeletal system and 
kidneys. A great number of patients suffer from 
obesity, disorders of lipid and carbohydrate 
metabolism, hypertension, which are integral 
parts of the metabolic syndrome [6, 7].

International Journal of Medicine and Medical Research 
2019, Volume 5, Issue 2, p. 40-46
copyright © 2019, TNMU, All Rights Reserved

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According to the literature, metabolic synd-
rome is often aggravated by fatty liver infil tra­
tion, which can significantly affect the course 
of the underlying disease. Nonalcoholic fatty 
liver disease is the most common liver disease 
in the world (46% of the population, and 74% 
among diabetes patients) [8, 9].

Thus, the increase of gout incidence and 
development of concomitant pathology, which 
complicates its course, leads to a decrease in 
the effectiveness of treatment, development of 
complications and mortality, is an urgent issue 
at present that requires improved diagnosis 
and treatment.

Treatment of the patients with gout should 
be comprehensive, and include non-pharma-
cological and pharmacological methods. 
Physicians should take into account the level of 
uric acid (with subsequent monitoring), the 
form and stage of gout, radiological stage and 
degree of functional failure of the joints, 
patient’s age, concomitant pathology and 
features of its pharmacotherapy. A key aspect 
of the treatment is strict diet, weight loss in 
obesity [10].

One of the current treatments is entero-
sorption, which is increasingly used in the 
treatment of acute and chronic diseases.

The objective of the study is to investigate 
clinical features of gout with concomitant 
nonalcoholic fatty liver disease (NAFLD) and to 
evaluate the effect of carbon enterosorbent on 
its course.

Methods
The study involved 123 patients with gout 

during the exacerbation period, including 118 
(95.9%) men and 5 (4.1%) women. The average 
age was (57.73±1.01). The diagnosis of gout was 
based on ACR/EULAR 2015 criteria and the 
order of the Ministry of Health of Ukraine No. 
676, dated October 12, 2006. The diagnosis of 
NAFLD was established according to the criteria 
of the Unified Clinical Protocol of Primary, 
Secondary (specialized) Medical Care “Non-
alcoholic fatty liver disease” (Order of the Mi-
nistry of Health of Ukraine No. 826, dated 
November 6, 2014).

The history of the disease (duration of the 
disease, frequency of attacks for the last 12 
months) was taken into account in clinical exa-
mination of the patients. They also underwent 
physical examination (determination of pain 
intensity by a visual analogue scale (VAS), 
evaluation of the number of tophi, affected 
joints, uric acid content (UA), C-reactive protein 

(CRP), erythrocyte sedimentation rate (ESR) in 
the blood serum.

To assess the effectiveness of therapy, the 
patients of both groups were monitored for 
complaints (pain and swelling of joints, res-
triction of movement in them, etc.), evaluated 
for joint syndrome development, dynamics of 
the level of UA, CRP and ESR.

Gout activity was assessed using the Gout 
Activity Score (GAS) suggested by Sciere C.A. 
et al.:

GAS = 0.09 × the number of attacks for the 
last 12 months + 1.01 × √UA + 0.34 × patient’s 

VAS + 0.53 × ln (1 + number of tophi);
where UA – uric acid (mg/dl), VAS – visual 

analogue pain scale (cm) [2, 11].
All the patients were divided into two 

groups. Group 1 included 65 patients with gout 
without liver damage, group 2 – 58 patients with 
concomitant NAFLD. The control group consis-
ted of 30 healthy individuals of the same age.

All the patients voluntarily agreed to par-
ticipate in the study. The Patient Safety Rules 
and the Ethical Standards and Procedures for 
Research Involving Human Beings (2000) were 
followed during the whole study. 

Statistical processing of the results was 
performed using Statistica 10.0 software 
package (StatSoft, USA) and Microsoft Office 
Excel 2016 statistical software package (Micro-
soft Corp., USA). The statistical significance of 
differences between the groups was evaluated 
using the nonparametric Wilcoxon U (Mann-
Whitney) method. The differences were 
considered statistically significant at p<0.05.

Results
According to the medical history, the ave-

rage duration of gout in all examined patients 
was (8.75±0.50) years. Clinical and laboratory 
characteristics of patients with gout are pre-
sented in Table. 1.

Tophi were detected in 80 (69 %) persons, 
in group 1 – in 36 (45 %) patients, in group 2 – 44 
(55 %). It is worth noting that patients with 
NAFLD were predominant with multiple tophi.

When assessing the frequency of exacer-
bations of gout per year, a statistically significant 
increase in 1.5 times among the patients with 
concomitant NAFLD, compare to those without 
liver damage (p<0.05) should be emphasized.

The analysis of the joints involved in the 
pathological process in the patients with gout 
without liver damage proved the following 
joints (3.75±0.30) disorders: monoarthritis was 
detected in 24.6%, oligoarthritis – in 29.2%, 



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polyarthritis – in 46.2%. In the patients with 
concomitant NAFLD, oligo- and polyarthritis 
were observed in the vast majority (96.5 ) and 
monoarthritis in only 3.5% of those surveyed. 
The average number of the affected joints in 
the group was (5.36±0.38).

The patients in group 2 were characterized 
by an increase in the number of patients with 
severe disease course – 18 (31%) and a decrease 
in the percentage with mild course – 7 patients 
(12%) and the average – 33 (57%). At the same 
time, in group 1, a severe course was diagnosed 
in 7 (11%), medium – in 41 (63%), mild – in 17 
(26%) patients.

The intensity of pain according to VAS in the 
patients of group 2 was in 1.2 times higher than 
in group 1 (p<0.05).

The GAS scale was used to evaluate gout 
activity. It was found that the majority of 
patients had a high disease activity and, on 
average, in the patients with concomitant NASH 
it was in 1.3 times higher than in the patients 
without liver damage. In 36 (55.4%) patients of 
group 1 moderate activity (GAS 4.5-7.4) was 

present, and 29 (44.6%) had a high (GAS>7.4) 
disease activity. 45 (77.6%) patients of group 2 
had high disease activity and 13 (22.4%) had 
moderate activity (p<0.05).

In the control group, the level of UA in the 
serum was (309.13±14.16) μmoL/L, CRP – 
(3.39±0.17) mg/l, ESR – (6.47±0.65) mm/h.

The analysis of laboratory parameters 
revealed that the examined group 2 experien-
ced an increase in the level of UA in the blood 
in 1.4 times compare to the patients in group 1, 
re s p e c   t i v e l y ,  u p  t o  ( 6 2 1 . 5 7 ± 1 3 . 4 7 )  a n d 
(459.72±11.44) μmoL/L (p<0.05). The inflam­
matory process, by the CRP level, was more 
significant in 1.7 times in the patients with con­
comitant NAFLD than in group 1. An increase 
in ESR, as a criterion for the activity and severity 
of the inflammatory process, occurred among 
all patients, but mostly in the patients with 
concomitant liver damage (29.12±1.04) mm/h, 
which was 1.5 times higher than the group 1 
parameters (p<0.05).

According to the treatment received by the 
patients, they were divided into subgroups. 

Table 1. Clinical and laboratory characteristics of the patients with gout 

Parameter Units
Group 1 (patients 
without NAFLD)

(n=65)

Group 2 (patients  
with NAFLD)

(n=58)
Age, years М±m 59.55±1.33 55.68±1.5
Number of patients with tophi n (%) 36 (45) 44 (55)
Number of tophi:
1-3
4-9
10 and more

n (%)
7 (19.4)

19 (52.8)
10 (27.8)

14 (31.8)
16 (36.4)
14 (31.8)

Number of attacks for the last 12 months: М±m 3.03±0.23 4.67±0.19*
0
1-2
3-5
6-10
More than 10

n (%) 8 (12.3)
14 (21.5)
38 (58.5)

5 (7.7)
–

–
4 (6.9)

41 (70.7)
13 (22.4)

–
Number of affected joints: М±m 3.75±0.30 5.36±0.38*
Monoarthritis
oligoarthritis (2-3 joints)
polyarthritis 4 and more joints

n (%) 16 (24.6)
19 (29.2)
30 (46.2)

2 (3.5)
17 (29.3)
39 (67.2)

Course:
mild
medium severity
severe

n (%)
17 (26)
41 (63)
7 (11)

7 (12)
33 (57)
18 (31)

Visual analogue scale (VAS), mm М±m 56.34±1.00 69.21±1.04*
Gout activity score (GAS) М±m 7.53±0.28 9.63±0.35*
Uric acid, μmoL/L М±m 459.72±11.44 621.57±13.47*
C-reactive protein, mg/l М±m 11.35±0.71 19.58±1.62*
Erythrocyte sedimentation rate (ESR), mm/h М±m 19.35±0.90 29.12±1.04*

Note: * – statistically significant differences in the parameters between the groups of patients without and with NAFLD (р<0.05).

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Group 1 – 27 people (subgroup 1A) received 
treatment in accordance with the order of the 
Ministry of Health of Ukraine No. 676, dated 
October 12, 2006: hypopuricemic therapy with 
allopurinol according to the scheme, anti-
inflammatory and analgesics (basic therapy); 
38 (subgroup 1B) – additionally enterosorbent 
carboline 1 teaspoon 3 times a day for 10 days 
2 hours before or after meals or medication. 
Among the patients of group 2 – 27 (subgroup 
2 A) received basic therapy, 35 (subgroup 2 B), 
except basic treatment – carboline according 
to the scheme. The patients of group 2 were 
also treated according to the Unified Clinical 

Protocol of Primary, Secondary (Specialized) 
Medical Care “Nonalcoholic fatty liver disease” 
(Order of the Ministry of Health of Ukraine 
No. 826, dated November 6, 2014).

Pain, as one of the manifestations of arti-
cular syndrome, was the main complaint of all 
patients before treatment (Table 2). Swelling of 
the affected joint was present in 53 (81.5%) 
patients of group 1 and 54 (93.1%) of group 2, 
with redness of the skin in 45 (69.2%) and 56 
(97%), respectively, local temperature rise in 50 
(77%) and 54 (93.1%) individuals, body tem-
perature rise to subfebrile numbers took place 
in 11 (17%) and 13 (22.4%) of both groups.

Table 2. The frequency of clinical symptoms in the patients with gout

Symptoms
Patients with gout

Group 1, n=65 Group 2, n=58
Joint pain and change in joint motion 65 (100 %) 58 (100 %)
Swelling 53 (81.5 %) 54 (93.1 %)
Redness 45 (69.2 %) 56 (97 %)
Local temperature rise 50 (77 %) 54 (93.1 %)
Body temperature rise 11 (17 %) 13 (22.4 %)

Clinical manifestations of the disease and 
improvement of personal well-being decreased 
in the dynamics of treatment of the patients of 
both groups. In the patients of group 1 a signi-
ficant improvement of the general condition 
was observed on the 2nd-3rd day, and in the pa-
tients with concomitant liver damage – swelling, 
redness of the joint and the intensity of pain 
 decreased on the 3rd-4th day of the disease, accor-
ding to VAS, the body temperature was normal.

Thus, in the patients of subgroup 1A after 
the treatment, the intensity of pain according 
to VAS decreased from (55.19±1.4) mm to 
( 1 8 . 4 1 ± 3 . 2 1 )  m m  ( p < 0 . 0 0 1 ) ,  a n d  f r o m 
(57.16±1.4) mm to (11.66 ±2.12) mm – in the 
subgroup 1B (p<0.001).

Before the treatment, the examined of 
group 2 complained of severe pain in the affec-
ted joints that significantly influenced the 
functional activity of the patients. After baseline 
treatment, the pain intensity according to VAS 
i n  t h e  s u b g r o u p  2 A  d e c r e a s e d  f r o m 
(69.04±1.67) mm to (30.48±4.68) mm (p<0.001), 
and in the subgroup 2B (in cases of enterosor-
bent ad ministration) – from (69.31±1.34) mm 
to (21.20±2.82) mm (p<0.001).

The dynamics of UA regression in blood 
serum during the course of treatment in the 
patients of group 1 was significantly better 
compare to those of group 2. In cases of the 
baseline treatment, the level of UA gradually 

d e c r e a s e d  i n  t h e  s u b g r o u p  1 A  f r o m 
(444.01±18.57) to (389.03±14.55) μmoL/L, 
p<0.001, and in the subgroup 1B with additional 
carboline administration – from (470.87±14.38) 
to (353.01±7.96) μmoL/L, p<0.001. Compare to 
the control group, this parameter was higher 
in 1.26 and 1.14 times, respectively. In the 
subgroup 2A, the level of UA decreased from 
(657.03±11.64) to (529.27±12.32) μmoL/L, 
p < 0 . 0 0 1 ,  i n  t h e  s u b g r o u p  2 B  –  f r o m 
(598.29±20.14) to (473.95±7.75) μmoL/L, 
p<0.001, however, it was higher than in the 
control group in 1.71 and 1.53 times.

Regarding the inflammatory process acti­
vity (ESR, CRP), there was a decrease in the level 
of ESR (p<0.001) and CRP (p<0.001) in the 
dynamics of treatment in both groups. It should 
be noted that in the patients of subgroup 1B 
after enterosorbent administration the CRP 
concentration decreased from (12.06±1.01) to 
(3.51±0.37) mg/l (p<0.001), and ESR – from 
(18.47±1.14) to (7.95±0.59) mm/h (p<0.001), 
compare to the control group these values be-
came normal (p>0.05). In the patients with 
con comitant NAFLD, in cases of the basic treat-
ment in combination with enterosorbent there 
was a decrease of CRP – from (19.94±1.92) to 
( 7 . 7 9 ± 0 . 3 6 )  m g / l  ( p < 0 . 0 0 1 ) ,  E S R  –  f ro m 
(30.51±1.37) to (11.94±0.42) mm/h (p<0.001), 
but they were in 2.3 and 1.8 times higher than 
in the almost healthy individuals (p<0.001).



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Discussion
Comorbidity is still an important problem 

in medicine, since studying the manifestations 
of the combined pathology of different body 
systems can help uncover the mechanisms of 
disease formation  an d  development  of 
pathogenetically profound therapy [12].

At present gout is an urgent problem 
because its prevalence has doubled in the last 
decades. This disease becomes even more 
significant due to its comorbidity. Frequent 
combination of gout with concomitant patho-
logy leads to a decrease in the effectiveness of 
treatment and progression of complications 
[13].

Currently, there is a high morbidity of 
NAFLD in the world, and there is a tendency to 
increasing incidence of this chronic liver disease 
in the population, development of severe 
complications in the disease progression that 
is an urgent issue of contemporary medicine. 
The presence of NAFLD, as a comorbid condition, 
enhances the inflammatory response in the 
body and significantly complicates the course 
of the underlying disease [14].

It is indisputable fact that the main link of 
gout pathogenesis is UA metabolism. The 
determination of the dynamics of UA levels in 
the blood in gout and concomitant NAFLD is 
increasingly significant as a risk factor for 
cardiovascular events [15].

In most such patients, prior to treatment, 
an increase in CRP and ESR is proved. It is 
established that in this pathology an inflam­
matory process develops, which is not only 
limited to local changes in the joints, but also 
causes a response of the whole body. The 
increase in CRP in the patients with gout in 
combination with NAFLD confirms the presence 
of chronic subclinical inflammation in them, and 

with the progression of the disease there is an 
increase in the level of CRP [16].

Treatment of the patients with gout should 
be aimed at eliminating the acute attack of 
arthritis and inflammatory changes in the 
joints, reducing the content of UA compounds 
in the body, eliminating extra-articular lesions 
associated with gout, restoring the function of 
the musculoskeletal system, etc. [17].

It should be noted that the use of entero-
sorption together with basic therapy has a 
positive effect on the clinical course of the 
disease, promotes faster regression of intoxi-
cation, pain and articular syndromes, as well as 
is accompanied by a decrease of inflammatory 
process activity in the body (CRP, ESR) and uric 
acid level in blood serum.

Conclusions
The course of gout in the patients with 

concomitant nonalcoholic fatty liver disease is 
more severe than in its absence. With this 
combination, the number of the affected joints, 
tophi, acute conditions increases for the period 
of a year. There is an increase of the intensity 
of pain according to visual analogue scale, as 
well as its activity by the Gout activity score. The 
inflammatory process intensifies. The inclusion 
of carbon granulated enterosorbent carboline 
in the complex treatment of the patients with 
gout or without concomitant nonalcoholic fatty 
liver disease, contributes to a faster reverse 
dynamic of clinical manifestations of the di-
sease, accompanied by a more significant de­
crease in C-reactive protein, erythrocyte sedi-
mentation rate and uric acid in blood serum.

Funding
This research received no external funding.
Conflict of Interests
The author declares no conflict of interest.

подагра і неалкоголЬна ЖироВа хВороБа печінки: еФект 
додаткоВого застосуВання ентеросорБціЇ В загалЬному 
лікуВанні

У.О. Мудра
ТЕРНОПІЛЬСЬКИЙ НАЦІОНАЛЬНИЙ МЕДИЧНИЙ УНІВЕРСИТЕТ ІМЕНІ І.Я. ГОРБАЧЕВСЬКОГО,  

ТЕРНОПІЛЬ, УКРАЇНА

Вступ. Незважаючи на те, що за останні роки досягнуто значних успіхів у лікуванні, подагра 
залишається однією із серйозних проблем охорони здоров'я. Особливістю сучасних хронічних захворювань 
є коморбідність. Доведена спільність патогенетичних механізмів у розвитку і прогресуванні подагри 

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та неалкогольного стеатогепатиту. Комплексне патогентичне лікування хворих, спрямоване на різні 
ланки патологічного процесу, останнім часом доповнене застосуванням ентеросорбентів.

Мета дослідження. Вивчити клінічні особливості перебігу подагри при супутньому неалкогольному 
стеатогепатиті (НАСГ) й оцінити вплив вуглецевого ентеросорбенту на її перебіг. 

Методи дослідження. Обстежено 123 хворих на подагру, які перебували на стаціонарному 
лікуванні. Їх було поділено на 2 групи. До 1-ї групи ввійшли пацієнти з подагрою без ураження печінки, 
до 2-ї – хворі із супутнім НАСГ. Кожну із цих груп було розділено на підгрупи, пацієнти однієї з яких, окрім 
базоваго лікування, отримували вуглецевий ентеросорбент карболайн. Контрольну групу склали 30 
практично здорових осіб. В клінічному обстеженні хворих враховували скарги, дані анамнезу, проводили 
фізикальний огляд, визначали вміст сечової кислоти (СК), С-реактивного білка (СРБ), швидкості осідання 
еритроцитів (ШОЕ) в сироватці крові. Активність подагри оцінювали за допомогою шкали Gout Activity 
Score (GAS).

Результати. Застосування базового лікування в поєднанні з вуглецевим ентеросорбентом сприяло 
швидшій регресії інтоксикаційного, больового й суглобового синдромів, а також показників активності 
запального процесу.

Висновки. Перебіг подагри у хворих з супутнім НАСГ тяжчий, ніж за його відсутності. Включення 
вуглецевого гранульованого ентеросорбенту карболайн в комплексне лікування хворих на подагру з 
супутнім НАСГ чи без нього у фазі загострення, сприяє швидшій зворотній динаміці клінічних і 
лабораторних проявів захворювання, супроводжується більш значним зниженням рівня СРБ, ШОЕ та 
СК у сироватці крові. 

КЛЮЧОВІ СЛОВА: подагра; неалкогольний стеатогепатит; ентеросорбент; лікування.

Відомості про автора
Мудра Уляна Олегівна – аспірант кафедри пропедевтики внутрішньої медицини та фтизіатрії 

Тернопільського національного медичного університету імені І.Я. Горбачевського.

Information about the author 
Uliana O. Mudra – Ph.D. student, Department of Internal Medicine Propedeutics and Phthisiology 

of I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. 
ORCID 0000­0001­8160­4962, e­mail: heliosmuo@gmail.com

References
1. Herasymenko SI, Poluliakh MV, Duda MS, 

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Received 06 September 2019; revised 11 October 2019; 
accepted 21 October 2019.

This is open access article distributed under the Creative Com-
mons Attribution License, which permits unrestricted use, 
distribution, and reproduction in any medium, provided the 
original work is properly cited.

u.O. Mudra