Evidence of degraded BMD and geometry at the proximal femora in male patients with alcoholic liver cirrhosis.

UNLABELLED: We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. INTRODUCTION: Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. METHODS: The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. RESULTS: After adjusting for age, body height, and weight, we found lower cross-sectional area (p = 0.005) and section modulus (p = 0.005), thinner cortex (p = 0.012), and higher buckling ratio (p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. CONCLUSION: Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis.

[Role of Helicobacter pylori infection and use of NSAIDs in the etiopathogenesis of upper gastrointestinal bleeding].

INTRODUCTION: Non-steroid antiinflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) infection are two most important independent risk factors involved in the etiopathogenesis of gastroduodenal mucosal injury with a clear and critical role in both uncomplicated and complicated peptic ulcer disease. It is estimated that upto 90% of all peptic ulcers result from the effect of one or both of these factors. AIM: To determine the frequency of NSAIDs use and Hp infection in patients with acute upper gastrointestinal bleeding. PATIENTS AND METHODS: Study evaluated data from 500 patients in whom esophagogastroduodenoscopy was performed following presentation in emergency unit with acute upper gastrointestinal bleeding. Anamnestic data was collected together with detailed information on previous salicilates and/or NSAIDs use. Hp status was determined and anatomic localisation of bleeding lesion was also registered. RESULTS: Acute upper GIT bleading was caused solely by NSAIDs in 55 (11%), by aspirin in 66 (13.2%), while combined NSAID/aspirin therapy was identified in 19 (3.8%) of patients. In total NSAID and/or aspirin use were diagnosed in 139 (27.8%). while in 122 (24.4%) only Hp infection was diagnosed. Both risk factors were identified in 144 (28.8%) patients (Hp+NSAIDs in 12.2%, Hp+aspirin in 10.8% and Hp+aspirin+NSAIDs in 5.8%). In 19.8% of the cases (14% of males and 27% of females) neither NSAID/aspirin use nor presence of Hp infection was noted. Out of 500 patients enrolled, 63% were mails. In females, bleeding lesion was most frequently localized in gastric mucosa, while males had equal chance of bleeding from either gastric or duodenal mucosa. Fortunatelly, only 5 to 7% of patients were bleeding from both gastric and duodenal lesion. CONCLUSION: Prevention of acute upper gastrointestinal bleeding can be achieved trough strict and limited use of aspirin and NSAIDs, eradication of Hp infection and use of gastroprotective therapy in well-defined risk patients that need chronic NSAIDs and/or aspirin therapy. In all patients starting long-term NSAID and/or aspirin therapy and all patients already on long-term aspirin therapy test and treat strategy for Hp infection should be used. On the other hand, only in high risk patients (more than 65 years, history of peptic ulcer disease, concomitant corticosteroid, aspirin, clopidogrel or warfarin therapy) already on chronic NSAID therapy long-term PPI therapy should be prescribed after testing and treating of Hp infection.

[Myeloproliferative diseases as causative agents of portal and hepatic veins thrombosis].

Thrombosis of portal and hepatic veins is one of the most severe complications and most important causes of death of patients with chronic myeloproliferative diseases. Based on results of the past studies, myeloproliferative diseases were the causes of hepatic veins thrombosis in 30% and portal vein thrombosis in 20% of patients. The study presented 4 patients with myeloproliferative diseases complicated by thrombosis of splanchnic veins, aiming at the illustration of issue complexity in diagnostics and therapy. Two patients with portal vein thrombosis and recurring hemorrhage from esophageal varicosity were described. The first case was planned for shunting, while another case sustained bleeding on what account his anticoagulant therapy was discontinued, but it caused mesenterial thrombosis resulting in lethal outcome. Another two patients had hepatic veins thrombosis. Due to frequent, life-threatening bleeding from the esophageal and gastric varices, a patient with chronic Budd-Chiari syndrome and lineal vein thrombosis underwent mesocaval shunting. An immediate postoperative period was manifested by multiple thrombosis and hemorrhages that ended in his death. A patient with the acute Budd-Chiari syndrome was administered myelosuppressants and anticoagulants on time so reperfusion was restored. In myeloproliferative diseases, thrombosis of portal and hepatic veins gives rise to excessive portal hypertension with profuse hemorrhage from the esophageal and gastric varicosity which is difficult to manage because of complex coagulation disorders.

[Bleeding oesophageal varices--therapeutic options].

INTRODUCTION: Emergency endoscopy plays the most important role in diagnosis and treatment of patients with esophageal variceal bleeding. Endoscopic sclerotherapy (EST), placement of esophageal band ligatures (EVL), medicamentous treatment using somatostatin and its derivatives and balloon tamponade are the methods most frequently applied in treatment of the bleeding esophageal varices. PATIENTS AND METHODS: Endoscopic reports on the patients with bleeding esophageal and gastric varices were retrospectively analyzed in the emergency unit of the Clinic of Gastroenterology and Hepatology, Clinical Center of Serbia over the five-year period--since January 2001 till December 2005. RESULTS: The total of approximately 3, 954 emergency upper endoscopies were performed due to the upper gastrointestinal tract bleeding. Out of the total number of patients, bleeding was diagnosed in 324 (8.2%) patients due to the esophageal varices. In the group of patients with bleeding esophageal varices, the total of 252 (77.8%) males and 72 (22.2%) females averagely aged 56.8 + 7.5 years (range 24 - 80 years) were examined. The primary sclerosant therapy with absolute alcohol was applied in 118 (36.4%) patients, while Blakemore probe tamponade was performed in 145 (44.8%) patients with bleeding esophageal varices. The total of 240 (74.1%) patientswere treated with vasoactive substances (somatostatin and its analogues), as additional therapy and control of the primary hemostasis. It was evidenced that out of 118 patients intra and paravariceally treated with the sclerosant agent (absolute alcohol) hemostasis was achieved in 47 (39.8%). Out of 145 patients subjected to Blakemore probe placement, bleeding was successfully arrested in 117 (80.7%) patients. Somatostatin and its analogues as primary and only treatment of the bleeding esophageal varices were applied in 71 (29.6%) patients, while in the remaining 169 (70.4%) patients, they were applied as additional therapy to the endoscopic sclerotherapy and mechanical treatment of bleeding. Out of 71 patients treated with somatostatin preparations as the only therapeutic option, 45 (63.4%) responded positively by arrest of bleeding for 72 hours. CONCLUSION: Treatment of the acute bleeding esophageal varices is focused on the arrest of bleeding, prevention of early recurrent bleeding and reduction of mortality. Based on the most recent studies, efficacy of the modern endoscopic therapy in the form of sclerotherapy and band ligature placement, as well as application of vasoactive substances reaches up to 90%. Our results evidence minimal efficacy of the sclerotherapy (approximately 40%), which indicates the need of better preparation of patients for the intervention itself and additional education of the personnel.

[Endoscopic haemostasis of bleeding duodenal ulcer].

INTRODUCTION: Acute upper gastrointestinal bleeding is the commonest emergency managed by gastroenterologists. It manifests like: haematemesis, melaena or haemochezia. Diagnostic endoscopy accurately defining the cause of haemorrhage, while therapeutic endoscopy improves prognosis in patients who present with severe bleeding. Endoscopic therapies can be classified as those based on injection, application of heat, or mechanical clips. PATIENTS AND METHODS: This investigation was conducted in Department of endoscopic haemostasis, Clinic for gastroenterology and hepatology, CCS, using retrospective analysis of patients with acute upper gastrointestinal bleeding during the last five years. The aim of this study was to establish the number of upper gastrointestinal bleeding in our hospital during the last five years, and distribution of income according to type, difficulty, cause factors and risk factors of gastrointestinal bleeding and method of haemostasis. RESULTS: In Department of endoscopic haemostasis 3954 patients with upper gastrointestinal bleeding were endoscoped, and 33.4% of them had bleeding duodenal ulcer. Male patients were statistically significant more present than female patients in group with duodenal ulcer 71.8%: 28.2%). 79.7% patients with duodenal ulcer had only haematemesis, while 14.4% patients had haematemesis and melaena. 59.1% patients with bleeding duodenal ulcer consumed salicylates and/or non-steroidal anti-inflammatory drugs (NSAIDS) (statistical significant differences chi2 test; p = 0.007). Only endoscopic injection was used: in 36.8% of patients used injection of adrenaline solutions, while in 5.9% of patients used injection of adrenaline and absolute alcohol solutions. CONCLUSION: Using of therapeutic endoscopy improves better prognosis in patients who present with severe acute upper gastrointestinal bleeding. Endoscopist's experience is an important independent prognostic factor for acute upper gastrointestinal bleeding.

[Non-surgical approach to bleeding gastric ulcer].

Bleeding gastric ulcers is a common reason for emergency upper endoscopy in Emergency Center of Clinical Center of Serbia. Randomized controlled trials have shown that endoscopic hemostasis is beneficial for patients with a bleeding peptic ulcer. Aim of this study was to analyze the frequency, etiological factors and localization of bleeding gastric ulcer. At the same time we were evaluated a degree of bleeding activity according to Forrest's classification and modality of performed endoscopic hemostasis. All patients who underwent upper gastrointestinal (UGI) endoscopy for bleeding gastric ulcer in Emergency Center (January 2001 - December 2005.) were identified from an endoscopy database and the clinical records were reviewed retrospectivel. A total of 3954 patients underwent UGI endoscopy for presumed acute UGI hemorrhage. More than thirty % of them (31.1)-1230 had an endoscopic diagnosis of bleeding gastric ulcer. We observed 1230 bleeding patients (60% male and 40% female) with a mean age of 64.3. The commonest localization of bleeding gastric ulcers was antrum (54 - 15%). Percentage of patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and/or salicilates before bleeding was 54 6%. The main symptom was melaena, which was observed in 82, 44% of patients with bleeding gastric ulcer. According to Forrest's classification of bleeding activity, the most of patients had F IB and F III degree (23, 41% and 22, 76%). Injection endoscopic hemostasis was performed in 26.34% patients, which had active bleeding (F IA, F IB) Hemostasis was initially obtained in 96% of bleeding patients. Bleeding gastric ulcer is one of the commonest endoscopic diagnosis in Emergency Center of Clinical Center of Serbia. The most frequent etiology factor was no--steroid antinflammatory drugs and/or salicilates. Injection endoscopic hemostasis is a safe procedure with a low cost, and, if successful, substantially reduces the need for emergency surgery.

Specificity of splenic blood flow in liver cirrhosis.

UNLABELLED: The association between portal hypertension, splenomegaly and splenic hemodynamics has not been clearly defined until these days. Therefore, hemodynamics of splenic blood vessels and the role of spleen in portal hypertension were the aim of our study. METHODS: Study included 44 patients with liver cirrhosis and splenomegaly and 25 healthy controls. Using color Doppler duplex ultrasonography, morphological and hemodynamic parameters of portal hypertension were analysed: liver and spleen diameters, presence of ascites, morphology of portal and splenic vein; portal and splenic vein flow velocity, hepatic and splenic artery velocity, arterial resistive and pulsatile Doppler indices. RESULTS: In patients with liver cirrhosis, significant differences of venous flow in the liver and spleen were found, compared to the control group (p<0.05). Also, splenic vein flow was significantly faster than in the portal vein. On the contrary, in healthy controls, splenic vein flow was significantly slower than in the portal vein. Mean systolic splenic artery velocity in liver cirrhosis was considerably slower (51.07+/-11.91 cm/sec) than in the control group (58.50+/-13.31 cm/sec), while mean diastolic velocity in splenic artery (18.3+/-7.9 cm/sec) was approximate to the flow in the controls (19.76+/-5.58 cm/sec) (p>0.05). In patients with liver cirrhosis, mean systolic (51.07+/-11.91 cm/sec) and mean diastolic velocities (18.3+/-7.9 cm/sec) in the splenic artery were significantly faster than the mean systolic (42.58+/-14.54 cm/sec) and mean diastolic (12.07+/-5.59 cm/sec) velocities in hepatic artery (p<0.05). In patients with liver cirrhosis, mean resistive index (RI) of splenic artery was significantly lower (0.64+/-0.11) compared to mean RI of hepatic artery (0.72+/-0.08) (p<0.001). In healthy controls, mean RI of splenic artery was also significantly lower than mean RI of hepatic artery (p<0.001). In patients with liver cirrhosis, mean pulsatile index (PI) of splenic artery was significantly lower (1.24+/-0.47) than mean PI of hepatic artery (1.56+/-0.46) (p<0.01). In healthy controls, mean PI of spenic artery was significantly lower (1.17+/-0.36) than mean PI of hepatic artery (1.64+/-0.48) (p<0.001), as the result of high diastolic velocity in splenic artery. CONCLUSION: We consider that high diastolic velocity in splenic artery is a specific phenomenon and may be a kind of modulated response to hypokinetic venous flow in portal hypertension.

The significance of hepatopulmonary syndrome in liver transplantation.

The objective of the study is to determine the diagnostic role of pulmonary functional tests and perfusion pulmonary scintigraphy for quantifying the oxygenation and vascular abnormality in patients with liver cirrhosis. The prospective study included 70 patients with liver cirrhosis. Arterial blood gases analysis were performed in both supine and sitting positions while inhaling room air, and 15 minutes after exposure of hyperoxic mixture. Perfusion pulmonary scintigraphy using albumin macroagregate labelled with radioactive technetium (99mTc-MAA) was performed for the visualisation of intrapulmonary vascular dilatation. The diagnosis of hepatopulmonary syndrome was made in 10 (14.3%) patients. The patients with hepatopulmonary syndrome had severe hypoxemia (Pa,O2 7.41 +/- 1.81 kPa), and poor response to 100% oxygen inhalation (Pa,O2 21.07 +/- 14.41 kPa) and higher alveolo-arterial gradient (5.73 +/- 2.65 kPa). Radioisotope marker 99mTc-MAA skipped intrapulmonary circulation in all patients with HPS and in no one without pulmonary vascular dilatations. The combined approach of 100% inspired oxygen and perfusion pulmonary scintigraphy may identify early oxygenation disorders and alter the priority for liver transplantation, especially in view of potential syndrome resolution.

[Hepatopulmonary syndrome in liver cirrhosis]. / Hepatopulmonalni sindrom u cirozi jetre.

UNLABELLED: Hepatopulmonary syndrome (HPS) is defined by liver disease, hypoxaemia, increase of alveolar-arterial gradient, when inhaling room air, and intrapulmonary vascular dilatation. Pathoanatomical substrate of intrapulmonary vascular dilatation consists of dilated precapillary network, direct arterio-venous communication and dilated pleural blood vessels, "pleural spiders" [2]. Recently, hepatopulmonary syndrome gained clinical significance. Deterioration of arterial oxygenation in patients with liver disease indicates a very poor prognosis, because of which there are suggestions to classify hepatopulmonary syndrome as a new indication of liver transplantation [4]. AIM OF THE STUDY: The aim of the study was to examine the clinical and pathogenetic significance of intrapulmonary shunts in the development of respiratory disorders, and determination of correlation between intrapulmonary shunts and clinical, biochemical parameters in patients with liver cirrhosis. METHOD: In a prospective study over the period 1996-1999, we observed 50 patients with liver cirrhosis who were examined and treated at the Department of Gastroenterology and Hepatology of the Clinical Centre of Serbia in Belgrade. Hepatic examinations were based on medical history, physical examination, laboratory tests, ultrasound, duplex Doppler ultrasound, and histopathological findings. Hepatic failure was classified into 3 stages according to Child's classification. In this study we used 2 groups of pulmonary functional tests: analysis of arterial blood gas exchange and ventilation tests (spirometry, flow-volume curve and body pletismography). Arterial blood gas analysis was performed in supine and sitting positions while inhaling room air and after 15 min of inhaling hyperoxic mixture. RESULTS: Patients were classified according to the generally accepted Child's classification into 3 stages: Sixteen patients (32%) were in Child's A stage, 20 patients (40%) in Child's B stage, and 14 (28%) in stage Child's C. HPS was diagnosed in 9 (18%) patients with liver cirrhosis. The majority of patients with HPS (6) were in Child's C stage, while the other 3 patients were in Child's B stage. Biochemical parameters were considerably worse in patients with shunts in comparison to those without shunts. However, t-test shoved no significant difference. Hypoxaemia caused by intrapulmonary arterio-venous shunt in supine position was found in 7 (14%) patients. Mean value of PaO2 was 8.72 kPa (SD = 1.02). Hypoxaemia caused by arterio-venous shunt in sitting position was found in 9 (18%) patients. The mean PaO2 value was 7.41 kPa, SD = 1.81. Orthodeoxia was confirmed in all patients with intrapulmonary shunt. Hypoxaemia without shunt in supine position was found in 18 (36%) patients, while 12 (24%) patients had hypoxaemia without shunt in sitting position. Comparing groups of patients with shunt and without shunt in supine position, we found a borderline statistically significant difference in PaO2 values (p = 0.057, t-test). In sitting position the difference in PaO2 values between these groups was statistically very significant (p = 0.001, t-test). DISCUSSION: It is supposed that approximately 50% of patients with indication for liver transplantation have some form of arterial oxygenation disorder and 13-47% of these patients may have HPS [6, 7]. In our study, HPS was diagnosed in 18% of patients. We explain this high incidence by the fact that our study included the patients with advanced liver cirrhosis (stages Child's B and C). In studies performed up to date, there was neither correlation between biochemical liver function parameters and intrapulmonary shunts, nor any strong relation between severity of hepatic failure and degree of hypoxaemia [12, 13]. We noticed no correlation between hepatic functions (synthetic, excretory, transaminases) and PaO2 and/or intrapulmonary shunts. Some authors suggested that ventilation-perfusion disorder (Va/Q) is an important cause of hypoxaemia in