Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Metastatic multifocal melanoma of multiple organ systems: A case report.

BACKGROUND: Malignant melanoma is becoming more common among middle-aged individuals all over the world. Melanoma metastasis can be found in various organs, although metastases to the spleen and stomach are rare. Herein we present a rare metastatic multifocal melanoma, clinically and histologically mimicking lymphoma, with metastases of multiple organs. CASE SUMMARY: A 46-year-old Caucasian male with a history of nodular cutaneous malignant melanoma was presented with nausea, general weakness, shortness of breath, abdominal enlargement, and night sweating. The abdominal ultrasound revealed enlarged liver and spleen with multiple lesions. Computed tomography demonstrated multiple lesions in the lungs, liver, spleen, subcutaneous tissue, bones and a pathological lymphadenopathy of the neck. Trephine biopsy and the biopsy from the enlarged lymph node were taken. Tumor cells showed diffuse or partial positivity for melanocytic markers, such as microphthalmia - associated transcription factor, S100, HMB45 and Melan-A. The tumor harbored BRAF V600E mutation, demonstrated by immunohistochemical labelling for BRAF V600E and detected by real-time polymerase chain reaction test. Having combined all the findings, a diagnosis was made of a metastatic multifocal melanoma of the stomach, duodenum, liver, spleen, lungs, lymph nodes and bones. The patient refused treatment and died a week later. CONCLUSION: This case report highlights the clinical relevance of rare metastatic multifocal melanoma of multiple organ systems.

Management of Flood syndrome: What can we do better?

Approximately 20% of cirrhotic patients with ascites develop umbilical herniation. These patients usually suffer from multisystemic complications of cirrhosis, have a significantly higher risk of infection, and require accurate surveillance- especially in the context of the coronavirus disease 2019 pandemic. The rupture of an umbilical hernia, is an uncommon, life-threatening complication of large-volume ascites and end-stage liver disease resulting in spontaneous paracentesis, also known as Flood syndrome. Flood syndrome remains a challenging condition for clinicians, as recommendations for its management are lacking, and the available evidence for the best treatment approach remains controversial. In this paper, four key questions are addressed regarding the management and prevention of Flood syndrome: (1) Which is the best treatment approach-conservative treatment or urgent surgery? (2) How can we establish the individual risk for herniation and possible hernia rupture in cirrhotic patients? (3) How can we prevent umbilical hernia ruptures? And (4) How can we manage these patients in the conditions created by the coronavirus disease 2019 pandemic?

Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is a rare, idiopathic, usually benign, mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells. Although it can affect various organs, the biliary tract is a rare localization of primary IMT, clinically, endoscopically and radiologically imitating cholangiocarcinoma. The treatment options are based only on clinical practice experience. CASE SUMMARY: A 70-year-old woman was referred to our center due to progressive fatigue, weight loss, abdominal pain, night sweats, and elevated liver enzymes. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts. Although initial clinical, endoscopic and radiological signs were typical for hilar cholangiocarcinoma, histological examination showed no signs of malignancy. In total, 8 biopsies using different approaches were performed (several biopsies from dominant stricture during ERCP and direct cholangioscopy; ultrasound-guided liver biopsy; diagnostic laparoscopy with liver and lymph node biopsies). Histological examination revealed signs of IMT, and the final diagnosis of biliary IMT was stated. Although IMT is usually a benign disease, in our case, it was complicated. All pharmacological treatment measures were ineffective. The patient still needs permanent stenting, suffers from recurrent infections and mechanical jaundice. Despite that, the patient already survived 24 mo. CONCLUSION: IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma, and there are no evidence-based treatment options. Our goal is to increase the understanding of this rare disease and its possible course.

Comparison of Endoscopy First and Laparoscopic Cholecystectomy First Strategies for Patients With Gallstone Disease and Intermediate Risk of Choledocholithiasis: Protocol for a Clinical Randomized Controlled Trial.

BACKGROUND: The optimal approach for patients with gallbladder stones and intermediate risk of choledocholithiasis remains undetermined. The use of endoscopic retrograde cholangiopancreatography for diagnosis should be minimized as it carries considerable risk of postprocedural complications, and nowadays, less invasive and safer techniques are available. OBJECTIVE: This study compares the two management strategies of endoscopic ultrasound before laparoscopic cholecystectomy and intraoperative cholangiography for patients with symptomatic cholecystolithiasis and intermediate risk of choledocholithiasis. METHODS: This is a randomized, active-controlled, single-center clinical trial enrolling adult patients undergoing laparoscopic cholecystectomy for symptomatic gallbladder stones with intermediate risk of choledocholithiasis. The risk of choledocholithiasis is calculated using an original prognostic score (the Vilnius University Hospital Index). This index in a retrospective evaluation showed better prognostic performance than the score proposed by the American Society for Gastrointestinal Endoscopy in 2010. A total of 106 participants will be included and randomized into two groups. Evaluation of bile ducts using endoscopic ultrasound and endoscopic retrograde cholangiography on demand will be performed before laparoscopic cholecystectomy for one arm ("endoscopy first"). Intraoperative cholangiography during laparoscopic cholecystectomy and postoperative endoscopic retrograde cholangiopancreatography on demand will be performed in another arm ("cholecystectomy first"). Postoperative follow-up is 6 months. The primary endpoint is the length of hospital stay. The secondary endpoints are accuracy of the different management strategies, adverse events of the interventions, duct clearance and technical success of the interventions (intraoperative cholangiography, endoscopic ultrasound, and endoscopic retrograde cholangiography), and cost of treatment. RESULTS: The trial protocol was approved by the Vilnius Regional Biomedical Research Ethics Committee in December 2017. Enrollment of patients was started in January 2018. As of June 2020, 66 patients have been enrolled. CONCLUSIONS: This trial is planned to determine the superior strategy for patients with intermediate risk of common bile duct stones and to define a simple and safe algorithm for managing choledocholithiasis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03658863; https://clinicaltrials.gov/ct2/show/NCT03658863. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18837.

Paraneoplastic Phenomena of Disseminated Intravascular Coagulopathy in Hepatic Angiosarcoma - Rare, Challenging and Fatal. Case Report and Literature Review.

Background: Hepatic angiosarcoma is an uncommon, malignant, primary liver tumor, comprising 2% of liver cancers and accounting for < 1% of all sarcomas. Patients usually present with nonspecific symptoms, such as fatigue, weight loss, right upper quadrant pain, anemia, which leads to late diagnosis of an advanced stage tumor. The median life expectancy after the diagnosis of hepatic angiosarcoma is about 6 months, with only 3% of patients surviving more than 2 years. Liver failure and hemoperitoneum are the leading causes of death in patients with liver angiosarcoma. In rarer cases, it might cause paraneoplastic syndromes such as disseminated intravascular coagulopathy. The treatment of angiosarcomas is complicated as there are no established and effective treatment guidelines due to the tumor's low frequency and aggressive nature. Case summary: We present the case of a 68-year old woman who was admitted to the hospital due to fatigue and severe anemia (hemoglobin 65 g/l). Laboratory results also revealed high-grade thrombocytopenia (8 × 109/l). The abdominal ultrasound and computed tomography scan showed multiple lesions throughout the liver, spleen and kidneys. After the histological examination of the liver biopsy, the patient was diagnosed with hepatic angiosarcoma. The treatment with first-line chemotherapy (doxorubicin) was initiated despite ongoing paraneoplastic syndrome - disseminative intravascular coagulopathy. However, the disease was terminal, and the patient died 2 months since diagnosed. Conclusions: Hepatic angiosarcoma is a rare and terminal tumor. Therefore, knowledge about its manifestations and effective treatment methods is lacking. Disseminative intravascular coagulopathy is a unique clinical characteristic of angiosarcoma seen in a subset of patients.

Evaluation of Upper Endoscopic and Endoscopic Ultrasound Features in the Differential Diagnosis of Gastrointestinal Stromal Tumors and Leiomyomas in the Upper Gastrointestinal Tract.

BACKGROUND: Differentiation between benign and malignant subepithelial lesions (SELs) in the upper gastrointestinal tract (UGT) leads to far-reaching clinical consequences. An accurate diagnosis can be challenging because of the insufficient diagnostic yield of upper endoscopy, endoscopic ultrasound (EUS), and different types of biopsy. AIM: Our aim was to reveal the efficacy of upper endoscopic and EUS features for the differential diagnosis of hypoechogenic SELs (gastrointestinal stromal tumors [GISTs] and leiomyomas) in the UGT. MATERIALS AND METHODS: The research covers a case series study of 27 hypoechogenic SELs in the UGT between 2012 and 2015 at Vilnius University Hospital Santaros Klinikos. Upper endoscopic and EUS features of SELs were recorded. In order to standardize the diagnostic approach to GISTs and leiomyomas, we assigned scores for seven upper endoscopic and EUS features. RESULTS: The mean total scores in the GIST group were significantly higher than those in the leiomyoma group: 3.25 ± 1.71 and 0.53 ± 0.83 (p < 0.0001), respectively. Increment by one score increased the odds ratio for GIST 5.87 times (95% CI 1.63-21.11; p = 0.007). The total score demonstrated very good discriminatory features of GISTs against leiomyomas (area under the receiver operating characteristic curve 0.94 [0.86-1]). The cutoff value of 1.5 total score indicated 83.3% sensitivity and 93.3% specificity in diagnosing GISTs. CONCLUSIONS: Upper endoscopy and EUS are useful methods in making a definite diagnosis of SELs. Their diagnostic accuracy for the differential diagnosis of GISTs and leiomyomas is sufficient.

Multi-organ IgG4-related disease continues to mislead clinicians: A case report and literature review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic mass forming immune-mediated disease that affects almost every organ and is a diagnostic challenge for every clinician. There is a lack of adequate epidemiological data worldwide, and evidence-based treatment recommendations are not yet established. We report the first case of IgG4-RD from Lithuania and the Baltic Sea region presented with thyroiditis, orbital myositis, orbitopathy, uveitis, scleritis, sialadenitis, autoimmune pancreatitis and prostatitis. CASE SUMMARY: A 54-year-old Caucasian male was admitted to our tertiary Centre complaining of severe weight loss, diarrhoea, abdominal pain, salivary gland swelling, sicca symptoms and diplopia. On examination, bilateral palpable masses in the projection of major salivary glands, severe protrusion of the left eyeball and cachexia were noted. The patient was previously diagnosed with autoimmune thyroiditis and endocrine ophthalmopathy. The magnetic resonance imaging (MRI) of the head revealed enlarged extraocular muscles indicating orbital myositis. The biopsy from the salivary gland mass indicated sialadenitis. Abdominal MRI showed signs of autoimmune pancreatitis, and a serological test revealed the elevated serum IgG4 concentration. The patient was then diagnosed with IgG4-RD and successfully treated with prednisolone. There was a significant clinical, serological and radiological improvement after one month of treatment and no signs of relapse within twenty months. However, it took almost 18 years and the efforts of eight different medical specialists to establish the correct diagnosis. CONCLUSION: A comprehensive approach to the patient is essential to improving the recognition of rare immune system conditions, such as IgG4-RD.

Mucosa-associated lymphoid tissue lymphoma simulating Crohn's disease: A case report.

BACKGROUND: Differential diagnosis between extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and inflammatory bowel disease is mainly based on histopathologic evaluation of intestinal biopsies, although there is no single definitive diagnostic investigation and that circumstance can lead to misdiagnosis in particular cases. Herein we present a rare, ulcerative form of marginal zone lymphoma which mimics the Crohn's disease (CD) of upper digestive tract. CASE SUMMARY: A 50-year-old man was presented with recurrent episodes of malaise and melena also weight loss. Enteroscopy of the small bowel demonstrated an ulcer in the jejunum. Microscopically, biopsies showed lymphoplasmacytic infiltrate. Diagnosis of CD was made. Primary treatment consisted of prednisone and azathioprine and was followed by azathioprine 100 mg per day with good clinical response in the following 2 years until relapse. At this time the results of endoscopic biopsies derived from proximal wall of stomach revealed Helicobacter pylori-negative marginal zone lymphoma of the gastric fundus. Immunophenotyping confirmed atypical CD20-positive cell population. Based on these biopsies, marginal zone lymphoma of mucosa-associated lymphoid tissue was diagnosed. Unfortunately, the contact with the patient was lost until one year later he was hospitalized with nausea, vomiting and severe pain because of gastrointestinal perforation. Four months later after laparotomy, the patient was treated with a course of chemotherapy. Complete remission was observed following 6 cycles of treatment. CONCLUSION: This case report highlights the clinical relevance of knowledge and awareness of marginal zone lymphoma simulating CD.

Liver cirrhosis and left ventricle diastolic dysfunction: Systematic review.

BACKGROUND: Liver cirrhosis is a chronic hepatic disease which is associated with cardiovascular abnormalities. Hyperdynamic circulation in liver cirrhosis causes functional and structural cardiac alterations. The prevalence of left ventricle diastolic dysfunction (LVDD) in cirrhotic patients ranges from 25.7% to as high as 81.4% as reported in different studies. In several studies the severity of diastolic dysfunction (DD) correlated with a degree of liver failure and the rate of dysfunction was higher in patients with decompensated cirrhosis compared with compensated. Future directions of comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients. AIM: To clarify the correlation between the severity of liver cirrhosis and left ventricle diastolic dysfunction in the existing literature. METHODS: Through January and February of 2019 at Vilnius University we conducted a systematic review of the global existing literature on the prevalence of left ventricle diastolic dysfunction in patients with liver cirrhosis. We searched for articles in PubMed, Medline and Web of science databases. Articles were selected by using adequate inclusion and exclusion criteria. Our interest was the outcome of likely correlation between the severity of cirrhosis [evaluated by Child-Pugh classes, Model For End-Stage Liver Disease (MELD) scores] and left ventricle diastolic dysfunction [classified according to American Society of Echocardiography (ASE) guidelines (2009, 2016)], as well as relative risk of dysfunction in cirrhotic patients. Subgroup analyses were performed to evaluate the ratio and grades of left ventricle diastolic dysfunction with respect to cirrhosis severity. RESULTS: A total of 1149 articles and abstracts met the initial search criteria. Sixteen articles which met the predefined eligibility criteria were included in the final analysis. Overall, 1067 patients (out of them 723 men) with liver cirrhosis were evaluated for left ventricle diastolic dysfunction. In our systemic analysis we have found that 51.2% of cirrhotic patients had left ventricle diastolic dysfunction diagnosed and the grade 1 was the most prevalent (59.2%, P < 0.001) among them, the grade 3 had been rarely diagnosed - only 5.1%. The data about the prevalence of diastolic dysfunction in cirrhotic patients depending on Child-Pugh Classes was available from 5 studies (365 patients overall) and only in 1 research diastolic dysfunction was found being associated with severity of liver cirrhosis (P < 0.005). We established that diastolic dysfunction was diagnosed in 44.6% of Child-Pugh A class patients, in 62% of Child B class and in 63.3% of Child C patients (P = 0.028). The proportion of patients with higher diastolic dysfunction grades increases in more severe cirrhosis presentation (P < 0.001). There was no difference between mean MELD scores in patients with and without diastolic dysfunction and in different diastolic dysfunction groups. In all studies diastolic dysfunction was more frequent in patients with ascites. CONCLUSION: This systemic analysis suggests that left ventricle diastolic dysfunction is an attribute of liver cirrhosis which has not received sufficient attention from clinicians so far. Future suggestions of a comprehensive assessment of cardiac function in cirrhotic patients might provide a better prognosis for these patients and give hint for better understanding of the left ventricle diastolic dysfunction pathogenesis in liver cirrhosis.

Changes in the Velocity of Blood in the Portal Vein in Mild Acute Pancreatitis-A Preliminary Clinical Study.

Background and objective: Portal vein thrombosis is associated with a decrease in the main blood velocity in this vessel. While most studies examine etiological factors of portal vein thrombosis after its occurrence, we aimed to evaluate portal vessels and assess whether mild acute pancreatitis affects blood flow in the portal vein and increases the risk of thrombosis. Materials and methods: This prospective single centered follow-up study enrolled 66 adult participants. Fifty of them were diagnosed with mild acute pancreatitis based on the Revised Atlanta classification, and 16 healthy participants formed the control group. All participants were examined three times. The first examination was carried out at the beginning of the disease and the next two at three-month intervals. Blood samples were taken and color Doppler ultrasound performed the first time, whereas ultrasound alone was performed during the second and third visits. Mean and maximal blood velocities and resistivity index in the main portal vein and its left and right branches were evaluated. Results: Mean velocity of the blood flow in the main portal vein and its right and left branches was not significantly different from healthy individuals during the acute pancreatitis phase: 23.1 ± 8.5 cm/s vs. 24.5 ± 8.2 cm/s (p = 0.827); 16.4 ± 7.9 cm/s vs. 16.4 ± 8.1 cm/s (p = 1.000); and 8 ± 3.4 cm/s vs. 7.4 ± 2.5 cm/s (p = 0.826), respectively. The same was observed when comparing the maximal blood flow velocity: 67.9 ± 29 cm/s vs. 67.5 ± 21 cm/s (p > 0.05); 45.4 ± 27 cm/s vs. 44 ± 23.8 cm/s (p = 0.853); and 22.2 ± 9.8 cm/s vs. 20 ± 7.3 cm/s (p = 0.926), respectively. Changes in venous blood velocities were not significant during the follow-up period in separate study groups. Conclusions: Portal blood flow velocities do not change during mild acute pancreatitis in the inflammatory and postinflammatory periods. This observation suggests that mild acute pancreatitis does not increase the risk of portal vein thrombosis.

A case of ectopic pancreas in the ileum presenting as obscure gastrointestinal bleeding and abdominal pain.

BACKGROUND: Ectopic pancreas is an infrequent submucosal tumor in the gastrointestinal tract defined as a pancreatic tissue lacking vascular or anatomic continuity with the main body of the pancreas. Ectopic pancreas in the ileum is a rare and often an incidental finding. We report a case of ectopic pancreas in the ileum causing obscure gastrointestinal bleeding and episodes of abdominal pain. CASE PRESENTATION: 59-year-old man with 3 months history of intermittent melena, accompanied by the episodes of abdominal pain in the left upper quadrant and generalized fatigue was admitted to our department. The investigations showed that the patient had a low hemoglobin level, i.e. 10.9 g/dL with hypochromic microcytic anemia pattern seen in complete blood count (MCV 70.2 fl, MCH 21.4 pg). Esophagogastroduodenoscopy and colonoscopy did not reveal any abnormalities. Magnetic resonance enterography revealed a large (2.5 × 2.3 cm) pedunculated polyp in the ileum. Examination by single-balloon enteroscopy revealed a polyp with long pedicle located approximately 1.5 m distal to terminal ileum. Polypectomy was performed. Histopathologic examination stated, that the specimen contained ectopic pancreatic tissue which was involving muscular layer of the ileum. Ectopic pancreatic tissue included acinar cells and cystically dilated secretory ducts without islets of Langerhans. CONCLUSION: Our case report reveals a very rare cause of obscure gastrointestinal bleeding accompanied by the episodes of abdominal pain - an ectopic pancreas located in the ileum.

Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine⁻cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.

Risk assessment of choledocholithiasis prior to laparoscopic cholecystectomy and its management options.

BACKGROUND: Accurate risk evaluation of choledocholithiasis prior to laparoscopic cholecystectomy is essential to determine optimal management strategy. OBJECTIVE: Our study aimed to evaluate the accuracy of separate predictors and Vilnius University Hospital Index (VUHI = A/30 + 0.4 × B; A = total bilirubin concentration (µmol/l), B = common bile duct (CBD) diameter (mm) measured by ultrasound) diagnosing choledocholithiasis and to assess different management strategies (cholecystectomy with intraoperative cholangiography and endoscopic retrograde cholangiopancreatography (ERCP)). METHODS: The retrospective study included 350 patients admitted to a tertiary care centre for laparoscopic cholecystectomy for cholecystolithiasis who were investigated for concomitant choledocholithiasis. RESULTS: Choledocholithiasis was diagnosed in 182 (76.2%) cases in the high-risk group (VUHI value ≥4.7) and 44 (39.6%) in the low, odds ratio is 4.86 (95% CI: 3.00-7.88). Its sensitivity was 80.5%, specificity 54.0%, accuracy 71.1%. Dilated CBD had the highest sensitivity (92.5%) of predictors.ERCP showed better diagnostic performance than intraoperative cholangiography. Complications of ERCP were more frequent for patients without stones. There was no significant difference of outcomes between the two management strategies. CONCLUSION: The prognostic index has good diagnostic accuracy but dividing patients into two risk groups is insufficient. The suggested model allows determining an intermediate-risk group, which requires additional investigation. Both management approaches are appropriate.

IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study.

BACKGROUND AND PURPOSE: Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. METHODS: A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. RESULTS: 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. CONCLUSION: This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East.

Efficacy of deep biopsy for subepithelial lesions in the upper gastrointestinal tract.

INTRODUCTION: Accurate diagnosis of subepithelial lesions (SELs) in the gastrointestinal tract depends on a variety of methods: endoscopy, endoscopic ultrasound and different types of biopsy. Making an error-free diagnosis is vital for the subsequent application of an appropriate treatment. AIM: To evaluate the efficacy of deep biopsy via the endoscopic submucosal dissection (ESD) technique for SELs in the upper gastrointestinal tract. MATERIAL AND METHODS: It was a case series study. Deep biopsy via the ESD technique was completed in 38 patients between November 2012 and October 2014. Thirty-eight SELs in the upper gastrointestinal tract of varying size (very small ≤ 1 cm, small 1-2 cm and large ≥ 2 cm) by means of the ESD technique after an incision with an electrosurgical knife of the overlying layers and revealing a small part of the lesion were biopsied under direct endoscopic view. RESULTS: Deep biopsy via the ESD technique was diagnostic in 28 of 38 patients (73.3%; 95% CI: 59.7-89.7%). The diagnostic yield for SELs with a clear endophytic shape increased to 91.3%. An evident endophytic appearance of a subepithelial lesion, the mean number of biopsied samples (6.65 ±1.36) and the total size in length of all samples per case (19.88 ±8.07 mm) were the main criteria influencing the positiveness of deep biopsy in the diagnostic group compared to the nondiagnostic one (p = 0.001; p = 0.025; p = 0.008). CONCLUSIONS: Deep biopsy via the ESD technique is an effective and safe method for the diagnosis of SELs especially with a clear endophytic appearance in a large number of biopsied samples.

TPMT and ITPA genetic variants in Lithuanian inflammatory bowel disease patients: Prevalence and azathioprine-related side effects.

PURPOSE: Inter-individual thiopurine metabolism variability can influence treatment outcomes in inflammatory bowel disease (IBD) patients. Genetic polymorphisms in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) were linked with toxicity of azathioprine (AZA). The aim of the study was to investigate frequencies of TPMT and ITPA polymorphisms in Lithuanian IBD patients and analyze their association with AZA-related adverse events. MATERIALS/METHODS: Polymorphisms in TPMT (TPMT*2,*3B,*3C,*3A) and ITPA (rs1127354, rs7270101) genes were determined using PCR-RFLP and TaqMan(®) genotyping assays. 551 consecutive Lithuanian IBD patients were genotyped. The use of AZA and its side effects were assessed retrospectively according to hospital medical records. RESULTS: Frequencies of TPMT*3A, TPMT*3B and TPMT*3C alleles were 3.1%, 0.5% and 0.1%, respectively. TPMT*2 genetic variant was not detected in the study group. The distribution of minor alleles for ITPA rs1127354 and rs7270101 polymorphisms was 9.9% and 10.5%, respectively. AZA was prescribed in 82 patients and it provoked myelotoxicity in 11%, hepatotoxicity in 6.1%, dyspepsia in 6.1%, and pancreatitis in 3.6% of cases. Among patients who had AZA-related myelotoxicity, 11.1% were TPMT compound heterozygous, 44.4% had heterozygous genotype (P<0.01). Frequencies of ITPA minor alleles were similar among the patients with and without AZA-related side effects. CONCLUSION: Frequencies of TPMT and ITPA variant alleles in Lithuanian IBD group were similar to those observed in the Northern-Eastern Europe Caucasian populations. Polymorphisms in TPMT might be associated with myelotoxicity and leukopenia in AZA treated patients, while ITPA variant alleles appear not to be linked with treatment-related side effects.

Endoscopic ultrasound findings predict the recurrence of esophageal varices after endoscopic band ligation: a prospective cohort study.

OBJECTIVE: Variceal recurrence following endoscopic band ligation (EBL) is common. Esophageal collateral veins (ECV) are observed by endoscopic ultrasound (EUS) in patients with portal hypertension. The aim of the present study was to assess the role of EUS in predicting the recurrence of esophageal varices following EBL. MATERIAL AND METHODS: Forty patients who had undergone EBL for eradication of varices were examined over a 12-month period to detect variceal recurrence. EUS was performed before ligation to detect and describe the type, grade, and the number of ECV. EUS findings obtained prior to EBL were compared in the variceal recurrence and non-recurrence groups. RESULTS: Of the 40 patients, 19 (47.5%) had variceal recurrence within 12 months of EBL. Univariate logistic regression analysis showed that severe peri-ECV (p < 0.001), multiple peri-ECV (p < 0.001), and the presence of perforating veins (p < 0.014) were statistically significantly related to the variceal recurrence after EBL. Multivariate logistic regression model found that only severe peri-ECV (odds ratio [OR] = 24.39; 95% confidence interval [CI]: 2.34-253.78) and multiple peri-ECV (OR = 24.39; 95% CI: 2.34-253.78) remained as independent prognostic factors for variceal recurrence. The sensitivity and specificity of multivariate logistic regression model in predicting variceal recurrence was 89.2% and 90.5%, respectively (prognostic value (AUC) = 0.946). CONCLUSION: Recurrence rate of esophageal varices after EBL is high (47.5%). EUS can clearly depict ECV and has a value in predicting variceal recurrence after EBL; severe peri-ECV and multiple peri-ECV were significant and independent prognostic factors associated with variceal recurrence risk.

Concise review of current concepts on nomenclature and pathophysiology of hepatic encephalopathy.

Hepatic encephalopathy is a neuropsychiatric complication of liver cirrhosis the symptoms of which may vary from imperceptible to severe, invaliding, and even lethal. Minimal hepatic encephalopathy is also important because of its tendency to impair patients' cognitive functions and quality of life. The polyetiological pathogenesis of hepatic encephalopathy is intensively studied. A general consensus exists that not only excess of ammonia but also inflammatory, oxidative, and other processes are significant in the development of hepatic encephalopathy.

The role of collateral veins detected by endosonography in predicting the recurrence of esophageal varices after endoscopic treatment: a systematic review.

Endoscopic therapy is the principal method of treatment for esophageal varices. The recurrence of varices is still common following endoscopic treatment. The aim was to identify predictive factors for variceal recurrence detected by endosonography. We performed a systematic review of studies published prior to June 2013. Studies analyzing gastroesophageal collateral veins as risk factors for variceal recurrence after endoscopic treatment were included. The primary outcome was to identify predictive factors for variceal recurrence investigated by endosonography. After a full-text review, 13 studies were included in our analysis. Analysis of risk factors was not possible for all studies included. Perforating veins and periesophageal collateral veins were related to a higher risk of variceal recurrence (OR = 3.93; 95 % CI 1.06-14.51; I (2) = 96 %; OR = 2.29; 95 % CI 1.58-3.33; I (2) = 55 %). Analysis of cardiac intramural veins and paragastric/cardiac collateral veins showed the same trend, but without reaching statistical significance because of the small group size and wide CI (OR = 3.72; 95 % CI 0.14-101.53; I (2) = 91 %; OR = 1.85; 95 % CI 0.84-4.07; I (2) = 0 %). Analysis of other collateral veins as risk factors for variceal recurrence and analysis of risk factors with regard to the endoscopic treatment method was not possible because of the limited number of cases and different methodologies. A positive association between variceal recurrence and type and grade of collateral veins, investigated by endosonography, was demonstrated. Endosonography is a promising tool for predicting recurrence of esophageal varices following endoscopic treatment. These findings should be interpreted with caution because of the heterogeneity of the studies.