Isolated nonspecific terminal ileitis: prevalence, clinical evolution and correlation with metachronous diagnosis of Crohn's disease: a retrospective study and review of the literature.

Background: The existing literature does not provide adequate guidance on the diagnosis and management of patients with nonspecific terminal ileitis, while data regarding the percentage of patients who ultimately develop Crohn's disease (CD) are scarce. We evaluated the prevalence and natural course of nonspecific terminal ileitis in patients who underwent colonoscopy during a 11-year period. Methods: All patients with endoscopic findings of terminal ileitis and nonspecific histological findings were included. Exclusion criteria were a clinical history of CD or any other disease that can cause terminal ileitis, or a recent history of using drugs implicated in lesions of the terminal ileum. Results: From 5353 colonoscopies, 92 patients with nonspecific terminal ileitis were identified (prevalence: 1.7%). Among these patients, 56 (61%) had available follow up for ≥6 months after the initial endoscopy. Main indications for endoscopy were chronic diarrhea (37.5%), screening endoscopy (23%), and abdominal pain (20%). Sixteen (29%) patients received medical treatment, while recession of symptoms was recorded in 19 of 43 symptomatic patients (44.1%). Twenty-three (41%) of the 56 patients underwent a second endoscopy and 15 (65.2%) cases had persistent endoscopic findings. Eleven (19.6%) of the 56 patients were eventually diagnosed with CD. The probability of CD diagnosis was significantly higher in patients with persistent symptoms (P=0.002) and endoscopic findings at follow up (P=0.038). Conclusions: Nonspecific terminal ileitis generally has a benign clinical course. However, patients with persistent symptoms and endoscopic lesions are at increased risk for subsequent development of CD.

Prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria: alterations in ultrasonographic parameters of both left and right ventricles before and after stress.

Background: We estimated the frequency of cirrhotic cardiomyopathy (CCM) using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations, and to investigate the role of stress in unmasking latent cases of CCM. Methods: Ninety consecutive patients were recruited. CCM was evaluated using the Montreal, the American Society of Echocardiography 2009 criteria, and the 2019 modified criteria of the CCM consortium. A dobutamine stress test was also performed. Results: Left ventricular diastolic dysfunction (LVDD) was identified in 72 (80%), 36 (40%), and 10 (11.1%) patients based on the above criteria, respectively. None of the patients had right ventricular systolic dysfunction, either at rest or after stress. The dobutamine stress test revealed left systolic dysfunction in 4 (4.5%) patients. There was agreement among the 3 criteria that the presence of LVDD was not associated with the severity of liver disease, using Child-Pugh stage. However, patients with Child-B/C had longer QTc intervals (P=0.004), higher levels of brain natriuretic peptide (P=0.016), and greater echocardiographic E/e' ratio (P<0.001) and E/e'(s) (P=0.003), compared to Child-A patients, while a significant correlation was demonstrated between Child-Pugh score and E/e' (P<0.001), or E/e'(s) (P=0.002). Conclusions: The prevalence of LVDD seems to be lower than previously considered. Right ventricular function seems to remain unimpaired. A dobutamine stress uncovered only a small percentage of patients with left systolic dysfunction. Nevertheless, the aggravation of several sonographic variables during stress, particularly in Child-B/C patients, potentially indicates a higher risk for clinical heart failure during stressful invasive interventions.

Efficacy of citalopram or amitriptyline versus no treatment in patients with functional chest pain.

Background: Functional chest pain (FCP) is characterized by the presence of chest pain of presumed esophageal origin, but with a negative workup on routine investigations, including ruling out gastroesophageal reflux disease (GERD). Antidepressants are frequently prescribed to treat FCP and are presumed to act as neuromodulators of visceral hypersensitivity. However, there is little evidence of their efficacy in patients with FCP. We retrospectively assessed the efficacy of citalopram or amitriptyline vs. no treatment in patients with FCP. Methods: Esophageal diseases, including GERD, eosinophilic esophagitis and major esophageal motility disorders, were excluded. Thus, patients with established FCP according to Rome IV criteria were included in the study. Then, patients treated for at least 3 months with citalopram 20 mg, amitriptyline 50 mg, or observation were selected. The primary endpoint was complete disappearance or significant amelioration of symptoms at the end of treatment. Results: Over a 5-year period, 102 patients (74 female; mean age 49±10 years) were diagnosed with FCP and were recognized to have received once daily citalopram (n=32), amitriptyline (n=34), or no treatment (n=36). After a 3-month follow up, improvement in chest pain was reported by 16 (47.1%) patients treated with citalopram, 18 (56.3%) patients treated with amitriptyline, and 4 (11.1%) patients without treatment (P=0.02 and 0.01 for no treatment vs. citalopram and amitriptyline therapy, respectively). Conclusion: Both citalopram and amitriptyline are effective pharmacological options in the symptomatic relief of almost 50% patients with well characterized FCP.

Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI < 30 kg/m2] nonalcoholic steatohepatitis) and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] > 10 mmHg and/or liver stiffness by transient elastography > 25 kPa) should receive, if no contraindications, nonselective beta blocker (NSBB) therapy (preferably carvedilol) to prevent the development of variceal bleeding.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in those patients unable to receive NSBB therapy with a screening upper gastrointestinal (GI) endoscopy that demonstrates high risk esophageal varices, endoscopic band ligation (EBL) is the endoscopic prophylactic treatment of choice. EBL should be repeated every 2-4 weeks until variceal eradication is achieved. Thereafter, surveillance EGD should be performed every 3-6 months in the first year following eradication.Strong recommendation, moderate quality evidence. 3: ESGE recommends, in hemodynamically stable patients with acute upper GI hemorrhage (UGIH) and no history of cardiovascular disease, a restrictive red blood cell (RBC) transfusion strategy, with a hemoglobin threshold of ≤ 70 g/L prompting RBC transfusion. A post-transfusion target hemoglobin of 70-90 g/L is desired.Strong recommendation, moderate quality evidence. 4 : ESGE recommends that patients with ACLD presenting with suspected acute variceal bleeding be risk stratified according to the Child-Pugh score and MELD score, and by documentation of active/inactive bleeding at the time of upper GI endoscopy.Strong recommendation, high quality of evidence. 5 : ESGE recommends the vasoactive agents terlipressin, octreotide, or somatostatin be initiated at the time of presentation in patients with suspected acute variceal bleeding and be continued for a duration of up to 5 days.Strong recommendation, high quality evidence. 6 : ESGE recommends antibiotic prophylaxis using ceftriaxone 1 g/day for up to 7 days for all patients with ACLD presenting with acute variceal hemorrhage, or in accordance with local antibiotic resistance and patient allergies.Strong recommendation, high quality evidence. 7 : ESGE recommends, in the absence of contraindications, intravenous erythromycin 250 mg be given 30-120 minutes prior to upper GI endoscopy in patients with suspected acute variceal hemorrhage.Strong recommendation, high quality evidence. 8 : ESGE recommends that, in patients with suspected variceal hemorrhage, endoscopic evaluation should take place within 12 hours from the time of patient presentation provided the patient has been hemodynamically resuscitated.Strong recommendation, moderate quality evidence. 9 : ESGE recommends EBL for the treatment of acute esophageal variceal hemorrhage (EVH).Strong recommendation, high quality evidence. 10 : ESGE recommends that, in patients at high risk for recurrent esophageal variceal bleeding following successful endoscopic hemostasis (Child-Pugh C  ≤ 13 or Child-Pugh B > 7 with active EVH at the time of endoscopy despite vasoactive agents, or HVPG > 20 mmHg), pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) within 72 hours (preferably within 24 hours) must be considered.Strong recommendation, high quality evidence. 11 : ESGE recommends that, for persistent esophageal variceal bleeding despite vasoactive pharmacological and endoscopic hemostasis therapy, urgent rescue TIPS should be considered (where available).Strong recommendation, moderate quality evidence. 12 : ESGE recommends endoscopic cyanoacrylate injection for acute gastric (cardiofundal) variceal (GOV2, IGV1) hemorrhage.Strong recommendation, high quality evidence. 13: ESGE recommends endoscopic cyanoacrylate injection or EBL in patients with GOV1-specific bleeding.Strong recommendations, moderate quality evidence. 14: ESGE suggests urgent rescue TIPS or balloon-occluded retrograde transvenous obliteration (BRTO) for gastric variceal bleeding when there is a failure of endoscopic hemostasis or early recurrent bleeding.Weak recommendation, low quality evidence. 15: ESGE recommends that patients who have undergone EBL for acute EVH should be scheduled for follow-up EBLs at 1- to 4-weekly intervals to eradicate esophageal varices (secondary prophylaxis).Strong recommendation, moderate quality evidence. 16: ESGE recommends the use of NSBBs (propranolol or carvedilol) in combination with endoscopic therapy for secondary prophylaxis in EVH in patients with ACLD.Strong recommendation, high quality evidence.

The Lyon Consensus Criteria for GERD Diagnosis in a Greek Population: The Clinical Impact and Changes in GERD Diagnosis in a Real-World, Retrospective Study.

(1) Introduction/aim: Gastroesophageal reflux disease (GERD) affects 8−33% globally. The gold standard examination technique in diagnosing GERD is 24 h pHmetry ± impedance. Recently, new diagnostic criteria were introduced by the Lyon Consensus for GERD diagnosis. Our aim was to investigate the diagnostic yield of pHmetry + impedance using the Lyon Consensus criteria in a real-world study. (2) Patients and methods: Our study included 249 consecutive patients (M/F: 120/129, mean age 50 ± 15 years) who underwent 24 h pH+ impedance monitoring in our department, during a 5-year period. Epidemiological, endoscopic, clinical, and 24 h pH+ impedance data were retrospectively collected. (3) Results: Typical GERD symptoms were reported by 140/249 (56.2%) patients, whereas 99/249 (39.6%) patients reported various extraesophageal symptoms. Endoscopic findings supportive of GERD based on the Lyon Consensus were present in 42/185 (22.7%). An AET value of >6% was observed in 60/249 (24.1%). GERD diagnosis according to the Lyon Consensus criteria was set in 63/249 (25.3%) patients; a rate significantly lower than that observed by implementing the older criteria (32.1%), p < 0.001. In the multivariate analysis, the existence of endoscopic findings supportive of GERD diagnosis as defined by the Lyon Consensus (p = 0.036), a De Meester score of over 14.7, and the presence of typical GERD symptoms were correlated to GERD diagnosis (p < 0.001, respectively) using the criteria defined for pH−impedance monitoring. (4) Conclusions: Changes in the diagnostic criteria concerning the 24 h pH−impedance monitoring of GERD based on the Lyon Consensus led to a conclusive GERD diagnosis in approximately 25% of the patients. This rate of GERD diagnosis is reduced in comparison to the one confirmed with the use of previously established criteria.

Comparing 2D-shear wave to transient elastography for the evaluation of liver fibrosis in nonalcoholic fatty liver disease.

BACKGROUND AND AIM: The aim of this study is to evaluate the performance of 2D-shear wave elastography (2D-SWE) in patients with nonalcoholic fatty liver disease (NAFLD) and compare it to transient elastography. METHODS: Over 6 months, 552 patients with NAFLD underwent liver stiffness measurement (LSM) by both 2D-SWE and transient elastography with controlled attenuation parameter (CAP) at the same visit. RESULTS: LSM was not feasible by transient elastography (M/XL probe) in 18 (3.3%) and by 2D-SWE in 26 (4.7%) patients. The median LSM of transient elastography was 5.5 (2.8-75) kPa and of 2D-SWE 6.2 (3.7-46.2) kPa. LSMs by transient elastography and 2D-SWE were correlated regardless of the obesity status (r, 0.774; P < 0.001; r, 0.774; P < 0.001; r, 0.75; P < 0.001 in BMI <25, 25-30 and ≥30 kg/m2 respectively), or the degree of liver steatosis (r = 0.63; P < 0.001 and r = 0.743; P < 0.001 in mild and moderate/severe steatosis, respectively). According to transient elastography, 88 (15.9%) patients were classified with at least severe fibrosis (≥F3) and 55 (10%) with cirrhosis. By using the 2D-SWE, 85 (15.4%) patients had at least severe fibrosis and 52 (9.4%) cirrhosis. The correlation between the two methods was strong in patients with at least severe fibrosis (r, 0.84; P < 0.001) or cirrhosis (r, 0.658; P < 0.001). When transient elastography was used as reference, 2D-SWE showed an excellent accuracy of 98.8 and 99.8% in diagnosing severe fibrosis and cirrhosis, respectively. CONCLUSIONS: In NAFLD, 2D-SWE and transient elastography have comparable feasibility and clinical applicability providing LSMs with strong correlation, even in overweight/obese patients, independently of the severity of liver steatosis and fibrosis. Thus, either of the two methods can be effectively used for the assessment of fibrosis in this setting.

Comparative Utility of Transient and 2D Shear Wave Elastography for the Assessment of Liver Fibrosis in Clinical Practice.

The aim of the study was to investigate the feasibility and correlation of liver stiffness measurements (LSM) between 2D-shear wave elastography (2D-SWE) and transient elastography (TE) in patients with chronic liver disease. Over 4 months, 421 patients with chronic liver disease of any cause underwent LSM by 2D-SWE and TE (M and/or XL probe) and controlled attenuation parameter at the same visit. LSM was not feasible by TE in 16 (3.8%) and by 2D-SWE in 17 (4.0%) patients. Median LSM were 8.9 and 8.7 kPa with TE and 2D-SWE, respectively, having a strong correlation (r = 0.774, p < 0.001) in the total cohort and in any cause of liver disease (r = 0.747-0.806, p < 0.001). There was a strong agreement on diagnosis of severe fibrosis (k-statistic: 0.841, p < 0.001) or cirrhosis (k-statistic: 0.823, p < 0.001). Both methods had increased failure rates in patients with obesity and/or increased waist circumference. Among 104 obese patients, TE was more feasible than 2D-SWE (92.3% vs 85.6%, p < 0.001]. LSM by 2D-SWE are strongly correlated to LSM by TE independently of the etiology of chronic liver disease, stage of fibrosis, degree of liver steatosis, and patients' characteristics. TE with the XL probe may be superior in a minority of obese patients.

Platelet activation and hypercoagulability in patients with early primary biliary cholangitis compared with healthy controls.

BACKGROUND: Patients with primary biliary cholangitis (PBC) who have advanced disease are hypercoagulable, with no thrombophilic factors compared to non-cholestatic cirrhotics. We investigated whether hypercoagulability is present in early-stage PBC. METHODS: PBC patients with biopsy-documented early disease and healthy controls matched by sex and age were asked to participate in the study. All were evaluated using rotational thromboelastometry (ROTEM), platelet aggregation, and flow cytometry. Four ROTEM parameters were evaluated (clotting time, clotting formation time, α-angle, and maximum clot firmness [MCF]). Platelet aggregation was determined as the maximal change in light transmission after the addition of adenosine diphosphate, collagen and epinephrine. Flow cytometry was used to evaluate the expression of glycoprotein (GP) IIb, GPIIa, and P-selectin on the platelet surface. RESULTS: We enrolled 50 individuals in the study (25 PBC patients, 25 controls). Prothrombin time and activated partial thromboplastin time did not differ significantly between PBC patients and controls (P-value not significant). In ROTEM, aaaaaaaa-angle and MCF parameters were abnormally elevated in 9 (36%) PBC patients compared to 3 (12%) healthy controls and the difference was statistically significant (P=0.026). Platelet aggregation in PBC patients was not significantly different from controls. In flow cytometry, GPIIb and P-selectin expression was greater in PBC patients than in the control group and the difference was statistically significant (P=0.005 and P=0.006 respectively). CONCLUSION: In this study, we used a combination of sophisticated methods to detect evidence of platelet activation and hypercoagulability in patients with early PBC. Our findings may have important clinical implications and merit further investigation.

Differences between fellows and fellowship program directors in their perception of the impact of the COVID-19 pandemic on gastroenterology training: results from a nationwide survey in Greece.

BACKGROUND: Lockdown measures applied during the SARS-CoV-2 outbreak caused a significant disturbance to hospital routine. We assessed trainees' and fellowship directors' perceptions regarding the impact of the pandemic on gastroenterology fellowship training. METHODS: A web-based survey was anonymously disseminated to all Greek gastroenterology fellows and fellowship program directors. Participants completed electronically a questionnaire comprised of 5 domains that assessed participants' perception of: 1) overall impact on training; 2) impact on training in gastroenterology-specific fields (endoscopy, inflammatory bowel disease, hepatology); 3) impact on different aspects of endoscopy training; 4) impact on academic training; and 5) training perspectives for the post-pandemic era. RESULTS: A total of 77/128 fellows (60.1%) and 18/28 fellowship program directors (64.3%) responded. More fellows reported that the COVID-19 pandemic would have an adverse impact on fellowship training compared to their fellowship program directors (81.8% vs. 55.6%, P=0.038). This concern was mainly focused on endoscopy training (83.1% vs. 27.8%, P<0.001), with no difference regarding training in gastroenterology's other specific fields. The difference was consistent for technical skills (79.2% vs. 38.9%, P=0.001), and for the performance of basic diagnostic (70.1% vs. 22.2%, P<0.001) and emergency (48.1% vs. 11.1%, P=0.004) procedures. Fellows and fellowship program directors identified the unknown timeframe of measure implementation and the postponement of scheduled endoscopic procedures as the main factors that negatively affected training. Extension of the fellowship training program was deemed the optimal option by fellows for addressing the training decrement in the post-pandemic era, while fellowship program directors favored an increase in workload. CONCLUSION: Fellows and their fellowship program directors do not share the same concerns about the impact of COVID-19 pandemic on training programs and they propose different measures to remedy its effects.

New epidemiology of hepatitis delta.

Hepatitis D virus (HDV) is a defective pathogen that needs hepatitis B virus (HBV) for infection. Co-infection of HBsAg-positive individuals with HDV is commonly associated with a more rapid progression to cirrhosis, a higher incidence of hepatocellular carcinoma (HCC) and increased mortality. Initial studies have shown that about 5% of chronic HBV carriers worldwide (15-20 millions) were also infected with HDV. However, recent studies suggest that the prevalence of HDV is at least two- to three-fold higher than previous estimations. Improved diagnostic techniques have shown that HDV infection remains endemic in certain areas of the world. Injection drug users, individuals with high-risk sexual behaviour and patients co-infected with human immunodeficiency virus (HIV) represent the major reservoir of the disease in the Western world. Although the burden of HDV infection significantly decreased in Europe in the nineties, there has been no further decrease in the last decade, probably because of migration from HDV endemic countries. Until new and more effective therapies are available, public health measures should be reinforced by increasing prophylactic HBV vaccination programs, preventing transmission of the virus among parenteral drug users and implementing universal HDV screening of all HBV-infected individuals.

Hepatitis B: Who and when to treat?

As current treatment options almost never achieve eradication of hepatitis B virus (HBV), the most realistic goal for HBV treatment is persistent inhibition of viral replication and ALT normalization. Thus, the decision to start treatment should be based on careful patient selection and individualized decisions. Treatment is generally indicated in chronic hepatitis B patients with HBV DNA >2000 IU/mL, elevated ALT and/or at least moderate histological lesions, while all patients with cirrhosis and detectable HBV DNA should be treated. Patients with HBV DNA >20 000 IU/mL and ALT >2xULN (upper limit of normal), HBV DNA >2000 IU/mL and liver stiffness >9 or >12 kPa in case of normal or ≤5xULN, HBV DNA >2000 IU/mL and a family history of cirrhosis and/or HCC as well as HBeAg-positive patients with HBV DNA >20 000 IU/mL and over 30 years old can begin treatment whatever the liver histology. Moreover, patients with HBV DNA >2000 IU/mL and at least moderate histological lesions can begin treatment whatever the ALT levels. Prophylactic treatment is indicated in HBV-related liver transplantation patients to prevent recurrence, in the last trimester of pregnancy in women with high viraemia to prevent vertical transmission and in patients receiving immunosuppression/chemotherapy to prevent the reactivation of HBV. Treatment is also indicated in patients with co-infections, extrahepatic manifestations and severe acute hepatitis B, or healthcare workers with viraemia. These treatment indications can only change if HBV eradication or at least HBsAg clearance can be achieved in the future in a significant proportion of patients.

The effect of minimal dietary changes with raisins in NAFLD patients with non-significant fibrosis: a randomized controlled intervention.

Aiming at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a randomized controlled clinical trial. Patients were assigned into two isocaloric dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N = 27), (b) nutritional counseling with currants included (two fruit servings, 36 g per day), substituting snacks of similar caloric content (Currant arm, N = 28). Clinical tests, anthropometrics, inflammatory and oxidative stress markers were conducted pre- and post-intervention. A total of 50 patients completed the trial. Significant differences between the two arms post-intervention were observed in fasting glucose and in IL-6 levels, these being significantly decreased only in Currant patients. Body weight, BMI, HbA1c, CRP and EUS values decreased in both arms, differences being insignificant between the two arms post-intervention. Participants in the Currant arm had significantly reduced total body fat, WC and trunk fat. Ultrasound scanning improved significantly in patients snacking currants daily. Also, volunteers enrolled in the Currant arm showed a reduced intake of saturated fatty acids. Because BW regulation has been officially recognised as a treatment approach in NAFLD an additional analysis was repeated in patients adhering to this. Post-intervention, the decrease in IL-6 and in fasting glucose was significantly higher in Currant patients who lost BW compared to their counterparts in the Control arm. Conclusively, minimal modifications in snacking choices, such as the inclusion of dried grapes in diet, are beneficial in NAFLD patients with non-significant fibrosis.

HBV: Do I treat my immunotolerant patients?

Immunotolerant patients with chronic hepatitis B virus (HBV) infection are characterized by positive HBeAg, high viral replication, persistently normal ALT and no or minimal liver damage. Since the risk of the progression of liver disease and the chance of a sustained response with existing anti-HBV agents are low, current guidelines do not recommend treatment but close monitoring with serial alanine aminotransferase (ALT) and HBV DNA measurements instead. However, not treating all these patients is a concern because advanced histological lesions have been reported in certain cases who are usually older (>30-40 years old), and continued high HBV replication could increase the risk of hepatocellular carcinoma (HCC). Thus, the optimal management of immunotolerant patients is often individualised according to age, which is associated with histological severity and patient outcome. In particular, immunotolerant patients <30 years old can be monitored for ALT and HBV DNA, while treatment is often recommended in the few patients over 40. A liver biopsy and/or non-invasive assessment of fibrosis may be helpful to determine the therapeutic strategy in patients between 30 and 40 years old. Moreover, there are three specific subgroups of immunotolerant patients who often require treatment with oral anti-HBV agents: patients who will receive immunosuppressive treatment or chemotherapy, women with serum HBV DNA >10(6-7) IU/ml during the last trimester of pregnancy and certain healthcare professionals with high viraemia levels. More studies are needed to further clarify the natural history for the optimal timing of treatment in this setting.

Systemic levels of human ß-defensin 1 are elevated in patients with cirrhosis.

BACKGROUND: Bacterial translocation (BT) commonly occurs in cirrhosis. Reliable biomarkers for BT are currently lacking. Human beta defensin-1 (hBD-1) is a member of the family of natural antimicrobial peptides produced by epithelial cells and participates in the mucosal defensive mechanisms that prevent BT. The aim of the present study was to examine the local and systemic expression of hBD-1 in patients with cirrhosis. METHODS: Plasma concentrations of hBD-1 and of soluble CD14 (sCD14) proteins were measured by ELISA in patients with chronic viral hepatitis, cirrhosis, and healthy controls. Relative mRNA expression of various natural antimicrobial peptides was determined by real-time PCR in biopsies from the terminal ileum and colon. RESULTS: We found significant upregulation of hBD-1 and sCD14 in the peripheral blood of patients with cirrhosis compared to patients with chronic viral hepatitis and healthy controls. The etiology of cirrhosis did not affect the concentration of either protein. The levels of hBD-1 protein correlated significantly with the levels of sCD14 in blood collected from hepatic veins of cirrhotic patients. In contrast, no significant differences were observed in the intestinal mucosal mRNA expression of the Paneth cell specific defensin A5 or hBD-1 between patients with cirrhosis and healthy controls. CONCLUSIONS: hBD-1 is upregulated in patients with cirrhosis and highly correlates with the lipopolysaccharide-induced protein sCD14. hBD-1 may serve as a biomarker of BT in patients with cirrhosis.

Recent advances in cirrhotic cardiomyopathy.

Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.

Optimal therapy of chronic hepatitis B: how do I treat HBeAg-positive patients?

Current agents for the treatment of chronic hepatitis B (CHB) can be classified into interferon-α (standard or pegylated) (IFN) and nucleos(t)ide analogues (NAs). IFN therapy has the advantage of a finite duration (48 weeks) with a chance for durable sustained off-treatment response in HBeAg positive CHB patients. However, these benefits are limited to approximately 30% of HBeAg positive patients, while parenteral administration and potential side effects are common patient concerns. Thus, patients who can benefit from IFN therapy must be carefully selected and monitored. Recently, stopping rules for IFN non-responders were developed based on 12-week HBsAg levels. NAs are currently used in most CHB patients. They are administered in one tablet daily and can be used in all patients with excellent tolerability and a good safety profile. The current first-line options, entecavir (ETV) and tenofovir (TDF), are highly potent with a minimal risk of resistance during long-term monotherapy. Prolongation of entecavir or tenofovir maintains the initially high virological remission rates in adherent HBeAg positive patients and modifies the long-term outcomes. The need for a long-term, perhaps indefinite, treatment duration is the main limitation of ETV or TDF, which may sometimes be safely discontinued in HBeAg positive patients who achieve stable HBeAg seroconversion. Since there will always be safety concerns and family planning issues with long-term therapy, NAs should be used carefully particularly in young HBeAg positive patients with minimal-mild liver disease.

HBeAg-negative chronic hepatitis B: why do I treat my patients with pegylated interferon-alfa?

HBeAg-negative chronic hepatitis B (CHB) is the most frequent and aggressive type of CHB. The current therapeutic options for CHB include pegylated-interferon-alfa (PEG-IFNα) and nucleos(t)ide analogues (NAs). NAs are well-tolerated and safe agents that effectively inhibit viral replication, but they should be given as long-term, probably lifelong therapy, in particular in HBeAg-negative CHB. Thus, the finite, usually 48-week, duration is the main advantage of PEG-IFNα, providing sustained virological responses (SVR) off-therapy in approximately one-fourth of patients with HBeAg-negative CHB and often leading to HBsAg loss. However, the limited efficacy is the main factor restricting the use of PEG-IFNα in CHB and therefore identifying the predictors of response is of great clinical importance. No reliable baseline predictors of response to PEG-IFNα have been identified to date, but certain studies have identified satisfactory predictors of post-PEG-IFNα response using on-treatment serological markers, mostly HBsAg levels. In particular, in HBeAg-negative CHB patients mostly with genotype D a lack of decline in HBsAg levels and a lack of decrease in HBV DNA levels ≥2 log10 copies/ml at week-12 has a nearly 100% negative predictive value for SVR off-treatment and is now recommended as a stopping rule for early discontinuation of ineffective PEG-IFNα. Prolonging PEG-IFNα therapy to 96 weeks seems to provide higher SVR rates but the application and efficacy of this approach requires further study. The combination of PEG-IFNα with NAs, mostly lamivudine, has not resulted in any therapeutic benefit so far, but newer combined approaches with PEG-IFNα and NA(s) are currently under study.

Diastolic cardiac dysfunction is a predictor of dismal prognosis in patients with liver cirrhosis.

BACKGROUND AND PURPOSE: Left ventricular diastolic dysfunction (LVDD) constitutes the prominent characteristic of cirrhotic cardiomyopathy, but its relevance on the clinical course of cirrhotic patients has not been clearly defined. The aim of the study was to evaluate the relationship of LVDD with the severity and etiology of liver disease and to investigate whether it affects the outcome of cirrhotic patients. METHODS: Cardiac function of 45 cirrhotics was studied by a tissue Doppler imaging echocardiography. Diagnosis of LVDD was made according to the latest guidelines of the American Society of Echocardiography. All patients were followed up for a period of 2 years. Death or liver transplantation was the endpoint of the study. RESULTS: LVDD was found in 17 (38 %) of 45 patients. Its presence was not found to be associated with the etiology and stage of cirrhosis, but its severity was directly correlated with the Child-Pugh score. At the end of follow-up, 14 patients had died; 9 had LVDD (9/17, 53 %) and 5 had not (5/28, 18 %). Patients who died at the beginning of observation period had a higher Child-Pugh and MELD score, higher BNP, lower albumin and more prolonged QTc. On Kaplan-Meier analysis, patients with LVDD had statistically significantly worse prognosis compared to those without (p = 0.013, log rank: 5.495). Low albumin values (p = 0.003) and presence of LVDD (p = 0.017) were independent predictive factors of mortality. CONCLUSIONS: LVDD is a common complication of cirrhosis. As its development seems to be related to a worse prognosis, patients with LVDD must be under a strict follow-up.

Combined use of metallic endoclips and endoloops using a single-channel scope in closing iatrogenic perforations and fistulas: two case reports and a literature review.

Iatrogenic perforation of the gastrointestinal tract is a rare complication of endoscopic procedures, whereas anastomotic leakage after surgery is not uncommon. Both conditions are associated with gut wall defects leading to significant morbidity and mortality of the patients. We describe two case reports, a colonic perforation and an esophagogastric anastomosis leakage successfully managed endoscopically using the combined technique with endoclips and endoloops. A literature review is performed on similar endoscopic techniques aiming to avoid surgical treatment in these patients.