Journal of Life Science and Biomedicine  
J Life Sci Biomed, 8(6): 90-93, 2018  
ISSN 2251-9939  
Acetylation Phenotype Impact on Early Postoperative  
Period in Viral Liver Cirrhosis  
Ravshan Aliyevich IBADOV1, Oybek Avazkhonovich OMONOV2, and Sardor Khamdamovich IBRAGIMOV 1  
1Intensive Care Unit, Republican Specialized ScientificPractical Medical Center of Surgery named after Academician V.Vakhidov, Tashkent, Uzbekistan  
2Department of Portal Hypertension and Pancreatoduodenal Zone Surgery, Republican Specialized ScientificPractical Medical Center of Surgery named after  
Academician V.Vakhidov, Tashkent, Uzbekistan  
Corresponding author's Email: dr.sardor.ibragimov@gmail.com  
ABSTRACT  
Original Article  
PII: S225199391800014-8  
Objective. The aim of our study was to identify some pathogenetic mechanisms and unify  
prediction factors for the development of complications after portosystemic shunting.  
Material and Methods: The present research involved 45 patients with liver cirrhosis  
complicated by portal hypertension. Buccal swabs and spot urine samples were used to  
Rec. 02 Nov 2018  
Rev. 24 Nov 2018  
determine acetylation phenotypes. The genotype of each individual was determined by  
polymerase chain reaction. High-performance liquid chromatography was used to determine  
acetylation phenotypes. Results: Rapid acetylation was revealed in 7 patients (15.6%) and slow  
acetylation was found in 38 patients (84.4%). In slow acetylation phenotype, a considerable  
progression of liver cirrhosis was observed in comparison with rapid acetylators alanin  
aminotransferaz (ALT) on 74.4 % in slow acetylation phenotype (SAcP) against 29.5 % in rapid  
acetylation phenotype (RAcP); total bilirubin on 111.8 % in comparison with 42%, respectively;  
the level of ammonia in blood was 247.8% compared to 62.5%). Recommendation: Taking into  
consideration the acetylation phenotype of liver cirrhosis patients can help in predicting  
possible side-effects and evaluate efficiency of drugs that are metabolized by N-acetylation.  
Pub. 25 Nov 2018  
Keywords  
Acetylation Phenotype,  
Viral Liver Cirrhosis,  
Portal Hypertension,  
Central Portosystemic  
Shunting,  
Postoperative Period  
INTRODUCTION  
Management of patients with liver cirrhosis complicated with portal hypertension after central portosystemic  
shunting. Hence, studying of acetylation polymorphism is currently relevant not only because many medical  
products are metabolized by acetylation reactions but also owing to better understanding the molecular basis  
of acetylation. These genetically caused metabolism variations of pharmaceuticals explain specific features of  
pharmacologic and therapeutic effect of drugs. Two genes found in humans are known to be responsible for  
activity of N-acetyl transferase. Recent research has shown that some alleles of these genes influence individual  
susceptibility to some diseases.  
One of urgent problems in current pathologic physiology is studying the mechanisms of a disorder of  
detoxification functions of the liver in patients with various forms of liver pathology [1]. The hepatic  
endoplasmic network contains a family of isoenzymes of cytochrome Р450 that is specific to various substrata.  
The processes of acetylation play an important part in interstitial metabolism. At present, acetylation  
phenotypes are considered to be a genetically determined ability of the body to metabolize compounds  
containing amino groups [2].  
All pharmaceuticals pass the specific pharmacokinetic pathway by virtue of certain enzymes controlled  
genetically. Wide polymorphism in humans suggests that the fate of a pharmaceutical at any pharmacokinetic  
stage is associated with the polymorphic system of an enzyme or protein. It also causes diverse reactions of  
individuals to medicines [3].  
To neutralize toxic products of metabolism or toxic substances in tissues some adaptable mechanisms,  
including those arranged in the toxigenic-kinetic, humoral, immunologic, and metabolic systems responsible  
for maintaining homeostasis in the body, have been developed in the course of evolution. Among them, the  
oxygen-dependent enzymes of the monooxygenase system play the important role [2]. Genetic differences in  
regulation, expression and activity of the genes, that code production of enzymes during the first and second  
To cite this paper: Ibadov RA, Omonov OA, and Ibragimov SKh 2018. Acetylation Phenotype Impact on Early Postoperative Period in Viral Liver Cirrhosis. J. Life  
Sci. Biomed. 8(6): 90-93; www.jlsb.science-line.com  
phases of xenobiotic biotransformation, can become a key factor of susceptibility to toxic effect of xenobiotics  
and development of a pathological process in the liver [4, 5].  
Recently modern approaches of personalized medicine have been developed, e.g. assessment of the gene  
activity on the basis of studying the matrix RNA and drug metabolism [4]. Pharmacologic and kinetic research  
of pharmaceuticals is being conducted in many countries to evaluate the modes of drug dosing, considering  
individual variability of phenotypes of genetically determined biotransformation systems [5]. These studies will  
help not only to select the optimum doses of pharmaceuticals but to predict possible complications of the  
primary disease as well.  
The aim of study was to identify some pathogenetic mechanisms and unify prediction factors for the development of  
complications after portosystemic shunting.  
MATERIAL AND METHODS  
Ethical approval  
The review board and ethics committee of RSSPMCS named after acad. V.Vakhidov approved the study  
protocol and informed consents were taken from all the participants.  
The results of examination of 45 patients with viral liver cirrhosis complicated by portal hypertension  
(PH) have been analyzed. Morphological examination revealed large-nodule liver cirrhosis (LNLC) in over half of  
them (26 patients; 57.8%); 19 patients (42.2 %) had small-nodule liver cirrhosis (SNLC). In 39 patients, cirrhotic  
transformations of the liver were caused by viral hepatitis B, and in 6 patients it developed after viral hepatitis  
C. At the time of examination, antibodies to HCV were found in all 6 patients, and 39 patients had positive HBs-  
Ag. The patients were examined before and after central portosystemic shunting (PSS) with spleen preservation  
and after selective distal splenic-renal anastomosis (DSRA). The clinical course after the surgery was severe in 3  
(6.7 %) patients, rather satisfactory in 5 (11.1 %) and uneventful in 37 (82.2 %) patients.  
In addition to standard tests, the examination included evaluation of the level of reopirin metabolites,  
namely 4-amino-antipirin (4ААP) and N-acetyl-4-amino-antipirina (N-ac-4ААP) in urine. The latter method is  
specific because 4-AAP discharged with urine is a direct product of N- demethylation performed with  
microsomal monooxygenase system, while N-ac-4ААP is a product of further acetylation. The acetylating  
ability of the body was assessed by the method of Prebsting-Gavrilova modified by Anilova and Tolkachevsky. It  
was interpreted as slow if it did not reach 50%, and rapid when it made 50 % and more.  
Before the surgery, a considerable decrease in excretion of reopirin metabolites was observed in all  
patients under study. For instance, in the SNLC patients, the level of 4 ААP in daily urine specimen was 3.6  
times below the controls, and the level of the same metabolites in the LNLC patients was 7.36 times lower. The  
SNLC patients had 3-times lower N-ac-4ААP level, and that one in LNLC patients was 5.74 times lower. Rapid  
acetylation was revealed in 7 (15.6 %) patients, while slow acetylation was found in 38 patients (84.4 %).  
RESULTS AND DISCUSSION  
According to our findings, slow acetylation prevailed in patients with morphological variants of liver cirrhosis.  
For instance, the slow acetylation phenotype (SAcP) was found in 38 of 45 liver cirrhosis patients (84.4 %), while  
7 (15.6 %) patients had the rapid acetylation phenotype (RAcP).  
The comparative analysis of the basic blood biochemical parameters of patients with various types of  
acetylation made before and during the postoperative period has shown that an increase in the basic  
biochemical indicators of the liver did not depend on the type of acetylation. However, the values of these  
indicators were different in the compared groups. For instance, if a cytolytic component manifested itself as an  
increase in the levels of ALT and aspartate aminotransferase (AST) in blood of the patients before the surgery  
was almost identical in both groups, the postoperative indicator in the group of patients with RAcP was a little  
lower, than in the ones with SAcP.  
The basic biochemical tests of blood before and after the postoperative period in patients with various  
morphological forms of cirrhosis demonstrated aggravation of these indicators depending on the liver cirrhosis  
form. As Figure 1 shows, a more favorable liver cirrhosis course in patients with rapid acetylation is obvious.  
For instance, if the ALT level increased from 212.7±46.5 nmol\l to 383.4±127.2 nmol\l in slow acetylation (i.e. a  
gain made 74.4 %), in the rapid type, the gain appeared to be considerably smaller: 29.5 % (P <0.05). After surgery  
the total bilirubin level in the blood of patients with SAcP increased from 25.4±6.7 to 53.8±19.7 mcmol/l that  
To cite this paper: Ibadov RA, Omonov OA, and Ibragimov SKh 2018. Acetylation Phenotype Impact on Early Postoperative Period in Viral Liver Cirrhosis. J. Life  
Sci. Biomed. 8(6): 90-93; www.jlsb.science-line.com  
made 111.8 %, while in the group with RAcP, hyperbilirubinemia was less expressed: before the surgery it was  
23.1±4.2 32.8±8.1 mcmol/l or 42 % (P <0.01) and after it.  
100%  
Slow acetylators  
Rapid acetylators  
111.8%  
247.8%  
74.4%  
80%  
60%  
40%  
20%  
0%  
62.5%  
42.0%  
29.5%  
16.3%  
12.3%  
10.5%  
7.9%  
ALT  
Total bilir.  
Albumin fraction  
Ammonia  
PT  
Figure 1. Progression of the basic biochemical indicators of blood depending on the acetylation type in early  
postoperative period  
When analyzing the total protein levels, it was revealed that in the patients with slow acetylation, the  
albumin fraction before the surgery had been 39.2±2.9 g/L, while in the early postoperative period it had  
decreased to 32.8±3.9 g/L. The ammonia level in the blood of patients with cirrhosis is rather demonstrative.  
The indicator before the surgery and in early postoperative periods again demonstrates the advantage of rapid  
acetylation. For instance, in the patients with slow acetylation, the ammonia level increased by 247.8 %, while in  
the patients with the rapid one, it increased by 62.5 % (P<0.01).  
The prothrombin time (PT) values before and after the surgery also differed, although to a lesser degree. In  
slow acetylation, PT decreased from 84.2±6.8 to 75.4±9.8, (i.e. by 10.5 %), and in the rapid type, a decrease  
appeared to be considerably smaller: 7.9 % (P <0.5).  
Figure 2 presents the list and frequency of specific postoperative complications in the patients with  
different types of acetylation. The number of complications in patients with SAsP was observed to exceed the  
average incidence and specific complications developed more often than in rapid acetylators. Portosystemic  
encephalopathy was diagnosed in 6 patients and hepatic coma developed in 1 patient with SAcP, while in RAcP,  
only one patent had portosystemic encephalopathy of grades 1-2. Cholestasis was not observed in rapid  
acetylators, while in slow ones, it was observed in 2 cases. Edema and ascites developed in 7 patients with SAcP.  
The correlation and comparative analysis demonstrated that parenhymatous-vascular decompensation in  
liver is characterized by: hepatic encephalopathy and mesenchimal and inflammatory response was observed in  
36.8 % of patients with SAsP whereas in RAsP this complication developed only in one patient (14.3 %). No  
hemorrhage was observed in RAsP; in SAsP, it was found in 7.9 % of cases.  
50%  
40%  
30%  
20%  
10%  
0%  
Number of patients with specific complications  
LV activity  
36.8%  
Edema-ascites syndrom  
Hemorrhage associated with PH  
Ascites-peritonitis  
31.6%  
18.4%  
14.3 %  
7.9%  
2.60%  
0.00%  
Slow acetylators  
Rapid acetylators  
Figure 2. Progression of main biochemical indicators depending on the acetylation type  
To cite this paper: Ibadov RA, Omonov OA, and Ibragimov SKh 2018. Acetylation Phenotype Impact on Early Postoperative Period in Viral Liver Cirrhosis. J. Life  
Sci. Biomed. 8(6): 90-93; www.jlsb.science-line.com  
CONCLUSION  
Slow acetylation phenotype mainly develops in liver cirrhosis patients (84.4 %), it being characterized by more  
often specific and nonspecific complications in the postoperative period irrespectively of the morphological  
form of cirrhosis. In slow acetylation, considerable liver cirrhotic progression in comparison with rapid  
acetylators was observed (ALT on 74.4 % in SAcP, against 29.5 % in RAcP, total bilirubin on 111.8 % compared to  
42 %, the level of ammonia in blood was 247.8 % against 62.5 %, etc.).  
Therefore, acetylation phenotypes of all patients with liver cirrhosis should be determined in the  
preoperative period since those ones with slow acetylation are at risk of possible specific and nonspecific  
complications in the postoperative period. Taking into consideration the acetylation phenotype of liver  
cirrhosis patients can help in predicting possible side-effects and evaluate efficiency of drugs that are  
metabolized by N-acetylation.  
DECLARATIONS  
Acknowledgements  
This work was supported by Republican specialized scientificpractical medical center of surgery  
named after academician V.Vakhidov, Tashkent, Uzbekistan  
Authors’ Contributions  
All authors contributed equally to this work.  
Competing interests  
The authors declare that they have no competing interests.  
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To cite this paper: Ibadov RA, Omonov OA, and Ibragimov SKh 2018. Acetylation Phenotype Impact on Early Postoperative Period in Viral Liver Cirrhosis. J. Life  
Sci. Biomed. 8(6): 90-93; www.jlsb.science-line.com