Background & Aims
Most studies of angiodysplasia are small and performed at a single center. We investigated the epidemiology and management of colonic angiodysplasia using a national endoscopy database.
Colonoscopy reports (n=229,727; generated from January 2000 to December 2002) from patients with documented angiodysplasia (n=4159) were retrieved from the Clinical Outcomes Research Initiative. Predictors of occult or overt blood loss and endoscopic treatment were identified using multivariate logistic regression.
Most patients with documented angiodysplasia were more than 60 years old (73%) or had right-sided lesions (62%). There was evidence of blood loss in 56% of patients with angiodysplasia. Predictors of blood loss included inpatient status (odds ratio [OR]: 8.74; 95% confidence interval [CI]: 5.42–14.10], 2–10 angiodysplasias (OR: 1.50, 95% CI: 1.29–1.75), more than 10 lesions (OR: 2.18, 95% CI: 1.69–2.80), black race (OR:1.95, 95% CI: 1.46–2.62, severe illness (OR: 1.97, 95% CI: 1.62–2.41), Hispanic ethnicity (OR: 1.71, 95% CI: 1.32–2.22), and age greater than 80 years (OR: 1.32, 95% CI: 1.06–1.63). Endoscopic therapy was given to 28% of patients with evidence of blood loss and in 68% with active bleeding. Endoscopic treatment increased among patients in a university practice setting (vs. community setting, OR: 2.53, 95% CI: 1.96–3.27) and decreased in Northwest geographic locations (vs. Southwest, OR: 0.60, 95% CI: 0.4–0.84].
Predictors of blood loss in patients with colonic angiodysplasia include inpatient status, comorbities, age, race/ethnicity, and lesion number. Endoscopic therapy for angiodysplasia varied according to practice setting and region.
CORI; lower gastrointestinal bleeding; practice patterns
Non-alcoholic fatty liver disease (NAFLD) has been implicated as a possible cause of hepatocellular carcinoma (HCC) in several general review articles. We performed the first systematic review of the epidemiologic literature.
We searched PubMed for original reports published between 1/1992–12/2011 evaluating the association between NAFLD, non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) presumptively NASH-related and the risk of HCC. Studies were categorized as offering potential direct evidence (e.g., cohort studies) or indirect evidence (e.g., case-control or cross-sectional studies or case-series) of an association.
A total of 17 cohort studies [3 population-based, 9 clinic-based (6 limited to cirrhotics), and 5 natural history], 18 case-control and cross-sectional studies, and 26 case-series were study-eligible. NAFLD or NASH cohorts with few or no cirrhosis cases demonstrated a minimal HCC risk (cumulative HCC mortality between 0%–3% for study periods up to two decades). Consistently increased risk was observed in NASH-cirrhosis cohorts (cumulative incidence between 2.4% over 7-years to 12.8% over 3-years). However, HCC risk was substantially lower in NASH-cirrhosis (NASH-C) cohorts than in HCV-related cirrhosis cohorts. The determinants of elevated risk among NASH-C cohorts were unclear as most studies were underpowered to perform multivariate analysis.
This systematic review shows that despite several limitations, the epidemiologic evidence supports an association between NAFLD or NASH and an increased HCC risk that seems to be predominantly limited to individuals with cirrhosis.
epidemiology; hepatology; gastroenterology; endocrinology; obesity; metabolic syndrome
Background & Aims
Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD); it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies.
We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine.
The time to remission was a median 6.9 months for patients that received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 months for randomized patients), a difference that was not significant (Log Rank P=.06 and P=.95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 0.95–5.06) for all patients. Patients that received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment.
Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response.
4-aminoquinolines; clinical trial; drug; liver disease
Background & Aims
Colonoscopy is consistently associated with reduced left-sided, but not right-sided, colorectal cancer (CRC) incidence and mortality. This might be because polyps with advanced pathology are smaller and more easily missed in the right vs left colon. We explored this postulate by evaluating the relationship among size, location, and histology of polyps from a large nationwide sample.
We conducted a cross-sectional study of 233,414 polyps from 142,686 patients (47% women; mean age, 60 years), which were reviewed by Miraca Life Sciences in 2009. We assessed polyp histology, location, and size of largest fragment submitted. We compared size distribution of right vs left polyps with high-grade dysplasia (HGD) or adenocarcinoma as well as any advanced neoplasia.
The average size of right-sided polyps was smaller than that of left-sided polyps with HGD or adenocarcinoma (8.2 vs 12.4 mm, respectively); the same was true for polyps with advanced neoplasia (7.6 vs 11.1 mm, respectively) (P < .001). Most right-sided polyps with HGD, adenocarcinoma, or any advanced neoplasia were ≤9 mm, whereas most left-sided polyps with these findings were >9 mm. Polyps with advanced pathology were 5-fold more likely to be <6 mm in the right vs left colon: odds ratio, 5.27; 95% confidence interval, 4.06–6.82 for HGD or adenocarcinoma; odds ratio, 4.89; 95% confidence interval, 4.34–5.51 for advanced neoplasia.
Polyps with features of HGD, adenocarcinoma, or advanced neoplasia were significantly smaller in the right vs left colon. Strategies to prevent right-sided CRC require more accurate detection of small, advanced polyps.
Colorectal Neoplasms; Epidemiology; Colon Cancer Screening; Early Detection
Background & Aims
We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the US. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.
We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study endpoints were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of α-fetal protein approximately every 6 months, for a median time of 34 months (range, 6–99 months).
The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% non-viral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with non-viral diseases in Kaplan-Meier analysis (P=.04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was significantly associated with HCC, compared to non-viral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3–10.1; P=.02) but Asian ethnicity was not.
In a diverse cohort of patients in the US with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.
epidemiology; liver cancer risk factor; HCV; HBV
One of the major frontiers in biomedical optics has been as an adjunct to gastrointestinal endoscopy. In particular, spectroscopy of elastic light scattering has the potential of addressing many of the vexing challenges confronting endoscopists. This review discusses the principles of spectroscopy and critically evaluates performance in clinically significant scenarios. One of the best established applications is optical biopsy (in situ histological determination), and a number of techniques such as elastic scattering spectroscopy have demonstrated the ability to discriminate between neoplastic and non-neoplastic polyps. For flat dysplasia detection in Barrett’s esophagus, some of the most promising spectroscopic technologies are angle-resolved low-coherence interferometry and endoscopic polarized scanning spectroscopy (the next generation light scattering spectroscopy). A new and exciting biological approach involves optical detection of field carcinogenesis. This can be exploited to reduce colonoscopic adenoma miss rate by assessing microcirculatory augmentation in the mucosa in the vicinity of the polyp using polarization-gatedspectroscopy. Furthermore, there are nano/micro-architectural correlates with diffuse field carcinogenesis throughout the colon. Indeed, technologies such as low coherence enhanced backscattering spectroscopy and partial wave spectroscopic microscopy have demonstrated that the detection of the nano-architectural alterations in the rectal mucosa can accurately sense advanced adenomas elsewhere in the colon. This may lend itself to a minimally intrusive risk stratification to identify patients who are most likely to harbor neoplasia and thus benefit from colonoscopy. Bridging these advances into the endoscopy suite requires pragmatic future development. Future studies need to focus on efficacy, cost, practicality (time required, etc), and particularly developing the paradigms that will impact upon clinical decision making.
Spectroscopy; Endoscopy; Cancer Screening; Biophotonics; Field Carcinogenesis
BACKGROUND & AIMS
Liver disease is a significant cause of mortality among adults with α-1 antitrypsin (AAT) deficiency. Age and male sex are reported risk factors for liver disease. In the absence of adequate risk stratification, current recommendations are to intermittently test AAT-deficient adults for liver function. We evaluated this recommendation in a large group of adults with AAT deficiency, to determine the prevalence of increased levels of alanine aminotransferase (ALT) and identify risk factors for liver disease.
We used the Alpha-1 Foundation DNA and Tissue Bank to identify a cross-section of AAT-deficient adults (n=647) with and without liver disease; individuals without AAT-deficiency were used as controls (n=152). Results from ALT tests were compared between groups.
The prevalence of liver disease among individuals with ATT-deficiency was 7.9%; an increased level of ALT was observed in 7.8% of ATT-deficient individuals, which did not differ significantly from controls. Mean levels of ALT fell within normal range for all groups. An increased level of ALT identified patients with liver disease with 11.9% sensitivity. The level of only γ- glutamyl transpeptidase was significantly higher in the AAT-deficient group than in controls (43 vs 30 IU/ml; P<.003). A childhood history of liver disease and male sex were risk factors for adult liver disease in the multivariate analysis.
An increased level of ALT does not identify adults with AAT deficiency who have liver disease. Male sex and liver disease during childhood might help identify those at risk.
diagnostic factor; prognosis; protease inhibitor; cirrhosis
Despite the development of consensus guidelines in ulcerative colitis (UC), there remain several areas of uncertainty in the everyday management of this incompletely understood disease. We performed a national vignette survey to measure variations in decision-making in areas of controversy.
We constructed a survey with 3 vignettes to measure decision-making in 4 areas of controversy in UC: (1) dysplasia management, (2) 5-ASA dosing, (3) diagnostic testing for underlying Crohn’s Disease, and (4) treatment of steroid-refractory inpatient UC. We compared responses between a group of community gastroenterologists and UC experts.
We received 192 responses (36% response). Compared to community gastroenterologists, UC experts were more likely to endorse colectomy for both unifocal and multifocal low grade dysplasia, use narrow band imaging and chromoendoscopy for surveillance colonoscopy, use high-dose 5-ASA for inducing remission, use long-term 5-ASA for cancer chemoprevention, order CT enterography to evaluate for Crohn’s disease, and to have a lower threshold to call for surgery consultation in steroid-refractory UC. There was little agreement regarding the optimal frequency of surveillance colonoscopy, even among experts. Most respondents favored using infliximab over cyclosporin in steroid-refractory UC.
Community gastroenterologists and UC experts vary dramatically in their approach to many areas of uncertainty in UC. The only area of consensus between groups is the use of infliximab over CSA in steroid-refractory UC – itself a controversial decision. These data suggest that current practice patterns are highly disparate, and focus attention on specific areas of disconnect that should be further investigated.
Ulcerative Colitis; Provider Survey
In this review, we will examine various molecular biomarkers for their potential to serve as independent prognostic factors for predicting survival outcome in postoperative patients with progressive intrahepatic cholangiocarcinoma. Specific rodent models of intrahepatic cholangiocarcinoma that mimic relevant cellular, molecular, and clinical features of the human disease are also described, not only in terms of their usefulness in identifying molecular pathways and mechanisms linked to cholangiocarcinoma development and progression, but also for their potential value as preclinical platforms for suggesting and testing novel molecular strategies for cholangiocarcinoma therapy. Last, recent studies aimed at addressing the role of desmoplastic stroma in promoting intrahepatic cholangiocarcinoma progression are highlighted in an effort to underline the potential value of targeting tumor stromal components together with that of cholangiocarcinoma cells as a novel therapeutic option for this devastating cancer.
Celiac Disease (CD) is an autoimmune enteropathy which occurs in genetically susceptible individuals carrying the prerequisite genetic markers HLA DQ2 or DQ8. These genetic markers are present in approximately 30% of the population, and the worldwide prevalence of CD is estimated to be approximately 1-2%. Currently a gluten-free diet is the only treatment for CD, but novel therapies aimed at gluten modification are underway. This review will discuss gluten based therapies including wheat alternatives and wheat selection, enzymatic alteration of wheat, oral enzyme supplements, and polymeric binders as exciting new therapies for treatment of Celiac Disease.
One of the most important and overlooked function of the gastrointestinal tract is to provide a dynamic barrier to tightly control antigen trafficking both through the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. While steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiologic modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, since the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases.
BACKGROUND & AIMS
Patients with celiac disease have been reported to be at increased risk for pancreatitis and pancreatic insufficiency, but the risk might have been overestimated because of patient selection and limited numbers of patients for analysis. Furthermore, no distinction has been made between patients with gallstone-related and non gallstone-related pancreatitis. We performed a nationwide study to determine the risk for any pancreatitis or subtype of pancreatitis among patients with biopsy-verified celiac disease.
We analyzed data from patients in Sweden with celiac disease (n=28,908), identified based on small intestinal biopsy records from 28 pathology departments (those with villous atrophy, Marsh 3). Biopsies were performed from 1969 to 2008 and biopsy report data were collected from 2006 to 2008. Patients with pancreatitis were identified based on diagnostic codes in the Swedish Patient Register and records of pancreatic enzyme use in the Swedish Prescribed Drug Register. Data were matched with those from 143,746 individuals in the general population; Cox regression was used to estimate hazard ratios (HRs) for pancreatitis.
We identified 406 individuals with celiac disease who were later diagnosed with pancreatitis (and 143 with expected pancreatitis) (HR=2.85; 95% confidence interval [CI], 2.53–3.21). The absolute risk of any pancreatitis among patients with celiac disease was 126/100,000 person-years with an excess risk of 81/100,000 person-years. The HR for gallstone-related acute pancreatitis was 1.59 (95% CI, 1.06–2.40), for non-gallstone-related acute pancreatitis was 1.86 (1.52–2.26), for chronic pancreatitis was 3.33 (95% CI, 2.33–4.76), and for supplementation with pancreatic enzymes was 5.34 (95% CI, 2.99–9.53). The risk of any pancreatitis within 5 years of diagnosis was 2.76 (95% CI, 2.36–3.22).
Based on an analysis of medical records in Sweden, patients with celiac disease were at an almost 3-fold increase in risk of developing pancreatitis.
Coeliac Disease; Celiac Disease; Cohort study; Inflammation; Pancreatitis; Epidemiology; retrospective analysis; gluten intolerance; complication
Background & Aims
Large-volume paracentesis (LVP) is the treatment of choice for patients with cirrhosis and refractory ascites. However, LVP can lead to post-paracentesis circulatory dysfunction (PCD), which is associated with faster ascites recurrence and renal failure. PCD results from vasodilatation, which reduces effective blood volume, and is prevented by intravenous administration of albumin. Vasoconstrictors could be used instead of albumin and, with longer use, prevent PCD and delay ascites recurrence.
We performed a multicenter, randomized, double-blind, placebo controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP. Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide (n=13). Patients in the vasoconstrictor group received saline solution (as a placebo for albumin), 10 mg of oral midodrine (3 times daily), and a monthly, 20 mcg intra-muscular injection of long-acting octreotide (n=12). Patients were followed until recurrence of ascites.
The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group (P=.318). There were no significant differences in PCD between the albumin group (18%) and the vasoconstrictor group (25%, P=.574). When ascites recurred, serum levels of creatinine were higher in the vasoconstrictor group (1.2 vs 0.9 mg/dL in the albumin group, P=.051).
The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis. Outcomes appear to be worse in patients given octreotide and midodrine.
cirrhosis; circulatory dysfunction; renal failure; randomized clinical trial
Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients.
SeHCAT; C4; glycocholate; fecal; diarrhea
Background & Aims
The aim of this study was to assess the analytic validity of self-reported family history of hemochromatosis or iron overload.
A total of 141 probands, 549 family members, and 641 controls participated in the primary care Hemochromatosis and Iron Overload Screening Study. Participants received a postscreening clinical examination and completed questionnaires about personal and family histories of hemochromatosis or iron overload, arthritis, diabetes, liver disease, and heart disease. We evaluated sensitivities and specificities of proband-reported family history, and concordance of HFE genotype C282Y/C282Y in probands and siblings who reported having hemochromatosis or iron overload.
The sensitivities of proband-reported family history ranged from 81.4% for hemochromatosis or iron overload to 18.4% for liver disease; specificities for diabetes, liver disease, and heart disease were greater than 94%. Hemochromatosis or iron overload was associated with a positive family history across all racial/ethnic groups in the study (odds ratio, 14.53; 95% confidence intervals, 7.41–28.49; P < .0001) and among Caucasians (odds ratio, 16.98; 95% confidence intervals, 7.53–38.32; P < .0001). There was 100% concordance of HFE genotype C282Y/C282Y in 6 probands and 8 of their siblings who reported having hemochromatosis or iron overload.
Self-reported family history of hemochromatosis or iron overload can be used to identify individuals whose risk of hemochromatosis or iron overload and associated conditions is increased. These individuals could benefit from further evaluation with iron phenotyping and HFE mutation analysis.
BACKGROUND & AIMS
Over-the-counter analgesics have been proposed to lead to decompensation of compensated cirrhosis or to further decompensation of an already decompensated patient. We performed a prospective, case-control study to investigate the effects of analgesics on acute hepatic decompensation.
Data from consecutive cirrhotic patients hospitalized at 2 tertiary care hospitals for decompensation of cirrhosis (cases, n = 91) were compared with that from consecutive patients with compensated cirrhosis that were followed in the liver clinic (n = 153) and with randomly selected noncirrhotic patients concurrently hospitalized with the cases (n = 89). All patients were given a structured questionnaire to collect information on recent use of acetaminophen, nonsteroidal anti-inflammatory drugs and alcohol.
Only 32 (35%) of the cirrhotic patients used over-the-counter analgesics (19% acetaminophen, 16% nonsteroidal anti-inflammatory drugs), compared with 80 of the cirrhotic controls (52%; 25% acetaminophen, 31% nonsteroidal anti-inflammatory drugs), and 62 (70%) of the noncirrhotic controls. Acetaminophen use did not differ between groups, even for those with recent alcohol use. The doses and days of nonsteroidal anti-inflammatory drug use were higher among cirrhotic patients, compared with controls. Alcohol ingestion was significantly greater among patients with alcoholic cirrhosis, compared with controls.
In patients with cirrhosis, acetaminophen use at doses lower than those recommended is not associated with acute hepatic decompensation, even in patients with recent alcohol ingestion. Nonsteroidal anti-inflammatory drugs might be associated with deleterious effects on cirrhosis. Alcohol ingestion is associated with decompensation in patients with alcoholic cirrhosis.
Background & Aims
Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis that were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial.
Standard case report forms from 2,740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, along with information from questionnaires completed by investigators about details of biopsy techniques used at each hospital.
There were 29 serious adverse events (1.1%); the most common was bleeding (16 cases, 0.6%). There were no biopsy-related deaths. The bleeding rate was higher among patients with platelet counts ≤60,000/mm3 and among those with an international normalized ratio (INR) ≥1.3, although none of the patients with an INR >1.5 bled. Excluding subjects with a platelet count ≤60,000/mm3 would have reduced the bleeding rate by 25% (4/16), eliminating only 2.8% (77/2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under ultrasound guidance did not influence the frequencies of adverse events.
Approximately 0.5% of persons with hepatitis C and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in patients with platelet counts ≤60,000/mm3.(K2).
liver biopsy; complications; adverse event; serious adverse events; bleeding; platelet count; INR
BACKGROUND & AIMS
Serum fibrosis marker levels during antiviral treatment in chronic hepatitis C (CHC) patients enrolled in the lead-in phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial were determined.
Week 0, 24, 48 and 72 serum samples were analyzed for YKL-40, TIMP-1, PIIINP, and HA levels. All 456 CHC patients received peginterferon alfa2a and ribavirin for 24 to 48 weeks.
Mean age was 49.2 years, 71% were male, and 39% had cirrhosis. Lower pretreatment serum YKL-40, TIMP-1, PIIINP, and HA levels were significantly associated with week 20 virological response (p < 0.0001). In multivariate analysis, non-1 CHC genotype, non-black race, prior Interferon monotherapy, and lower baseline serum AST/ALT and log10 YKL-40 levels were independently associated with week 20 virological response. Statistically significant declines in all marker levels were observed at week 72 compared to baseline in the 81 patients with a sustained virological response (SVR) but not in the 72 subjects with breakthrough or relapse. At weeks 24 and 48, significant increases were observed in serum PIIINP and HA levels compared to baseline in virological responders and non-responders (p < 0.0001).
Pretreatment YKL-40 levels are an independent predictor of initial virological response to pegInterferon and ribavirin treatment. Levels of all 4 serum fibrosis markers significantly decreased in the SVR patients, consistent with reduced hepatic fibrogenesis. Measuring serum fibrosis marker levels before and after antiviral therapy may provide important prognostic information in CHC patients.
The enteric microbiota contributes to gastrointestinal health and its disruption has been associated with many disease states. Some patients consume probiotic products in attempts to manipulate the intestinal microbiota for health benefit. It is important for gastroenterologists to improve their understanding of the mechanisms of probiotics and the evidence that support their use in practice. Clinical trials have assessed the therapeutic effects of probiotics for several disorders, including antibiotic-or Clostridium difficile-associated diarrhea, irritable bowel syndrome, and the inflammatory bowel diseases. Although probiotic research is a rapidly evolving field, there are sufficient data to justify a trial of probiotics for treatment or prevention of some of these conditions. However, the capacity of probiotics to modify disease symptoms is likely to be modest and varies among probiotic strains—not all probiotics are right for all diseases. The current review provides condition-specific rationale for using probiotics as therapy and literature-based recommendations.
Clostridium difficile; IBD; IBS; irritable bowel; clinical practice; evidence based practice; Crohn’s disease and colitis; yogurt; pouchitis
Background & Aims
Little is known about the prevalence and severity of portal hypertension in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the prevalence and non-invasive predictors of portal hypertension in patients with NAFLD.
Signs of portal hypertension, including esophageal varices, splenomegaly, portosystemic encephalopathy, and ascites where investigated in 354 patients with NAFLD.
One-hundred patients had portal hypertension at the time of NAFLD diagnosis (28.2%), 88 of these with septal fibrosis or cirrhosis (88%). Fibrosis stage correlated with presence (r=0.41, P<.0001) and number of findings (r=0.48, P=.006) of portal hypertension. Of the 204 patients with no or mild fibrosis (stages 0–2), 12 had portal hypertension (6%); they had a significantly higher grade of steatosis, based on biopsy analysis, compared to the 192 patients without portal hypertension (94%). Thrombocytopenia, hyperbilirubinemia, cirrhosis, and obesity were independently associated with portal hypertension. Esophageal varices were found in 57 of the 128 patients undergoing endoscopic screening (44.5%) and independently associated with thrombocytopenia, type 2 diabetes, and splenomegaly.
Signs of portal hypertension are present in 25% of patients at the time of diagnosis of NAFLD; most had advanced fibrosis or cirrhosis. Portal hypertension can occur in a small proportion of patients with mild or no fibrosis and is associated with the extent of steatosis. Features of advanced liver disease and insulin resistance might identify patients with NAFLD and portal hypertension, and those expected to derive the most benefit from endoscopic screening for esophageal varices.
prognostic factor; obesity; disease progression; steatosis
Background & Aims
Endoscopic findings such as esophageal rings, strictures, narrow-caliber esophagus, linear furrows, white plaques, and pallor or decreased vasculature might indicate the presence of eosinophilic esophagitis (EoE). We aimed to determine the prevalence and diagnostic utility of endoscopic features of EoE.
We conducted a systematic review and meta-analysis. PubMed, EMBASE, and GI meeting abstracts were searched to identify studies that included ≥ 10 patients with EoE and reported endoscopic findings. Pooled prevalence, sensitivity, specificity, and predictive values were calculated using random- and mixed-effects models.
The search yielded 100 articles and abstracts on 4678 patients with EoE and 2742 without (controls). In subjects with EoE, the overall pooled prevalence of esophageal rings was 44%, strictures 21%, narrow-caliber esophagus 9%, linear furrows 48%, white plaques 27%, and pallor/decreased vasculature 41%. Substantial heterogeneity existed among studies. Results from endoscopy examinations were normal in 17% of patients, but this number decreased to 7% when the analysis was limited to prospective studies (P<.05). Overall levels of sensitivity were modest, ranging from 15% to 48%, whereas levels of specificity were greater, ranging from 90% to 95%. Positive predictive values ranged from 51% to 73% and negative predictive values ranged from 74% to 84%.
There is heterogeneity among studies in the reported prevalence of endoscopic findings in patients with EoE, but in prospective studies, at least 1 abnormality was detected by endoscopy in 93% of patients. The operating characteristics of endoscopic findings alone are inadequate for diagnosis of EoE. Esophageal biopsies should be obtained from all patients with clinical features of EoE, regardless of the endoscopic appearance of the esophagus.
esophagus; inflammation; immune response; detection
BACKGROUND & AIMS
Variations in genes that regulate bile acid (BA) synthesis are associated with colonic transit in patients with irritable bowel syndrome (IBS). We investigated features of BA synthesis and excretion and genetic features of patients with different types of IBS.
In 26 healthy volunteers, 26 patients with IBS and constipation (IBS-C), and 26 with IBS and diarrhea (IBS-D), we measured serum levels of 7α-hydroxy-4-cholesten-3-one (C4; a surrogate for BA synthesis) and fibroblast growth factor (FGF) 19 (an ileal hormone that downregulates BA synthesis). For stool samples, we measured concentration of BA, weight, and amount of fat when participants were given high-fat diets. Spearman correlations were used to explore relationships among factors. We analyzed 1 polymorphism in Klotho-β (KLB) and 3 in fibroblast growth factor receptor-4 (FGFR4) for all members of each group using analysis of covariance.
The concentration of BA in stool was associated with group (for a comparison of 3 groups; P = .057); it was higher in patients with IBS-D than IBS-C (P = .017). The serum level of C4 was higher in patients with IBS-D than IBS-C (P = .02) or healthy volunteers (P = .01); 38% of patients with IBS-D had increased serum levels of C4, compared with healthy volunteers. Serum level of C4 correlated with stool concentration of BA (rs = 0.606; P < .001), serum FGF19 (rs = −0.324; P = .007), and stool weight (rs = 0.366; P = .003). Stool concentration of BA correlated with weight (rs = 0.737; P < .001) and level of fat (rs = 0.528; P < .001). Body mass index correlated with serum level of C4 (rs = 0.423, P < .001) and stool concentration of BA (rs = 0.507, P < .001), and was higher in patients with IBS-D compared with other groups (overall P = .036). FGFR4 rs1966265 was associated with stool level of BA (P = .032).
Patients with IBS-D have greater body mass index and synthesize and excrete higher levels of BA than individuals with IBS-C or healthy volunteers. Serum levels of C4 might be used to identify patients with IBS-D who have BA malabsorption; studies are needed to determine if some patients have a genetic predisposition to this disorder.
Colon; Malabsorption; Liver; Metabolism
Background and Aim
The ability to identify children with Crohn’s disease who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. Aim: To determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression.
Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer membrane protein C (anti-OmpC), anti-Saccharomyces-cerevisiae (ASCA) and perinuclear anti-neutrophil cytoplasmic antibody (pANCA) using ELISA. Genotyping (TaqmanMGB) was performed for 3 CARD15 variants (SNPs 8, 12, 13). Associations between immune responses (antibody sum (AS) and quartile sum score (QSS), CARD15, and clinical phenotype were evaluated.
32% of patients developed at least one disease complication within a median of 32 months and 18% underwent surgery. The frequency of internal penetrating (IP), stricturing (S) and surgery significantly increased (p trend < 0.0001 for all 3 outcomes) with increasing AS and QSS. 9% of seropositive groups had IP/S vs. 2.9% in the seronegative group (p=0.01). 12% of seropositive groups underwent surgery vs. 2% in the seronegative group (p=0.0001). The highest AS group (3) and QSS group (4) demonstrated the most rapid disease progression (p < 0.0001). Increased hazard ratio was observed for AS group 3 (7.8 [2.2–28.7] p < 0.002 and QSS group 4 (11.0 [1.5,83.0] p < 0.02).
The rate of complicated CD increases in children as the number and magnitude of immune reactivity increases. Disease progression is significantly faster in children expressing immune reactivity.