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Nosocomial infections (NIs) in critically ill patients with cirrhosis result in higher death and transplant delisting. NIs are promoted by staff, visitors, and the environment, all of which were altered to reduce pathogen transmission after COVID-19. Two cohorts of intensive care unit patients with cirrhosis from March 2019 to February 2020 (pre-COVID, n = 234) and March 2020 to March 2021 (COVID era, n = 296) were included. We found that despite a higher admission MELD-Na, qSOFA, and WBC count and requiring a longer intensive care unit stay, COVID-era patients developed lower NIs (3% vs 10%, P0.001) and had higher liver transplant rates vs pre-COVID patients. COVID-era restrictions could reduce NIs in critically ill patients with cirrhosis.

In patients with cirrhosis and chronic liver disease, acute-on-chronic liver failure is emerging as a major cause of mortality. These guidelines indicate the preferred approach to the management of patients with acute-on-chronic liver failure and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.

Hepatic encephalopathy (HE) affects numerous stakeholders from a clinical, psychosocial, and financial perspective. The multilayered impact of HE is threefold and affects different groups or, for the purpose of this commentary, villages. The first village mediates HE development, including genetics, microbiome, and disease severity. The second village consists of those affected by HE-related consequences, including the patient, caregivers, society, and medical system. The third village required to manage HE includes a multidisciplinary team of inpatient and outpatient providers, mental health experts, physical therapists, and dietary specialists. Understanding and integration of these three villages can encourage individualized care for patients and families affected by hepatic encephalopathy.

Readmission and death in cirrhosis are common, expensive, and difficult to predict. Our aim was to evaluate the abilities of multiple artificial intelligence (AI) techniques to predict clinical outcomes based on variables collected at admission, during hospitalization, and at discharge.We used the multicenter North American Consortium for the Study of End-Stage Liver Disease (NACSELD) cohort of cirrhotic inpatients who are followed up through 90-days postdischarge for readmission and death. We used statistical methods to select variables that are significant for readmission and death and trained 3 AI models, including logistic regression (LR), kernel support vector machine (SVM), and random forest classifiers (RFC), to predict readmission and death. We used the area under the receiver operating characteristic curve (AUC) from 10-fold crossvalidation for evaluation to compare sexes. Data were compared with model for end-stage liver disease (MELD) at discharge.We included 2,170 patients (57 ± 11 years, MELD 18 ± 7, 61% men, 79% White, and 8% Hispanic). The 30-day and 90-day readmission rates were 28% and 47%, respectively, and 13% died at 90 days. Prediction for 30-day readmission resulted in 0.60 AUC for all patients with RFC, 0.57 AUC with LR for women-only subpopulation, and 0.61 AUC with LR for men-only subpopulation. For 90-day readmission, the highest AUC was achieved with kernel SVM and RFC (AUC = 0.62). We observed higher predictive value when training models with only women (AUC = 0.68 LR) vs men (AUC = 0.62 kernel SVM). Prediction for death resulted in 0.67 AUC for all patients, 0.72 for women-only subpopulation, and 0.69 for men-only subpopulation, all with LR. MELD-Na model AUC was similar to those from the AI models.Despite using multiple AI techniques, it is difficult to predict 30- and 90-day readmissions and death in cirrhosis. AI model accuracies were equivalent to models generated using only MELD-Na scores. Additional biomarkers are needed to improve our predictive capability (See also the visual abstract at http://links.lww.com/AJG/B710).

INTRODUCTION Ammonia levels are used to assess hepatic encephalopathy, but their levels are highly variable in clinical practice. METHODS We studied factors associated with variation in ammonia values in cirrhotic patients without previous hepatic encephalopathy and healthy volunteers (HVs). RESULTS Ammonia increased by 12% and 18% at 1 and 2 hour, respectively, after a protein meal in 64 cirrhotic patients (P < 0.001). In 237 HVs, ammonia levels varied significantly between sites (P < 0.0001). New site-specific ammonia upper limits based on HV levels using a strict analysis protocol differed from routinely used values. Correlation between paired fresh samples was high (r = 0.83) but modest between fresh and frozen samples (r = 0.62). DISCUSSION Sample handling, processing, and protein intake impact ammonia levels across sites.

Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE.Outpatients with cirrhosis underwent stool collection and MHE testing with psychometric hepatic encephalopathy score (PHES), inhibitory control test, and EncephalApp Stroop. A subset provided saliva samples. Minimal hepatic encephalopathy diagnosis/concordance between tests was compared. Stool/salivary microbiota were analyzed using 16srRNA sequencing. Microbial profiles were compared between patients with/without MHE on individual tests. Logistic regression was used to evaluate clinical and microbial predictors of MHE diagnosis.Two hundred forty-seven patients with cirrhosis (123 prior overt HE, MELD 13) underwent stool collection and PHES testing; 175 underwent inhibitory control test and 125 underwent Stroop testing. One hundred twelve patients also provided saliva samples. Depending on the modality, 59%-82% of patients had MHE. Intertest Kappa for MHE was 0.15-0.35. Stool and salivary microbiota profiles with MHE were different from those without MHE. Individual microbiota signatures were associated with MHE in specific modalities. However, the relative abundance of Lactobacillaceae in the stool and saliva samples was higher in MHE, regardless of the modality used, whereas autochthonous Lachnospiraceae were higher in those without MHE, especially on PHES. On logistic regression, stool and salivary Lachnospiraceae genera (Ruminococcus and Clostridium XIVb) were associated with good cognition independent of clinical variables.Specific stool and salivary microbial signatures exist for individual cognitive testing strategies in MHE. The presence of specific taxa associated with good cognitive function regardless of modality could potentially be used to circumvent MHE testing.

Hepatic encephalopathy is a state of brain dysfunction resulting from decompensation of cirrhosis. The mortality and morbidity associated with the overt form of hepatic encephalopathy are high, and even the covert form associates with poor outcomes and poor quality of life. We know that the dysfunction is not just an acute insult to the brain but rather results in long-standing cognitive issues that get worse with each episode of HE. Hence, there is an urgency to accurately diagnose these conditions, start appropriate therapy, and to maintain remission. Currently, we have two mainstay pharmacological treatment options (lactulose and rifaximin), but the narrative is evolving with new therapies under trial. Microbiome manipulation resulting in a favorable change to the gut microbiota seems to be a promising new area of therapy.

Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-a-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention. Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline. PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Hyponatremia is associated with poor outcomes in cirrhosis independent of MELD. While intravenous albumin has been used in small series, its role in hyponatremia is unclear. The aim of this study is to determine the effect of albumin therapy on hyponatremia.Hospitalized cirrhotic patients included in the NACSELD (North American Consortium for End-Stage Liver Disease) cohort with hyponatremia (Na130mmol/L) were divided into those receiving intravenous albumin or not. Determinants of hyponatremia resolution (Na ≥135 meq/L) and 30-day survival were analyzed using regression and ANCOVA models.Overall, 2435 patients, of whom 1126 had admission hyponatremia, were included. Of these, 777 received 225 (IQR 100,400) g of albumin, while 349 did not. Patients given albumin had a higher admission MELD score, and serum creatinine and lower admission Na and mean arterial pressure (MAP). However they experienced a higher maximum Na and hyponatremia resolution (69% vs 61%, p = 0.008) compared to those who did not. On regression, delta Na was independently associated with admission creatinine, MAP and albumin use. On ANCOVA with logistic regression, there was a significant difference in hyponatremia resolution between those who did or did not receive albumin, even after adjustment for admission Na and GFR (85.41% vs 44.78%, p = 0.0057, OR: 1.50 95% CI: 1.13-2.00). Independent predictors of 30-day survival were hyponatremia resolution, age, ACLF, and admission GFR.Hospitalized patients with cirrhosis and hyponatremia who received intravenous albumin had a higher rate of hyponatremia resolution independent of renal function and baseline sodium levels, which was in turn associated with a better 30-day survival.

Despite the associated adverse outcomes, pharmacologic intervention for covert hepatic encephalopathy (CHE) is not the standard of care. We hypothesized that a video game-based rehabilitation program would improve white matter integrity and brain connectivity in the visuospatial network on brain magnetic resonance imaging (MRI), resulting in improved cognitive function in CHE subjects on measures consistent with the cognitive skill set emphasized by the two video games (e.g., IQ Boost-visual working memory, and Aim and Fire Challenge-psychomotor speed), but also generalize to thinking skills beyond the focus of the cognitive training (Hopkins verbal learning test (HVLT)-verbal learning/memory) and improve their health-related quality of life (HRQOL). The trial included three phases over 8 weeks; during the learning phase (cognitive tests administered twice over 2 weeks without intervening intervention), training phase (daily video game training for 4 weeks), and post-training phase (testing 2 weeks after the video game training ended). Thirty CHE patients completed all visits with significant daily achievement on the video games. In a subset of 13 subjects that underwent brain MRI, there was a significant decrease in fractional anisotropy, and increased radial diffusivity (suggesting axonal sprouting or increased cross-fiber formation) involving similar brain regions (i.e., corpus callosum, internal capsule, and sections of the corticospinal tract) and improvement in the visuospatial resting-state connectivity corresponding to the video game training domains. No significant corresponding improvement in HRQOL or HVLT performance was noted, but cognitive performance did transiently improve on cognitive tests similar to the video games during training. Although multimodal brain imaging changes suggest reductions in tract edema and improved neural network connectivity, this trial of video game brain training did not improve the HRQOL or produce lasting improvement in cognitive function in patients with CHE.

Objectives Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence. Methods Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence. Results Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71%vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed. Conclusions This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

To compare inhibitory control test (ICT), a simple/rapid test of attention, to a standard psychometric battery (SPT) to diagnose minimal hepatic encephalopathy (MHE) and predict development of overt hepatic encephalopathy (OHE) in cirrhotic patients.Fifty nonalcoholic cirrhotics and 50 age/educational-status-matched controls were given ICT and SPT in the same sitting. Performance impaired beyond two standard deviations of controls was considered MHE in cirrhotics. ICT results (lure/target response and lures/person) were compared between controls and cirrhotics and within cirrhotics with/without MHE. Receiver-operating characteristic analysis was used to study ICT for MHE diagnosis. Twenty subjects were administered SPT and ICT twice to assess test-retest reliability. All cirrhotics were followed routinely for the development of OHE.Cirrhotics performed worse than controls on SPT and ICT. Using SPT, 39 cirrhotics had MHE. ICT was administered faster than SPT (15 vs 37 min). Cirrhotics with MHE had significantly higher lure (28%vs 3%) and lower target response (91%vs 96%) compared with those without MHE. Lure/person5 had 90% sensitivity/specificity for MHE diagnosis. AUC for receiver-operating characteristic for lures alone was 95.8%. Lure and target responses were highly correlated (r= 0.9) between sessions showing high test-retest reliability. Five (10%) patients developed OHE on f/u of 26 +/- 10 months; all five had been diagnosed with MHE using ICT and SPT. None of the five patients with discordant results on SPT and ICT developed OHE.ICT has good sensitivity/specificity for MHE diagnosis, is reliable and is equivalent to SPT for predicting OHE development.

Cirrhosis and hepatic encephalopathy (HE) can adversely affect survival, but their effect on socioeconomic and emotional burden on the family is not clear. The aim was to study the emotional and socioeconomic burden of cirrhosis and HE on patients and informal caregivers.A cross-sectional study in two transplant centers (Veterans and University) of cirrhotic patients and their informal caregivers was performed. Demographics for patient/caregivers, model-for-end-stage liver disease (MELD) score, and cirrhosis complications were recorded. Patients underwent a cognitive battery, sociodemographic, and financial questionnaires. Caregivers were given the perceived caregiver burden (PCB; maximum=155) and Zarit Burden Interview (ZBI)-Short Form (maximum=48) and questionnaires for depression, anxiety, and social support.A total of 104 cirrhotics (70% men, 44% previous HE, median MELD 12, 49% veterans) and their caregivers (66% women, 77% married, relationship duration 32±14 years) were included. Cirrhosis severely impacted the family unit with respect to work (only 56% employed), finances, and adherence. Those with previous HE had worse unemployment (87.5 vs. 19%, P=0.0001) and financial status (85 vs. 61%, P=0.019) and posed a higher caregiver burden; PCB (75 vs. 65, P=0.019) and ZBI (16 vs. 11, P=0.015) compared with others. Cognitive performance and MELD score were significantly correlated with employment and caregiver burden. Veterans and non-veterans were equally affected. On regression, depression score, MELD, and cognitive tests predicted both PCB and ZBI score.Previous HE and cognitive dysfunction are associated with worse employment, financial status, and caregiver burden. Cirrhosis-related expenses impact the family unit's daily functioning and medical adherence. A multidisciplinary approach to address this burden is required.

Spontaneous bacterial peritonitis (SBP) is a frequent complication of cirrhosis. Bacterial contamination of ascites fluid leading to SBP is caused by bacterial translocation with subsequent bacteremia. Proton pump inhibitors (PPIs) suppress gastric acid secretion, allowing bacterial colonization of the upper gastrointestinal tract, and may predispose to bacterial overgrowth and translocation. The aim of this study was to determine whether PPI use in cirrhotics with ascites is associated with SBP.A retrospective case-control study was performed. Seventy cirrhotics admitted with paracentesis-proven SBP between 2002 and 2007 were matched 1:1 (for age and Child's class) with comparable cirrhotics with ascites who were admitted for conditions other than SBP. We excluded patients on chronic antibiotic prophylaxis or with antecedent gastrointestinal bleeding. Outpatient PPI use at the time of admission was compared between groups, and the effect of covariates was analyzed.Patients with SBP had a significantly higher rate of prehospital PPI use (69%) compared with ascitic cirrhotics hospitalized without SBP (31%, P = 0.0001). There was no significant difference in demographics, diabetes, etiology, or survival between groups. On multivariate analysis, PPI use was independently associated with SBP (odds ratio (OR) 4.31, confidence interval (CI) 1.34-11.7), and ascitic fluid protein was protective (OR 0.1, CI 0.03-0.25). In total, 47% of cirrhotic patients receiving PPI in this study had no documented indication for PPI treatment.PPI therapy is associated with SBP in patients with advanced cirrhosis. Prospective studies are needed to determine whether PPI avoidance can reduce the incidence of SBP and improve outcomes.

OBJECTIVES: Hepatic encephalopathy, both overt (OHE) and minimal (MHE), is associated with poor quality of life and fatigue. The aim of this study was to define the effect of fatigue on driving skills in MHE and OHE patients. METHODS: Cirrhotics and age/education-matched controls were administered a psychometric battery of tests to diagnose MHE. Cirrhotics with recent OHE on lactulose were also included. All subjects underwent a driving simulation; to assess fatigue, the second half performance was compared with the first half of the simulation. The outcomes were collisions, speeding, road excursions, and center crossings. Actual driving-associated fatigue was assessed by the American Medical Association (AMA) driver survey. RESULTS: A total of 100 cirrhotics (51 MHE, 27 no MHE, and 22 OHE) and 67 controls were included. A significantly higher proportion of OHE and MHE patients admitted to fatigue after actual driving on the AMA survey compared with no MHE patients (P=0.02). All patients who admitted to fatigue and none who denied fatigue on the AMA survey had simulator collisions. Psychometric and simulator performance in treated OHE patients was similarly impaired to MHE patients despite therapy. Within groups, a significant increase in collisions, speeding, and center crossings in the second half (P=0.01) was seen only in MHE patients. CONCLUSIONS: Psychometric and simulator performance in patients with recent OHE on treatment is similarly impaired as that of untreated MHE patients. Simulator performance in MHE worsens over time with fatigue. OHE and MHE patients had a higher rate of actual driving-associated fatigue on the AMA survey, which was significantly predictive of simulator collisions. Language: en

OBJECTIVES: MHE patients have impairment on driving tests. However, it is unclear whether this impairment is restricted to the testing environment or is associated with increased traffic violations and/or motor vehicle accidents. METHODS: An anonymous driving history and driving behavior questionnaire (DBQ: self-scored, best score 104), coded according to MHE status, was sent to 200 cirrhotics without overt hepatic encephalopathy and 100 age/education-matched controls. The questionnaire inquired about demographics, alcohol/illegal drug use, and violations/accidents within 1 and 5 yr. The cirrhotics had been divided into those with MHE (MHE+), without MHE (MHE-), and those not tested for MHE because of psychoactive drug use, on a previous study. RESULTS: Cirrhotics versus controls had similar driving duration, alcohol/illegal drug use but significantly higher percentage with violations within both 1 and 5 yr (25%vs 4%[5 yr]), 13%vs 2%[(1 yr]), accidents (17%vs 4%[5 yr]), 9%vs 1%[1 yr]), and both (34%vs 7%[5 yr], 18%vs 3%[1 yr]). MHE+ cirrhotics had significantly higher percentage with violations (36%[5 yr], 21%[1 yr]), accidents (33%[5 yr]), 17%[1 yr]), and both (53%[5 yr], 33%[1 yr]) versus other cirrhotics. DBQ score was significantly lower in cirrhotics than controls (92 vs 99). Within cirrhotics, DBQ score was highest in MHE-versus other groups. MHE+ status was the only risk factor (odds ratios: 4.2-7.6) for violations and for accidents on multivariate logistic regression. CONCLUSIONS: Cirrhotics have a higher self-reported occurrence of violations and accidents compared to controls. MHE+ a is strong predictor for violations and accidents. Prospective studies investigating the effect of MHE treatment on violations and accidents are warranted. Language: en

Idiosyncratic drug hypersensitivity may occur at increased rates in specific patient populations. Azathioprine has a significant early adverse reaction (EAR) profile, which includes an acute syndrome of constitutional symptoms, fever, rash, and acute pancreatitis and often requires discontinuation of drug. EAR precludes azathioprine use in patients with Crohn's disease (CD) and autoimmune hepatitis (AIH). Our aims were to investigate differential rates of EAR to azathioprine in CD compared to AIH in a tertiary referral center population.Retrospective chart review of consecutive CD and AIH patients who were initiated on azathioprine in our inflammatory bowel disease (IBD) and hepatology centers was performed. EAR (fevers and constitutional symptoms, severe arthralgias, nausea, and vomiting) were defined as those occurring within 1 month of initiation. EAR rates between AIH and CD patients were compared using the Fisher's exact test.One hundred and forty-three CD (88F/55M; age 39.2 +/- 13 yr) and 40 AIH (35F/5M; age 53.1 +/- 14 yr) patients were studied. All patients were initiated with equivalent azathioprine dosage (50 mg qd). All AIH patients were on prednisone (mean daily dose 7.5 mg) compared to 51% of CD patients (median daily dose 20 mg). EAR rates were significantly higher in CD patients (42/143; 29%) compared to AIH (2/40; 5%) (Fisher's exact test; p= 0.008). EAR excluding nausea and vomiting were still significantly higher in CD patients (27/143; 19%) compared to AIH (1/40; 2.5%) (Fisher's exact test; p= 0.01). All patients with EAR required drug discontinuation and 7% of CD patients required hospitalization for management of these complications.CD patients represent a unique subgroup at increased risk of EAR to azathioprine. Mechanisms behind these reactions need to be further defined.

We report a 17-yr-old Caucasian male who was initially seen in our Dysphagia Institute with complaints of chest pain and phlegm production after ingesting certain vegetables. He started noticing these symptoms 7 yr prior to this evaluation; however, worsening of symptoms over the past 4 months prompted this clinic visit. The patient was only recently able to narrow the offending food items to green peppers and raw onions. The chest pain was substernal, nonradiating and was not associated with heartburn, nausea, vomiting, or shortness of breath. It started within 1‐2 min of eating green peppers or onions. The chest pain was relieved for less than a minute by drinking water and it lasted for about 30 min before resolving spontaneously. During these episodes the patient could not swallow his oral secretions and had excessive phlegm in his mouth. The patient had undergone an allergy evaluation prior to this clinic visit for similar symptoms. The phlegm production and chest pain were initially thought to be manifestations of an underlying food allergy, however, the tests were inconclusive. The patient was started on decongestants, which did not relieve his symptoms and were subsequently discontinued. He also denied cough or choking sensation during these periods. There was no history of sensitivity of his extremities to cold, skin changes, fatigue, or easy bruisability. His appetite and weight remained stable in the preceding months. The patient was a high-school student at that time and denied alcohol, tobacco, or illicit drug use. He was currently on a daily proton pump inhibitor (PPI) that had failed to relieve the above symptoms. There was no family history of similar symptoms. On examination the patient was of normal body weight and did not have any abnormalities on chest and abdominal examination. There was no sclerodactyly, telangiectasia, or signs of Raynaud’s phenomenon. A standard esophageal manometry was performed with the patient off PPI. The manometry test (Fig. 1) showed normal peristalsis, normal esophageal body, and lower esophageal sphincter (LES) pressures and adequate LES relaxation in response to swallows. A Bernstein test performed subsequently did not reveal any motor abnormality or reproduce the patient’s symptoms. The manometry test was then repeated in the same sitting. The patient ate green peppers and within 1 min started complaining of similar chest pain that had motivated him for evaluation. The esophageal body showed isobaric, high-pressure contractions consistent with spasms. These complexes were repetitive, had durations of 20‐30 s and coincided with the “chest pain” phenomena (Fig. 2). This pattern continued for 30 min until the patient was administered amyl nitrite by inhalation. Amyl nitrite obliterated the spasms (Fig. 3) and the patient felt symptomatically better. The patient was advised to avoid all forms of green peppers and onions in his diet. He has remained asymptomatic for at least 3 yr on this relatively restricted diet.