Clinical Gastroenterology and Hepatology

Hepatic Artery Compression of the Common Hepatic Duct: Direct Visualization by Single-Operator Peroral Cholangioscopy

Daniel Eshtiaghpour, Viktor E. Eysselein, Sofiya Reicher — 2011-12-02

A 54-year-old man presented with right upper-quadrant abdominal pain, jaundice, and pruritis. His initial total bilirubin level was 5.8 mg/dL, aspartate aminotransferase level was 186 U/L, alanine aminotransferase level was 409 U/L, alkaline phosphatase level was 402 U/L, and carbohydrate antigen 19-9 level was 74 U/mL. Endoscopic retrograde cholangiopancreatography (ERCP) performed at an outside facility revealed small stones, sludge, and a proximal biliary stricture. A plastic biliary stent was placed to facilitate biliary drainage. Subsequently, liver function tests and carbohydrate antigen 19-9 levels normalized. The patient was then referred to our facility for further work-up of the biliary stricture. ERCP showed a 1- to 2-cm smooth stricture in the common hepatic duct below bifurcation with mild intrahepatic duct dilation ( A, arrow). There was no obvious hilar mass on endoscopic ultrasound. Biopsies of the stricture showed normal bile duct epithelium. Single-operator direct peroral cholangioscopy was then performed with the SpyGlass system (Boston Scientific Corp, Natick, MA). Mild extrinsic pulsatile compression of the common hepatic duct was observed at the stricture level, with intact bile duct epithelium ( B, arrow; ); the duct above and below the stricture was of normal size. Intraductal ultrasound then was performed with a 20-MHz endoscopic ultrasound miniprobe. The hepatic artery was found wrapped around the bile duct at the level of the stricture ( C, arrow). There was adequate biliary drainage during ERCP, and the stent was removed. The patient remained asymptomatic with normal total bilirubin and alkaline phosphatase levels 3 months after stent removal.

Solitary Liver Mass in a Patient With Hepatitis C

Nora E. Renthal, Judy Peih Ying Tsai, Dennis K. Burns — 2011-12-26

A 64-year-old man with a history of intravenous drug use and chronic hepatitis C virus (HCV) presented with shortness of breath, 1 month of severe right upper quadrant abdominal pain, and a 10-pound weight loss. He denied fever, nausea, or vomiting. He consumed alcohol rarely. Examination revealed a mildly tender liver, without jaundice, ascites, or asterixis.

Exam 1: Identification of Cholangiocarcinoma by Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection

Shyam S. Varadarajulu — 2012-03-19

Exam 2: A Predictive Model Identifies Patients Most Likely to Have Inadequate Bowel Preparation for Colonoscopy

Shyam S. Varadarajulu — 2012-03-19

Abstracts from Around the World

2012-03-19

While we appreciate that the risk of progression to carcinoma is infrequent in patients with nondysplastic Barrett's esophagus (BE), it is unclear if there are any lifestyle factors that may enhance this risk. This study identified patients from a population-based cohort of patients with BE and specialized intestinal metaplasia. Lifestyle factors were evaluated to assess their association with the risk of progression. Of the patients with BE who progressed to high-grade dysplasia or cancer, current tobacco smoking was significantly associated with this risk of progression (hazard ratio, 2.03; 95% CI, 1.29–3.17) compared with never smoking. Alcohol and body size were not found to be associated.

Predicting Outcomes After Restorative Proctocolectomy for Ulcerative Colitis

Konstantinos A. Papadakis — 2012-01-30

An estimated 1 million Americans have ulcerative colitis (UC) and Crohn's disease (CD). The majority of CD patients will require at least one surgery during the course of their disease, and 30%–40% of UC patients also will require surgery. Abdominal proctocolectomy with ileoanal pouch–anal anastomosis (IPAA) has become the surgery of choice for the majority of patients with UC. Although surgical management of UC provides satisfactory outcomes in most patients, it can be associated with a variety of surgical complications with significant morbidity. Acute and chronic pouchitis (CP), cuffitis, Crohn's disease–like phenotype (CDL) of the pouch, bowel obstruction caused by adhesions, and irritable pouch syndrome are some of the most common postsurgical complications after an IPAA. Among these complications, CDL of the pouch is the most serious one that might often be associated with a higher risk of pouch loss. Approximately 8%–10% of patients operated on for UC with an IPAA will have pouch failure, which requires removal of the pouch and conversion to a permanent ileostomy. Identifying clinical, genetic, or immunologic factors that might predict inflammatory complications after IPAA is of major clinical importance for risk stratification, patient education, and therapeutic intervention to prevent disease expression.

Safety of Cardiac Surgery in Cirrhotic Patients: Going to the Heart of the Matter

Edoardo G. Giannini — 2012-01-30

Liver cirrhosis is associated with several cardiac alterations that include both diastolic and systolic dysfunction and electrical abnormalities such as QT prolongation. Impaired myocardial contractility and electrophysiological abnormalities caused by liver disease have been termed cirrhotic cardiomyopathy. Moreover, despite being often characterized by the presence of low blood pressure and cholesterol levels, liver cirrhosis per se does not confer protection against coronary artery disease, and subjects with a history of previous intravenous drug use, as can be observed in patients with chronic viral hepatitis, might have an increased incidence of cardiac valvular diseases. Taken together, these findings clearly highlight that although cirrhotic patients have long been believed to be somehow “protected” from atherosclerosis and cardiac diseases, they are nonetheless prone to liver disease–related cardiac abnormalities and are not exempt from the occurrence of common cardiovascular diseases.

An Algorithm for Risk Assessment and Intervention of Mother to Child Transmission of Hepatitis B Virus

2011-11-10

Background & Aims: Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)–positive mothers. We analyzed methods of risk assessment and interventions for MTCT. Methods: We reviewed 63 articles and abstracts published from 1975–2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. Results: Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6–12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%–30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (106 copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. Conclusions: HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT.

Initiating Azathioprine for Crohn's Disease

Barrett G. Levesque, Edward V. Loftus — 2012-02-13

Azathioprine (AZA) and 6-mercaptopurine are therapeutic options for patients with moderate to severe inflammatory Crohn's disease. AZA has both a complex metabolism and potential for adverse events that can be clinically challenging. AZA has been shown to maintain remission and reduce corticosteroid use in patients with Crohn's disease. There is heterogeneous thiopurine methyltransferase metabolism among patients, which has implications for clinical dosing and risk for adverse events. Routine thiopurine methyltransferase testing before the initiation of AZA will reduce early leukopenia and is mandatory to avoid potentially life-threatening myelotoxicity. Thiopurine metabolite assays may aid in the assessment of adherence and adverse events. Patients who do not respond to AZA therapy may benefit from the addition of biologic therapy or methotrexate.

Identification of Cholangiocarcinoma by Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection

2011-12-19

Background & Aims: It is a challenge to collect samples from bile duct strictures to diagnose patients with cholangiocarcinoma. We investigated the utility of the Spyglass Spyscope, a single-operator endoscope that is used to perform cholangiopancreatoscopy, to identify extrahepatic cholangiocarcinoma in patients who were not diagnosed with this disorder by endoscopic retrograde cholangiopancreatography (ERCP) cytology or endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) analyses. Methods: We conducted a retrospective analysis of data from 30 patients (median age, 67 years; 67% male) with indeterminate extrahepatic biliary strictures who were ultimately diagnosed with cholangiocarcinoma but had inconclusive results from initial biliary ductal brush cytology and EUS-FNA analyses. Patients then underwent cholangioscopy by using the Spyglass Spyscope and intraductal biopsy analysis. None of the patients had a definitive mass in abdominal imaging or EUS analyses. Results: The biliary stricture was located in the common bile duct in 13 patients and in the common hepatic duct in 17 patients. The Spyglass Spyscope system had 77% accuracy (23 of 30) in the diagnosis of malignancies that were inconclusive on the basis of ERCP-guided brush or EUS-FNA analyses. Conclusions: The Spyglass Spyscope for cholangioscopy and biopsy collection identified malignancies with 77% accuracy in patients with suspected cholangiocarcinoma.

Can the Humanities Mend Medicine?

Howard Spiro — 2012-05-01

Dr Howard Spiro passed away on March 11, 2012. He was the founding chief of the Gastroenterology Section at Yale, a position he held from 1955–1982. During that time, he became widely known for his clinical acumen as well as his teaching style, abilities, and innovations. He was also a prolific writer; in addition to publishing numerous scientific manuscripts, he authored several books and was the founding editor of Journal of Clinical Gastroenterology. For these and related contributions, the American Gastroenterological Association awarded him with the Julius Friedenwald Medal in 2000. After stepping down as section chief, Dr Spiro founded the Yale Program for Humanities and Medicine, which provided a forum for examining the boundaries between medicine and the humanities and exploration of “the culture of medicine, medical care, and experiences of illness.” He remained active in this program until his passing. Therefore, it is appropriate that this, perhaps his final manuscript, bridges his two loves by discussing humanistic considerations in the doctor-patient relationship for an audience of gastroenterologists.

Erosive Reflux Disease Increases Risk for Esophageal Adenocarcinoma, Compared With Nonerosive Reflux

2012-01-16

Background & Aims: Gastroesophageal reflux disease is a strong risk factor for esophageal adenocarcinoma, but it is not clear whether the mucosal inflammation that develops in patients with reflux disease promotes this cancer. We determined the development of adenocarcinoma among patients who underwent esophagogastroduodenoscopy and were found to have erosive (with esophagitis) or nonerosive (without esophagitis) reflux. Methods: We performed a nationwide cohort study using data from 33,849 patients with reflux disease (52% men; median age, 59.3 y) from population-based Danish medical registries, from 1996 through 2008. The observed incidences of adenocarcinoma were compared with the expected incidence for the general population, standardized by age, sex, and calendar time. Absolute risks were estimated using Kaplan–Meier methods. Results: In the study cohort, 26,194 of the patients (77%) had erosive reflux disease and 37 subsequently developed esophageal adenocarcinoma after a mean follow-up time of 7.4 years. Their absolute risk after 10 years was 0.24% (95% confidence interval [CI], 0.15%–0.32%). The incidence of cancer among patients with erosive reflux disease was significantly greater than that expected for the general population (standardized incidence ratio, 2.2; 95% CI, 1.6–3.0). In contrast, of the 7655 patients with nonerosive reflux disease, only 1 was diagnosed with esophageal adenocarcinoma after 4.5 years of follow-up evaluation (standardized incidence ratio, 0.3; 95% CI, 0.01–1.5). Conclusions: Erosive reflux disease, but not nonerosive disease, increased the risk of esophageal adenocarcinoma, based on analysis of population-based Danish medical registries. Inflammation therefore might be an important factor in the progression from reflux to esophageal adenocarcinoma.

Esophageal Diameter Is Decreased in Some Patients With Eosinophilic Esophagitis and Might Increase With Topical Corticosteroid Therapy

2012-02-10

Background & Aims: The rapid response to topical corticosteroids makes it hard to implicate fibrosis as the cause of dysphagia in patients with eosinophilic esophagitis (EoE). We examined surrogates of esophageal expansion using minimal and maximal esophageal diameter (EDmin and EDmax) in barium swallow examinations. Methods: Eleven patients evaluated at Mayo Clinic, Rochester (8 female, median age 40, median diagnosis 36 months, median symptom duration 132 months) underwent barium esophagrams to determine EDmin and EDmax before and after 6 weeks of topical corticosteroid therapy. We assessed parameter reproducibility (in healthy volunteers), baseline EDmin and EDmax, postcorticosteroid changes in EoE patients, and correlation with clinical response. Results: EDmin and EDmax were reproducible, with nonsignificant variance in the 2 esophagrams in control subjects (P = .44 and P = .66, respectively). Baseline EDmax was reduced in EoE at 19 mm (range, 13–26 mm) vs 24 mm (range, 19–29 mm) in controls (P = .004). About 50% of the EoE patients had EDmax and min values within the 10th to 90th percentile of controls (45% and 55%, respectively). Clinical improvement by Mayo Dsyphagia Questionnaire did not correlate with postcorticosteroid luminal change (P = .19 for EDmax; P = .75 for EDmin). Median increases in postcorticosteroid EDmax and EDmin were not statistically significant (P = .15 and .1, respectively). However, they were significant in patients with abnormal baseline EDmax (n = 6; 2 mm; P = .01) and EDmin (n = 5; 3 mm; P = .02). Conclusions: Esophageal diameter is a reproducible parameter that is frequently decreased in EoE, but normal in approximately 50% of patients. Those with narrowing might respond to steroids, but it is unclear if narrowing causes dysphagia.

Helicobacter pylori Infection Is Strongly Associated With Gastric and Duodenal Ulcers in a Large Prospective Study

Ben Schöttker, Mariam A. Adamu, Melanie N. Weck, Hermann Brenner — 2012-01-10

Background & aims: Infection with Helicobacter pylori (H pylori) is a risk factor for peptic ulcer disease (PUD), but there are limited longitudinal data on the associations between infection and incident gastric or duodenal ulcers. Methods: Information on potential risk factors, lifetime history of PUD, and serologic measurements of H pylori infection were obtained from a German cohort of 9953 adults, 50 to 74 years old at baseline (2000–2002). The incidence of ulcers was determined by questionnaires sent to study participants and general practitioners 2 and 5 years later, and was validated by medical records. Results: A lifetime history of PUD was reported by 1030 participants, and during the follow-up period 48 had a first gastric and 22 had a first duodenal ulcer. Infection with H pylori strains that express cytotoxin-associated gene A (cagA) was significantly associated with a lifetime history of PUD (odds ratio, 1.75; 95% confidence interval [CI], 1.50–2.04). Based on longitudinal analyses with physician-validated end points, the adjusted hazard ratios for incident gastric and duodenal ulcer disease were 2.9 (95% CI, 1.5–5.5) and 18.4 (95% CI, 4.2–79.9), respectively, among patients infected with cagA-positive strains of H pylori. Conclusions: In cross-sectional analysis, infection with cagA-positive strains of H pylori was associated with a 1.75-fold increased risk of peptic ulcer disease. Longitudinal analyses revealed an 18.4- and 2.9-fold increased risk for duodenal ulcer and gastric ulcer, respectively. The proportion of PUD that is attributable to H pylori infection might be larger than previously believed.

Factors Associated With Persistent and Nonpersistent Chronic Constipation, Over 20 Years

2012-01-30

Background & Aims: The prevalence of chronic constipation (CC) has been reported to be as high as 20% in the general population, but little is known about its natural history. We estimated the natural history of CC and characterized features of persistent CC and nonpersistent CC, compared with individuals without constipation. Methods: In a prospective cohort study, we analyzed data collected from multiple, validated surveys (minimum of 2) of 2853 randomly selected subjects, over a 20-year period (median, 11.6 years). Based on responses, subjects were characterized as having persistent CC, nonpersistent CC, or no constipation. We assessed the association between constipation status and potential risk factors using logistic regression models, adjusting for age and sex. Results: Of the respondents, 84 had persistent CC (3%), 605 had nonpersistent CC (21%), and 2164 had no symptoms of constipation (76%). High scores from the somatic symptom checklist (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.3–3.4) and frequent doctor visits (OR = 2.0; 95% CI, 1.0–3.8) were significantly associated with persistent CC, compared with subjects with no constipation symptoms. The only factor that differed was increased use of laxatives or fiber among subjects with persistent CC (OR = 3.0; 95% CI, 1.9–4.9). Conclusions: The prevalence of constipation might be exaggerated—the proportion of the population with persistent CC is low (3%). Patients with persistent and nonpersistent CC have similar clinical characteristics, although individuals with persistent CC use more laxatives or fiber. CC therefore appears and disappears among certain patients, but we do not have enough information to identify these individuals in advance.

A Predictive Model Identifies Patients Most Likely to Have Inadequate Bowel Preparation for Colonoscopy

2012-01-11

Background & Aims: An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. Methods: We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. Results: Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. Conclusions: We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.

Antimicrobial Antibodies Are Associated With a Crohn's Disease–Like Phenotype After Ileal Pouch–Anal Anastomosis

2011-10-03

Background & Aims: Pouchitis and Crohn's disease (CD)-like (CDL) complications of the pouch occur at rates near 50% and 20%, respectively, after colectomy with ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). We investigated whether antimicrobial antibodies are associated with pouch outcome after IPAA. Methods: We studied clinical and endoscopic data from 399 individuals with UC who underwent colectomy with IPAA at Mount Sinai Hospital in Toronto, Canada; patients were classified as no pouchitis (NP), chronic pouchitis (CP), or CDL. Serum samples were analyzed from 341 patients for antibodies against Saccharomyces cerevisiae (ASCA), OmpC, CBir1, and perinuclear antineutrophil cytoplasmic antibody (pANCA). Results: Of the subjects, 70.7% had NP, 16.8% developed CP, and 12.5% developed CDL. Smoking was associated with CDL (P = .003). Ashkenazi Jewish individuals more commonly had CP (P = .008). Of patients with CDL, 53.5% and 14.0% had positive test results for anti-CBir1 and ASCA (immunoglobulin G), respectively, compared with 21.4% and 3.8% of those with NP and 28.3% and 5.0% of those with CP (P < .0001 and P = .03). Anti-CBir1 was associated with CDL, compared with NP (P = 2.8 × 10–5; odds ratio [OR], 4.2; 95% confidence interval [CI], 2.2–8.3) or CP (P = .011; OR, 2.9; 95% CI, 1.3–6.6). ASCA immunoglobulin G was associated with CDL, compared with patients with NP (P = .01; OR, 4.1; 95% CI, 1.4–12.3). In a combined model, pANCA and the antimicrobial antibodies were associated with CP (P = .029) and CDL (P = 4.7 × 10–4). Conclusions: Antimicrobial antibodies and pANCA are associated with inflammatory complications of the pouch. The CDL phenotype is associated with factors that characterize Crohn's disease, including smoking, anti-CBir1, and ASCA.

Efficacy of Topical 5-Aminosalicylates in Preventing Relapse of Quiescent Ulcerative Colitis: A Meta-analysis

2011-11-14

Background & Aims: Topical 5-aminosalicylates (5-ASAs) such as mesalamine are effective in inducing remission in patients with mild to moderately active ulcerative colitis (UC). However, there has been no meta-analysis of their efficacy in preventing relapse of quiescent UC. Methods: We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials through July 2011 for randomized controlled trials comparing the effects of topical 5-ASAs with placebo in adults with quiescent UC. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity. The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Adverse events data were summarized. Results: The search identified 3061 citations; we analyzed data from seven (555 patients). All trials used mesalamine, but only one included patients with extensive disease. The duration of therapy ranged from 6–24 months. The RR of relapse of disease activity in patients with quiescent UC who were given topical mesalamine, compared with placebo, was 0.60 (95% confidence interval, 0.49–0.73; NNT = 3); there was no significant heterogeneity between studies (I2 = 21%, P = .27). No significant differences in rates of adverse events rates were detected (RR = 1.01; 95% confidence interval, 0.59–1.72). Conclusions: On the basis of a meta-analysis of 7 randomized controlled trials, topical mesalamine is effective in preventing relapse of quiescent UC, with no greater number of adverse events than placebo. However, because most studies included only patients with left-sided disease or proctitis, the efficacy of topical mesalamine in preventing relapse in patients with more extensive quiescent UC is not known.

Telbivudine Prevents Vertical Transmission From HBeAg-Positive Women With Chronic Hepatitis B

2012-02-16

Background & Aims: Telbivudine reduces hepatitis B virus (HBV) DNA and normalizes levels of alanine aminotransferase (ALT) in patients with chronic hepatitis B (CHB). We investigated its use in preventing vertical transmission. Methods: We performed an open-label, prospective study of 88 hepatitis B (HB) e antigen (HBeAg)-positive pregnant women with CHB, levels of HBV DNA >6 log10 copies/mL, and increased levels of ALT. Women were given telbivudine (n = 53) starting in the 2nd or 3rd trimester, or no treatment (controls, n = 35) and followed until postpartum week (PPW) 28. All infants received standard immunoprophylaxis after birth. Results: At 28 weeks, none of the infants whose mothers received telbivudine had immunoprophylaxis failure, whereas 8.6% of the infants of control mothers did (P = .029). There were no differences between groups in mothers' adverse events or infants' congenital deformities, gestational age, height, and weight, or Apgar scores. At postpartum week 28, significantly more telbivudine-treated mothers had levels of HBV DNA <500 copies/mL, normalized levels of ALT, and hepatitis B e antigen seroconversion compared with controls (58% vs none, P < .001; 92% vs 71%; P = .008; and 15% vs none; P < .001, respectively) but none had loss of hepatitis B surface antigen. Telbivudine-treated mothers had no virologic breakthrough (HBV DNA >1 log10 increase from <500 copies/mL) or discontinuations from adverse events. After delivery, 13/52 patients discontinued telbivudine due to preference. There were no episodes of severe hepatitis (levels of ALT >10 times the upper limit of normal) in either group during 28 weeks of postpartum observation. Conclusions: Women with CHB given telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission. Telbivudine produced no adverse events in mothers or infants by 28 weeks.

Incidence and Determinants of Spontaneous Seroclearance of Hepatitis B e Antigen and DNA in Patients With Chronic Hepatitis B

2011-12-19

Background & Aims: The spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA are important markers of progression of chronic HBV infection. We performed a long-term cohort study to elucidate the incidence and determinants of HBeAg and HBV DNA seroclearance in patients with chronic hepatitis B. Methods: A total of 1289 participants with a serum HBV DNA level of 10,000 copies/mL or more and without cirrhosis when the study began (1991–1992) were followed up until June 2004. A subset of patients that tested positive for HBeAg at baseline (n = 439) was included in the analysis of HBeAg seroclearance. Cox proportional hazards models were used to estimate seroclearance rate ratios for various determinants associated with the outcomes. Results: After 3161.2 person-years of follow-up evaluation, HBeAg seroclearance occurred in 187 participants (incidence rate, 5.9 per 100 person-years). The cumulative lifetime incidence of HBeAg seroclearance among patients who were 30 to 40, or 50, 60, 70, or 74 years old was 38.8%, 69.4%, 81.9%, 89.1%, and 95.5%, respectively. Major predictors of HBeAg seroclearance included female sex, genotype B, the precore 1896 mutant, increased serum levels of alanine aminotransferase, and low baseline serum levels of HBV DNA. The median (interquartile range) serum level of HBV DNA at the time of HBeAg seroclearance was 177,801 copies/mL (4941–3,247,560 copies/mL). HBV DNA seroclearance occurred in 199 participants (15.4%) during the mean follow-up period of 7.8 years (incidence rate, 1.97 per 100 person-years). The cumulative lifetime incidence of HBV DNA seroclearance at 40, 50, 60, 70, and 77 years old was 10.0%, 25.0%, 38.8%, 54.2%, and 82.8%, respectively. Lower levels of HBV DNA at study entry and among those with the precore 1896 wild-type variant were associated with an increased rate of HBV DNA seroclearance. Among individuals who were HBeAg-seropositive at study entry and cleared serum HBV DNA during the follow-up period, 89% had cleared HBeAg by the time they had an undetectable serum level of HBV DNA. Conclusions: Serum level of HBV DNA is the most important predictor of seroclearance of HBeAg and HBV DNA. This finding supports current clinical guidelines for antiviral treatments of chronic hepatitis B.

Safety of Cardiac Surgery for Patients With Cirrhosis and Child–Pugh Scores Less Than 8

2011-12-29

Background & Aims: Advanced liver disease is a significant risk factor for perioperative complications after cardiac surgery. However, no published studies have adjusted the observed outcomes for other well-known, non–liver–related factors that affect mortality. We evaluated the effects of cirrhosis on operative mortality and morbidity after cardiac surgery, after adjusting for nonrelated risk factors associated with liver disease. Methods: We analyzed data from patients with cirrhosis who underwent cardiac surgery with cardiopulmonary bypass from 1992 to 2009 (n = 54). Patients who underwent cardiac surgery at the same institution were identified during the same time period and matched 1:4 by using propensity score matching (controls, n = 216). Child–Pugh (CP) class and score were calculated for the patients with cirrhosis. Mortality and morbidity were determined after 30 and 90 days. Results: Within 90 days, 4.6% of patients with CP score <8 and 70% of patients with CP score ≥8 died (P < .017). Mortality of patients with CP score <8 was comparable to that of matched controls. Patients with CP scores <8 had significantly shorter average length of hospital stay (15.6 vs 26 days; P < .017) and were less likely to develop renal failure (P < .017) and require dialysis (P < .017) than patients with CP scores ≥8; these values were similar between patients with CP scores <8 and their matched controls. Conclusions: After adjusting for non–liver-related risk factors, patients with compensated cirrhosis (defined by CP score <8) can undergo cardiac surgery with cardiopulmonary bypass with no significant increases in postoperative mortality and morbidity. For this group of patients, comorbidities, rather than liver failure, appear to account for the occasional death.

Progressive Primary Sclerosing Cholangitis Requiring Liver Transplantation Is Associated With Reduced Need for Colectomy in Patients With Ulcerative Colitis

2012-01-16

Background & aims: We investigated the association between the severity of primary sclerosing cholangitis (PSC) and clinical outcomes of patients with ulcerative colitis (UC) on the basis of need for colectomy. Methods: We analyzed data from 167 patients with PSC and UC who were followed from 1985 to 2011. Patients with PSC and UC were divided into groups that received orthotopic liver transplantation (OLT) (n = 86) or did not (non-OLT, n = 81). Clinical and demographic variables were obtained, and patients were followed until they received OLT or the date of their last clinical visit. Results: The OLT group had significantly more subjects with less severe symptoms of UC (59, 68.6%) than the non-OLT group (12, 14.8%; P < .001). The subjects in the OLT group had a median of 0 UC flares compared with 3 in the non-OLT group (P < .001); fewer subjects in the OLT group required use of azathioprine or mercaptopurine (1, 1.2%), compared with the non-OLT group (14, 17.3%; P = .006). More subjects in the non-OLT group required colectomies (61, 75.3%) than in the OLT group (23, 26.7%; P < .001). On the basis of Cox regression analysis, OLT for PSC independently reduces the need for colectomy (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.25–0.75; P = .003), as does a high Mayo risk score at diagnosis (HR, 0.52; 95% CI, 0.37–0.72; P < .001). Development of colon neoplasia increased the risk for colectomy (HR, 2.47; 95% CI, 1.63–3.75; P < .001). Conclusions: Severe progressive PSC that requires liver transplantation appears to reduce the disease activity of UC and the need for colectomy.

Medical Care Costs and Survival Associated With Hepatocellular Carcinoma Among the Elderly

2011-12-30

Background & Aims: We assessed the burden of hepatocellular carcinoma (HCC), in terms of mortality and medical care costs, based on analysis of the Surveillance, Epidemiology and End Results (SEER)–Medicare database. Methods: We analyzed data from the SEER-Medicare database on patients 66 years or older who were diagnosed with primary HCC from 1991 to 2007, entitled for Medicare Parts A and B, and not enrolled in health maintenance organizations (n = 5712). Controls were individuals without HCC, identified from a 5% sample of Medicare beneficiaries residing in SEER areas; they were matched 1:1 with individuals with HCC (cases) for age, sex, race, and geographic region (average age, 75 y; 34.7% female). Kaplan–Meier analysis was used to estimate survival distributions. Costs were reported in 2009 dollars; per-patient-per-month (PPPM) costs were compared between cases and controls using the Wilcoxon rank sum test. Results: The largest proportion of cases had localized disease (38.2%), followed by regional (24.0%), unstaged (20.4%), and distant (17.3%) disease. The median survival times were 5 months for cases and 60 months for controls; they were 3 months for patients with distant disease, 4 months for patients with regional disease, and 9 months for those with localized disease. The mean PPPM costs were $7863 for cases and $1243 for controls (P < .001). These costs were primarily driven by inpatient (mean, $5439 vs $682 without HCC; P < .001) and hospice (mean $554 vs $42 without HCC; P < .001) care. Mean PPPM costs by stage were $7265 for localized disease, $8072 for regional disease, and $9585 for distant disease (P < .001 for trend). Conclusions: Based on analysis of the SEER-Medicare database, costs for patients with HCC are approximately 6- to 8-fold higher than for those without this cancer. Patients with distant HCC had the greatest costs. These findings highlight that HCC is a substantial medical cost burden for elderly patients.

The Clinical Relevance of the Increasing Incidence of Intraductal Papillary Mucinous Neoplasm

David A. Klibansky, Kaye M. Reid–Lombardo, Stuart R. Gordon, Timothy B. Gardner — 2011-12-29

Background & Aims: The incidence of intraductal papillary mucinous neoplasm (IPMN) is believed to be increasing; we investigated whether this is the result of increasing burden of disease or more diagnostic scrutiny. Methods: In a retrospective cohort study, we calculated a trend in reported incidence of IPMN using data collected from Olmsted County, Minnesota, from 1985 to 2005. Total IPMN cases from the Olmsted database were identified through a keyword and International Classification of Diseases, 9th revision, search using a database from the Rochester Epidemiology Project, with all cases verified by subsequent chart review. The subsequent rate of IPMN-related carcinoma was calculated using data from the national Surveillance Epidemiology and End Results-9 database, reflecting trends from 1982 to 2007. Cases of IPMN-related carcinoma were identified in the Surveillance Epidemiology and End Results-9 database by limiting the search to histology codes for noninvasive and invasive IPMN. Results: Between 1985 and 2005, there was a 14-fold increase in the age- and sex-adjusted incidence of IPMN, from 0.31 to 4.35 per 100,000 persons. From 2000 to 2001, the rate of reported carcinoma increased from 0.008 to 0.032 per 100,000 persons, but stabilized afterward, with a rate of 0.06 per 100,000 persons in 2007. Mortality from all causes of pancreatic cancer was stable between 1975 and 2007 (approximately 11 deaths per 100,000 individuals). Conclusions: The incidence of IPMN has increased in the absence of an increase in IPMN-related or overall pancreatic cancer–related mortality, so it likely results from an increase in diagnostic scrutiny, rather than greater numbers of patients with clinically relevant disease.

Characteristics of Ascites in Patients With Pregnancy-Specific Liver Diseases

2011-12-16

Background & Aims: The characteristics of ascites in patients with pregnancy-specific liver disease (PsLD), which comprise acute fatty liver of pregnancy, hemolysis, increased levels of liver enzymes, low platelet syndrome, and preeclampsia-associated liver dysfunction, are unknown. We evaluated the cellular and biochemical characteristics, and model for end-stage liver disease scores, in patients with PsLD. Methods: We evaluated 46 consecutive patients with PsLD for the presence of ascites. We assessed cellular and biochemical characteristics of the ascites fluid from these patients. Results: Ascites was observed in 35 of 46 patients with PsLD (76%). In 25 patients tested (71.4%), the ascites fluid had low levels of albumin (<0.2 g/dL) and protein (<1 g/dL) and high serum ascites albumin gradients, indicating portal hypertension. Spontaneous bacterial peritonitis was observed in 48% of patients tested and was not associated with mortality. Patients with ascites had significantly low serum levels of protein and albumin (P < .001). Model for end-stage liver disease scores did not differ between patients with or without ascites (32 vs 27; P = .1). Conclusions: Ascites occur in 76% of women with PsLD, is transient, and has characteristics of portal hypertension, based on high serum ascites albumin gradients. Almost half of patients with PsLD develop spontaneous bacterial peritonitis, which does not affect survival.

Immunoglobulin E Level and Its Significance in Patients With Primary Sclerosing Cholangitis

Udayakumar Navaneethan, Preethi G.K. Venkatesh, Ravi P. Kiran — 2012-01-30

We read with great interest the article by Hirano et al. The authors analyzed data from 44 patients with primary sclerosing cholangitis (PSC) with serum levels of immunoglobulin (Ig)E and found that high serum levels of IgE were observed in older patients with PSC and were associated with a reduced incidence of biliary carcinoma. This study has increased our knowledge about the role of IgE in PSC. However, the role of IgE has not been investigated outside of Japan, and the role of increased IgE is controversial in the Western population. This prompted us to explore our PSC cohort of 273 patients seen and followed up at our institution from 1985 to 2011. We analyzed data from 19 patients (14 men; median age, 51 y) with PSC and IgE measured before colectomy and orthotopic liver transplantation. Increased IgE levels (>170 IU/L) were found in 8 PSC patients (42.1%), of whom 6 had inflammatory bowel disease (IBD). The age at onset of PSC for the high IgE group did not differ from the normal IgE group (26.4 ± 19.8 vs 31.6 ± 16.5 y; P = .56); in addition, the association with IBD did not differ significantly between groups (6 of 8 vs 10 of 11; P = .55). The median initial Mayo PSC risk score in the high IgE group (1.21) was similar to the normal IgE (−0.19) group (P = .22). These patients were followed up for a median of 8 years (range, 1–12 y). One patient in the increased IgE group had cholangiocarcinoma compared with none in the normal IgE group (P = .42); colon neoplasia development also did not differ between the high IgE and normal IgE groups (3 of 8 vs 4 of 11; P = 1), respectively. None of the patients had bronchial asthma or parasitic infection.

Reply

Kenji Hirano, Suguru Mizuno, Kazuhiko Koike — 2012-02-13

We thank Nevaneethan et al for their interest in our study and giving us an opportunity to clarify some specific issues regarding ethnic differences in primary sclerosing cholangitis (PSC).

Gastric Acid Suppression and Clostridium difficile Infection: Is There a Causal Connection?

Sahil Khanna, Darrell S. Pardi — 2012-01-30

We read the article by Deshpande et al with great interest. The authors performed a meta-analysis to evaluate the association between proton pump inhibitor (PPI) therapy and the risk of Clostridium difficile infection (CDI) and found a 2-fold increase in the risk of CDI in patients using PPIs. However, 2 additional important studies that have not shown an association between PPI and CDI incidence were omitted. In a prospective cohort study of 252 patients, PPI or histamine-2 (H2) blocker use was not associated with the risk of CDI (odds ratio, 2.2; 95% confidence interval [CI], 0.96–5.0). In another cohort study, evaluating 7421 episodes of inpatient care on univariate analysis PPIs (hazard ratio [HR], 1.67; 95% CI, 1.32–2.1) and H2 blockers (HR, 1.53; 95% CI, 1.17–2.01) were associated with the risk of CDI. However, after adjusting for important confounders including age, length of stay, comorbidities, prior history of CDI, and antibiotic exposure, the relationship between CDI and the use of PPIs (adjusted HR, 1.00; 95% CI, 0.79–1.28) and H2 blockers (adjusted HR, 1.07; 95% CI, 0.80–1.43) was no longer seen. Inclusion of the 2 omitted studies in this meta-analysis performed to evaluate the risk of CDI from PPI would have impacted the results and decreased the reported odds ratio. More importantly, studies assessing the association between PPI and CDI incidence should control for important confounders before concluding that there is an association.

Reply

2012-02-13

We recognize the concerns raised by Drs Khanna and Pardi in their letter. Regarding the omission of studies from our meta-analysis, the 2 specific papers discussed in their letter are indeed important in the field and contribute to our understanding of the risk factors involved in the development of Clostridium difficile infections (CDIs). Each of these studies was considered for our analysis of the association between proton pump inhibitor (PPI) therapy and CDI. However, neither met the inclusion criteria, as stated in the methods section of the manuscript. The study by Kyne and colleagues was excluded because the authors did not differentiate between the use of PPI and H2-receptor antagonists (exclusion criteria 2 in our manuscript). Patients receiving acid-suppressive therapy were reported as a single group consisting of those receiving either or both classes of drugs. Thus, the subgroups of patients who received PPI therapy exclusively or in combination with an H2-receptor antagonist could not be determined from the presented data. In the work by Pepin and colleagues, the data are presented and analyzed based upon episodes of CDI and not on a per-patient basis. Thus, this study was excluded due to the inability to determine the number of actual patients with CDI (exclusion criteria 3 in our manuscript).

Cover

2012-05-01

Diffuse Hepatic Calcification Following Ischemic Insult in the Setting of Impaired Renal Function

Ali Raza, Kashif Ahmed, Richard P. Rood — 2011-11-02

A 25-year-old man who had undergone liver transplantation 21 years earlier for fulminant hepatitis was admitted to the hospital for elective kidney transplantation for renal failure secondary to calcineurin inhibitor (tacrolimus) toxicity. Postoperatively, the patient became profoundly hypotensive from massive intra-abdominal hemorrhage, leading to acute tubular necrosis and failure of the transplanted kidney. Physical examination at that point showed mild jaundice and well healed incision from the surgery. Laboratory findings included: calcium 8.1 mg/dL, phosphate 8.5 mg/dL, aspartate transaminase 11,212 U/L, alanine aminotransferase 4884 U/L, total bilirubin 5.9 mg/dL, direct bilirubin 4.8 mg/dL, and international normalized ratio 1.6. An abdominal computed tomography scan demonstrated focal areas of low attenuation in the liver ( A, white arrow) consistent with ischemic injury. After resuscitation, the patient's liver enzymes improved. A repeat computed tomography scan performed 3 weeks later revealed diffuse calcifications throughout the liver, most prominently in the areas of ischemic injury, as well as in muscle tissue ( B, white arrows). Liver biopsy showed marked hepatocytic and canalicular cholestasis without any calcium deposits in the endothelium ( C). After supportive therapy, the patient's clinical condition stabilized, and he was discharged to a rehabilitation center.

Liver Invasion of the Duodenum Due to Hepatocellular Carcinoma

Bryan G. Sauer, Simone M. Dustin, Stephen H. Caldwell — 2012-01-10

A 68-year-old man with hepatocellular carcinoma (HCC) presented with upper-gastrointestinal bleeding for the fifth time in 7 months and new-onset severe nausea and vomiting. Over the past year, the patient had undergone transarterial chemoembolization as well as radiotherapy with concurrent capecitabine (Xeloda; Genetech, San Francisco, CA) for treatment of HCC. Prior upper endoscopies showed a pyloric channel ulceration with numerous interventional attempts to control bleeding, including epinephrine injection and endoscopic clipping, and angiographic coiling of branches of the gastroduodenal artery, left gastric artery, and left hepatic artery. A biopsy obtained 5 months before the presentation revealed fibrinopurulent debris in addition to large atypical cells with relatively abundant eosinophilic cytoplasm that reacted with the hepatocyte paraffin 1 (Hep Par 1) antibody (a monoclonal antibody to hepatocyte mitochondria) ( A, 40×). On upper endoscopy, a large mass was seen penetrating the pyloric channel wall and occupying more than 90% of the lumen, causing gastric outlet obstruction. After clearing the debris, the mass appeared to be relatively normal-appearing liver and upon probing was firm ( B). A computed tomography scan after endoscopy showed a large, rapidly expanding hepatocellular carcinoma (arrowheads) and a pointed hepatic wedge in the location of the pyloric channel (arrow) ( C). The patient was transitioned to palliative care and died approximately 1 month later. Direct invasion of HCC into the gastrointestinal lumen typically shows a fungating mass consistent with malignancy. This case shows normal-appearing liver that was pushed through the duodenal wall by an enlarging HCC.

Kayexalate-Induced Esophageal Ulcer in a Patient With Gastroparesis

Emmanuel C. Gorospe, Jason T. Lewis, David H. Bruining — 2011-12-26

A 53-year-old man presented with an episode of coffee-ground emesis. He had undergone bilateral lung transplantation for idiopathic pulmonary fibrosis 1 month before admission. On presentation, his vital signs were stable (heart rate, 95/min; blood pressure, 106/80 mm Hg), with a hemoglobin of 11.4 g/dL. He was on tacrolimus immunosuppression, with trough levels within the therapeutic range (10–12 ng/mL). His serum potassium level had been elevated (range, 5.5–5.9 mmol/L) for 1 week before admission, for which he was being treated with sodium polystyrene sulfonate in sorbitol (Kayexalate 30 g/d orally). Other pertinent laboratory studies included white blood cell count 3700/μL, creatinine 1.1 mg/dL, blood urea nitrogen 28 mg/dL, and sodium 135 mmol/L.

Isolated Jejunal Varices: A Cause of Occult Gastrointestinal Hemorrhage in a Cirrhotic Patient With Mild Portal Hypertension

Noam Shussman, Gadi Lalazar, Allan I. Bloom — 2012-01-30

A 60-year-old woman with hepatitis C cirrhosis and a history of lymphoma was admitted to our medical center because of recurrent melena. Although hemodynamically stable, she required frequent blood transfusions. Upper and lower endoscopies failed to reveal the source of hemorrhage. Capsule endoscopy showed an isolated bleeding jejunal varix ( A). Abdominal/pelvic computed tomography venography showed a cluster of isolated jejunal varices ( B, arrowhead) draining via a patent umbilical vein ( B, arrow) and right inferior epigastric vein to the external iliac vein. Superselective venography of the mesenteric varix was performed ( C) during a transjugular intrahepatic portosystemic shunt procedure, confirming the computed tomography venography findings.

Editorial Board

2012-05-01

Information for Authors and Readers

2012-05-01

Clinical Gastroenterology and Hepatology is the go-to resource on a broad spectrum of themes in clinical gastroenterology and hepatology. The official clinical practice journal of the AGA Institute brings you the best original research in the field with a unique combination of reviews, editorials, podcasts, video abstracts, and outcomes research-all supporting clinical practice. Articles on education, policy, and practice management highlight issues pertinent to clinicians.

Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/Animal Care Committee Approval, and Sponsorship

2012-05-01

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Clinical Gastroenterology and Hepatology

Hepatic Artery Compression of the Common Hepatic Duct: Direct Visualization by Single-Operator Peroral Cholangioscopy

Solitary Liver Mass in a Patient With Hepatitis C

Exam 1: Identification of Cholangiocarcinoma by Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection

Exam 2: A Predictive Model Identifies Patients Most Likely to Have Inadequate Bowel Preparation for Colonoscopy

Abstracts from Around the World

Predicting Outcomes After Restorative Proctocolectomy for Ulcerative Colitis

Safety of Cardiac Surgery in Cirrhotic Patients: Going to the Heart of the Matter

An Algorithm for Risk Assessment and Intervention of Mother to Child Transmission of Hepatitis B Virus

Initiating Azathioprine for Crohn's Disease

Identification of Cholangiocarcinoma by Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection

Can the Humanities Mend Medicine?

Erosive Reflux Disease Increases Risk for Esophageal Adenocarcinoma, Compared With Nonerosive Reflux

Esophageal Diameter Is Decreased in Some Patients With Eosinophilic Esophagitis and Might Increase With Topical Corticosteroid Therapy

Helicobacter pylori Infection Is Strongly Associated With Gastric and Duodenal Ulcers in a Large Prospective Study

Factors Associated With Persistent and Nonpersistent Chronic Constipation, Over 20 Years

A Predictive Model Identifies Patients Most Likely to Have Inadequate Bowel Preparation for Colonoscopy

Antimicrobial Antibodies Are Associated With a Crohn's Disease–Like Phenotype After Ileal Pouch–Anal Anastomosis

Efficacy of Topical 5-Aminosalicylates in Preventing Relapse of Quiescent Ulcerative Colitis: A Meta-analysis

Telbivudine Prevents Vertical Transmission From HBeAg-Positive Women With Chronic Hepatitis B

Incidence and Determinants of Spontaneous Seroclearance of Hepatitis B e Antigen and DNA in Patients With Chronic Hepatitis B

Safety of Cardiac Surgery for Patients With Cirrhosis and Child–Pugh Scores Less Than 8

Progressive Primary Sclerosing Cholangitis Requiring Liver Transplantation Is Associated With Reduced Need for Colectomy in Patients With Ulcerative Colitis

Medical Care Costs and Survival Associated With Hepatocellular Carcinoma Among the Elderly

The Clinical Relevance of the Increasing Incidence of Intraductal Papillary Mucinous Neoplasm

Characteristics of Ascites in Patients With Pregnancy-Specific Liver Diseases

Immunoglobulin E Level and Its Significance in Patients With Primary Sclerosing Cholangitis

Reply

Gastric Acid Suppression and Clostridium difficile Infection: Is There a Causal Connection?

Reply

Cover

Diffuse Hepatic Calcification Following Ischemic Insult in the Setting of Impaired Renal Function

Liver Invasion of the Duodenum Due to Hepatocellular Carcinoma

Kayexalate-Induced Esophageal Ulcer in a Patient With Gastroparesis

Isolated Jejunal Varices: A Cause of Occult Gastrointestinal Hemorrhage in a Cirrhotic Patient With Mild Portal Hypertension

Editorial Board

Contents

Information for Authors and Readers

Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/Animal Care Committee Approval, and Sponsorship