Vol 45, No 5 (2017)


Pruritus in chronic cholestatic liver diseases

Vinnitskaya E.V., Sandler Y.G., Keyan V.A., Khaymenova T.Y., Orlova E.A., Polukhina A.V., Gendrikson L.N.


Pruritus can be a prominent symptom  in patients with chronic liver disorders, especially those  with cholestasis,  and  substantially  affects  quality  of life. Management of pruritus  in cholestatic  liver diseases  remains  a  complicated   medical  problem. The review article deals with pathophysiological mechanisms of pruritus in cholestatic liver diseases, in particular, with the role of bile acids, endogenous opioids, serotonin, and histamine. There is new data on the key pathophysiological elements, such as neuronal activation lysophosphatidic acid and autotaxin, an enzyme that produces lysophosphatidic acid and whose serum activity is associated with the intensity of pruritus. Pathophysiology-based management approaches include administration of anionic exchange resin cholestyramine, ursodeoxycholic acid, rifampicin agonists, an opioid antagonist naltrexone and a  serotonin-reuptake inhibitor sertraline. These agents are recommended for the use as a stepped treatment algorithm. Patients who do not respond to these therapies can become candidates for albumin dialysis, plasmapheresis, ultraviolet B phototherapy, or need some other individualized approaches. New knowledge on the pathophysiology of pruritus may potentially result in the development of new agents for cholestatic pruritus.

Almanac of Clinical Medicine. 2017;45(5):366-376
pages 366-376 views


Functional pancreatic insufficiency after surgical treatment in the light of the latest international recommendations

Bordin D.S., Dubtsova E.A., Vinokurova L.V., Kolbasnikov S.V., Nikolskaya K.A., Banifatov P.V.


Exocrine  and  endocrine   insufficiencies  are  frequent complications of surgical treatment for pancreatic diseases. The presence  and  extent  of the insufficiency depend on the underlying  disorder, type of surgical procedure, extent of pancreatic resection, and anatomical reconstruction. Increased surgical  activity  determines  the  importance  of the  evidence-based guidelines  for management of patients  after  pancreatic  surgery. The article presents  an  overview of international Evidence-based Guidelines for the Management of Exocrine Pancreatic  Insufficiency after  Pancreatic  Surgery (2016) and United European Gastroenterology evidence-based guidelines  for the  diagnosis  and therapy of chronic pancreatitis (HaPanEU, 2017).

Almanac of Clinical Medicine. 2017;45(5):358-365
pages 358-365 views


Investigation of gastric motility in patients with the overlap syndrome of the gastroesophageal reflux disease and functional dyspepsia

Pasechnikov V.D., Golub I.V.


Rationale:  The phenomenon of overlap  of two disorders, non-erosive gastroesophageal reflux disease (NERD) and functional dyspepsia (FD) is an important clinical problem,  while the  symptoms in such  patients  are  more  severe  and  prevalent than  in those  with non-overlapping NERD or FD. This phenomenon may lead to treatment failure, if therapy  does not take into account  the specific pathophysiological mechanisms  of the NERD and FD overlap.

Aim: To study motility of the proximal and  distal parts  of the  stomach  in patients  with the overlap syndrome of NERD with FD.

Materials and  methods:  The  study  enrolled  56  patients (34 women and 22 men), aged from 18 to 45 years, who met the diagnostic  criteria for NERD and FD (the Rome criteria III, esophageal endoscopy, 24-hour  pH  measurement  or  24-hour  impedance pH measurement), and  had  both  NERD  and  FD symptoms  simultaneously  (overlap); 46 healthy volunteers. The accommodation of the  proximal (fundal) part  of the  stomach  and  motility of the distal gastric part  was assessed  by ultrasonography (Aixplorer, SuperSonic Imagine, France, with convex probe  1–6 MHz) before  and  after the  intake of the liquid test food. The patients  filled in questionnaires to assess the symptoms  and their severity (scored from 0 to 3). The difference  between their mean ± standard  deviation (SD) values was assessed  by Students  t-test  and  was considered  significant at p < 0.05.

Results: After intake of the  liquid test  food, the  patients  with the  FD and NERD overlap syndrome demonstrated an advanced and statistically significant gastric motility abnormality  both  in its proximal and distal parts, compared to healthy control: accommodation disturbances and its reduction, decreased amplitude  (61.4 ± 7.5 vs 90.2 ± 6.9%, p < 0.05), frequency of contractions of the antrum during 3-minute interval (4.3 ± 1.5 vs 9.7 ± 1.4, p < 0.05), antral motility index (4.3 ± 1.4 vs 8.8 ± 1.3%, p < 0.05), and gastric emptying   (37.1 ± 14.5   vs  69.1 ± 19.5%,  p < 0.05). Gastric accommodation abnormalities  were associated with a statistically significant increase in the severity  of the  following  symptoms: abdominal distention, postprandial feeling of fullness, early satiety, eructation, and heartburn (р< 0.05 for all symptoms).

Conclusion: Detection  of gastric accommodation and evacuation  abnormalities  that determine the  overlap  syndrome,  indicate  some common  mechanisms  of pathophysiology of FD and NERD, which should be taken into account for therapy optimization.

Almanac of Clinical Medicine. 2017;45(5):377-383
pages 377-383 views

The influence of cholecystectomy at young age on the course of metabolic syndrome in women

Lebedeva O.V., Bueverov A.O., Bueverova E.L., Nikitina L.O.


Rationale:  At present, the  metabolic  syndrome and  pathophysiology  of non-alcoholic  fatty  liver disease, as well as identification of factors that may  influence  the  rate  of development of dystrophy and fibrosis in the liver are in the focus of investigators'  attention. This study represents an attempt to  detail  metabolic  derangements and liver tissue  abnormalities  after  cholecystectomy in patients  with metabolic  syndrome  at baseline.

Aim: To study  the  influence  of cholecystectomy performed  at younger  age on the course of metabolic syndrome in women.

Materials and methods: This was a retrospective analytical study  in a sample  of 57 female  patients  with  metabolic syndrome (International Diabetes Federation criteria 2005) aged  from 18 to 44 years (young age according  to the World Health Organization definition). From those, 30 patients  with cholelithiasis were included  into the control group  and 27 patients  who  had  undergone  cholecystectomy in this age range were included into the comparison group. We analyzed  their past  history, results  of clinical examination, laboratory  tests, abdominal ultrasound  examination, esophagogastroduodenoscopy, hydrogen  respiration  test  with lactulose, as well as the results of needle  liver biopsy.

Results: Non-alcoholic steatohepatitis after cholecystectomy was associated with the excessive bacterial growth  in the small intestine  (р = 0.026), ultrasound signs of cholangitis (р = 0.041), and diarrhea syndrome (р = 0.027). Liver fibrosis was significantly more frequent in association with chronic diarrhea  (р = 0.034)  and  past  clinical signs  of post-cholecystectomy syndrome (р = 0.044). There was a strong direct correlation between the grade of fibrosis and  the  time  since  cholecystectomy (r = 0.77; р = 0.047).

Conclusion: Cholecystectomy performed  at young  age predicts  progression  of metabolic abnormalities  in women with metabolic syndrome.

Almanac of Clinical Medicine. 2017;45(5):384-391
pages 384-391 views

Predicting the rate of liver fibrosis in patients with chronic hepatitis C virus infection based on the combination of genetic and environmental factors

Taratina O.V., Samokhodskaia L.M., Krasnova T.N., Mukhin N.A.


Rationale: Search for predictors of aggressive course of chronic hepatitis C virus (HCV) infection in individual patients, including genetic studies, is considered  to be a major urgent  goal. High rates of fibrosis progression  in chronic HCV infection is associated with several gene polymorphisms  coding for the components of renin-angiotensin system and involved in the formation of endothelial dysfunction and oxidative stress.

Aim: To develop a predictive  model  to  assess  the  probability  of rapid fibrosis progression  in patients  with chronic HCV infection based on the combination of the known genetic markers, clinical and demographic parameters.

Materials and methods:  One hundred  and  nine  patients  with  chronic  HCV  infection (79 women  and 30 men) of known duration and liver fibrosis were categorized  into the groups with “rapid fibrosis” (n = 54, the rate of fibrosis progression ≥ 0.13 fibrosis units / year) and with “slow fibrosis”  (n = 55, the  rate  of progression < 0.13  fibrosis units / year). Polymorphisms  of the studied genes were assessed by molecular genetic assays. Multivariate analysis of the influence of combination of genetic  variants, as well as of the interaction of genetic, clinical and demographic factors on the rate of fibrosis progression  in the patients with chronic HCV infection was performed by logistic  regression   method. 

Results:  The  rapid rate of fibrosis progression  was significantly associated with patient's  age at the time of infection (Wald statistics  14.955;  p = 0.00011), male gender (Wald statistics  6.787;  p = 0.00918),  (-6)АА genotype  of the  AGT  gene  carriage  (Wald statistics 6.512;  p = 0.01072), 242ТТ-genotype  of the  CYBA gene   (Wald  statistics   4.347;   p = 0.03708),   and 235МТ genotype of the AGT gene  (Wald statistics 4.306; p = 0.03799). The model to predict the probability of rapid fibrosis progression  in individuals with chronic HCV infection included the above mentioned factors; its use was demonstrated with two clinical cases.

Conclusion: The analysis of the AGT  gene  (M235T and  G-6A loci) and  the  СYBA gene  (C242T  locus) polymorphisms  are  relevant to  identify patients  at  risk of rapid  liver fibrosis progression. In this case, 242ТТ genotype of the CYBA gene  and  (-6)AA and  235MT genotypes of the AGT gene  are considered  unfavorable. To refine the prognosis, it is necessary to take into account  demographic parameters (gender  and age at the moment of infection contraction), because male gender and older age of getting the infection would increase the probability of rapidly progressive of hepatitis C.

Almanac of Clinical Medicine. 2017;45(5):392-407
pages 392-407 views

Molecular and genetic diagnostics of inflammatory bowel diseases

Kuznetsova D.A., Razumov A.S., Merzlyakov M.V., Vavin G.V., Repnikova R.V.


Background: In the last two decades, more attention  has  been   paid  to  the   development and implementation of molecular and genetic technologies  for  the   diagnosis   and   prediction of the  development and  course  of inflammatory bowel diseases (IBD). However, the published evidence   on   their   diagnostic   significance   are rather   controversial   and   equivocal   that   may be explained by some characteristics of their frequencies, differences  in pathogenetic, clinical and diagnostic vales of the genetic polymorphisms in various countries and regions.

Aim: To evaluate the frequency, clinical, diagnostic, and prognostic significance  of  the  3020insC  and  G2722С nucleotide  polymorphisms  of the CARD15 (NOD2) gene  in Crohn's disease (CD) and ulcerative colitis (UC) in  the   Kemerovo  Region  of  the   Russian Federation.

Materials and methods:  The study included 144 patients with IBD (58 with CD, 86 with UC), and 44 patients  without  any gastrointestinal tract disorders in the control group. The 3020insC and 2722С allelic frequencies  of the CARD15 gene were determined. All patients  were of the Russian ethnicity  and  were  living in the  territory  of the Kemerovo Region at the time of the study.

Results: The frequency of the 3020insC allele of the CARD15 gene  in CD patients  was significantly higher than in those with UC (16% vs 3%, p < 0.001) and in the control  group   (5%,  р = 0.04).  The  homozygous genotype of 3020insC/insC was found only in the CD patients. The carriage  of the  3020insC allele was associated  with an average  3.5-fold increase of the probability of CD development (odds ratio [OR] 3.6;  95% confidential  interval  [CI]:  1.3–10.3) and was not significantly linked to an increased risk of UC (OR 0.6; 95% CI: 0.1–2.5). The 3020insC allelic frequency in the pooled group of the patients with complicated  CD variants (with stricture formation and  penetrative)  was  significantly  higher, compared to those with the luminal forms (79% vs 21%, р = 0.03) and with the penetrative CD forms compared to  the  luminal (50% vs 21%, р = 0.05). The 3020insC allele carriage in the CD patients was associated with a 3.3-fold increase in the risk of the penetrative forms of the disease  (OR 3.3; 95% CI: 1.8–6.1) and with a 14-fold increase of the overall risk of the complicated  CD variants (OR 14.1; 95% CI: 7.1–27.9). The 2722С allelic frequency in CD and UC patients  and  in the  control  group  were  not significantly different.

Conclusion: The detection of the  3020insC allele of the  CARD15 gene  in the Kemerovo Region of the Russian Federation is appropriate for the early CD diagnosis, assessment of the prognosis for the risk of development of CD phenotypic variants, as well as for the differential diagnosis between CD and UC.

Almanac of Clinical Medicine. 2017;45(5):408-415
pages 408-415 views

Non-operative management of blunt abdominal trauma: positive predictors

Pankratov A.A., Izrailov R.E., Chudnykh S.M., Khat'kov I.E.


Background: Over the last years a non-operative management (NOM) of blunt  abdominal  trauma has been included into the standard treatment guidelines  in leading  trauma  centers  all over the world.  The  success  of NOM is based  on  careful patient  selection. Nevertheless, the selection  criteria have not been clearly determined up to now.

Aim: To identify predictors of successful NOM and to  create  a diagnostic  and  treatment algorithm for its implementation.

Materials and methods: 209 patients  with abdominal  trauma  who underwent  laparoscopy  or NOM from January 2006 to September 2015 were included  in the  study. The hemoperitoneum volume  and  organ  injury rate evaluated   by  using  ultrasonography  and  computed  tomography scan, as well as hemoglobin level, blood  pressure,  and  peripheral  pulse  were analyzed. We performed  comparative  analysis of prognostic  values of various selection  criteria for NOM, such as: 1) Huang and McKenney ultrasound scoring systems for hemoperitoneum quantification; 2) hemodynamic parameters; 3) hemoglobin levels;  4) various combinations  of the  above mentioned factors; 5) Sonographic  Scoring for Operating  Room Triage in Trauma (SSORTT) scoring system.

Results: Positive prognostic  values of parameters included into the study varied from 88 to 91.7% when used separately or in combination with other scored factors. Furthermore, there was no  significant  difference  between positive  predictive value  of all combinations of factors  and McKenney ultrasound hemoperitoneum scoring system used alone.

Conclusion: The proposed predictors  as  well as  diagnostic  and  treatment algorithm are easy-to-use  and available in clinical practice.

Almanac of Clinical Medicine. 2017;45(5):416-422
pages 416-422 views


A clinical case of hereditary thrombophilia in a patient with ulcerative colitis

Fadeeva N.A., Donchenko I.A., Knyazev O.V., Lishchinskaya A.A., Dudina G.A., Ruchkina I.N., Subbotin V.V., Noskova K.K., Rogozina V.A., Parfenov A.I.


We present  a clinical case of a 24-year old female patient  who was hospitalized  with high active ulcerative  colitis associated  with  latent  hereditary thrombophilia  uncontrolled  due  to  the  exacerbation  of ulcerative colitis and local steroid treatment. The patient  was treated with combination of systemic steroids, adalimumab and anticoagulants. We emphasize  the necessity of the multidisciplinary approach  to her treatment. The clinical case demonstrates the possibility of safe use of anticoagulants to prevent  thromboembolic complications in patients  with ulcerative colitis and high risk of thrombus formation, under careful monitoring of coagulation  parameters and thromboelastography. We discuss the need  in clear guidelines to determine treatment strategy for patients  with inflammatory bowel diseases, coagulopathies and thromboembolic complications.

Almanac of Clinical Medicine. 2017;45(5):423-428
pages 423-428 views

Hematologic manifestations of Crohn's disease: two clinical cases

Taratina O.V., Lomakina E.Y., Belousova E.A., Stashuk G.A.


Inflammatory bowel diseases (IBD) are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohn's disease reported in the literature. Combination of Crohn's disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a  combination of severe fistula-forming Crohn's disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohn's disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohn's disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohn's disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind potential cobalamin deficiency. However, in severe anemia it is important to perform diagnostic assessment for IBD, first of all, for Crohn's disease, especially, if any intestinal symptoms are present.

Almanac of Clinical Medicine. 2017;45(5):429-438
pages 429-438 views

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