From the AGA Journals

Among patients with single-nodule hepatocellular carcinomas diagnosed by computed tomography, further imaging with gadoxetic acid–enhanced magnetic resonance (MR) revealed more tumors and was tied to a 28% drop in cancer recurrence and a 35% drop in mortality, a retrospective cohort study reported in the June issue of Gastroenterology (doi.org/10.1053/j.gastro.2015.02.051) found.

“To the best of our knowledge, this is the first study to demonstrate that evaluation of hepatocellular carcinoma [HCC] with gadoxetic acid–enhanced MR imaging is associated with an improvement in the clinical outcome of patients, compared with that of a standard evaluation with dynamic CT,” said Dr. Hyung-Don Kim at the University of Ulsan in Seoul, South Korea and his associates. “This is clinically meaningful, given that the prognosis of patients with early-stage HCC is poor even after a curative treatment, mainly because of the high rate of early intrahepatic recurrence, and because there is no form of adjuvant therapy with a proven clinical benefit.” At least a third of early HCC recurrences might result from dissemination of primary tumor that went undetected at initial treatment, the researchers noted. To investigate the effects of gadoxetic acid–enhanced magnetic resonance imaging on HCC detection and subsequent survival, they retrospectively studied 700 patients in Seoul, South Korea, who had single-nodule HCCs diagnosed by dynamic four-phase CT. A total of 323 patients underwent additional imaging with gadoxetic acid–enhanced MR. These patients resembled CT-only patients in terms of baseline demographic characteristics, except that they were an average of 3 years younger (P < .001), had significantly higher median ALT levels (66 vs. 57 IU/mL; P < .006) and significantly higher platelet counts and lower alpha-fetoprotein levels, the investigators said.Gadoxetic acid–enhanced MR detected additional small HCC nodules in 16% of patients, and was tied to a 28% drop in likelihood of recurrence (hazard ratio, 0.72; 95% confidence interval, 0.54-0.96) and a 35% drop in risk of mortality (HR, 0.65; 95% CI, 0.44-0.96), the investigators reported. Rates of both recurrence-free and overall survival also were significantly higher for patients who underwent contrast-enhanced MR in addition to CT, compared with patients who underwent CT alone, and the differences held true in univariate, multivariate, inverse probability weighting analyses, and propensity score-matched analyses, they added.

“The major limitation of this study is that it was based on observational data,” commented the researchers. “Further studies that evaluate the effectiveness of gadoxetic acid–enhanced MR imaging for the evaluation of HCC in patients in other clinical settings are warranted.” The findings also need cautious interpretation because of the chance that selection bias led to more curable cases among patients who underwent MR in addition to CT, they said. The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.

Courtesy American Gastroenterological Association

Among patients with single-nodule hepatocellular carcinomas diagnosed by computed tomography, further imaging with gadoxetic acid–enhanced magnetic resonance (MR) revealed more tumors and was tied to a 28% drop in cancer recurrence and a 35% drop in mortality, a retrospective cohort study reported in the June issue of Gastroenterology (doi.org/10.1053/j.gastro.2015.02.051) found.

“To the best of our knowledge, this is the first study to demonstrate that evaluation of hepatocellular carcinoma [HCC] with gadoxetic acid–enhanced MR imaging is associated with an improvement in the clinical outcome of patients, compared with that of a standard evaluation with dynamic CT,” said Dr. Hyung-Don Kim at the University of Ulsan in Seoul, South Korea and his associates. “This is clinically meaningful, given that the prognosis of patients with early-stage HCC is poor even after a curative treatment, mainly because of the high rate of early intrahepatic recurrence, and because there is no form of adjuvant therapy with a proven clinical benefit.” At least a third of early HCC recurrences might result from dissemination of primary tumor that went undetected at initial treatment, the researchers noted. To investigate the effects of gadoxetic acid–enhanced magnetic resonance imaging on HCC detection and subsequent survival, they retrospectively studied 700 patients in Seoul, South Korea, who had single-nodule HCCs diagnosed by dynamic four-phase CT. A total of 323 patients underwent additional imaging with gadoxetic acid–enhanced MR. These patients resembled CT-only patients in terms of baseline demographic characteristics, except that they were an average of 3 years younger (P < .001), had significantly higher median ALT levels (66 vs. 57 IU/mL; P < .006) and significantly higher platelet counts and lower alpha-fetoprotein levels, the investigators said.Gadoxetic acid–enhanced MR detected additional small HCC nodules in 16% of patients, and was tied to a 28% drop in likelihood of recurrence (hazard ratio, 0.72; 95% confidence interval, 0.54-0.96) and a 35% drop in risk of mortality (HR, 0.65; 95% CI, 0.44-0.96), the investigators reported. Rates of both recurrence-free and overall survival also were significantly higher for patients who underwent contrast-enhanced MR in addition to CT, compared with patients who underwent CT alone, and the differences held true in univariate, multivariate, inverse probability weighting analyses, and propensity score-matched analyses, they added.

“The major limitation of this study is that it was based on observational data,” commented the researchers. “Further studies that evaluate the effectiveness of gadoxetic acid–enhanced MR imaging for the evaluation of HCC in patients in other clinical settings are warranted.” The findings also need cautious interpretation because of the chance that selection bias led to more curable cases among patients who underwent MR in addition to CT, they said. The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.

Courtesy American Gastroenterological Association

Among patients with single-nodule hepatocellular carcinomas diagnosed by computed tomography, further imaging with gadoxetic acid–enhanced magnetic resonance (MR) revealed more tumors and was tied to a 28% drop in cancer recurrence and a 35% drop in mortality, a retrospective cohort study reported in the June issue of Gastroenterology (doi.org/10.1053/j.gastro.2015.02.051) found.

“To the best of our knowledge, this is the first study to demonstrate that evaluation of hepatocellular carcinoma [HCC] with gadoxetic acid–enhanced MR imaging is associated with an improvement in the clinical outcome of patients, compared with that of a standard evaluation with dynamic CT,” said Dr. Hyung-Don Kim at the University of Ulsan in Seoul, South Korea and his associates. “This is clinically meaningful, given that the prognosis of patients with early-stage HCC is poor even after a curative treatment, mainly because of the high rate of early intrahepatic recurrence, and because there is no form of adjuvant therapy with a proven clinical benefit.” At least a third of early HCC recurrences might result from dissemination of primary tumor that went undetected at initial treatment, the researchers noted. To investigate the effects of gadoxetic acid–enhanced magnetic resonance imaging on HCC detection and subsequent survival, they retrospectively studied 700 patients in Seoul, South Korea, who had single-nodule HCCs diagnosed by dynamic four-phase CT. A total of 323 patients underwent additional imaging with gadoxetic acid–enhanced MR. These patients resembled CT-only patients in terms of baseline demographic characteristics, except that they were an average of 3 years younger (P < .001), had significantly higher median ALT levels (66 vs. 57 IU/mL; P < .006) and significantly higher platelet counts and lower alpha-fetoprotein levels, the investigators said.Gadoxetic acid–enhanced MR detected additional small HCC nodules in 16% of patients, and was tied to a 28% drop in likelihood of recurrence (hazard ratio, 0.72; 95% confidence interval, 0.54-0.96) and a 35% drop in risk of mortality (HR, 0.65; 95% CI, 0.44-0.96), the investigators reported. Rates of both recurrence-free and overall survival also were significantly higher for patients who underwent contrast-enhanced MR in addition to CT, compared with patients who underwent CT alone, and the differences held true in univariate, multivariate, inverse probability weighting analyses, and propensity score-matched analyses, they added.

“The major limitation of this study is that it was based on observational data,” commented the researchers. “Further studies that evaluate the effectiveness of gadoxetic acid–enhanced MR imaging for the evaluation of HCC in patients in other clinical settings are warranted.” The findings also need cautious interpretation because of the chance that selection bias led to more curable cases among patients who underwent MR in addition to CT, they said. The Korean Ministry of Health & Welfare and the Korean Association for the Study of Liver helped fund the research. One coauthor reported serving on the advisory boards of Bayer Healthcare, Bristol-Myers Squibb, and Gilead Science, and receiving research funding from Bayer, Gilead, and Novartis. The other investigators reported no conflicts of interest.

Courtesy American Gastroenterological Association

Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.

“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”

New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.

Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.

Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”

The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.

The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.

Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.

“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”

New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.

Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.

Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”

The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.

The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.

Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.

“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”

New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.

Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.

Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”

The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.

The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.

Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).

“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.

Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.

Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.

Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).

“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.

Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.

Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.

Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).

“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.

Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.

Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.

When compared with conventional colonoscopy, capsule colonoscopy had a sensitivity of 88% and a specificity of 82% for detecting adenomas of at least 6 mm in asymptomatic subjects, a multicenter prospective study showed.

But the capsule detected only 29% of subjects who had sessile serrated polyps of at least 6 mm, and required more extensive bowel preparation than did conventional colonoscopy, Dr. Douglas K. Rex at Indiana University Hospital in Indianapolis and his associates reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.025]). “Given these considerations ... colonoscopy remains the gold standard for the detection of colorectal polyps,” said the researchers. “The capsule is a good test for the detection of patients with conventional adenomas 6 mm or larger in size and appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy.”

Capsule endoscopy is useful for small-bowel imaging, but adapting the technology for colorectal studies has been difficult. A first-generation capsule detected only 74% of advanced adenomas in one prospective multicenter trial, the researchers noted. Since then, the PillCam COLON 2 capsule has been updated with motion detection, variable frame speed, and a wider angle view, they said. In smaller studies, it detected up to 89% of subjects with polyps of at least 6 mm, but its specificity was as low as 64%.

To further investigate the technology, researchers at 16 centers in the United States and Israel compared the second-generation capsule with conventional colonoscopy in an average-risk screening population of 884 asymptomatic subjects. Endoscopists were blinded as to technique, but performed unblinded follow-up colonoscopies in subjects who were positive on capsule but negative on conventional colonoscopy.

The capsule’s sensitivity was 81% (95% confidence interval, 77%-84%) and its specificity was 93% (91%-95%) for detecting subjects who had polyps of at least 6 mm, the researchers reported. Sensitivity was 80% (74%-86%) and specificity was 97% (96%-98%) for detecting subjects with polyps of at least 10 mm. For conventional adenomas of at least 6 mm, sensitivity was 88% (82%-93%) and specificity was 82% (80%-83%), and for adenomas of 10 mm or larger, sensitivity was 92% (82%-97%) and specificity was 95% (94%-95%).

“Lesions in the serrated class were not detected well by the capsule in this study, compared with conventional adenomas,” the researchers reported. Prior studies of the capsule did not look for serrated lesions, and in the current study sensitivities were only 29% and 33% for 6-mm and 10-mm lesions, respectively.

The software used to measure polyps during capsule colonoscopy had a 40% error range when tested on balls of known size, the researchers said. Therefore, there is a strict location-matching rule within the colon, but a liberal size rule that only required measurements to fall within 50% of one another to be considered a match. “Any set of matching rules for polyps detected by the capsule and colonoscopy might operate to increase or decrease the calculated sensitivity of the capsule incorrectly,” they added. Also, the adenoma detection rate for conventional colonoscopy was only 39%, and some polyps that were clearly seen on capsule were not visualized on regular colonoscopy. “In these cases, a polyp that should be a true positive for the capsule was counted as false,” they added. “Both colonoscopy and capsule are inferior for localization, compared with CT colonography. Inaccurate localization by one or both tests in this study could have reduced the sensitivity of the capsule.”

The investigators also had to exclude 77 patients because of inadequate cleansing and short transit times related to using sodium phosphate as a boost, they noted. The Food and Drug Administration label for the capsule is expected to reflect those limitations, they added.

Given Imaging funded the study and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported having no relevant conflicts of interest.

When compared with conventional colonoscopy, capsule colonoscopy had a sensitivity of 88% and a specificity of 82% for detecting adenomas of at least 6 mm in asymptomatic subjects, a multicenter prospective study showed.

But the capsule detected only 29% of subjects who had sessile serrated polyps of at least 6 mm, and required more extensive bowel preparation than did conventional colonoscopy, Dr. Douglas K. Rex at Indiana University Hospital in Indianapolis and his associates reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.025]). “Given these considerations ... colonoscopy remains the gold standard for the detection of colorectal polyps,” said the researchers. “The capsule is a good test for the detection of patients with conventional adenomas 6 mm or larger in size and appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy.”

Capsule endoscopy is useful for small-bowel imaging, but adapting the technology for colorectal studies has been difficult. A first-generation capsule detected only 74% of advanced adenomas in one prospective multicenter trial, the researchers noted. Since then, the PillCam COLON 2 capsule has been updated with motion detection, variable frame speed, and a wider angle view, they said. In smaller studies, it detected up to 89% of subjects with polyps of at least 6 mm, but its specificity was as low as 64%.

To further investigate the technology, researchers at 16 centers in the United States and Israel compared the second-generation capsule with conventional colonoscopy in an average-risk screening population of 884 asymptomatic subjects. Endoscopists were blinded as to technique, but performed unblinded follow-up colonoscopies in subjects who were positive on capsule but negative on conventional colonoscopy.

The capsule’s sensitivity was 81% (95% confidence interval, 77%-84%) and its specificity was 93% (91%-95%) for detecting subjects who had polyps of at least 6 mm, the researchers reported. Sensitivity was 80% (74%-86%) and specificity was 97% (96%-98%) for detecting subjects with polyps of at least 10 mm. For conventional adenomas of at least 6 mm, sensitivity was 88% (82%-93%) and specificity was 82% (80%-83%), and for adenomas of 10 mm or larger, sensitivity was 92% (82%-97%) and specificity was 95% (94%-95%).

“Lesions in the serrated class were not detected well by the capsule in this study, compared with conventional adenomas,” the researchers reported. Prior studies of the capsule did not look for serrated lesions, and in the current study sensitivities were only 29% and 33% for 6-mm and 10-mm lesions, respectively.

The software used to measure polyps during capsule colonoscopy had a 40% error range when tested on balls of known size, the researchers said. Therefore, there is a strict location-matching rule within the colon, but a liberal size rule that only required measurements to fall within 50% of one another to be considered a match. “Any set of matching rules for polyps detected by the capsule and colonoscopy might operate to increase or decrease the calculated sensitivity of the capsule incorrectly,” they added. Also, the adenoma detection rate for conventional colonoscopy was only 39%, and some polyps that were clearly seen on capsule were not visualized on regular colonoscopy. “In these cases, a polyp that should be a true positive for the capsule was counted as false,” they added. “Both colonoscopy and capsule are inferior for localization, compared with CT colonography. Inaccurate localization by one or both tests in this study could have reduced the sensitivity of the capsule.”

The investigators also had to exclude 77 patients because of inadequate cleansing and short transit times related to using sodium phosphate as a boost, they noted. The Food and Drug Administration label for the capsule is expected to reflect those limitations, they added.

Given Imaging funded the study and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported having no relevant conflicts of interest.

When compared with conventional colonoscopy, capsule colonoscopy had a sensitivity of 88% and a specificity of 82% for detecting adenomas of at least 6 mm in asymptomatic subjects, a multicenter prospective study showed.

But the capsule detected only 29% of subjects who had sessile serrated polyps of at least 6 mm, and required more extensive bowel preparation than did conventional colonoscopy, Dr. Douglas K. Rex at Indiana University Hospital in Indianapolis and his associates reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.025]). “Given these considerations ... colonoscopy remains the gold standard for the detection of colorectal polyps,” said the researchers. “The capsule is a good test for the detection of patients with conventional adenomas 6 mm or larger in size and appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy.”

Capsule endoscopy is useful for small-bowel imaging, but adapting the technology for colorectal studies has been difficult. A first-generation capsule detected only 74% of advanced adenomas in one prospective multicenter trial, the researchers noted. Since then, the PillCam COLON 2 capsule has been updated with motion detection, variable frame speed, and a wider angle view, they said. In smaller studies, it detected up to 89% of subjects with polyps of at least 6 mm, but its specificity was as low as 64%.

To further investigate the technology, researchers at 16 centers in the United States and Israel compared the second-generation capsule with conventional colonoscopy in an average-risk screening population of 884 asymptomatic subjects. Endoscopists were blinded as to technique, but performed unblinded follow-up colonoscopies in subjects who were positive on capsule but negative on conventional colonoscopy.

The capsule’s sensitivity was 81% (95% confidence interval, 77%-84%) and its specificity was 93% (91%-95%) for detecting subjects who had polyps of at least 6 mm, the researchers reported. Sensitivity was 80% (74%-86%) and specificity was 97% (96%-98%) for detecting subjects with polyps of at least 10 mm. For conventional adenomas of at least 6 mm, sensitivity was 88% (82%-93%) and specificity was 82% (80%-83%), and for adenomas of 10 mm or larger, sensitivity was 92% (82%-97%) and specificity was 95% (94%-95%).

“Lesions in the serrated class were not detected well by the capsule in this study, compared with conventional adenomas,” the researchers reported. Prior studies of the capsule did not look for serrated lesions, and in the current study sensitivities were only 29% and 33% for 6-mm and 10-mm lesions, respectively.

The software used to measure polyps during capsule colonoscopy had a 40% error range when tested on balls of known size, the researchers said. Therefore, there is a strict location-matching rule within the colon, but a liberal size rule that only required measurements to fall within 50% of one another to be considered a match. “Any set of matching rules for polyps detected by the capsule and colonoscopy might operate to increase or decrease the calculated sensitivity of the capsule incorrectly,” they added. Also, the adenoma detection rate for conventional colonoscopy was only 39%, and some polyps that were clearly seen on capsule were not visualized on regular colonoscopy. “In these cases, a polyp that should be a true positive for the capsule was counted as false,” they added. “Both colonoscopy and capsule are inferior for localization, compared with CT colonography. Inaccurate localization by one or both tests in this study could have reduced the sensitivity of the capsule.”

The investigators also had to exclude 77 patients because of inadequate cleansing and short transit times related to using sodium phosphate as a boost, they noted. The Food and Drug Administration label for the capsule is expected to reflect those limitations, they added.

Given Imaging funded the study and paid consulting or other fees to Dr. Rex and six coauthors. The other authors reported having no relevant conflicts of interest.

Oxidized low-density lipoprotein prevented hepatitis C virus from entering liver cells and predicted interferon response among patients with chronic HCV infection, researchers reported online in the May issue of Cellular and Molecular Gastroenterology and Hepatology (2015 March 14 [doi:10.1016/j.jcmgh.2015.03.002]).

“Even as all-oral regimens begin to reach the market, interferon-based treatment will continue to be used in cost-restrained settings. Thus, there is a need for predictors of who is likely to respond to interferon and who will require a more expensive direct-acting antiviral combination regimen,” said Dr. Philipp Solbach of Medizinische Hochschule Hannover and the German Center for Infection Research and his associates. Combinations of interferon and viral entry inhibitors might benefit patients with chronic HCV infection (CHC), the investigators added.

Hepatitis C virus spreads between hepatocytes with the help of several cell surface receptors, including scavenger receptor class B type 1 (SR-BI). Research has shown that oxidized low-density lipoprotein (oxLDL) noncompetitively inhibits the interaction between SR-B1 and HCV. To further study the role of oxLDL in CHC pathology, the investigators used a commercial enzyme-linked immunosorbent assay test to measure serum levels in 379 patients with genotype 1 CHC from the INDIV-2 study. Patients in that study received a pegylated interferon-ribavirin combination for 24-72 weeks, depending on baseline viral load. Dr. Solbach and his associates also studied the effects of oxLDL on HCV replication in hepatoma cells.

Average serum oxLDL levels were significantly higher among patients who achieved SVR on peg-IFN/RBV than in those who did not (7.1 mU/L [standard deviation, 3.2] vs. 5.9 mU/L [SD, 2.6]; P < .001), the researchers reported. In the multivariate analysis, oxLDL levels independently predicted SVR, but were not associated with increased ALT or ferritin levels, both of which point to liver inflammation. Increased serum oxLDL also was linked to decreased infected cell loss rate, further supporting the idea that oxLDL helps inhibit cell-to-cell spread of HCV in chronically infected patients, they said.

Area under the receiver operative curve (AUROC) values were similar for LDL and oxLDL, indicating that one value was a good clinical indicator of the other, the investigators said. The optimal cutoff points to predict SVR in their model were 8.85 mU/L for oxLDL and 3.6 mmol/L for LDL.

In the in vitro study, oxLDL did not affect the sensitivity of HCV replication to interferon, but strongly inhibited the spread of HCV between adjacent hepatocytes, the investigators reported. “We found that oxLDL but not LDL potently inhibits cell-to-cell spread between neighboring cells,” they noted. “Cell-to-cell spread is thought to be the dominant route of new cell infection within the chronically infected liver.”

Taken together, the findings suggest that HCV needs to interact with SR-BI in order to spread between hepatocytes, that oxLDL can impede that interaction and thereby limit infection of naive cells, and that oxLDL is neither an inflammatory marker nor a modulator of interferon response, Dr. Solback and his associates said. “The slower second-phase decline of viral load during interferon-based therapy is thought to reflect a declining pool of infected hepatocytes, and the slope of second-phase decline and even more the estimated viral kinetic parameter describing the infected cell loss rate is predictive of eventual SVR,” they added. “The presence of an agent reducing the rate at which naive cells get infected might thus be beneficial.”

The Germany Center for Infection Research partially funded the study. Five coauthors reported having served as clinical researchers, consultants, or speakers for MSD/Merck and Roche. The other authors declared no conflicts of interest.

Oxidized low-density lipoprotein prevented hepatitis C virus from entering liver cells and predicted interferon response among patients with chronic HCV infection, researchers reported online in the May issue of Cellular and Molecular Gastroenterology and Hepatology (2015 March 14 [doi:10.1016/j.jcmgh.2015.03.002]).

“Even as all-oral regimens begin to reach the market, interferon-based treatment will continue to be used in cost-restrained settings. Thus, there is a need for predictors of who is likely to respond to interferon and who will require a more expensive direct-acting antiviral combination regimen,” said Dr. Philipp Solbach of Medizinische Hochschule Hannover and the German Center for Infection Research and his associates. Combinations of interferon and viral entry inhibitors might benefit patients with chronic HCV infection (CHC), the investigators added.

Hepatitis C virus spreads between hepatocytes with the help of several cell surface receptors, including scavenger receptor class B type 1 (SR-BI). Research has shown that oxidized low-density lipoprotein (oxLDL) noncompetitively inhibits the interaction between SR-B1 and HCV. To further study the role of oxLDL in CHC pathology, the investigators used a commercial enzyme-linked immunosorbent assay test to measure serum levels in 379 patients with genotype 1 CHC from the INDIV-2 study. Patients in that study received a pegylated interferon-ribavirin combination for 24-72 weeks, depending on baseline viral load. Dr. Solbach and his associates also studied the effects of oxLDL on HCV replication in hepatoma cells.

Average serum oxLDL levels were significantly higher among patients who achieved SVR on peg-IFN/RBV than in those who did not (7.1 mU/L [standard deviation, 3.2] vs. 5.9 mU/L [SD, 2.6]; P < .001), the researchers reported. In the multivariate analysis, oxLDL levels independently predicted SVR, but were not associated with increased ALT or ferritin levels, both of which point to liver inflammation. Increased serum oxLDL also was linked to decreased infected cell loss rate, further supporting the idea that oxLDL helps inhibit cell-to-cell spread of HCV in chronically infected patients, they said.

Area under the receiver operative curve (AUROC) values were similar for LDL and oxLDL, indicating that one value was a good clinical indicator of the other, the investigators said. The optimal cutoff points to predict SVR in their model were 8.85 mU/L for oxLDL and 3.6 mmol/L for LDL.

In the in vitro study, oxLDL did not affect the sensitivity of HCV replication to interferon, but strongly inhibited the spread of HCV between adjacent hepatocytes, the investigators reported. “We found that oxLDL but not LDL potently inhibits cell-to-cell spread between neighboring cells,” they noted. “Cell-to-cell spread is thought to be the dominant route of new cell infection within the chronically infected liver.”

Taken together, the findings suggest that HCV needs to interact with SR-BI in order to spread between hepatocytes, that oxLDL can impede that interaction and thereby limit infection of naive cells, and that oxLDL is neither an inflammatory marker nor a modulator of interferon response, Dr. Solback and his associates said. “The slower second-phase decline of viral load during interferon-based therapy is thought to reflect a declining pool of infected hepatocytes, and the slope of second-phase decline and even more the estimated viral kinetic parameter describing the infected cell loss rate is predictive of eventual SVR,” they added. “The presence of an agent reducing the rate at which naive cells get infected might thus be beneficial.”

The Germany Center for Infection Research partially funded the study. Five coauthors reported having served as clinical researchers, consultants, or speakers for MSD/Merck and Roche. The other authors declared no conflicts of interest.

Oxidized low-density lipoprotein prevented hepatitis C virus from entering liver cells and predicted interferon response among patients with chronic HCV infection, researchers reported online in the May issue of Cellular and Molecular Gastroenterology and Hepatology (2015 March 14 [doi:10.1016/j.jcmgh.2015.03.002]).

“Even as all-oral regimens begin to reach the market, interferon-based treatment will continue to be used in cost-restrained settings. Thus, there is a need for predictors of who is likely to respond to interferon and who will require a more expensive direct-acting antiviral combination regimen,” said Dr. Philipp Solbach of Medizinische Hochschule Hannover and the German Center for Infection Research and his associates. Combinations of interferon and viral entry inhibitors might benefit patients with chronic HCV infection (CHC), the investigators added.

Hepatitis C virus spreads between hepatocytes with the help of several cell surface receptors, including scavenger receptor class B type 1 (SR-BI). Research has shown that oxidized low-density lipoprotein (oxLDL) noncompetitively inhibits the interaction between SR-B1 and HCV. To further study the role of oxLDL in CHC pathology, the investigators used a commercial enzyme-linked immunosorbent assay test to measure serum levels in 379 patients with genotype 1 CHC from the INDIV-2 study. Patients in that study received a pegylated interferon-ribavirin combination for 24-72 weeks, depending on baseline viral load. Dr. Solbach and his associates also studied the effects of oxLDL on HCV replication in hepatoma cells.

Average serum oxLDL levels were significantly higher among patients who achieved SVR on peg-IFN/RBV than in those who did not (7.1 mU/L [standard deviation, 3.2] vs. 5.9 mU/L [SD, 2.6]; P < .001), the researchers reported. In the multivariate analysis, oxLDL levels independently predicted SVR, but were not associated with increased ALT or ferritin levels, both of which point to liver inflammation. Increased serum oxLDL also was linked to decreased infected cell loss rate, further supporting the idea that oxLDL helps inhibit cell-to-cell spread of HCV in chronically infected patients, they said.

Area under the receiver operative curve (AUROC) values were similar for LDL and oxLDL, indicating that one value was a good clinical indicator of the other, the investigators said. The optimal cutoff points to predict SVR in their model were 8.85 mU/L for oxLDL and 3.6 mmol/L for LDL.

In the in vitro study, oxLDL did not affect the sensitivity of HCV replication to interferon, but strongly inhibited the spread of HCV between adjacent hepatocytes, the investigators reported. “We found that oxLDL but not LDL potently inhibits cell-to-cell spread between neighboring cells,” they noted. “Cell-to-cell spread is thought to be the dominant route of new cell infection within the chronically infected liver.”

Taken together, the findings suggest that HCV needs to interact with SR-BI in order to spread between hepatocytes, that oxLDL can impede that interaction and thereby limit infection of naive cells, and that oxLDL is neither an inflammatory marker nor a modulator of interferon response, Dr. Solback and his associates said. “The slower second-phase decline of viral load during interferon-based therapy is thought to reflect a declining pool of infected hepatocytes, and the slope of second-phase decline and even more the estimated viral kinetic parameter describing the infected cell loss rate is predictive of eventual SVR,” they added. “The presence of an agent reducing the rate at which naive cells get infected might thus be beneficial.”

The Germany Center for Infection Research partially funded the study. Five coauthors reported having served as clinical researchers, consultants, or speakers for MSD/Merck and Roche. The other authors declared no conflicts of interest.

Hospital mortality among patients with cirrhosis fell by 41% in the United States between 2002 and 2010, far outpacing improvements in survival among inpatients who did not have cirrhosis, researchers reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.032]).

The drop occurred even though cirrhosis inpatients were older and had more comorbidities by the end, compared with the beginning of the study, said Monica Schmidtat the University of North Carolina Liver Center and the Gillings School of Global Public Health in Chapel Hill, N.C., and her associates. The finding was “remarkably consistent across several cirrhosis complications, and [suggested] improving cirrhosis care that may extend beyond general improvements in inpatient care,” the researchers added. “On the other hand, sepsis had an increasing mortality risk, suggesting that cirrhotic patients may need a more tailored approach to sepsis,” they said.

©Sebastian Kaulitzki/thinkstockphotos.com

Source: American Gastroenterological Association

New treatments have emerged in the past 10-15 years for several complications of cirrhosis, including hepatorenal syndrome, variceal bleeding, spontaneous bacterial peritonitis, ascites, and hepatocellular carcinoma, Ms. Schmidt and her associates noted. To study the extent to which these advances and updated guidelines have entered hospital practice, they examined 781,515 hospitalizations with a diagnosis of cirrhosis, and equal numbers of hospitalizations without cirrhosis or with congestive heart failure. Data were from the National Inpatient Sample of the Healthcare Cost and Utilization Project, which includes 46 states and is the single largest all-payer inpatient database in the country. Cohorts were matched by age, sex, and year of hospital discharge from 2002 through 2010.

Hospital mortality among cirrhosis patients dropped by 41% (from 9.1% to 5.4%) during the 8 years of the study, compared with declines of 44% for inpatients with congestive heart failure and 19% for inpatients without cirrhosis, the investigators said. Furthermore, the independent risk of dying in the hospital among cirrhosis patients declined steadily to 0.50 by the end of the study (95% confidence interval, 0.48-0.52), despite the population’s increasing age and medical complexity. Hospital mortality rates were higher for subgroups of cirrhosis patients with hepatorenal syndrome, hepatocellular carcinoma, variceal bleeding, and spontaneous bacterial peritonitis, but independent mortality risks for each of these conditions fell progressively over time, the investigators noted.

In contrast, cirrhosis inpatients with sepsis were 22% more likely to die in the hospital in 2010 than in 2002 (relative risk in 2002, 3.6; 95% CI, 3.3-3.95; RR in 2010, 4.6; 95% CI, 4.4-4.8), the researchers found. The increase was so marked that the mortality risk related to sepsis in 2010 exceeded even that for hepatorenal syndrome, they said. The unexpected finding contradicted a report of declining overall sepsis-related mortality, which was based on the same data source and a similar time period, the investigators noted.

“Cirrhosis patients have particularly poor hemodynamic reserve, with wider perturbations in immune inflammatory and compensatory responses that could hinder survival,” they commented. “Therefore, it is possible that cirrhosis patients are doing much worse with sepsis, compared with other patients. The surviving sepsis campaign may need guidelines that specifically target cirrhosis patients.”

The National Institutes of Health partly funded the study. The authors reported having no relevant conflicts of interest.

Hospital mortality among patients with cirrhosis fell by 41% in the United States between 2002 and 2010, far outpacing improvements in survival among inpatients who did not have cirrhosis, researchers reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.032]).

The drop occurred even though cirrhosis inpatients were older and had more comorbidities by the end, compared with the beginning of the study, said Monica Schmidtat the University of North Carolina Liver Center and the Gillings School of Global Public Health in Chapel Hill, N.C., and her associates. The finding was “remarkably consistent across several cirrhosis complications, and [suggested] improving cirrhosis care that may extend beyond general improvements in inpatient care,” the researchers added. “On the other hand, sepsis had an increasing mortality risk, suggesting that cirrhotic patients may need a more tailored approach to sepsis,” they said.

©Sebastian Kaulitzki/thinkstockphotos.com

Source: American Gastroenterological Association

New treatments have emerged in the past 10-15 years for several complications of cirrhosis, including hepatorenal syndrome, variceal bleeding, spontaneous bacterial peritonitis, ascites, and hepatocellular carcinoma, Ms. Schmidt and her associates noted. To study the extent to which these advances and updated guidelines have entered hospital practice, they examined 781,515 hospitalizations with a diagnosis of cirrhosis, and equal numbers of hospitalizations without cirrhosis or with congestive heart failure. Data were from the National Inpatient Sample of the Healthcare Cost and Utilization Project, which includes 46 states and is the single largest all-payer inpatient database in the country. Cohorts were matched by age, sex, and year of hospital discharge from 2002 through 2010.

Hospital mortality among cirrhosis patients dropped by 41% (from 9.1% to 5.4%) during the 8 years of the study, compared with declines of 44% for inpatients with congestive heart failure and 19% for inpatients without cirrhosis, the investigators said. Furthermore, the independent risk of dying in the hospital among cirrhosis patients declined steadily to 0.50 by the end of the study (95% confidence interval, 0.48-0.52), despite the population’s increasing age and medical complexity. Hospital mortality rates were higher for subgroups of cirrhosis patients with hepatorenal syndrome, hepatocellular carcinoma, variceal bleeding, and spontaneous bacterial peritonitis, but independent mortality risks for each of these conditions fell progressively over time, the investigators noted.

In contrast, cirrhosis inpatients with sepsis were 22% more likely to die in the hospital in 2010 than in 2002 (relative risk in 2002, 3.6; 95% CI, 3.3-3.95; RR in 2010, 4.6; 95% CI, 4.4-4.8), the researchers found. The increase was so marked that the mortality risk related to sepsis in 2010 exceeded even that for hepatorenal syndrome, they said. The unexpected finding contradicted a report of declining overall sepsis-related mortality, which was based on the same data source and a similar time period, the investigators noted.

“Cirrhosis patients have particularly poor hemodynamic reserve, with wider perturbations in immune inflammatory and compensatory responses that could hinder survival,” they commented. “Therefore, it is possible that cirrhosis patients are doing much worse with sepsis, compared with other patients. The surviving sepsis campaign may need guidelines that specifically target cirrhosis patients.”

The National Institutes of Health partly funded the study. The authors reported having no relevant conflicts of interest.

Hospital mortality among patients with cirrhosis fell by 41% in the United States between 2002 and 2010, far outpacing improvements in survival among inpatients who did not have cirrhosis, researchers reported in the May issue of Gastroenterology (2015 [doi:10.1053/j.gastro.2015.01.032]).

The drop occurred even though cirrhosis inpatients were older and had more comorbidities by the end, compared with the beginning of the study, said Monica Schmidtat the University of North Carolina Liver Center and the Gillings School of Global Public Health in Chapel Hill, N.C., and her associates. The finding was “remarkably consistent across several cirrhosis complications, and [suggested] improving cirrhosis care that may extend beyond general improvements in inpatient care,” the researchers added. “On the other hand, sepsis had an increasing mortality risk, suggesting that cirrhotic patients may need a more tailored approach to sepsis,” they said.

©Sebastian Kaulitzki/thinkstockphotos.com

Source: American Gastroenterological Association

New treatments have emerged in the past 10-15 years for several complications of cirrhosis, including hepatorenal syndrome, variceal bleeding, spontaneous bacterial peritonitis, ascites, and hepatocellular carcinoma, Ms. Schmidt and her associates noted. To study the extent to which these advances and updated guidelines have entered hospital practice, they examined 781,515 hospitalizations with a diagnosis of cirrhosis, and equal numbers of hospitalizations without cirrhosis or with congestive heart failure. Data were from the National Inpatient Sample of the Healthcare Cost and Utilization Project, which includes 46 states and is the single largest all-payer inpatient database in the country. Cohorts were matched by age, sex, and year of hospital discharge from 2002 through 2010.

Hospital mortality among cirrhosis patients dropped by 41% (from 9.1% to 5.4%) during the 8 years of the study, compared with declines of 44% for inpatients with congestive heart failure and 19% for inpatients without cirrhosis, the investigators said. Furthermore, the independent risk of dying in the hospital among cirrhosis patients declined steadily to 0.50 by the end of the study (95% confidence interval, 0.48-0.52), despite the population’s increasing age and medical complexity. Hospital mortality rates were higher for subgroups of cirrhosis patients with hepatorenal syndrome, hepatocellular carcinoma, variceal bleeding, and spontaneous bacterial peritonitis, but independent mortality risks for each of these conditions fell progressively over time, the investigators noted.

In contrast, cirrhosis inpatients with sepsis were 22% more likely to die in the hospital in 2010 than in 2002 (relative risk in 2002, 3.6; 95% CI, 3.3-3.95; RR in 2010, 4.6; 95% CI, 4.4-4.8), the researchers found. The increase was so marked that the mortality risk related to sepsis in 2010 exceeded even that for hepatorenal syndrome, they said. The unexpected finding contradicted a report of declining overall sepsis-related mortality, which was based on the same data source and a similar time period, the investigators noted.

“Cirrhosis patients have particularly poor hemodynamic reserve, with wider perturbations in immune inflammatory and compensatory responses that could hinder survival,” they commented. “Therefore, it is possible that cirrhosis patients are doing much worse with sepsis, compared with other patients. The surviving sepsis campaign may need guidelines that specifically target cirrhosis patients.”

The National Institutes of Health partly funded the study. The authors reported having no relevant conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.