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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

BackgroundPrevalence of cirrhotic cardiomyopathy (CC) remains controversial. Several guidelines have been proposed for its assessment.AimTo estimate the frequency of CC by using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations and investigate the role of stress in unmasking latent cases of CC.MethodsNinety consecutive patients were recruited. CC was evaluated by using the Montreal, the 2009 and 2019 criteria. Dobutamine stress test was also performed.ResultsLVDD 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, neither at rest, nor after stress. Stress test revealed left systolic dysfunction in 4(4.5%) patients. According to 2019 criteria, presence of LVDD was not associated with gender, etiology, or staging of liver disease. Patients with LVDD had longer QTc (p=0.002), larger LAvol (p=0.0001), lower TAPSE(s) (p=0.012), lower SRV(s) (p=0.0001) and lower ΔCI (p=0.009) compared to those without. Patients with Child-B/C had longer QTc (p=0.004), higher BNP (p=0.016), higher E/e’ (p=0.0001) and higher E/e’(s) (p=0.003), compared to Child-A patients. A significant correlation was demonstrated between Child-Pugh score and E/e’ (p=0.0001), or E/e’(s) (p=0.002).ConclusionsIn accordance with the recent guidelines the prevalence of CC seems to be lower. LVDD is the predominant feature of CC and aggravates along with the severity of liver disease. After dobutamine administration several sonographic variables exacerbate, particularly in Child-B/C patients, indicating a potential higher risk for clinical heart failure during stressful invasive interventions.

Main Recommendations 1 ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI 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.

(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.

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.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.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; P0.001; r, 0.774; P0.001; r, 0.75; P0.001 in BMI25, 25-30 and ≥30 kg/m2 respectively), or the degree of liver steatosis (r = 0.63; P0.001 and r = 0.743; P0.001 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; P0.001) or cirrhosis (r, 0.658; P0.001). 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.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.

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.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.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).Both citalopram and amitriptyline are effective pharmacological options in the symptomatic relief of almost 50% patients with well characterized FCP.

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.

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

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.

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.

Portal hypertension (PH) is a major complication of liver cirrhosis, as it predisposes to the development of serious clinical manifestations such as ascites, hepatic encephalopathy and variceal bleeding. Till now, the measurement of hepatic vein pressure gradient (HVPG) is the gold standard method to ascertain the presence and significance of PH, as many studies have shown its correlation with the appearance of varices and the possibility of variceal bleeding. However, the invasiveness of this procedure makes it difficult to be used in daily clinical practice. Several noninvasive methods with adequate capability of evaluating liver fibrosis, including elastographic techniques, are currently used as alternatives to HVPG in order to assess the presence and the severity of PH. The aim of this paper is to express an overview of the literature about the actual role of HVPG and all available noninvasive tests on the prediction of development of PH complications, to highlight their advantages and their potential limitations, and to provide the latest trends on clinical practice.

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.

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. 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. 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. 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.

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.

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.

To compare the incidence of persistent abnormal acid exposure, hypersensitive esophagus (HE), and functional heartburn (FH) in obese/overweight and normal-weight patients referred for impedance-pH monitoring, because of persisting gastroesophageal reflux disease (GERD) symptoms despite therapy with proton pump inhibitors (PPIs). ΜETHODS: Patients with normal endoscopy and typical GERD symptoms, despite PPI therapy twice daily, underwent 24-h impedance-pH monitoring while on therapy. Distal esophageal acid exposure (% time pH4) was measured and reflux episodes were classified into acid or nonacid. A positive symptom index was defined when at least 50% of symptom events were preceded by reflux episodes. Patients were categorized as those with persistent abnormal acid exposure, those with HE, and those with FH. The incidence of persistent abnormal acid exposure, HE, and FH between overweight/obese patients (BMI≥25 kg/m) and normal-weight patients (BMI25 kg/m) was subsequently evaluated.A total of 246 patients (women: 158, men: 88, increased BMI: 151, normal BMI: 95, mean age 55, range 18-75 years) were included. Persistent abnormal acid exposure was found in 39 patients (increased BMI: 31, normal BMI: 8), HE in 77 patients (increased BMI: 43, normal BMI: 34), and FH in 118 patients (increased BMI: 69, normal BMI: 49). When comparing BMI among all three groups, patients with increased BMI were more likely to have acid reflux than HE or FH (P=0.03).In patients with GERD symptoms refractory to double-dose PPI therapy, those with increased BMI are more likely to have persistent abnormal acid exposure than HE or FH.

Background. HCV infection and transfusional iron overload in Thalassemic patients may result in liver disease. HCV treatment in Thalassemia has raised safety concerns. Aim. Estimate effectiveness and tolerability of interferon-based therapy in HCV-infected Thalassemic patients. Material and methods. Over a 12-year period, consecutive patients with β Thalassemia major (TM) and chronic hepatitis C received treatment. Liver biopsy, HCV-RNA and genotyping were performed beforehand. Sustained virological response (SVR) was defined as negative HCV-RNA 6 months post-treatment. Forty eight patients (26 M-22 F, mean age 39.8) were enrolled. Twenty nine patients were treated with conventional interferon alpha (IFNa) for 48 weeks (group A). Nineteen patients (10 naive-9 previously IFNa experienced) received pegylated interferon (PEGIFN) (group B). Results. HCV-1 was found in 44%, HCV-2 in 14%, HCV-3 in 23% and HCV-4 in 19%. Group A: ten patients (38.5%) achieved SVR, 2 (7.5%) relapsed and 17 (54%) were non responders. Group B: five (28%) achieved SVR, 8 (44%) relapsed and 6 (28%) never responded. High HCV-RNA levels, genotype 1 and advanced liver fibrosis were independently associated with no response. Four patients (3 treated with IFNα, 1 with PEG-IFN) had to discontinue treatment due to complications. Conclusions. The response rate of IFN monotherapy in multi-transfused, HCV-infected Thalassemic patients is not inferior to that in nonmulti-transfused patients. IFNa administration is well-tolerated and should be recommended as initial treatment schedule in this setting.

Background and Aim Cirrhotic patients are predisposed to intestinal bacterial overgrowth with translocation of bacterial products which may deteriorate liver hemodynamics. Having shown that short-term administration of rifaximin improves liver hemodynamics in decompensated cirrhosis, we conducted this study to investigate the effect of intestinal decontamination with rifaximin on the long-term prognosis of patients with alcohol-related decompensated cirrhosis (Child-Pugh > 7) and ascites. Methods Patients who had received rifaximin and showed improved liver hemodynamics were enrolled in the current study and continued to receive rifaximin (1200 mg/day). Each patient was matched by age, sex, and Child-Pugh grade to two controls and followed up for up to 5 years, death or liver transplantation. Survival and risk of developing portal hypertension-related complications were compared between rifaximin group and controls. Results Twenty three patients fulfilled the inclusion criteria and matched with 46 controls. Patients who received rifaximin had a significant lower risk of developing variceal bleeding (35% vs 59.5%, P = 0.011), hepatic encephalopathy (31.5% vs 47%, P = 0.034), spontaneous bacterial peritonitis (4.5% vs 46%, P = 0.027), and hepatorenal syndrome (4.5% vs 51%, P = 0.037) than controls. Five-year cumulative probability of survival was significantly higher in patients receiving rifaximin than in controls (61% vs 13.5%, P = 0.012). In the multivariate analysis, rifaximin administration was independently associated with lower risk of developing variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and higher survival. Conclusions In patients with alcohol-related decompensated cirrhosis, long-term rifaximin administration is associated with reduced risk of developing complications of portal hypertension and improved survival.

Most tertiary gastroenterology centers currently offer an open-access capsule endoscopy (CE) service, including patients with obscure gastrointestinal bleeding. However, CE may identify lesions missed by conventional endoscopy.To determine the incidence of bleeding lesions missed by the preceding gastroscopy/colonoscopy that were revealed by CE and compare potential differences in the rate of identifying such lesions in patients that we investigated as opposed to those investigated elsewhere.We prospectively reviewed data from patients subjected to CE for obscure bleeding. We analyzed all cases where a source of bleeding was located in the stomach, duodenum, or colon.A total of 317 consecutive patients were subjected to CE for obscure gastrointestinal bleeding within 28 months. Prior to CE examination, 174 patients had gastroscopy and colonoscopy in our institutions and 143 were referrals, all with negative endoscopic investigation. We identified 11 (3.5%) cases where the source of bleeding was found in the stomach (n = 4) or the cecum (n = 7). There was a significant difference of extra small intestinal lesions diagnosed by CE between referrals (9/143, 6.3%) and endoscopic investigation performed in our institutions (2/174, 1.15%), (p = 0.026). The estimated cost of re-endoscoping in our institution all CE referrals would be 50,050 euro (143 patients × 350 euro), to avoid unnecessary CE examinations (9 patients × 600 euro = 5,400 euro).Reading the whole CE video is important, because small-bowel CE may identify lesions responsible for obscure bleeding missed by the preceding gastroscopy and colonoscopy. Repeating conventional endoscopy by experts before CE is not a cost-effective approach.

It is expected that the percentage of people >60 years of age will be 22% worldwide by the year 2050. Multi-morbidity and poly-pharmacy are common in individuals during old age, while adverse drug reactions are at least twice as common in the elderly compared to younger adults. Publications related to drug side effects are rather rare in this age group since most clinical trials exclude patients >75-80 years of age. Gastrointestinal adverse drug reactions studied in the elderly include non-steroidal anti-inflammatory drugs (NSAIDs) and anticoagulant-induced gastrointestinal tract mucosal injuries. Malabsorption, diarrhoea and constipation are common side effects of laxatives, antibiotics, anticholinergics and calcium channel blockers. Drug (amoxycilin/clavulanic acid, isoniazide, nitrofurantoin, diclifenac and methotrexate)-induced hepatotoxicity in the elderly is four times more common than in younger adults and may simulate almost all known liver disorders. Further clinical studies are needed to investigate gastrointestinal and hepatic side effects of drugs in elderly patients.

BACKGROUND/AIMS: Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS: We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS: At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION: In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

OBJECTIVES The aim of this study was to prospectively compare the diagnostic yield of wireless capsule endoscopy (WCE) and enteroclysis in the detection of Crohn's disease (CD) of the small bowel. METHODS Twenty-nine patients with known CD (group 1) suspected to have more extensive small-bowel involvement and 26 patients, who were suspected to suffer from CD but did not have an earlier history of it (group 2) were prospectively evaluated with enteroclysis and WCE. Each examiner was blinded to the results of other investigations. RESULTS Enteroclysis was unsuccessful in two patients from group 1 8 and six patients from group 2, respectively. In group 1, abnormal findings consistent with CD were detected in 20 patients by using WCE and in 11 patients by using enteroclysis, out of the total 27, at per-protocol analysis (74.1 vs. 40.7%, P

Background and Aim: We evaluated the effect of infection on the short- and long-term outcome of cirrhotic patients with upper gastrointestinal bleeding (UGIB), in a series of patients not submitted to antibiotic prophylaxis. Methods: The cirrhotic patients hospitalized for UGIB were prospectively followed up until the last visit, death, or transplantation. A standard screening protocol was used for bacterial infection at admission. Results: In total, 205 patients were included in the study. Antibiotics were administered in 79 (38.5%) patients and an infection was documented in 64 (31.4%) patients. In total, 130 (63.4%) patients died after a mean (SD) follow up of 23.8 (30.9) months. Six-week mortality was higher in the infected patients (P

Summary Background Hepatic venous pressure gradient (HVPG) increases significantly after endoscopic therapy in patients with bleeding oesophageal varices, which may precipitate further haemorrhage. Whether vasoactive drugs can suppress these changes remains unknown. Aim To investigate the efficacy of somatostatin when compared with octreotide in preventing the post-endoscopic increase in HVPG during acute bleeding and whether the changes affect outcome. Methods Thirty-three cirrhotics with bleeding varices were randomized to receive somatostatin (n = 17) or octreotide (n = 16) under double-blind conditions, soon after their admission. HVPG measurements were performed before and immediately after endoscopic treatment. Results In the somatostatin group, postendotherapy HVPG values did not change significantly when compared with pre-treatment values (18.9 vs. 17.2, P = 0.092). Conversely, in the octreotide group, HVPG increased significantly after endoscopy (18.2 vs. 20.8, P = 0.003). The probability of 6-week survival without treatment failure was significantly higher in the somatostatin group (P = 0.024). Post-endoscopic HVPG value was independently associated with 6-week failure. Conclusions Somatostatin, but not octreotide, effectively prevents the post-endoscopic increase in HVPG, which may be associated with low probability of treatment failure.

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 patients30 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 DNA10(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.

Summary Background Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined. Aim To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine. Methods Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. Results Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 106 copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. Conclusions In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 106 copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.

mer in the lower esophageal sphincter for gastroesophageal reflux: a pilot study. Gastrointest Endosc 2002;55:335-41. 6. Lehman GA, Deviere J, Haber G, et al. Lower esophageal sphincter augmentation therapy for GERD with Enteryx, a biocompatible inert polymer. Initial multi-center human trial results (abstract). Gastrointest Endosc 2001;53:AB123. 7. Nakadi E, Closset J, De Moor V, et al. Laparoscopic Nissen fundoplication after failure of Enteryx injection into the lower esophageal sphincter. Surg Endosc 2004;18:818-20. 8. Mason RJ, Hughes M, Lehman GA, et al. Endoscopic augmentation of the cardia with a biocompatible injectable polymer (Enteryx) in a porcine model. Surg Endosc 2002;163:386-91. 9. Summary of safety and effectiveness data: Enteryx procedure kit. Available at: http://www.fda.gov/cdrh/pdf2/p020006b.pdf. Accessed November 4, 2005. 10. Tintiller M, Chaput A, Kirch L, et al. Esophageal abscess complicating endoscopic treatment of refractory gastroesophageal reflux disease by Enteryx injection: a first case report. Am J Gastroenterol 2004;99: 1856-8.

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.

Distal esophageal (Schatzki's) rings are a frequent cause of dysphagia. Bougienage is generally effective, but relapses are common. The aim of this study was to evaluate the effect of long-term antisecretory therapy on the relapse rate of lower esophageal rings after successful bougienage with Savary dilators.The study was performed on 44 consecutive patients with symptomatic Schatzki's rings, detected endoscopically, and/or radiologically. Graded esophageal dilation was performed as an outpatient procedure in a single session. After appropriate assessment with esophageal manometry and 24-h ambulatory esophageal pH monitoring, patients with documented GERD (n = 14) were treated with long-term omeprazole therapy. The remaining patients were blindly randomized to receive maintenance treatment with either omeprazole (group A-15 patients) or placebo (group B-15 patients). The necessity for redilation after documentation of the ring with endoscopy and/or radiology was considered as a relapse of the ring. The relapse rate was evaluated in all groups.All bougienages were performed without significant side effects. Eight patients (8 of 44, 18.2%) had one or more relapses after a mean (SD) of 19.0 (10.1) months. Patients with (n = 14) or without (n = 30) GERD were comparable with respect to sex, age, body mass index, cigarette and alcohol consumption, diameter of the esophageal lumen at the level of the ring, resting lower esophageal sphincter pressure, duration of dysphagia, need for taking antacids during the follow-up period, and duration of follow-up. There were no recurrences of Schatzki's ring in the group of patients with documented GERD (follow-up [mean +/- SD]: 43.8 +/- 9.3 months, range: 27-62). In group A (follow-up [mean +/- SD]: 37.1 +/- 17.1 months, range: 11-66), one patient relapsed after 13 months, while in group B (follow-up [mean +/- SD]: 34.3 +/- 14.6 months, range: 10-58), seven patients relapsed after a mean (SD) of 19.9 (10.6) months. The actuarial probability of relapse was higher in patients without therapy (group B) (p= 0.008).Our data support the hypothesis that, in patients with symptomatic Schatzki's rings, acid suppressive maintenance therapy after bougienage may prevent relapse of the ring.

Summary Aim : To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to β-blockers for prevention of first bleeding in portal hypertension. Methods : A sample size of 214 was planned with all sizes of varices. However, the trial was stopped due to increased bleeding in 52 patients in the ligation group. The baseline severity liver disease and endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 ± 9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 ± 10.27). Results : The mean follow-up period was 19.5 ± 13.3months: five bled in the ligation group (20%), three from varices (two after banding at 11 and 17 days; one during the procedure), and two from gastropathy; two bled in the not-treated group (7%– two both varices) (P = 0.24). There were seven deaths in the ligation group and 11 in the not-treated group (P = 0.39). Conclusion : Sixty per cent of the bleeding in the banding group was probably iatrogenic, requiring the study to be stopped. Endoscopic banding ligation was no better than no treatment. This study suggests that ligation may be harmful when used as primary prophylaxis, similar to prophylactic sclerotherapy in the past.

Background: The aim of the present study was to evaluate the effect of gallstone disease (GD) and laparoscopic cholecystectomy on gastric electrical activity of slow waves, which was recorded via transcutaneous electrogastrography (EGG). Methods: Twenty-one consecutive patients (M/F: 12/9, 52.7 ± 15 years old) with GD and no previous history of abdominal operations or known disease affecting gastrointestinal motility were studied. The EGG was performed for 30 min prior to and 90 min after a standard meal, during a 4–6 month period prior to and after laparoscopic cholecystectomy. The percentile proportion of the three spectra of gastric slow waves frequency was studied, defined as follows: bradygastria, 1–2.1 cycles per min (c.p.m.); normogastria, 2.2–3.9 c.p.m.; and tachygastria, 4–9 c.p.m. The findings were compared to those of nine healthy subjects (M/F: 5/4, 49.5 ± 14.8 years old). Results: No statistically significant difference was found in percentile distribution of bradygastria, normogastria and tachygastria, pre- or post-prandially, neither before or after laparoscopic cholecystectomy, nor between patients and controls. Conclusions: Patients with GD do not exhibit differences in gastric electrical activity of slow waves in comparison to normal subjects and laparoscopic cholecystectomy does not alter gastric electrical activity. These findings suggest that cholelithiasis does not seem to cause dyspeptic symptoms due to gastric dysrythmias.

AIM We conducted a prospective, randomized comparison of endoscopic variceal ligation, sclerotherapy and metoclopramide injection in order to evaluate their early effect on lower oesophageal sphincter pressure. METHODS Twenty-six patients with established cirrhosis and an episode of variceal bleeding controlled by one session of endoscopic therapy were randomized to undergo an oesophageal manometry. The patients' lower oesophageal sphincter pressure was evaluated, prior to and immediately after a single session of ligation (n = 10), a single session of sclerotherapy (n = 8) or a bolus injection of 20 mg metoclopramide hydrochloride (n = 8). RESULTS Ligation produced a higher early increase in lower oesophageal sphincter pressure (from 12.3 +/- 2.3 to 27.8 +/- 3.0 mmHg) as compared with sclerotherapy (from 13.6 +/- 2.5 to 22.4 +/- 4.5 mmHg) or metoclopramide injection (from 14.6 +/- 3.2 to 22.5 +/- 2.9 mmHg); (P = 0.0001). CONCLUSION Our data indicate that ligation of oesophageal varices produces an early increase in lower oesophageal sphincter pressure in cirrhotic patients.

AIM Endoscopic methods are currently the most widely used techniques for the treatment of bleeding oesophageal varices (BOV). However, a number of complications may limit their usefulness. We conducted a prospective, randomized comparison of variceal ligation versus sclerotherapy in cirrhotics after the control of variceal haemorrhage to study the relative short-term risks of these two procedures with respect to oesophageal motility and gastro-oesophageal reflux. METHODS Seventy-three patients with established cirrhosis and an episode of variceal bleeding controlled by one session of endoscopic therapy were randomized to treatment with sclerotherapy or ligation until variceal eradication. In 60 of these patients, oesophageal manometry and 24-h intra-oesophageal pH monitoring were performed at inclusion and 1 month after variceal eradication. RESULTS After variceal eradication with sclerotherapy, peristaltic wave amplitude decreased from 76.2 +/- 14.7 mmHg to 61.6 +/- 17.7 mmHg (P = 0.0001), simultaneous contractions increased from 0% to 37.9% (P = 0.0008), and the percentage of time with pH < 4 increased from 1.60 +/- 0.25 to 4.91 +/- 1.16% in channel 1 (P = 0.0002) and from 1.82 +/- 0.27 to 5.69 +/- 1.37% in channel 2 (P = 0.0006). In contrast, the above parameters were not disturbed with ligation. CONCLUSION Our data define the advantages of ligation over sclerotherapy with respect to post-treatment oesophageal dysmotility and associated gastro-oesophageal reflux.

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.

Variceal bleeding is a consequence of portal hypertension, which in turn is the major complication of hepatic cirrhosis. Given the high rate of mortality of the first bleeding episode, primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identification of patients with varices who will bleed, before they do so, can justify a strategy of treating all patients with varices prophylactically. We evaluated the various therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta-analysis where applicable. The current first choice treatment is non-selective beta-blockers; it is cheap, easy to administer, and is effective in preventing the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug therapy of beta-blockers and nitrates looks promising, but needs further evaluation in randomized controlled trials. The conflicting results of the randomized studies of endoscopic banding ligation and the small number of patients and clinical events, as well as the cost, do not warrant any change in current practice. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to beta-blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials.

Background: Analysis of primary prevention studies of the use of β-blockers has shown clear reductions in variceal bleeding in cirrhotic patients with varices. In contrast, the usefulness of prophylactic endoscopic sclerotherapy, alone or in combination with propranolol, in the management of these patients is still under investigation. The present study compared the efficacy of combined sclerotherapy and propranolol versus propranolol alone in the primary prevention of hemorrhage in cirrhotic patients with varices and high (greater than 18 mm Hg) intraesophageal variceal pressure. Methods: Patients were randomly assigned to propranolol (42 patients) or to propranolol plus sclerotherapy (44 patients). The mean duration of follow-up was 26.8 ± 7.7 and 24.6 ± 9.8 months, respectively. Results: During this period 23% of the patients in the combination group experienced at least 1 episode of bleeding due to varices or congestive gastropathy as compared with 14% in the propranolol group (not significant). Twenty-three patients (52%) in the combination group developed complications as compared with 8 (19%) in the propranolol group (p = 0.002). The mortality rate was similar in both groups (14% and 18%, respectively). The only independent factor predictive of survival was the level of serum albumin. Conclusions: Endoscopic sclerotherapy should not be used for the primary prevention of hemorrhage in cirrhotic patients at high risk of variceal bleeding who are undergoing treatment with propranolol. (Gastrointest Endosc 2000;51:652-8.)

Background/Aim.In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its effect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs.Methods. Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between final mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration.Results. Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not significantly differ between UDCA- and placebo-treated patients, despite the UDCA effect on serum bilirubin. Therefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients.Conclusions. Our findings suggest that UDCA does not alter serum albumin in a way that is consistent with its effect on serum bilirubin. Therefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker.

The cardiac dysfunction presented in cirrhotic patients is already known as cirrhotic cardiomyopathy. The pathogenesis of this entity is not fully understood.The aim of this study was to evaluate the frequency and characteristics of cirrhotic cardiomyopathy and to investigate the possible role of bacterial endotoxemia on its aggravation.Forty-five cirrhotics were studied by a tissue Doppler imaging echocardiography at rest and after stress. The diagnosis of left ventricular diastolic dysfunction was based on the latest guidelines of the American Society of Echocardiography, whereas its severity was defined by the E/e'av ratio. Endotoxemia was estimated by measuring the serum levels of lipopolysaccharide-binding protein (LBP) and cytokines.None of the patients had systolic dysfunction, but 17/45 (37.8 %) had a diastolic one. Patients with grade II diastolic dysfunction had significantly longer QTc (p = 0.049), larger left atrium volume (p = 0.013), higher Brain Natriuretic Peptide levels (p = 0.007) and higher LBP levels (p = 0.02), compared to those with normal cardiac function, without differences in the systemic hemodynamics and the cytokines' levels. Moreover, the severity of diastolic dysfunction as reflected by the E/e'av. was significantly correlated with the LBP levels (p = 0.002). On the multivariate analysis, the LBP was independently associated with the presence of diastolic dysfunction.Cirrhosis is commonly complicated by cardiac dysfunction. Patients with severe cirrhotic cardiomyopathy have higher LBP levels, which are significantly correlated with the degree of diastolic dysfunction. Our findings support a potential role of bacterial endotoxemia on the aggravation of cardiomyopathy in cirrhotic patients.

Cirrhotic patients are predisposed to intestinal bacterial overgrowth with translocation of bacterial products which may deteriorate liver hemodynamics. Having shown that short-term administration of rifaximin improves liver hemodynamics in decompensated cirrhosis, we conducted this study to investigate the effect of intestinal decontamination with rifaximin on the long-term prognosis of patients with alcohol-related decompensated cirrhosis (Child-Pugh 7) and ascites.Patients who had received rifaximin and showed improved liver hemodynamics were enrolled in the current study and continued to receive rifaximin (1200 mg/day). Each patient was matched by age, sex, and Child-Pugh grade to two controls and followed up for up to 5 years, death or liver transplantation. Survival and risk of developing portal hypertension-related complications were compared between rifaximin group and controls.Twenty three patients fulfilled the inclusion criteria and matched with 46 controls. Patients who received rifaximin had a significant lower risk of developing variceal bleeding (35% vs. 59.5%, P = 0.011), hepatic encephalopathy (31.5% vs. 47%, P = 0.034), spontaneous bacterial peritonitis (4.5% vs. 46%, P = 0.027), and hepatorenal syndrome (4.5% vs. 51%, P = 0.037) than controls. Five-year cumulative probability of survival was significantly higher in patients receiving rifaximin than in controls (61% vs. 13.5%, P = 0.012). In the multivariate analysis, rifaximin administration was independently associated with lower risk of developing variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and higher survival.In patients with alcohol-related decompensated cirrhosis, long-term rifaximin administration is associated with reduced risk of developing complications of portal hypertension and improved survival.

Gastroesophageal reflux disease (GERD) is a chronic condition that usually requires long-term maintenance therapy with proton-pump inhibitors (PPIs). In clinical practice, patients receive PPIs at the lowest dose to control symptoms. However, it is not known whether this approach adequately controls acidic esophageal reflux. We sought to investigate the efficacy of three different dosages of esomeprazole in patients receiving maintenance therapy for GERD, using the Bravo pH system.Patients with a previous history of erosive esophagitis A or B (LA classification) that was healed at the time of enrollment or endoscopy-negative reflux disease (ENRD), documented with an abnormal pH study, were randomized to receive maintenance therapy with esomeprazole 40 mg twice daily (group A), once daily (group B), or every other day (group C). Intraesophageal pH was monitored for two consecutive days using the Bravo wireless system, 30 days after randomization. The parameters subjected to analysis were percent of total time pH4 and the De Meester score.The pH results from 73 patients (group A=24, group B=24, group C=25 patients) were subjected to final analysis. On the first day of the study, the mean (+/-s.d.) percent of total time pH4 and the De Meester score were group A: 0.9(1.2) and 4.1(4.0); group B: 1.5(1.6) and 7.0(6.9); group C: 1.3(1.0) and 6.0(3.3), respectively (P=0.262 and 0.134, respectively). On the second day of the study, the corresponding values were group A: 0.7(1.0) and 3.9(5.9); group B: 1.5(1.8) and 6.4(6.6); group C: 7.0(4.4) and 29.4(19.4), respectively. The difference was statistically significant (P0.0001 and0.0001, respectively). Further analysis showed that patients not receiving PPI had a significantly higher mean percent of total time pH4 and De Meester score as compared with patients on PPI once or twice daily (P0.001 and0.001 respectively).The administration of esomeprazole 40 mg every other day does not control acidic esophageal reflux on the day off PPI. Esomeprazole 40 mg once daily effectively controls reflux of acid in patients with history of mild esophagitis or ENRD, whereas doubling the dose does not seem to confer any further advantage.

Varices are a late complication in primary biliary cirrhosis (PBC). However, patients without clinical jaundice do bleed from varices; whether their prognosis differs is unknown.Evaluate PBC patients, particularly those with bilirubinor=34 micromol/l at the time of bleeding.One hundred and two variceal bleeders were present (median, follow-up 20.5 months, range 0-180), who at diagnosis had: pruritus (51%), fatigue (32%) and 23 (22.5%) variceal bleeding. Histologically advanced disease was present in 96 of 100 patients (stage 3: 14 and stage 4: 82); 83 died, 24 within 6 weeks of first bleeding. At the time of bleeding, 26 patients had bilirubinor=34 micromol/l. In this group, 24 patients were stage 4, in 13 bleeding was the first presentation of PBC and they were older (59.4 vs. 55.4 years, P=0.09), had lower alkaline phosphatase (491.5 vs. 510, P=0.03) but similar albumin values, surviving a median 61 versus 12 months, compared with the 76 patients with bilirubin34 micromol/l (P=0.001, log rank test). Hazard ratios (95% confidence intervals) for independent predictors of mortality after bleeding were: age 1.02 (1-1.05), log10 bilirubin 4.64 (2.56-8.41), ascites 2.13 (1.29-3.51) and hepatic encephalopathy 2.72 (1.56-4.74).Variceal bleeding complicates histologically advanced PBC. A distinct subgroup with near normal bilirubin and lower alkaline phosphatase first presents with variceal bleeding in 50% of cases and has a better prognosis than jaundiced PBC variceal bleeders.

Background/Aims: Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. Methods: We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >= 10 mm Hg treated with oral lamivudine (100 mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. Results: At 12 months, a significant reduction was observed in ALT (p = 0.001), HBV DNA (p = 0.002), Child-Pugh (p = 0.012) and MELD score (p = 0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4 +/- 3.9 and 12 months: 12.4 +/- 3.3 mm Hg (p = 0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >= 12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. Conclusion: In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

We observed that the formation of a fibrous ring following variceal eradication appeared to be associated with less variceal recurrence. We aimed to evaluate this formally.Twenty-one cirrhotic patients with a fibrous ring formation in the esophagus after eradication of varices (FR group) were compared with 21 controls of similar age, gender and liver function but without ring formation after eradication in terms of variceal recurrence, portal hypertension related bleeding and survival.Both groups were similar with regard to baseline demographic and clinical data. During a mean follow-up period of 28.8+/-18.3 (SD) months, variceal recurrence occurred in 2 (9.5%) patients in the FR group compared to 10 (47.6%) in the control group (p=0.005). Cox regression model revealed a significant difference in probability of variceal recurrence between the two groups (p=0.006). In the FR group 1 patient bled and 3 died vs. 2 and 6 patients in the control group respectively. The differences between the groups in relation to bleeding and death were not statistically significant.In cirrhotic patients undergoing band ligation for eradication of esophageal varices, the formation of a fibrous ring is followed by a lower variceal recurrence rate.

Background andAim: Currently, an increasing number of liver biopsies are performed by radiologists under real-time ultrasound control. A routine ultrasound assessment of a puncture site before performing percutaneous biopsy is reported to increase diagnostic yield and decrease complication rates. It is not clear if real-time ultrasound is superior to marking the puncture site before biopsy as regards reducing biopsy size and avoiding fragmentation and complications. The aim of this study was to compare ultrasound assess- ment of the puncture site before performing percutaneous liver biopsy with real-time ultrasound liver biopsy for suspected diffuse liver disease. Methods: Consecutive percutaneous liver biopsies (n = 631) for diffuse liver disease were evaluated. Group A consisted of patients who had real-time guided-ultrasound biopsy performed by radiologists (241 patients; M/F, 35/106; median age 48 year (range, 17-76); needle 18 G). Group B patients were assessed by radiologists using ultrasound of the puncture site on the same day that biopsies were performed by experienced gastroenterologists/hepatologists on the ward using the marked site (390 patients; M/F, 276/114; median age 43 year (range, 15-75); needle 16 G). Results: There were no differences in severity of liver disease, establishing a diagnosis (OR, 1.92 (95% CI, 0.84-4.34); P = 0.12), length of liver biopsy specimens, number of fragments or complications. Two independent variables were significantly associated with a histological diagnosis: longer biopsy length (P < 0001) and fragment number of two or less (P < 0.001). Conclusion: Real-time ultrasound did not improve diagnostic yield or result in fewer complications. Marking the puncture site seems adequate and has the practical advantage that it takes up less of the radiologists' time.