MR imaging of primary sclerosing cholangitis: additional value of diffusion-weighted imaging and ADC measurement.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with chronic inflammation and progressive destruction of biliary tree. Magnetic resonance (MR) examination with diffusion-weighted imaging (DWI) allows analysis of morphological liver parenchymal changes and non-invasive assessment of liver fibrosis. Moreover, MR cholangiopancreatography (MRCP), as a part of standard MR protocol, provides insight into bile duct irregularities. PURPOSE: To evaluate MR and MRCP findings in patients with primary sclerosing cholangitis and to determine the value of DWI in the assessment of liver fibrosis. MATERIAL AND METHODS: The following MR findings were reviewed in 38 patients: abnormalities in liver parenchyma signal intensity, changes in liver morphology, lymphadenopathy, signs of portal hypertension, and irregularities of intra- and extrahepatic bile ducts. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for b = 800 s/mm(2). RESULTS: T2-weighted hyperintensity was seen as peripheral wedge-shaped areas in 42.1% and as periportal edema in 28.9% of patients. Increased enhancement of liver parenchyma on arterial-phase imaging was observed in six (15.8%) patients. Caudate lobe hypertrophy was present in 10 (26.3%), while spherical liver shape was noted in 7.9% of patients. Liver cirrhosis was seen in 34.2% of patients; the most common pattern was micronodular cirrhosis (61.5%). Other findings included lymphadenopathy (28.9%), signs of portal hypertension (36.7%), and bile duct irregularities (78.9%). The mean ADCs (x10(-3)mm(2)/s) were significantly different at stage I vs. stages III and IV, and stage II vs. stage IV. No significant difference was found between stages II and III. For prediction of stage ≥II and stage ≥III, areas under receiver-operating characteristic curves were 0.891 and 0.887, respectively. CONCLUSION: MR with MRCP is a necessary diagnostic procedure for diagnosis of PSC and evaluation of disease severity. Moreover, DWI could be used in continuation with standard MR sequences for the evaluation of liver fibrosis stage and distribution.

Integrative role of MRI in the evaluation of primary biliary cirrhosis.

OBJECTIVES: To evaluate magnetic resonance imaging (MRI) findings in patients with primary biliary cirrhosis (PBC) and to determine the value of diffusion-weighted imaging (DWI) in the assessment of liver fibrosis. MATERIALS AND METHODS: The following MRI findings were reviewed in 44 patients: periportal T2-weighted hyperintensity, periportal halo sign (T1- and T2-weighted periportal hypointensity), lymphadenopathy, signs of portal hypertension and morphological liver changes. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for b = 800 s/mm(2). RESULTS: Periportal hyperintensity and periportal halo sign were observed in 72.7% and 66.7% of patients, respectively. Lymphadenopathy was noted in 28 patients (63.6%) and diffuse hepatomegaly in 18 (40.9%). Significant positive correlation was observed between histological stage and periportal halo sign (p = 0.613), hepatomegaly (p = 0.443), and portosystemic collaterals (p = 0.391). The mean ADCs (×10(-3) mm(2)/s) were significantly different at stage I versus III and IV, and stage II versus IV. No significant difference was found between stages II and III. For prediction of stage ≥ II and stage ≥ III areas under receiver operating characteristic curves were 0.879 and 0.906, respectively. CONCLUSION: MRI with DWI could be used as a part of diagnostic protocol in the further evaluation of PBC patients providing noninvasive assessment of liver fibrosis progression. KEY POINTS: • MRI provides insight into the morphological liver changes in primary biliary cirrhosis (PBC) • The periportal "halo" sign is a highly specific finding in PBC • Diffusion-weighted MR imaging allows noninvasive assessment of liver fibrosis grade.

Quality of life in patients with treated and clinically stable Wilson's disease.

Health-related quality of life (HRQoL) in Wilson's disease (WD) has not been extensively studied. Therefore, the purpose of this cross-sectional study was to identify clinical and demographic factors influencing HRQoL in 60 treated, clinically stable patients with WD using a generic questionnaire, the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36). The level of disability and grading of WD multisystemic manifestations were assessed by the Global Assessment Scale for WD (GAS for WD). The Mini Mental State Examination (MMSE) and the 21-item Hamilton Depression Rating Scale (HDRS) scoring were also applied by the same trained interviewers. Lower scores on the SF-36 domains were found in patients with neurological compared with those with a predominantly hepatic form of WD. The HRQoL of patients with WD and psychiatric symptoms was also lower than that of those without them. Finally, significant inverse correlations were obtained between the various SF-36 domains and all the following: period of latency from the first symptoms/signs appearance and treatment initiation, MMSE and HDRS scores, and different domains of the GAS for WD.

The Role of MIF in Hepatic Function, Oxidative Stress, and Inflammation in Thioacetamide-induced Liver Injury in Mice: Protective Effects of Betaine.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on the etiology and stage of liver disease. OBJECTIVE: Our study aimed to investigate the role of MIF in oxidative stress and inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice. METHODS: The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into the following groups: control; Bet-group that received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group that received TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received the same doses. After eight weeks of treatment, blood samples were collected for biochemical analysis, and liver specimens were prepared for the assessment of parameters of oxidative stress and inflammation. RESULTS: In MIF-/-mice, TAA reduced transaminases, γ-glutamyltranspeptidase, bilirubin, malondialdehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN-γ, and increased thiols and total antioxidant status (TAS). Betaine attenuated the mechanism of MIF and mediated effects in TAA-induced liver injury, reducing transaminases, γ-glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g, and increasing thiols. CONCLUSION: MIF is a mediator in hepatotoxic, pro-oxidative, and proinflammatoryeffects of TAA-induced liver injury. MIF-targeted therapy can potentially mitigate oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases anti-oxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.

The Effect of CB1 Antagonism on Hepatic Oxidative/Nitrosative Stress and Inflammation in Nonalcoholic Fatty Liver Disease.

Dysfunction of the endocannabinoid system (ES) has been identified in nonalcoholic fatty liver disease (NAFLD) and associated metabolic disorders. Cannabinoid receptor type 1 (CB1) expression is largely dependent on nutritional status. Thus, individuals suffering from NAFLD and metabolic syndrome (MS) have a significant increase in ES activity. Furthermore, oxidative/ nitrosative stress and inflammatory process modulation in the liver are highly influenced by the ES. Numerous experimental studies indicate that oxidative and nitrosative stress in the liver is associated with steatosis and portal inflammation during NAFLD. On the other hand, inflammation itself may also contribute to reactive oxygen species (ROS) production due to Kupffer cell activation and increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The pathways by which endocannabinoids and their lipid-related mediators modulate oxidative stress and lipid peroxidation represent a significant area of research that could yield novel pharmaceutical strategies for the treatment of NAFLD. Cumulative evidence suggested that the ES, particularly CB1 receptors, may also play a role in inflammation and disease progression toward steatohepatitis. Pharmacological inactivation of CB1 receptors in NAFLD exerts multiple beneficial effects, particularly due to the attenuation of hepatic oxidative/nitrosative stress parameters and significant reduction of proinflammatory cytokine production. However, further investigations regarding precise mechanisms by which CB1 blockade influences the reduction of hepatic oxidative/nitrosative stress and inflammation are required before moving toward the clinical phase of the investigation.

Tuberculous lymphadenitis as a cause of obstructive jaundice: a case report and literature review.

Obstructive jaundice secondary to tuberculosis (TB) is extremely rare. It can be caused by TB enlargement of the head of the pancreas, TB lymphadenitis, TB stricture of the biliary tree, or a TB mass of the retroperitoneum. A 29-year-old man with no previous history of TB presented with abdominal pain, obstructive jaundice, malaise and weight loss. Ultrasonography (US), computer tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) were suggestive of a stenosis of the distal common bile duct (CBD) caused by a mass in the posterior head of the pancreas. Tumor markers, CEA and CA19-9 were within normal limits. At operation, an enlarged, centrally caseous lymph node of the posterior head of the pancreas was found, causing inflammatory stenosis and a fistula with the distal CBD. The lymph node was removed and the bile duct resected and anastomosed with the Roux-en Y jejunal limb. Histology and PCR based-assay confirmed tuberculous lymphadenitis. After an uneventful postoperative recovery, the patient was treated with anti-tuberculous medication and remained well 2.5 years later. Though obstructive jaundice secondary to tuberculous lymphadenitis is rare, abdominal TB should be considered as a differential diagnosis in immunocompromised patients and in TB endemic areas. Any stenosis or fistulation into the CBD should also be taken into consideration, and biliary bypass surgery be performed to both relieve jaundice and prevent further stricture.

Right liver lobe/albumin ratio: contribution to non-invasive assessment of portal hypertension.

AIM: To study the value of biochemical and ultraso-nographic parameters in prediction of presence and size of esophageal varices. METHODS: The study includes selected cirrhotic patients who underwent a complete biochemical workup, upper digestive endoscopic and ultrasonographic examinations. Albumin/right liver lobe diameter and platelet count/spleen diameter ratios were calculated. The correlation between calculated ratio and the presence and degree of esophageal varices was evaluated. RESULTS: Ninety-four subjects (62 males, 32 females), with a mean age of 52.32 +/- 13.60 years, were studied. Child-Pugh class A accounted for 42.6%, class B 37.2%, whereas class C 20.2%. Esophageal varices (OE) were not demonstrated by upper digestive endoscopy in 24.5%, while OE grade I was found in 22.3% patients, grade II in 33.0%, grade III in 16.0%, and grade IV in 4.3%. The mean value of right liver lobe diameter/albumin ratio was 5.51 +/- 1.82 (range from 2.76 to 11.44), while the mean platelet count/spleen diameter ratio was 1017.75 +/- 729.36 (range from 117.39 to 3362.50), respectively. Statistically significant correlation was proved by Spearman's test between OE grade and calculated ratios. The P values were 0.481 and -0.686, respectively. CONCLUSION: The right liver lobe diameter/albumin and platelet count/spleen diameter ratios are non-invasive parameters providing accurate information pertinent to determination of presence of esophageal varices, and their grading in patients with liver cirrhosis.

Comparison of standard fibrinogen measurement methods with fibrin clot firmness assessed by thromboelastometry in patients with cirrhosis.

BACKGROUND: The Clauss fibrinogen method and thrombin clotting time (TCT) are still routinely used in patients with cirrhosis to define fibrinogen concentration and clotting potential. The thromboelastometric functional fibrinogen FIBTEM assay evaluates the strength of fibrin-based clots in whole blood, providing information on both quantitative deficit and fibrin polymerization disorders. OBJECTIVE: To compare these three methods of assessing fibrinogen in patients with cirrhosis of different aetiologies, characterized by impairment in fibrinogen concentration as well as functional aberrance. METHODS: Sixty patients with alcoholic and 24 patients with cholestatic cirrhosis were included (Child-Pugh score (CPs)A, n=24; B, n=32; C, n=28). All parameters were compared with those from a control group. Maximum clot firmness (MCF) in the FIBTEM test was assessed in regard to its relevance in detection of qualitative fibrinogen disorders in comparison with results obtained by standard measurement methods, i.e. the Clauss fibrinogen method and TCT. RESULTS: With increased cirrhosis severity, fibrinogen and FIBTEM-MCF levels significantly declined (p=0.002), while TCT was significantly prolonged (p=0.002). In all CPs groups, fibrinogen strongly correlated with FIBTEM-MCF (r=0.77, r=0.72, r=0.74; p<0.001), while cross-correlations of other assays were highly variable. The prevalence of decreased FIBTEM-MCF values (<9 mm) was significantly higher in advanced CPs categories (p=0.027), whereby the highest prevalence was detected in patients with CPsC (10/16; 62.5%). Nine of the 16 patients with decreased FIBTEM-MCF values had also decreased fibrinogen levels, while in the remaining 7 patients fibrinogen levels were within the reference range, indicating the possible presence of qualitatively altered fibrinogen that could be detected by FIBTEM-MCF. CONCLUSIONS: FIBTEM-MCF may be considered as a reliable alternative to standard plasma fibrinogen measurement in cirrhotic patients, especially in evaluating fibrin polymerization disorders in these patients. Further studies are needed to evaluate the usefulness of this assay in predicting bleeding complications in cirrhotic patients as well as monitoring replacement treatment.

Alcoholic liver disease/nonalcoholic fatty liver disease index: distinguishing alcoholic from nonalcoholic fatty liver disease.

OBJECTIVE: The alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) (ANI) scoring system was constructed as a response to a clinical need for avoiding the risks of liver biopsy in diagnosing the etiology of fatty liver disease. The aim of this study was to test the reliability of ANI as a noninvasive method to distinguish ALD from NAFLD. MATERIALS AND METHODS: One hundred and thirty-five patients were classified into two groups, ALD and NAFLD, according to the pathohistological results. Parameters for ANI are aspartate aminotransferase, alanine aminotransferase, mean corpuscular volume, BMI, and sex. ANI was calculated using an online calculator, official site of Mayo Clinic. RESULTS: ANI was significantly higher in patients with ALD than NAFLD (P<0.01). The cutoff point of ANI is -0.66. ANI greater than -0.66 indicates ALD, whereas ANI less than -0.66 yields a higher probability of NAFLD with high specificity (96.7%) and sensitivity (84.1%). The mean corpuscular volume and aspartate aminotransferase/alanine aminotransferase ratio were higher, whereas BMI was lower in patients with ALD than in NAFLD (P<0.01). CONCLUSION: The ANI scoring system may be used for the estimation of alcoholic origin of steatosis/steatohepatitis and may help in triaging patients for liver biopsy. ANI less than -0.66 indicates NAFLD, whereas ANI greater than -0.66 confirms the alcoholic etiology, but does not exclude the contribution of associated factors toward the development of fatty liver in a Serbian population.

Validation of the chronic liver disease questionnaire in Serbian patients.

AIM: To translate into Serbian and to investigate the validity of the cross-culturally adapted the chronic liver disease questionnaire (CLDQ). METHODS: The questionnaire was validated in 103 consecutive CLD patients treated between October 2009 and October 2010 at the Clinic for Gastroenterology, Clinical Centre of Serbia, Belgrade (Serbia). Exclusion criteria were: age < 18 years, psychiatric disorders, acute complications of CLD (acute liver failure, variceal bleeding, and spontaneous bacterial peritonitis), hepatic encephalopathy (grade > 2) and liver transplantation. Evaluation of the CLDQ was done based on the following parameters: (1) acceptance is shown by the proportion of missing items; (2) internal reliabilities were assessed for multiple item scales by using Cronbach alpha coefficient; and (3) in order to assess whether the allocation of items in the domain corresponds to their distribution in the original questionnaire (construction validity), an exploratory factor analysis was conducted. Discriminatory validity was determined by comparing the corresponding CLDQ score/sub-score in patients with different severity of the diseases. RESULTS: The Serbian version of CLDQ questionnaire completed 98% patients. Proportion of missing items was 0.06%. The total time needed to fill the questionnaire was ranged from 8 to 15 min. Assistance in completing the questionnaire required 4.8% patients, while 2.9% needed help in reading, and 1.9% involved writing assistance. The mean age of the selected patients was 53.8 ± 12.9 years and 54.4% were men. Average CLDQ score was 4.62 ± 1.11. Cronbach's alpha for the whole scale was 0.93. Reliability for all domains was above 0.70, except for the domain "Activity" (0.49). The exploratory factor analysis model revealed 6 factors with eigenvalue of greater than 1, explaining 69.7% of cumulative variance. The majority of the items (66%) in the Serbian version of the CLDQ presented the highest loading weight in the domain assigned by the CLDQ developers: "Fatigue" (5/5), "Emotional function" (6/8), "Worry" (5/5), "Abdominal symptoms" (0/3), "Activity" (0/3), "Systemic symptoms" (3/5). The scales "Fatigue" and "Worry" fully corresponded to the original. The factor analysis also revealed that the factors "Activity" and "Abdominal symptoms" could not be replicated, and two new domains "Sleep" and "Nutrition" were established. Analysis of the CLDQ score/sub-score distribution according to disease severity demonstrated that patients without cirrhosis had lower total CLDQ score (4.86 ± 1.05) than those with cirrhosis Child's C (4.31 ± 0.97). Statistically significant difference was detected for the domains "Abdominal symptoms" [F (3) = 5.818, P = 0.001] and "Fatigue" [F (3) = 3.39, P = 0.021]. Post hoc analysis revealed that patients with liver cirrhosis Child's C had significantly lower sub-score "Abdominal symptoms" than patients without cirrhosis or liver cirrhosis Child's A or B. For domain "Fatigue", patients with cirrhosis Child's C had significantly lower score, than non-cirrhotic patients. CONCLUSION: The Serbian version of CLDQ is well accepted and represents a valid and reliable instrument in Serbian sample of CLD patients.

Noninvasive assessment of portal hypertension in patients with alcoholic cirrhosis.

BACKGROUND/AIMS: Portal hypertension and development of esophageal varices is one of the major complications of liver cirrhosis. The aim of our study was to evaluate the possibility of the presence of esophageal varices and their size using biochemical and ultrasonography parameters in patients with alcoholic liver cirrhosis. MATERIAL AND METHODS: We included in our study 86 patients (74 males, mean age 55±7) with alcoholic liver cirrhosis. The control group consisted of 102 patients with cirrhosis of other etiologies. All patients underwent a complete biochemical workup, upper digestive endoscopy and ultrasonography examination. The right liver lobe diameter/albumin and platelet count/spleen diameter ratios were calculated. The correlation of the calculated ratios with the presence and degree of esophageal varices in patients with liver cirrhosis was also determined. RESULTS: The mean value of right liver lobe diameter-albumin ratio was 6.15±1.77, and statistically significantly differed from values determined in the control group (4.97±1.68). The mean platelet count-spleen diameter ratio was 972.5±599.0 in alcoholic liver cirrhosis and 1055.9±821.3 in controls (p>0.05). In patients with alcoholic liver cirrhosis, none of the analyzed noninvasive markers was shown to be a good predictor of the presence and size of esophageal varices. CONCLUSIONS: Despite the important role of noninvasive markers in providing information pertinent to determination of esophageal varices in patients with liver cirrhosis, these markers have limited relevance in patients with alcoholic cirrhosis.

Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases.

PURPOSE: To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. MATERIALS AND METHODS: Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b=0, 50, 200, 400 and 800 s/mm(2). A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. RESULTS: The mean ADCs (× 10(-3)mm(2)/s; b=0-800 s/mm(2)) were significantly different at stage F1 versus F ≥ 2 (p<0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV=9.54 ± 6.3%). CONCLUSION: DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution.

Ultrasound measurement of visceral fat in patients with primary biliary cirrhosis.

BACKGROUND/AIM: Primary biliary cirrhosis (PBC) is a progressive, chronic liver disease with elevated serum lipids, but it is unclear whether hyperlipidemia in PBC patients is associated with atherosclerosis. Metabolic syndrome promotes development of atherosclerotic cardiovascular disease related to abdominal type obesity and insulin resistance. The aim of our study was to assess abdominal adiposity in patients with PBC. METHODS: The study included 40 patients with PBC and 50 healthy controls. Age, sex and anthropometric measurements (weight, height, body mass index and waist circumference) were registered for all patients and controls. We used ultrasonography to measure subcutaneous (SF) and visceral fat (VF) diameter, subcutaneous area (SA) and visceral area (VA), as well as perirenal fat diameter (PF). RESULTS: Values of SF, VF and PF thicknesses in PBC patients were 19.23 +/- 5.85 mm, 10.92 +/- 3.63 mm, and 7.03 +/- 1.82 mm, respectively. In controls these measurements were 22.73 +/- 6.70 mm, 16.84 +/-5.51 mm and 10.50 +/- 2.70 mm respectively. In PBC patients SA and VA were calculated to 983.64 +/- 322.68 mm2 and 403.64 +/- 166.97 mm2 and in controls 1124.89 +/- 366.01 mm2 and 720.57 +/- 272.50 mm2 respectively. Significant difference was found for VF, VA and RF values. CONCLUSIONS: Considering that the amount of visceral fat plays an important role in development of metabolic syndrome and cardiovascular diseases, we concluded that the lower amount of visceral fat in PBC patients could be related to lower incidence of cardiovascular events, despite hyperlipidemia.

Role of serotonin in development of esophageal and gastric fundal varices.

AIM: to determine the effect of free serotonin concentrations in plasma on development of esophageal and gastric fundal varices. METHODS: this prospective study included 33 patients with liver cirrhosis and 24 healthy controls. Ultrasonography and measurement of serotonin concentration in plasma were carried out in both groups of subjects. The upper fiber panendoscopy was performed only in patients with liver cirrhosis. RESULTS: the mean plasma free serotonin levels were much higher in liver cirrhosis patients than in healthy controls (219.0 ± 24.2 nmol/L vs 65.4 ± 18.7 nmol/L, P < 0.0001). There was no significant correlation between serotonin concentration in plasma and the size of the esophageal varices according to Spearman coefficient of correlation (r(s) = -0.217, P > 0.05). However, the correlation of plasma serotonin concentration and gastric fundal varices was highly significant (r(s) = -0.601, P < 0.01). CONCLUSION: free serotonin is significant in pathogenesis of portal hypertension especially in development of fundal varices, indicating the clinical value of serotonergic receptor blockers in these patients.

[Sepsis as a cause of intrahepatic cholestasis].

INTRODUCTION: The causes of intrahepatic cholestasis include cholestatic viral hepatitis, primary biliary cirrhosis, benign recurrent cholestasis, primary sclerosing cholangitis and sepsis. During sepsis, proinflammatory cytokines and nitric oxide cause cholestasis by impairing hepatocellular and ductal bile formation. CASE OUTLINE: We report a 48-year-old woman who was admitted to hospital due to malaise, jaundice, fever and pain in the neck. Physical examination revealed jaundice, tachycardia (pulse rate was 120/min), hypotension 90/60 mm Hg. Laboratory findings showed normocytic normochromic anaemia, inflammatory syndrome and abnormal liver function tests indicating cholestasis and hepatocellular necrosis. Abdominal ultrasonography detected hepatosplenomegaly. Chest computed tomography showed bronchopneumonic infiltrates. Percutaneous liver biopsy was performed using a Menghini needle of 1.4 mm. Pathohystological analysis of the liver tissue confirmed reactive, intrahepatic cholestasis. Blood cultures isolated Staphylococcus aureus. After the diagnosis was established the treatment with broad-spectrum antibiotics was carried out, resulting in the improvement of general condition of the patient, regression of inflammatory syndrome, disappearance of cholestasis and regression of pulmonary infiltrates. Abdominal ultrasonography after antibiotic treatment did not show hepatosplenomegaly. CONCLUSION: Concerning patients with cholestasis of uncertain origin, we should always think of sepsis as a possible cause in order to start antibiotic treatment in time.

Biochemical markers for non-invasive assessment of disease stage in patients with primary biliary cirrhosis.

AIM: To evaluate different biochemical markers and their ratios in the assessment of primary biliary cirrhosis (PBC) stages. METHODS: This study included 112 patients with PBC who underwent a complete clinical investigation. We analyzed the correlation (Spearman's test) between ten biochemical markers and their ratios with different stages of PBC. The discriminative values were compared using areas under receiver operating characteristic (ROC) curves. RESULTS: The mean age of patients included in the study was 53.88 +/- 10.59 years, including 104 females and 8 males. We found a statistically significant correlation between PBC stage and Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) to platelet ratio (APRI), ALT/platelet count, AST/ALT, ALT/AST and ALT/Cholesterol ratios, with the values of Spearman's rho of 0.338, 0.476, 0.404, 0.356, 0.351 and 0.325, respectively. The best sensitivity and specificity was shown for AST/ALT, with an area under ROC of 0.660. CONCLUSION: Biochemical markers and their ratios do correlate with different sensitivity to and specificity of PBC disease stage. The use of biochemical markers and their ratios in clinical evaluation of PBC patients may reduce, but not eliminate, the need for liver biopsy.

Neuropsychiatric aspects of treated Wilson's disease.

The objective of the current cross-sectional study was to use standardized psychiatric interviews (the Structured Clinical Interview for DSM-IV Axis I Disorders and the Neuropsychiatric Inventory; NPI) in order to better characterize psychiatric symptoms in 50 consecutive, treated and clinically stable patients with Wilson's disease (WD). Nine patients (18%) had one, 7 patients (14%) had two, and 20 (40%) had >or= 3 neuropsychiatric symptoms present. The most often endosed symptoms were anxiety (62%), depression (36%), irritability (26%), as well as disinhibition and apathy (24% each). Twenty two patients (44%) had a score >or= 4 on at least one of the NPI items: again, most frequently anxiety (17 patients; 34%), depression (13 patients; 26%) and apathy (9 patients; 18%). Therefore, even among stable, long-term treated patients with WD approximately 70% experienced psychiatric symptoms.

[Epoprostenol in the treatment of portopulmonary hypertension]. / Epoprostenol u terapiji portnoplucne hipertenzije.

Primary or non-hemodynamic pulmonary hypertension is characterized by the increased pulmonary arterial pressure, higher than 3.32 kPa, and normal pulmonary capillary pressure less than 1.99 kPa. Primary pulmonary hypertension is a rare complication of portal hypertension, which significantly increases surgical morbidity and mortality, and it is not reversible after liver transplantation. As a rule, clinical manifestations of pulmonary hypertension are disguised by complications of portal hypertension. The symptoms of chronic pulmonary heart, such as peripheral edema and ascites, are usually ascribed to liver insufficiency and/or portal hypertension. Clinical significance of portopulmonary hypertension follows from the fact that the failure of the right heart is most commonly the direct cause of death in these patients. The majority of authors concurs that the right heart catheterization is the most valid method for diagnosis of portopulmonary hypertension. Doppler echocardiography represents quite valuable non-invasive diagnostic method, especially in patients with extensive spontaneous and surgical porto-systemic collaterals, rendering the high risk group of cases. Epoprostenol (prostacyclin), administered via continuous infusion, diminishes the platelet aggregation and causes the intense pulmonary and systemic vasodilatation. Good hemodynamic effect of this substance was verified in patients with primary pulmonary hypertension. Several articles have reported that long-term, continual epoprostenol administration in dose of 10 to 28 ng/kg/min. Has significantly reduced pulmonary vascular pressure and pulmonary vascular resistance. Portopulmonary hypertension represented the absolute contraindication for liver transplantation. Huge clinical significance of epoprostenol reflects in the fact that, along with the improvement of pulmonary hemodynamics, it provides the prerequisite for liver transplantation in patients with portopulmonary hypertension.

[Treatment of chronic hepatitis C with PEG-interferon]. / Lecenje hronicnog hepatitisa C peg-interferonom.

INTRODUCTION: Since the discovery of the hepatitis C virus, the etiology of chronic liver diseases has been revealed in great number of patients. However, the treatment of hepatitis C viral infection still hasn't been completely resolved. Antiviral and immunomodulatory effects of interferon, and antiviral effect on the nucleoside analogs were efficient only in small number of patients. Discovery of pegylated interferon brings progress in therapeutic success rates. MATERIAL AND METHODS: Combined therapy with peginterferon alfa-2a (Pegasys) 180 mg once a week plus Ribavirin 800 mg a day during a 24-week period was conducted in 20 patients (13 were previously treated with standard antiviral therapy). The aim of this study was to determine the safety and the efficacy of therapy in our patients. RESULTS AND DISCUSSION: Analysis of safety of the combined therapy was conduced in all 20 patients, and analysis of efficiency in 18 patients. Efficacy of the combined therapy was assessed regarding to biochemical response (normalization of aminotransferase activity at the end of therapy and at the end of 6-month follow-up) and virologic response (disappearance of RNA HCV in serum at the end of 6-month follow-up). 30% of treated patients experienced no troubles during treatment. Influenza-like symptoms, weight loss, depression, hair loss and reaction at the site of injection were mild and did not exclude patients from their usual activities in family, society and work place. Neutropenia, thrombocytopenia and anemia as well as elevated aminotransferase activity demanded periodical dose modification in 20% of patients. Unexpected unwanted effect emerged in one patient after cessation of therapy (pulmonary sarcoidosis). Good effects of combined therapy at the end of follow-up period showed biochemical and virologic response in 66% of patients. CONCLUSION: Combined therapy with Pegasys 180 mg/week and Ribavirin 80 mg/day is safe and well tolerated. Sustained biochemical and virologic response was achieved in 66% of patients.