Relationship between indocyanine green retention test, decompensation and survival in patients with Child-Pugh A cirrhosis and portal hypertension.

BACKGROUND & AIMS: Indocyanine green retention test (ICG-r15) is a non-invasive marker of functional hepatic reserve. Among patients with compensated cirrhosis, ICG-r15 correlates to the degree of portal hypertension (PH); however, its prognostic relationship with the occurrence of decompensation events still requires clarification. METHODS: ICG-r15 was prospectively measured in 154 patients with compensated cirrhosis. Patients with hepatocellular carcinoma (HCC), Child-Pugh B-C, MELD>15, bilirubin > 2 mg/dl, INR > 1.5 or portal vein thrombosis were excluded. All patients underwent laboratory tests, upper endoscopy and hepatic venous pressure gradient (HVPG). Decompensation, development of HCC, liver transplant and death were recorded and analysed through competing-risk analysis. RESULTS: The study group was composed of 134 patients who were followed for a median of 39 months. During follow-up, 46 patients (34.3%) developed liver decompensation. Hepatocellular carcinoma occurred in 18 patients and two patients died from non-liver-related causes. The 1-, 2- and 3-year cumulative incidences of decompensation were 9.7%, 28.4% and 33.4% respectively. Patients with ICG-r15 < 10% did not experience any decompensation events during follow-up, while the 3-year cumulative incidence of decompensation of patients with ICG-r15 between 10% and 22.9% was 29.2% and that of patients with ICG-r15 ≥ 23% was 70.0% (P < 0.001). ICG-r15 gave the lowest pseudo-log-likelihood value, in comparison to oesophageal varices present, MELD, low platelet count and HVPG. CONCLUSIONS: ICG-r15 appears to be strictly related to liver decompensation, longitudinally confirming the preliminary findings of its correlation with PH among patients with compensated cirrhosis, and can be used for patient prognostication.

Indocyanine green retention test as a noninvasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis.

UNLABELLED: Noninvasive markers would be useful for the assessment of portal hypertension (PH) and esophageal varices (EV) in patients with cirrhosis. The aim of our study was to evaluate the performance of the indocyanine green (ICG) retention test as a noninvasive marker of PH and EV, measured against the gold standards (hepatic venous pressure gradient [HVPG] measurement and upper endoscopy). We prospectively enrolled patients with compensated cirrhosis referral to our unit. All patients underwent laboratory tests, abdominal ultrasound, upper gastrointestinal endoscopy, HVPG measurement, and the ICG 15-minute retention (ICG-r15) test. We evaluated the sensitivity and specificity of the ICG retention test and other noninvasive tools for the diagnosis of PH and EV. Ninety-six consecutive Child-Pugh A patients (67 male and 29 female; 60.3 ± 11.8 years of age) were enrolled. Seventy-four patients had clinically significant portal hypertension (CSPH), of whom 59 had severe portal hypertension (SPH). ICG-r15 and Lok index were independently related to the presence of both CSPH and SPH, whereas ICG-r15 and INR were related to EV. ICG-r15 values (<6.7% and <6.9%, respectively) were able to rule out the presence of CSPH and SPH (LR(-) 0.15 and 0.14); ICG-r15 <10% provided a 97.8% sensitivity (LR(-) 0.042) for the exclusion of EV and a 100% sensitivity (LR(-) 0.0) for large EV. CONCLUSION: The ICG-r15 test is an effective tool for assessment of PH in patients with compensated cirrhosis. Although this would not replace endoscopy, the ICG-r15 appears able to identify patients with advanced liver disease in which endoscopy is mandatory as well as rule out the presence of EV in patients with compensated cirrhosis.

Acute Fitz-Hugh-Curtis syndrome in a man due to gonococcal infection.

BACKGROUND: Fitz-Hugh-Curtis syndrome is a rare extra-pelvic complication of genital infection involving the perihepatic capsule. Most cases have been described in women in association with pelvic inflammatory disease; in rare cases it has been reported in men. Because the main symptom is acute abdominal pain, and laboratory and imaging findings are frequently nonspecific, the differential diagnosis, considering other gastrointestinal or renal diseases, can be difficult in the early stage of the syndrome, leading to frequent misdiagnosis and mismanagement. CASE REPORT: We report a case of Fitz-Hugh-Curtis syndrome in a 26-year-old man who first presented to the emergency department with acute abdominal pain, vomiting, and fever. Diagnosis was possible on the basis of clinical signs of orchiepididymitis, abnormal ultrasound findings, and specialist consultation with the Sexually Transmitted Infection Clinic. An acute gonoccocal infection was revealed, which was complicated by a collection of free perihepatic fluid and a subcapsular hypoechoic focal lesion. Prompt antibiotic therapy was established, with complete resolution of the symptoms within a few days. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Awareness of the clinical presentation, imaging, and laboratory findings during the acute phase of Fitz-Hugh-Curtis syndrome could help emergency physicians to make an early diagnosis and to correctly manage such patients. Improved diagnostic skills could prevent chronic complications that are especially a risk in the case of delayed or minor genitourinary symptoms.

Transjugular intrahepatic portosystemic shunt placement for refractory ascites: a single-centre experience.

BACKGROUND: The presence of refractory ascites is a common indication for transjugular intrahepatic portosystemic shunt (TIPS). Different models have been proposed for the prediction of survival after TIPS. The aim of this study was to evaluate the predictive factors associated with patients' survival after TIPS placement for refractory ascites. METHODS: Data from all consecutive patients undergoing TIPS placement in our center for refractory ascites between February 2003 and January 2008 were prospectively recorded. RESULTS: Seventy-three patients (52M/21F; 57 ± 10 years) met the inclusion criteria; mean follow-up was 17 ± 2 months. Mean MELD value, before TIPS placement, was 15.7 ± 5.3. TIPS placement led to an effective resolution of refractory ascites in 54% of patients (n = 40) with no significant increase in severe portosystemic encephalopathy. The 1-year survival rate observed was 65.7%, while the overall mortality was 23.3% (n = 17) with a mean survival of 17 ± 14 months. MELD score (B = 0.161, p = 0.042), basal AST (B = 0.020, p = 0.090), and pre-TIPS HVPG (B = 0.016, p = 0.093) were independent predictors of overall mortality, while MELD (B = 0.419, p = 0.018) and HVPG (B = 0.223, p = 0.060) independently predicted 1-year survival. ROC curves identified MELD ≥ 19 and HVPG ≥ 25 mmHg as the best cut-off points for the prediction of 1-year mortality. CONCLUSIONS: TIPS is an effective treatment for refractory ascites in cirrhotic patients, leading to an effective ascites control in more than half patients. Improvement in patients' selection criteria could lead to better outcome and survival after this procedure. Liver function (MELD), presence of active necroinflammation (AST), and portal hypertension (HVPG) are independent predictors of patients' outcome after TIPS.

Quality of reporting in endoscopic ultrasound: Results of an international multicenter survey (the QUOREUS study).

Background and study aims The endoscopic report has a key role in quality improvement for gastrointestinal endoscopy. High quality standards have been set by the endoscopic societies in this field. Unlike other digestive endoscopy procedures, the quality of reporting in endoscopic ultrasound (EUS) has not been thoroughly evaluated and a reference standard is lacking. Methods We performed an international online survey concerning the attitudes of endosonographers towards EUS reports in order to understand the needs for standardization and quality improvement. Endosonographers from different countries and institutional setting, with varying case volume and experience were invited to take part to complete a structured questionnaire. Results We collected replies from 171 endosonographers. Overall analysis of results according to case volume, experience and working environment of respondents (academic, public hospital, private) are provided. In brief, everyone agreed on the need for standardization of EUS reporting. The use of minimal standard terminology and a structured tree with mandatory items was considered of primary importance. Image documentation was also deemed fundamental in complementing EUS reports both for patient documentation and research purposes. A strong demand for connection and consultation among endosonographers for clinical and training needs was also found. In this respect, a formal expert consultation network was advocated in order to improve the quality of reporting in EUS. Conclusions Our survey showed a strong agreement among endosonographers who expressed the need for a standardization in order to improve the report and, as a consequence, the quality of EUS.

CO 2 vs. air insufflation in endoscopic ultrasonography: a prospective study.

Background and study aims Carbon dioxide (CO 2 ) is being increasingly used for insufflation during endoscopy for safety and better tolerance. The role of CO 2 during endoscopic ultrasonography (EUS) has not been studied yet. Our main aim was to compare the effects of CO 2 vs. air insufflation on abdominal discomfort in patients undergoing EUS. Our secondary outcomes were to ascertain the effects of CO 2 insufflation on image quality/visual artifacts and on the amount of sedation. Patients and methods This was a prospective, controlled, single-blind, observational study. Abdominal discomfort was assessed before diagnostic EUS, and 1 and 3 hours post-procedure and recorded as a visual analogue scale. Image quality was also recorded as a 4-point scale from optimal to poor at four different scanning sites (esophagus, stomach, duodenal bulb and second portion). Results A total of 198 patients were enrolled. We observed that CO 2 resulted in less abdominal discomfort than air insufflation that was statistically significant at 3 hours ( P  = 0.048) but not at 1 hour after EUS ( P  = 0.112), probably due to the ongoing effects of sedation at the latter stage. On the other hand, no differences were found in the dose of sedation administered in the two groups. Image quality was significantly better in the CO 2 group compared to the air group at all four different scanning sites ( P  < 0.01). Similarly, CO 2 correlated with less visual artifacts and need of suction ( P  < 0.01). Conclusions Similarly to previous findings with other endoscopic procedures, EUS was associated with improved scores for abdominal discomfort with CO 2 rather than air insufflation. Moreover, overall EUS image quality was improved using CO 2 insufflation. Future studies are warranted to ascertain whether CO 2 insufflation should be regarded as the standard of care for diagnostic EUS.

Contrast-enhanced endoscopic ultrasound for the differential diagnosis between benign and malignant lymph nodes: a meta-analysis.

Background The differential diagnosis between benign and malignant lymph nodes (LNs) is crucial for patient management and clinical outcome. The use of contrast-enhanced endoscopic ultrasound (EUS) has been evaluated in several studies with diverse results. The aim of this meta-analysis was to evaluate the pooled diagnostic accuracy of contrast-enhanced EUS (CE-EUS) and contrast-enhanced harmonic EUS (CH-EUS) in this setting. Methods A systematic electronic search was performed, including all original papers dealing with assessment of the nature of the LNs using CE-EUS or CH-EUS. A meta-analysis was performed to obtain pooled sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. The Summary Receiver Operating Characteristic (ROC) Curve method was used to calculate the area under the curve. Statistical analysis was carried out using Meta-Disc V.1.4, Stata V.12.0 and Review Manager V.5.2. Results Among 210 pertinent studies, four (336 patients) were included in the analysis. The pooled sensitivity was 82.1 % (75.1 - 87.7 %) and pooled specificity was 90.7 % (85.9 - 94.3 %) with significant heterogeneity found in sensitivity; the positive-likelihood ratio (LR) was 7.77 (5.09 - 11.85) and the negative-LR was 0.15 (0.05 - 0.46); the pooled diagnostic odds ratio (DOR) was 54 (15 - 190). Subgroup analysis including studies performed using CH-EUS (two studies, 177 LNs) showed a pooled sensitivity of 87.7 % (77.0 - 93.9 %) and a pooled specificity of 91.8 % (84.5 % - 96.4 %) with no significant heterogeneity; the pooled positive-LR was 9.51 (4.95 - 18.28) and the pooled negative-LR was 0.14 (0.06 - 0.35); pooled DOR was 68.42 (15.5 - 301.4). Conclusions From these data, CE-EUS is not recommended due to inadequate sensitivity. On the other hand, CH-EUS studies showed optimal accuracy (pooled sensitivity 87.7 % and specificity 91.8 %), comparable to elastography and even EUS-guided fine needle aspiration (EUS-FNA), suggesting a role in the diagnostic algorithm.

Basics in Endoscopic Ultrasound Part 1: Diagnostic Indications and Tissue Sampling.

BACKGROUND: Endoscopic Ultrasound has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. METHOD: We conducted a systematic review of the available English-language articles. OBJECTIVE: The purpose of this review is to summarize all the relevant indications to endoscopic ultrasound and analyze its relevant data in terms of accuracy and clinical outcomes. RESULTS: More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. Staging indications include gastroesophageal and rectal cancers. Diagnostic, staging and therapeutic indications include diseases of the pancreaticobiliary area. Finally, differential diagnosis of submucosal tumors represents another important indication to this technique.

Basics in Endoscopic Ultrasound Part 2: EUS-guided Sampling and Therapeutic Applications.

BACKGROUND: Endoscopic ultrasound (EUS) has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. METHOD: We conducted a systematic review of the available English-language articles. OBJECTIVE: The purpose of this review is to summarize the relevant applications of operative EUS. RESULTS: More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. The main indications of operative EUS, both diagnostic and therapeutic, are related to its ability to combine ultrasound imaging and safe and effective needle insertion into lesions originating from the gut wall and from organs nearby. In addition, technologic advancements of echoendoscopes with a therapeutic working-channel have allowed to perform several EUS-guided interventions, i.e. celiac plexus neurolysis, drainage of fluid collections, drainage of dilated biliary and pancreatic ducts, and vascular interventions.

The Onset of de novo Hepatocellular Carcinoma after Liver Transplantation can be both of Donor and Recipient origin. A Case Report.

The occurrence of de novo hepatocellular carcinoma after liver transplantation is a rare event with only few cases reported in the literature. In a post liver transplantation setting distinguishing between a de novo hepatocellular carcinoma from recurrence should be tested with molecular analysis such as fluorescent in situ hybridization (for sex chromosomes) or microsatellite analysis. Nevertheless, a certain degree of epithelial chimerism between recipient and donor tissues could be responsible for the development of de novo hepatocellular carcinoma of recipient origin. We report two cases of de novo hepatocellular carcinoma after liver transplantation. The first one occurred in a patient receiving transplantation for hepatitis C related cirrhosis and hepatocellular carcinoma. A de novo hepatocellular carcinoma developed five years after transplantation and microsatellite analysis revealed the donor origin of the neoplasia. The second one occurred in a patient who received transplantation for secondary sclerosing cholangitis. Hepatocellular carcinoma was found six years after transplantation. Both microsatellite analysis and fluorescent in situ hybridization revealed the recipient origin of the tumor, potentially due to tissue chimerism.

Severe immune thrombocytopenia after peg-interferon-alpha2a, ribavirin and telaprevir treatment completion: A case report and systematic review of literature.

Mild to moderate autoimmune thrombocytopenia (AITP) is a common finding in patients receiving interferon-based antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus (HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferon-based antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment (i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferon-based treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but also after discontinuation.

Long-term leukocyte natural α-interferon and ribavirin treatment in hepatitis C virus recurrence after liver transplantation.

AIM: To evaluate the effect of long-term treatment with leukocyte natural α-interferon (ln-α-IFN) plus ribavirin (RBV). METHODS: Forty-six patients with hepatitis C virus (HCV) recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo; then, patients with good tolerability (n = 30) were switched to daily IFN administration, while the remaining were treated with the same schedule. Patients have been treated for 12 mo after viral clearance while non-responders (NR) entered in the long-term treatment group. Liver biopsies were planned at baseline, 1 year after sustained virological response (SVR) and at 36 mo after start of therapy in NR. MedCalc software package was used for statistical analysis. RESULTS: About 16.7% of genotype 1-4 and 70% of genotype 2-3 patients achieved SVR. Nine patients withdrew therapy because of non-tolerance or non-compliance. A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated; 100% of patients with SVR achieved a histological response (fibrosis stabilization or improvement) with a significant reduction in mean staging value (from 2.1 to 1.0; P = 0.0031); histological response was observed in 84% of long-term treated patients compared to 57% of drop-out. Six patients died during the entire study period (follow-up 40.6 ± 7.7 mo); of them, 5 presented with severe HCV recurrence on enrollment. Diabetes (OR = 0.38, 95%CI: 0.08-0.59, P = 0.01), leukopenia (OR = 0.54, 95%CI: 0.03-0.57, P = 0.03) and severe HCV recurrence (OR = 0.51, 95%CI: 0.25-0.69, P = 0.0003) were variables associated to survival. Long-term treatment was well tolerated; no patients developed rejection or autoimmune disease. CONCLUSION: Long-term treatment improves histology in SVR patients and slows disease progression also in NR, leading to a reduction in liver decompensation, graft failure and liver-related death.

The pharmacological management of intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy is the most common liver disease occurring in the second half of pregnancy, characterized by pruritus and elevated serum bile acids often coupled to abnormal liver tests. Maternal prognosis is favourable with a complete symptom resolution after delivery, while preterm deliveries, fetal respiratory distress and stillbirths may occur. The goal of the pharmacological treatment of the disease is to improve maternal symptoms and biochemical alterations and, most importantly, to reduce fetal adverse events.The present manuscript will review the current knowledge on the pharmacological treatment of intrahepatic cholestasis of pregnancy.

Pneumatosis cystoides intestinalis.

Pneumatosis cystoides intestinalis (PCI) is a rare condition that may be associated with a variety of diseases. The presenting clinical picture may be very heterogeneous and represent a challenge for the clinician. In the present paper we describe both a common and an uncommon clinical presentation of PCI and review the pertaining literature. Our cases confirm that, apart from asymptomatic cases, the clinical presentation of PCI may be widely different and suggest that a new onset of stipsis might be the presenting symptom. Diagnosis might be suggested by a simple X-ray of the digestive tract showing a change in the characteristics of the intestinal wall in two-thirds of these patients. However, one third of the patients do not have a suggestive X-ray and require a computed tomography (CT) scan/nuclear magnetic resonance that may reveal a thickened bowel wall containing gas to confirm the diagnosis and distinguish PCI from intraluminal air or submucosal fat. CT also allows the detection of additional findings that may suggest an underlying, potentially worrisome cause of PCI such as bowel wall thickening, altered contrast mucosal enhancement, dilated bowel, soft tissue stranding, ascites and the presence of portal air. Our results also point out that clinicians and endoscopists should be aware of the possible presentations of PCI in order to correctly manage the patients affected with this disease and avoid unnecessary surgeries. The increasing number of colonoscopies performed for colon cancer screening makes PCI more frequently casually encountered and/or provoked, therefore the possible endoscopic appearances of this disease should be well known by endoscopists.