Marcos Pedrosa

Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection

BACKGROUND:Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment.METHODS:We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician.RESULTS:Overall, 32.2% (95% CI, 30.8–33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2–42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24–25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85–13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70–13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42–16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0–78.3%) agreed to be treated and multivariable analysis showed that persons ≥50 yr of age (OR = 1.37; 95% CI, 1.07–1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08–1.93) were more likely to decline treatment.CONCLUSIONS:The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.

Bacterial overgrowth without clinical malabsorption in elderly hypochlorhydric subjects

BACKGROUND/AIMS Bacterial overgrowth of the small intestine commonly occurs in association with hypochlorhydria caused by atrophic gastritis or during treatment with omeprazole. The purpose of this study was to determine the clinical significance of bacterial overgrowth on small intestinal absorption and permeability and to evaluate the reliability of noninvasive breath tests to detect bacterial overgrowth in subjects with hypochlorhydria. METHODS Seventeen healthy, elderly subjects with atrophic gastritis or omeprazole treatment (40 mg/day) and documented bacterial overgrowth were studied. RESULTS There was no evidence of fat malabsorption (72-hour fecal fat) or clinically significant carbohydrate malabsorption (25 g D-xylose and fecal pH) in any subject. The ratio of lactulose to mannitol excreted was normal in both atrophic gastritis and omeprazole-treated groups. Three subjects in each group had abnormally high alpha 1-antitrypsin clearances. Lactulose (10 g) and glucose (80 g) hydrogen breath tests were only abnormal in 1 out of 17 subjects, whereas the 1 g [14C]D-xylose test was abnormal in 6 out of 17 subjects. CONCLUSIONS Bacterial overgrowth caused by atrophic gastritis or omeprazole treatment is typically not associated with clinically significant fat or carbohydrate malabsorption. Noninvasive breath tests for bacterial overgrowth are not reliable in subjects with hypochlorhydria.

Detection of high-grade dysplasia in Barrett's esophagus by spectroscopy measurement of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

BACKGROUND Preliminary studies with qualitative detection methods suggest that 5-aminolevulinic acid-induced protoporphyrin IX fluorescence might improve the detection of dysplastic Barretts epithelium. This study used quantitative methods to determine whether aminolevulinic acid-induced protoporphyrin IX fluorescence can differentiate between Barretts mucosa with and without dysplasia. METHODS Patients were given 10 mg/kg of aminolevulinic acid orally 3 hours before endoscopy. Quantitative fluorescence spectra were acquired by using a nitrogen-pumped dye laser (l 400 nm) spectrograph system. The protoporphyrin IX fluorescence intensity at 635 nm was compared with the histopathologic diagnosis for mucosal biopsy specimens taken immediately after the fluorescence measurements. RESULTS Ninety-seven spectra were obtained from 20 patients. The mean (+/- standard error) standardized protoporphyrin IX fluorescence intensity was significantly greater (p < 0.05) for high-grade dysplastic Barretts epithelium (0.29 +/- 0.07, n = 13) than for nondysplastic Barretts epithelium (0.11 +/- 0.02, n = 43). By using protoporphyrin IX fluorescence alone, high-grade dysplasia was distinguished from nondysplastic tissue types with 77% sensitivity and 71% specificity. Decreased autofluorescence was particularly found in nodular high-grade dysplasia. By using the fluorescence intensity ratio of 635 nm/480 nm, nodular high-grade dysplasia could be differentiated from nondysplastic tissue with 100% sensitivity and 100% specificity. CONCLUSION Protoporphyrin IX fluorescence may be useful for identifying areas of high-grade dysplasia in Barretts esophagus and for targeting of biopsies.

Squamous Overgrowth Is Not a Safety Concern for Photodynamic Therapy for Barrett's Esophagus With High-Grade Dysplasia

BACKGROUND & AIMS Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barretts esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Overtube use in gastrointestinal endoscopy.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic, and a MAUDE (Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the ‘‘related articles’’ feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but, in many cases, data from randomized controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the governing board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through March 2009 for articles related to overtube use in GI endoscopy by using the keywords overtube, intubation, enteral access, enteroscopy, and foreign bodies, paired with endoscopy, gastrointestinal. Practitioners should continue to monitor the medical literature for subsequent data about the efficacy, safety, and socioeconomic aspects of these technologies. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*.

Summary.  In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non‐Black patients but also a higher frequency of HCV genotype 1 (GT‐1) infection. The aim of this community‐based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha‐2b 3 MU three times weekly + RBV 1000–1200 mg/day for 24 weeks (GT‐2/3) or 48 weeks (GT‐1). Black patients were more commonly infected with GT‐1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non‐Black patients (8.4%vs 21.6%, P < 0.001). Within GT‐1, Black patients had a lower SVR rate than non‐Black patients (6.1%vs 14.1%, P = 0.004) but not within GT‐2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm3, P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT‐1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20–0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22–0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31–0.92; P = 0.023). In conclusion, Black patients infected with HCV GT‐1 (but not GT‐2/3) have a lower SVR rate than non‐Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.

Biliary and pancreatic stone extraction devices

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is employed by using a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the ‘‘related articles’’ feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases data from randomized controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the governing board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review the MEDLINE database was searched through February 2009 for articles related to endoscopy in patients with pancreatic and biliary stones requiring removal, by using the keywords choledocholithiasis, pancreaticolithiasis, stone, and extraction paired with ERCP, endoscopy, and gastrointestinal. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment. Biliary and pancreatic duct stones are a major cause of morbidity. Choledocholithiasis, if left untreated, can lead to pain, cholangitis, gallstone pancreatitis, and secondary sclerosing cholangitis. Pancreatic stones, most commonly

Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in cirrhosis patients. This provides an opportunity to target the highest‐risk population, yet surveillance rates in the United States and Europe range from 10% to 40%. The goal of this study was to identify barriers to HCC surveillance, using data from the Veterans Health Administration, the largest provider of liver‐related health care in the United States. We included all patients 75 years of age or younger who were diagnosed with cirrhosis from January 1, 2008, until December 31, 2010. The primary outcome was a continuous measure of the percentage of time up‐to‐date with HCC surveillance (PTUDS) based on abdominal ultrasound (secondary outcomes included computed tomography and magnetic resonance imaging). Among 26,577 patients with cirrhosis (median follow‐up = 4.7 years), the mean PTUDS was 17.8 ± 21.5% (ultrasounds) and 23.3 ± 24.1% when any liver imaging modality was included. The strongest predictor of increased PTUDS was the number of visits to a specialist (gastroenterologist/hepatologist and/or infectious diseases) in the first year after cirrhosis diagnosis; the association between visits to a primary care physician and increasing surveillance was very small. Increasing distance to the closest Veterans Administration center was associated with decreased PTUDS. There was an inverse association between ultrasound lead time (difference between the date an ultrasound was ordered and requested exam date) and the odds of it being performed: odds ratio = 0.77, 95% confidence interval 0.72‐0.82 when ordered > 180 days ahead of time; odds ratio = 0.90, 95% confidence interval 0.85‐0.94 if lead time 91‐180 days. Conclusions: The responsibility for suboptimal surveillance rests with patients, providers, and the overall health care system; several measures can be implemented to potentially increase HCC surveillance, including increasing patient–specialist visits and minimizing appointment lead time. (Hepatology 2017;65:864‐874).

Through-the-scope balloon dilation for endoscopic ultrasound staging of stenosing esophageal cancer.

Dilation of malignant esophageal strictures often is required to complete staging by endoscopic ultrasound (EUS). This study was designed to determine the successful dilation rate (ability to complete staging) and complication rate of through-the-scope (TTS) balloon dilation for malignant esophageal strictures during EUS. We retrospectively reviewed EUS reports for all cases of primary esophageal cancer staged at five centers between January 2002 and October 2004. All dilations were performed with TTS balloons. Among 272 endoscopic ultrasounds, dilation was required in 77 (28%) and was successful in 73 cases (95%). There was one esophageal perforation after dilation (1.3%; 95% confidence interval (CI), 0.2–7) and one esophageal perforation after EUS without dilation (0.5%; 95% CI, 0.1–2.8; P=0.48 by two-sided Fisher exact test). There were no other major complications. TTS balloon dilation is highly successful in permitting complete staging of obstructing tumors. The rate of complications after dilation with a TTS balloon dilator is low and similar to the baseline rate of EUS in this setting.

Gastric emptying and first-pass metabolism of ethanol in elderly subjects with and without atrophic gastritis

BACKGROUND Oral ethanol intake results in lower blood ethanol concentrations than intravenous administration of the same dose of ethanol. This first-pass metabolism is thought to be due to gastric metabolism of ethanol via alcohol dehydrogenase and also to hepatic first-pass metabolism. METHODS Since a loss of gastric mucosa may decrease first-pass metabolism of ethanol, this metabolism was studied in 10 elderly subjects (6 women and 4 men) with atrophic gastritis and bacterial overgrowth and in 17 control subjects with normal gastric secretory function. Atrophic gastritis was verified by means of the serum pepsinogen I to pepsinogen II ratio and the hypochlorhydria occurring after pentagastrin stimulation. Bacterial overgrowth was assessed by bacteria. In addition, gastric emptying rates of ethanol solution with technetium-99m sulfur colloid were calculated from scintigraphic images. Furthermore, gastric biopsy specimens were taken from 12 female patients with atrophic gastritis and from 12 controls for determination of alcohol dehydrogenase activity. RESULTS Neither gender (female versus male, 28 +/- 5% versus 42 +/- 5%), atrophic gastritis (normal versus atrophic gastritis, 35 +/- 4% versus 32 +/- 6%), nor tetracycline treatment in atrophic gastritis subjects (before versus after, 32 +/- 6% versus 41 +/- 5%) had a statistically significant effect on the first-pass metabolism of ethanol in the elderly. Gastric alcohol dehydrogenase activity was significantly lower in atrophic gastritis subjects than in controls (p < 0.01). A significant correlation was found between the first-pass metabolism of ethanol in healthy controls and gastric half-emptying time (p = 0.032). CONCLUSIONS We conclude from these data that the rate of gastric emptying modulates first-pass metabolism of ethanol in elderly individuals.