Prevalence and prognostic significance of vitamin C deficiency in patients with acute upper gastrointestinal bleeding: a prospective cohort study.

BACKGROUND: Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract. AIM: We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes. METHODS: We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 µmol/L, severe VCD < 12 µmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission. RESULTS: A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE. CONCLUSION: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax.

BACKGROUND: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with limited treatment options. AIM: To define the clinical outcomes of patients presenting with HH managed with current standards-of-care and to identify factors associated with mortality. METHODS: Cirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 were retrospectively identified. HH was defined as pleural effusion in the absence of cardiopulmonary disease. The primary outcomes were overall and transplant-free survival at 12-mo after the index admission. Cox proportional hazards analysis was used to determine factors associated with the primary outcomes. RESULTS: Overall, 84 patients were included (mean age, 58 years) with a mean model for end-stage liver disease score of 29. Management with diuretics alone achieved long-term resolution of HH in only 12% patients. At least one thoracocentesis was performed in 73.8% patients, transjugular intrahepatic portosystemic shunt insertion in 11.9% patients and 33% patients received liver transplantation within 12-mo of index admission. Overall patient survival and transplant-free survival at 12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidney injury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increased risk of mortality. CONCLUSION: Cirrhotic patients with HH are a challenging population with a poor 12-mo survival despite current treatments. Current smoking and episodes of AKI are potential modifiable factors affecting survival. HH is often refractory of diuretic therapy and transplant assessment should be considered in all cases.

Hepatoid adenocarcinoma: A wolf in hepatocellular carcinoma's clothing.

Hepatoid adenocarcinoma (HAC) is a rare malignancy that may mimic hepatocellular carcinoma (HCC) given its hepatoid histologic appearance and production of alpha fetoprotein. Clinical management and prognosis of HAC varies considerably from HCC. We present two cases of metastatic HAC in a cirrhotic liver diagnosed after biopsy and histopathological evaluation. The cases underscore the importance of recognizing the limitations of diagnostic imaging and pursuing a biopsy where there is diagnostic uncertainty.

Survival outcomes and predictors of mortality, re-bleeding and complications for acute severe variceal bleeding requiring balloon tamponade.

BACKGROUND: Acute severe variceal bleeding (AVB) refractory to medical and endoscopic therapy is infrequent but associated with high mortality. Historical cohort studies from 1970-1980s no longer represent the current population as balloon tamponade is no longer first-line therapy for variceal bleeding; treatments including vasoactive therapies, intravenous antibiotics, endoscopic variceal band ligation are routinely used, and there is improved access to definitive treatments including transjugular intrahepatic portosystemic shunts. However, only a few studies from the current era exist to describe the practice of balloon tamponade, its outcomes, and predictors with a requirement for further updated information. AIM: To describe current management of AVB requiring balloon tamponade and identify the outcomes and predictors of mortality, re-bleeding and complications. METHODS: A retrospective multi-centre cohort study of 80 adult patients across two large tertiary health networks from 2008 to 2019 in Australia who underwent balloon tamponade using a Sengstaken-Blakemore tube (SBT) were included for analysis. Patients were identified using coding for balloon tamponade. The primary outcome of this study was all-cause mortality at 6 wk after the index AVB. Secondary outcomes included re-bleeding during hospitalisation and complications of balloon tamponade. Predictors of these outcomes were determined using univariate and multivariate binomial regression. RESULTS: The all-cause mortality rates during admission and at 6-, 26- and 52 wk were 48.8%, 51.2% and 53.8%, respectively. Primary haemostasis was achieved in 91.3% and re-bleeding during hospitalisation occurred in 34.2%. Independent predictors of 6 wk mortality on multivariate analysis included the Model for Endstage Liver disease (MELD) score (OR 1.21, 95%CI 1.06-1.41, P = 0.006), advanced hepatocellular carcinoma (OR 11.51, 95%CI 1.61-82.20, P = 0.015) and re-bleeding (OR 13.06, 95%CI 3.06-55.71, P < 0.001). There were no relevant predictors of re-bleeding but a large proportion in which this occurred did not survive 6 wk (76.0% vs 24%). Although mucosal trauma was the most common documented complication after SBT insertion (89.5%), serious complications from SBT insertion were uncommon (6.3%) and included 1 patient who died from oesophageal perforation. CONCLUSION: In refractory AVB, balloon tamponade salvage therapy is associated with high rates of primary haemostasis with low rates of serious complications. Re-bleeding and mortality however, remain high.

Epidemiology and Prognostic Significance of Rapid Response System Activation in Patients Undergoing Liver Transplantation.

Patients undergoing liver transplantation have a high risk of perioperative clinical deterioration. The Rapid Response System is an intensive care unit-based approach for the early recognition and management of hospitalized patients identified as high-risk for clinical deterioration by a medical emergency team (MET). The etiology and prognostic significance of clinical deterioration events is poorly understood in liver transplant patients. We conducted a cohort study of 381 consecutive adult liver transplant recipients from a prospectively collected transplant database (2011-2017). Medical records identified patients who received MET activation pre- and post-transplantation. MET activation was recorded in 131 (34%) patients, with 266 MET activations in total. The commonest triggers for MET activation were tachypnea and hypotension pre-transplantation, and tachycardia post-transplantation. In multivariable analysis, female sex, increasing Model for End-Stage Liver Disease score and hepatorenal syndrome were independently associated with MET activation. The unplanned intensive care unit admission rate following MET activation was 24.1%. Inpatient mortality was 4.2% and did not differ by MET activation status; however, patients requiring MET activation had significantly longer intensive care unit and hospital length of stay and were more likely to require inpatient rehabilitation. In conclusion, liver transplant patients with perioperative complications requiring MET activation represent a high-risk group with increased morbidity and length of stay.

Amoebic colitis: A case series of a recurring missed diagnosis.

Entamoeba histolytica, a pathogenic protozoan that causes amoebiasis, remains the second leading cause of death from parasitic infections worldwide. We present a case series of patients presenting to metropolitan tertiary gastroenterology units in Melbourne, Australia, highlighting the complexities of diagnosing amoebic colitis and the potential for misdiagnosis. These cases illustrate four key lessons in the identification of amoebic colitis: (i) obtaining a thorough travel and exposure history, (ii) having a high index of suspicion, (iii) understanding the limitations of available investigations, and (iv) being aware that amoebic colitis may masquerade as other common conditions.

Cardiac Risk Stratification in Liver Transplantation: Results of a Tiered Assessment Protocol Based on Traditional Cardiovascular Risk Factors.

Coronary artery disease (CAD) confers increased perioperative risk in patients undergoing liver transplantation (LT). Although routine screening for CAD is recommended, there are limited data on the effectiveness of screening strategies. We evaluated the safety and efficacy of a 3-tiered cardiac risk-assessment protocol that stratifies patients based on age and traditional cardiac risk factors. We peformed a single-center, prospective, observational study of consecutive adult patients undergoing LT assessment (2010-2017). Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) cardiac groups and received standardized investigations with selective use of transthoracic echocardiography (TTE), dobutamine stress echocardiography (DSE), computed tomography coronary angiography (CTCA), and coronary angiography (CA). Primary outcomes were cardiac events (CEs) and cardiovascular death up to 30 days after LT. Overall, 569 patients were included, with 76 patients identified as LR, 256 as IR, and 237 as HR. Cardiac risk factors included diabetes mellitus (26.0%), smoking history (47.3%), hypertension (17.8%), hypercholesterolemia (7.2%), family (17.0%) or prior history of heart disease (6.0%), and obesity (27.6%). Of the patients, 42.0% had ≥2 risk factors. Overall compliance with the protocol was 90.3%. Abnormal findings on TTE, DSE, and CTCA were documented in 3, 23, and 44 patients, respectively, and 12 patients were not listed for transplantation following cardiac assessment (1 LR, 2 IR, and 9 HR). Moderate or severe CAD was identified in 25.4% of HR patients on CTCA following a normal DSE. CEs were recorded in 7 patients (1.2%), with 2 cardiovascular deaths (0.4%). Cardiac risk stratification based on traditional cardiac risk factors with the selective use of DSE, CTCA, and CA is a safe and feasible approach that results in a low perioperative cardiac event rate.

Prediction of Perioperative Cardiovascular Events in Liver Transplantation.

BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with poor survival in the absence of liver transplantation (LT). HRS represents a state of profound circulatory and cardiac dysfunction. Whether it increases risk of perioperative major adverse cardiovascular events (MACE) following LT remains unclear. METHODS: We performed a retrospective cohort study of 560 consecutive patients undergoing cardiac workup for LT of whom 319 proceeded to LT. All patients underwent standardized assessment including dobutamine stress echocardiography. HRS was defined according to International Club of Ascites criteria. RESULTS: Primary outcome of 30-day MACE occurred in 74 (23.2%) patients. A significantly higher proportion of patients with HRS experienced MACE (31 [41.9%] versus 54 [22.0%]; P = 0.001). After adjusting for age, model for end-stage liver disease score, cardiovascular risk index, history of coronary artery disease, and a positive stress test, HRS remained an independent predictor for MACE (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.13-5.78). Other independent predictors included poor functional status (OR, 3.38; 95% CI, 1.41-8.13), pulmonary hypertension (OR, 3.26; 95% CI, 1.17-5.56), and beta-blocker use (OR, 2.56; 95% CI, 1.10-6.48). Occurrence of perioperative MACE was associated with a trend toward poor age-adjusted survival over 3.6-year follow-up (hazard ratio, 2.0; 95% CI, 0.98-4.10; P = 0.057). CONCLUSIONS: HRS, beta-blocker use, pulmonary hypertension, and poor functional status were all associated with over a 2-fold higher risk of MACE following LT. Whether inclusion of these variables in routine preoperative assessment can facilitate cardiac risk stratification warrants further study.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM: To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS: All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS: 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION: Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Risk stratification in acute variceal bleeding: Comparison of the AIMS65 score to established upper gastrointestinal bleeding and liver disease severity risk stratification scoring systems in predicting mortality and rebleeding.

BACKGROUND AND AIM: Risk stratification is recommended in all patients with acute variceal bleeding (AVB). It remains unclear whether liver disease severity or upper gastrointestinal bleeding (UGIB) scoring algorithms offer superior predictive ability. We aimed to validate the AIMS65 score as a predictor of mortality in AVB, and to compare AIMS65 with established UGIB and liver disease severity risk stratification scores. METHODS: International Classification of Diseases, Tenth Revision codes identified patients presenting with AVB to three tertiary centers over a 48-month period. Patients were risk-stratified using AIMS65, Rockall, pre-endoscopy Rockall, Child-Pugh, Model for End-stage Liver Disease (MELD) and United Kingdom MELD (UKELD) scores. Primary outcomes were inpatient and 6-week mortality and inpatient rebleeding. RESULTS: Two hundred and twenty-three patients were included. Inpatient and 6-week mortality were 13.9% and 15.5% respectively. Prediction of inpatient mortality by AIMS65 (area under the receiver-operating characteristic curve [AUROC: 0.84]) was equivalent to UGIB (Rockall: 0.79, pre-Rockall: 0.78) and liver risk scores (MELD: 0.81, UKELD: 0.79, Child-Pugh: 0.78). AIMS65 score ≥3 best defined high- and low-risk groups for inpatient mortality (mortality 37.7% vs 4.9%). AIMS65 (AUROC: 0.62) was equivalent to UGIB risk scores (pre-Rockall: 0.64, Rockall: 0.70) in predicting inpatient rebleeding and superior to liver risk scores (MELD: 0.56, UKELD: 0.57, Child-Pugh: 0.60). CONCLUSIONS: AIMS65 is equivalent to established UGIB and liver disease severity risk stratification scores in predicting mortality, and superior to liver scores in predicting rebleeding.

Early radiological intervention and haematology screening is associated with excellent outcomes in Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder, resulting from thrombosis of the hepatic veins. Various treatments, including pharmacological, radiological and surgical interventions, have been used. AIM: To describe retrospectively our institution's experience with management of patients with BCS. METHODS: A retrospective study of all cases of primary Budd-Chiari syndrome presenting to our institution between January 2000 and August 2012 was performed. Patients with secondary Budd-Chiari syndrome due to malignancy or local mass compression were excluded. RESULTS: Between 2000 and 2012, 27 patients with primary BCS presented with a median Rotterdam score of 1.16 (range: 0.07-2.11). A total of 24 patients (89%) had at least one risk factor, with the commonest being myeloproliferative neoplasm (MPN), detected in 17 of 24 (71%) of the tested patients, including four patients with normal blood counts at diagnosis. All patients were anticoagulated with warfarin or low-molecular-weight heparin (LMWH). A total of 25 (92.6%) patients also had primary radiological interventions, consisting of transjugular intrahepatic portosystemic shunt (TIPS) in 18 (67%) patients and/or angioplasty/stenting in 11 (40%). A total of 14 patients developed TIPS stenoses, requiring a median of 1.5 (range: 1-14) revisions. No patient developed TIPS failure requiring alternative therapy. Two patients were lost to follow-up. At a median follow up of 59 months (range: 2-248 months), the overall survival was 96% at 1 year and 81% at 5 years, much greater than predicted by the Rotterdam score. No patients required liver transplantation. CONCLUSION: There is a high incidence of MPN in patients with primary BCS, including patients with normal peripheral blood counts at the time of diagnosis. Our approach of anticoagulation, aggressive and early radiological intervention aimed at rapid decompression of the congested liver resulted in excellent medium-term outcomes.

Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites.

BACKGROUND & AIMS: Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality. METHODS: A single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1st of January 2009 to 31st August 2012 was carried out. The primary outcome was all-cause and liver-specific mortality in patients receiving or not receiving carvedilol as prophylaxis against variceal bleeding. RESULTS: The final cohort after propensity score matching comprised 264 patients. Baseline ascites severity and UK end-stage liver disease (UKELD) score between carvedilol (n=132) and non-carvedilol (n=132) treated patient groups were comparable. Median follow-up time was 2.3years. Survival at the end of the follow-up was 24% and 2% for the carvedilol and the non-carvedilol groups respectively (log-rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (log-rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 (95% confidence interval [CI]: 0.44, 0.80; p=0.001), suggesting a 41% reduction in mortality risk. When stratified by the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 (95% CI: 0.29, 0.77; p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk. CONCLUSION: Long-term carvedilol therapy is not harmful in patients with decompensated cirrhosis and ascites. LAY SUMMARY: The safety of carvedilol and other non-selective beta-blocker drugs in patients with liver cirrhosis and ascites is still debated. In this study, we have shown that carvedilol therapy in these patients was associated with reduced risk of mortality, particularly in those with mild ascites. We concluded that low dose, chronic treatment with carvedilol in patients with liver cirrhosis and ascites is not detrimental.

Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems.

BACKGROUND AND AIMS: The American College of Gastroenterology recommends early risk stratification in patients presenting with upper GI bleeding (UGIB). The AIMS65 score is a risk stratification score previously validated to predict inpatient mortality. The aim of this study was to validate the AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB and to compare it with established pre- and postendoscopy risk scores. METHODS: ICD-10 (International Classification of Diseases, Tenth Revision) codes identified patients presenting with UGIB requiring endoscopy. All patients were risk stratified by using the AIMS65, Glasgow-Blatchford score (GBS), pre-endoscopy Rockall, and full Rockall scores. The primary outcome was inpatient mortality. Secondary outcomes were a composite endpoint of inpatient mortality, rebleeding, and endoscopic, radiologic, or surgical intervention; blood transfusion requirement; intensive care unit (ICU) admission; rebleeding; and hospital length of stay. The area under the receiver-operating characteristic curve (AUROC) was calculated for each score. RESULTS: Of the 424 study patients, 18 (4.2%) died and 69 (16%) achieved the composite endpoint. The AIMS65 score was superior to both the GBS (AUROC, 0.80 vs 0.76, P < .027) and the pre-endoscopy Rockall score (0.74, P = .001) and equivalent to the full Rockall score (0.78, P = .18) in predicting inpatient mortality. The AIMS65 score was superior to all other scores in predicting the need for ICU admission and length of hospital stay. AIMS65, GBS, and full Rockall scores were equivalent (AUROCs, 0.63 vs 0.62 vs 0.63, respectively) and superior to pre-endoscopy Rockall (AUROC, 0.55) in predicting the composite endpoint. GBS was superior to all other scores for predicting blood transfusion. CONCLUSION: The AIMS65 score is a simple risk stratification score for UGIB with accuracy superior to that of GBS and pre-endoscopy Rockall scores in predicting in-hospital mortality and the need for ICU admission.

AIMS65: a promising upper gastrointestinal bleeding risk score but further validation required.

A novel upper gastrointestinal bleeding risk stratification score (AIMS65) has recently been developed and validated. It has advantages over existing risk scores including being easy to remember and lack of subjectivity in calculation. We comment on a recent study that has cast doubt on the applicability of AIMS65 in the peptic ulcer disease population. Although promising, further studies are required to evaluate the validity of AIMS65 in various populations.

Predicting perinatal outcome through changes in umbilical artery Doppler studies after antenatal corticosteroids in the growth-restricted fetus.

OBJECTIVE: To investigate whether persistently absent umbilical artery end-diastolic flow in the intrauterine growth-restricted fetus after betamethasone administration is associated with altered perinatal outcomes. METHODS: This is a retrospective cohort study of 92 pregnancies complicated by intrauterine growth restriction (IUGR) and absent end-diastolic flow in which antenatal betamethasone was given. Predefined maternal outcomes (maternal age, gestational age at diagnosis of absent end-diastolic flow, gestational age at delivery, preexisting medical conditions) and neonatal outcomes (including birth weight; perinatal mortality; duration of neonatal intensive care unit admission; requirement for intubation, assisted ventilation, inotropic support; duration of supplemental oxygen, assisted ventilation; respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage) were analyzed. RESULTS: Betamethasone administration was associated with a transient return of end-diastolic umbilical artery flow in 58 pregnancies (63%) and persistent absent end-diastolic flow in 34 (37%). Persistent absent end-diastolic flow was seen more frequently in women with prepregnancy medical disorders (59% compared with 24%, P<.001). Neonates from the persistent absent end-diastolic flow subgroup were more likely to require assisted ventilation (93.1% compared with 73.5%, P=.03) and to have longer durations of assisted ventilation (median time 30 days compared with 4 days, P=.03) and supplemental oxygen (median time 45 days compared with 4 days, P=.04). CONCLUSION: Betamethasone administration is associated with a transient return of end-diastolic flow in two thirds of pregnancies complicated by IUGR and umbilical artery absent end-diastolic flow. Persistent absent end-diastolic flow in the umbilical artery after betamethasone administration may identify a subgroup of fetuses with IUGR at further heightened perinatal risk that, as neonates, are more likely to require assisted ventilation and a longer duration of ventilation and supplemental oxygen.

Identification of a novel fimbrial gene cluster related to long polar fimbriae in locus of enterocyte effacement-negative strains of enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) is a food-borne cause of bloody diarrhea and the hemolytic-uremic syndrome (HUS) in humans. Most strains of EHEC belong to a group of bacterial pathogens that cause distinctive lesions on the host intestine termed attaching-and-effacing (A/E) lesions. A/E strains of EHEC, including the predominant serotype, O157:H7, are responsible for the majority of HUS outbreaks worldwide. However, several serotypes of EHEC are not A/E pathogens because they lack the locus of enterocyte effacement (LEE) pathogenicity island. Nevertheless, such strains have been associated with sporadic cases and small outbreaks of hemorrhagic colitis and HUS. Of these LEE-negative organisms, O113:H21 is one of the most commonly isolated EHEC serotypes in many regions. Clinical isolates of LEE-negative EHEC typically express Shiga toxin 2 and carry an approximately 90-kb plasmid that encodes EHEC hemolysin, but in the absence of LEE, little is known about the way in which these pathogens colonize the host intestine. In this study we describe the identification of a novel fimbrial gene cluster related to long polar fimbriae in EHEC O113:H21. This chromosomal region comprises four open reading frames, lpfA to lfpD, and has the same location in the EHEC O113:H21 genome as O island 154 in the prototype EHEC O157:H7 strain, EDL933. In a survey of EHEC of other serotypes, homologues of lpfA(O113) were found in 26 of 28 LEE-negative and 8 of 11 non-O157:H7 LEE-positive EHEC strains. Deletion of the putative major fimbrial subunit gene, lpfA, from EHEC O113:H21 resulted in decreased adherence of this strain to epithelial cells, suggesting that lpf(O113) may function as an adhesin in LEE-negative isolates of EHEC.